bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16341: Trends of Inpatient Burden of Primary Pulmonary Hypertension in USA: Analysis of Nationwide Inpatient Sample Database From 2001-2012
Authors: Anand Vidhu , Thenappan Thenappan
Published: March 2022

Background:
Primary pulmonary hypertension (PPH) is a rare pulmonary vascular disease characterized by endothelial dysfunction and vascular remodeling of small pulmonary arteries, resulting in elevated pulmonary artery pressures. The cause of endothelial dysfunction is usually unknown. PPH is a progressive disease resulting in reduced cardiac output, right heart failure, and death. We aimed to evaluate the characteristics of hospitalizations for PPH in United States.

Methods:
We analyzed the National Inpatient Sample Database (NIS) for all subjects in which PPH (ICD code 416.0) was the principal discharge diagnosis from 2001-2012. Data is presented as mean ± SE.

Results:
In 2001, there were 3177 admissions with a principal discharge diagnosis of PPH as compared to 1345 in 2012 (p<0.001) (Figure). Rate of discharge per 100,000 persons decreased significantly from 1.1 ± 0.1 to 0.4± 0.0 (p<0.001). However, the mean length of stay (7.03±0.5 in 2001 vs 7.6±0.6 in 2001, p= 0.5) and in-patient mortality (7.75±1.07 % in 2001 vs 6.32±1.68 % in 2001, p= 0.47) has not changed significantly between 2001 and 2012. It is important to note that during this period the mean hospital charges increased by 269.8 % from $29507 per patient in 2001 to $79607 per patient in 2012 (p<0.0001).

In 2012, 68% of patients were between ages 45-84 years and 72.9% were females. Medicare was billed for about half the hospital stays in 2012 (49.4%). The routine discharges constituted about 62.45% of total discharges, followed by home health care (18.6%) and nursing home/ rehab (6.7%).

Conclusion:
The number of inpatient admissions and rate of discharge for primary pulmonary hypertension has decreased significantly over the last 13 years. The cost associated with these admissions has however increased substantially, even though there is no significant change in the duration of inpatient stay and inpatient mortality rates.
Abstract 16387: Preventing Cardiovascular Disease and Sudden Cardiac Death by Pre-screening Athletes
Authors: Greeley Kaitlyn
Published: March 2022

Background:
Cardiovascular disease (CVD) and sudden cardiac death (SCD) among young athletes (YA) remains consistent and continues to influence preventative practices and pre-screening debate. In the United States, screening for SCD in young athletes follows the American Heart Association 12-step screening questions focusing on personal history, family history, and physical examination. The European Society of Cardiology (ESC) outlines a pre-participation screening (PPS) method to minimize SCD and cardiac arrest (CA) by using family history, athlete’s history in sports, physical examination, and a resting 12-lead ECG. Negative findings allow athlete to continue with sports, whereas positive findings require athletes to continue with additional diagnostic tests (echo, stress test, etc.)

Method:
Using the U.S. National Registry of Sudden Death in Athletes from the National Heart, Lung, and Blood Institute Working Group, we analyzed the annual mortality rates of sudden cardiac death in young athletes in the U.S. compared to the sudden cardiac death rates as reported through the Veneto study.

Results:
In a 1980-2006 study, using the U.S. National Registry of Sudden Death in Athletes, 1866 sudden deaths were evaluated finding 690 cases were correlated to CVD, with a leading cause of hypertrophic cardiomyopathy. Research shows that every 3 days in the U.S., we lose an athlete to SCD. A study from 1979-2004 in the Veneto region in Italy reported an annual SCD incidence of 1.9 deaths/100,000 person-years in screened young athletes and 0.79 deaths/100,000 person-years in unscreened nonathletic participants. Additionally, the study found an 89% decrease in SCD in athletes with 3.6/100,000 person-years from 1979-1980 and a reported 0.4/100,000 person-years in 2003-2004.

Conclusion:
In the U.S., 690 sudden cardiac deaths out of 1866 sudden deaths (leading cause as hypertrophic cardiomyopathy) may have been detected using the PPS by adding an ECG to the pre-screening examination. It remains significant that the Veneto study demonstrated little change in SCD in unscreened non-athletes throughout 1979-2004 but notes a significant 89% decrease in SCD in screened athletes paralleling with the 1982 implementation of pre-participation screening.
Abstract 16405: Prevention of HeartMate II Pump Thrombosis - Recommendations and Preliminary Observations From the PREVENT Study
Authors: Emani Sitaramesh , Keebler Mary , Ransom John M , Kilic Ahmet , Egnacyzk Gregory , Gallegos Robert , Mather Paul , Stulak John , Gregoric Igor , Katz Jason , Klodell Charles T , Uriel Nir , O’Connell John B , Farrar David , Sundareswaran Kartik , Maltais Simon
Published: March 2022

Introduction and hypothesis:
Recent data have indicated an increase in the rate of early, confirmed pump thrombosis of the HeartMate II (HMII) left ventricular assist device. Factors related to this increase were not known, but one of the hypotheses was change in clinical management over time. The PREVENT (
PREVEN
tion of Heartmate II Pump
T
hrombosis through Clinical Management) study was designed to evaluate the impact of clinical practices developed to reduce the risk of HMII pump thrombosis.

Methods:
PREVENT is a prospective, multi-center, single-arm, non-randomized study of up to 300 patients at up to 25 sites. Patient and pump management, including implant technique, anticoagulation, and pump settings are guided by protocol (Table 1). Primary endpoint is incidence of confirmed pump thrombosis at 3 months, with a total follow-up of 6 months. Presented here are the preliminary results from the first 100 subjects enrolled.

Results:
Median age was 61 years [25-79], 87% were male, and 79% were destination therapy. At implant, 9% were in INTERMACS Profile1, 68% Profiles 2-3, and 22% Profiles 4-7. Preliminary analysis of 90-day outcomes demonstrated an incidence of 1% for confirmed and 2% for suspected thrombosis with a 38% incidence of INTERMACS-defined bleeding. Adherence to the protocol recommendations was as follows: 91% of the pumps were anchored, 97% of the patients were bridged with heparin, median pump speed at 1 month was 9190 [range: 8400-10000], with 93% of the patients having a pump speed > 8600, and 78% of the patients having pump speeds > 9000. Median INR per patient was 2.2 [IQR: 2.0-2.4]. Overall Kaplan-Meier survival was 93%.

Conclusions:
Preliminary results are encouraging and suggest good adherence to the PREVENT protocol and low rates of pump thrombosis without a resultant increase in bleeding complications. Overall survival after HM II implantation remains excellent.
Abstract 16493: Is it Possible to Achieve High Quality CPR by Mass Training? A Randomized Manikin Study
Authors: Contri Enrico , Baldi Enrico , Cornara Stefano , Fina Dario , Zelaschi Beatrice , Tonani Michela , Fichtner Ferdinando , Somaschini Alberto
Published: March 2022

Introduction:
ILCOR 2010 Guidelines stressed the importance of high-quality CPR to improve cardiac arrest survival. However, it is crucial to train the largest number of people. Mass Training could achieve both this goals, but there is a lack of data about its efficacy.

Hypothesis:
The aim of our randomized controlled manikin study was to assess the quality of chest compressions after Mass Training in comparison to standard BLS training.

Methods:
We randomly divided 200 CPR-untrained lay people in two groups with an allocation ratio 1:1. Group 1 was trained with a standard BLS course (1-h theory and 4-h practice) on a classic BLS manikin with an instructor:attendee:manikin ratio of 1:5:1. Group 2 was trained with a Mass Training course (30-mins theory and 45-mins practice) on a low-budget inflatable manikin with an instructor:attendee:manikin ratio of 1:15:15. At the end of both courses we recorded 1-min compression-only CPR for every participant using a skill evaluator manikin. We measured: percentage of adequate compression depth (target 5 cm) (Cdepth%), compressions per minute (Cmin), percentage of correctly released compressions (target 0 cm) (Crel%) and percentage of correct hand position (Cpos%).

Results:
Anthropometric variables did not significantly differ between the two groups. There was no significant difference (calculated with Mann-Whitney test) between group 1 and group 2 regarding Cdepth% (80.7% (95%CI, 51.9-95.2) vs 78% (95%CI, 57.9-90.6), p=0.733) and Cpos% (100% (95%CI, 100-100) vs 100% (95%CI, 100-100, p=0.418), whilst there was a significant difference in Crel% (96% (95%CI, 92-96) vs 70.5% (95%CI, 57.7-86.3), p<0.001) and in Cmin (120 (95%CI, 117-122) vs 116 (95%CI, 114-120), p=0.037).

Conclusions:
Mass Training achieves the goal of increasing the amount of people trained in high-quality CPR: percentage of compression with correct depth and with correct hand position are similar to classic BLS Training, moreover Mass Training attendees reached the target of compressions per minute more often than the others probably because of the continuous use of a personal manikin. Nevertheless correctly released compressions were better in group 1: this could be due to the fact that the manikin used in this course has a better pressure feedback.
Abstract 16511: Discoidin Domain Receptor-1: A Novel Molecular Switch Regulating Fibrocalcific Response in Vascular Smooth Muscle Cells
Authors: Krohn Jona B , Hutcheson Joshua D , Martinez-Martinez Eduardo , Bouten Carlijn , Bendeck Michelle P , Aikawa Elena
Published: March 2022

Background:
Extracellular vesicle (EV)-derived microcalcifications formed in collagen-poor fibrous caps contribute to plaque rupture. Collagen accumulation and calcification are major determinants of plaque stability, although the mechanisms linking fibrotic and calcific responses are unknown. The collagen receptor discoidin domain receptor-1 (DDR-1) regulates plaque calcification
in vivo
; however, its role in the release of calcifying EVs remains unclear. We hypothesize that DDR-1 regulates the processes of fibrosis and EV-induced calcification in atherosclerotic plaques.

Methods and results:
Smooth muscle cells (SMC) from the carotid arteries of wild type and DDR-1 knockout (DDR-1
-/-
) mice (n=5 per group) were cultured in control or calcifying media. At days 14 and 21, cells were harvested and EVs isolated for analysis. Compared to wild type cells, DDR-1
-/-
SMCs exhibited a 3.5-fold increase in EV release (p<0.001) as well as elevated EV calcifying potential determined by EV-bound alkaline phosphatase (ALP) activity (470.4±30.0 vs. 19.1±2.3 ng/well/mg protein). DDR-1
-/-
SMCs showed an increase in ALP activity (220.3±31.2 vs. 6.9±1.2 ng/well/mg protein), calcification measured by alizarin red S absorbance (3.56±0.11 vs. 0.10±0.0008), and collagen type I accumulation (p=0.04). Transforming growth factor-β (TGFβ) signaling has been implicated in both fibrotic and calcific responses. DDR-1
-/-
cells released significantly more TGFβ in calcifying medium (253.4±12.4 vs. 167.2±8.8 pg/ml, p<0.001), suggesting a connection between DDR-1 and TGFβ signaling. A selective TGFβ receptor I inhibitor mitigated the osteogenic potential of the DDR-1
-/-
phenotype with a significant decrease in EV release, ALP activity in SMCs and EVs, extracellular matrix calcification and collagen production. Analysis of TGFβ-associated pathways in DDR-1
-/-
SMCs revealed significantly increased p38 phosphorylation while phosphorylated Smad3 and JNK were inhibited.

Conclusion:
DDR-1 interferes with TGFβ-mediated p38 phosphorylation to restrict EV-induced calcification. DDR-1 concomitantly attenuates collagen accumulation in vascular SMCs, establishing a novel mechanism of cell-matrix interaction in arterial fibrocalcific responses.
Abstract 16514: Screening for Outflow Cannula Malfunction of Left Ventricular Assist Devices Using Doppler Echocardiography: Establishing New Reference Values
Authors: Grinstein Jonathan , Kruse Eric , Sayer Gabriel , Fedson Savitri , Kim Gene H , Sarswat Nitasha , Adatya Sirtaz , Ota Takeyoshi , Jeevanandam Valluvan , Mor-Avi Victor , Uriel Nir , Lang Roberto
Published: March 2022

Background:
Echocardiographic assessment of left ventricular assist devices (LVAD) is used as a screening tool to evaluate the integrity and mechanics of the pump and circuit. We aimed to 1) establish the normal range and upper reference limit of peak velocity of the outflow cannula for the modern era of LVADs and 2) assess the performance of the current reference limit and our new reference limit in patients with continuous flow LVADs as a screening tool for cannula malfunction.

Methods:
LVAD outflow peak velocities were measured with Doppler echocardiography (TTE) in 57 patients with LVADs (HeartMate II (HMII) = 44, HeartWare (HW) = 13). The average velocity and the upper and lower normal reference limits (defined as +/- two standard deviations from the mean) for each LVAD type was then calculated. The upper reference limit was then used as a screening threshold for cannula malfunction.

Results:
The average outflow cannula peak velocity for the HMII cohort was 1.94 m/sec +/- 0.42 with an upper and lower reference limit of 2.78 m/sec and 1.10 m/sec, respectively. The average outflow cannula peak velocity for the HW cohort was 2.36 +/- 0.53 with an upper and lower reference limit of 3.42 m/sec and 1.3 m/sec, respectively, which was significantly higher than the HMII cohort (p=0.004). Velocities from both cohorts were dramatically higher than the commonly citied upper reference limit velocities of 2 m/sec. Use of the previously cited reference limit poorly discriminated between normal and malfunctioning LVAD cannulas whereas our new reference limit identified all four patients with outlet cannula malfunction (Figure1).

Conclusions:
In both HeartMate II and HeartWare LVADs, the average peak outflow velocity and reference limit for the normal population as measured by Doppler-TTE was markedly higher than currently cited LVAD reference limits. Patients with peak outflow velocities above our upper reference limit should be evaluated for LVAD outflow cannula malfunction.
Abstract 16520: Association Between Blush Grade and Wound Healing or Amputation in Critical Limb Ischemia
Authors: Kang Won Yu , Campia Umberto , Bernardo Nelson L , Didier Romain , Negi Smita , Kiramijyan Sarkis , Koifman Edward , Baker Nevin , Lipinski Michael , Escarcega Ricardo , Torguson Rebecca , Waksman Ron
Published: March 2022

Background:
Percutaneous endovascular intervention (PEI) of below-the-knee arteries is the first-line approach for treatment in critical limb ischemia (CLI). However, intraprocedural predictors of outcomes in CLI have not been established. We aimed to investigate the role of blush grade in predicting wound healing and amputation in patients undergoing PEI for CLI.

Methods:
This study is a retrospective analysis of data of consecutive patients who underwent PEI for CLI and had follow-up for outcomes between January 2011 and December 2014 at the MedStar Washington Hospital Center in Washington, DC. Blush grade was defined as the percent value of blush on the wound area compared to the blush on an area supplied by normal blood flow. The patients were classified into two groups (Group I: blush grade ≥50% [n=26] vs. Group II: <50% [n=28]) and examined wound healing at 6 month and amputation.

Results:
A total of 54 patients were included in the present study. Blush grade was ≥50% in 26 patients and <50% in 28. Participants had a high prevalence of male sex (72%), diabetes (74%), hypertension (98%), hyperlipidemia (94%), hemodialysis (24%), and previous diagnosis of peripheral arterial disease (74%). No significant differences in the prevalence of these variables were shown between groups. Angiosome-based treatment was performed for the majority of patients, without significant difference between groups (88.5% in Group I vs. 85.7% in Group II, p=1.0). Direct flow to wound could be obtained more frequently in Group I (76.9% vs. 21.4%, p<0.001). Wound healing within 6 month was observed in 65.4% in Group I compared with 10.7% in Group II (p<0.001). Rates of amputation were 15.4% and 57.1%, respectively (p=0.001), with longer time-to-amputation in Group I compared with Group II (403.52±337.55 vs. 233.16±267.89, respectively; p=0.044). On multivariable analysis, a blush grade ≥50% was an independent predictor of wound healing (RR 0.051, 95% CI: 0.008-0.319, p=0.001) and amputation free survival (RR 4.12, 95% CI: 1.206-14.755, p=0.024).

Conclusion:
Our single-center data indicate that blush grade is an independent intraprocedural predictor of wound healing and amputation in patients with CLI.
Abstract 16524: Cardiac MRI Evaluation of Myocardial Deformation in Repaired Tetralogy of Fallot Provides Insight Into Right Ventricular Mechanics
Authors: Goot Benjamin , Punithakumar Kumaradevan , Tham Edythe , Noga Michelle
Published: March 2022

Introduction:
Pulmonary regurgitation or stenosis after repaired tetralogy of Fallot (TOF) impacts the long-term ventricular mechanics. Our objective was to measure RV myocardial deformation using novel CMR software in repaired TOF. We postulate that RV strain will correlate with cardiac MRI (CMR) volumetric data.

Methods:
Retrospective study of 55 patients s/p TOF repair compared to 40 normal controls. RV longitudinal strain was measured from the standard 4-chamber view and circumferential strain from the short axis slice apical to the RV outflow tract. Using CMR software developed in-house that utilizes a semi-automatic segmentation program, peak strain was identified. Unpaired t test assessed differences between groups and correlation was performed between strain and volumetric data.

Results:
The predominant lesion was regurgitation in 48 (regurgitant fraction (RF) 43±2%), stenosis in 10 (peak gradient 32±2 mmHg), and mixed in 4. Longitudinal strain was reduced in TOF compared to controls while circumferential strain was preserved (Table 1). Correlations found reduced strain with increasing volumes and decreasing right ventricular ejection fraction (RVEF) (Table 2). Longitudinal:circumferential ratio (L/C) increased with increasing volumes and decreasing RVEF. No relationship was found between RV strain and RF.

Conclusions:
The relationships between longitudinal and circumferential strain, and the L/C ratio with RV volumes and RVEF suggest that preservation of circumferential strain is important in maintaining RV systolic function. Measurement of RV deformation may provide insight into the RV’s response to volume or pressure overload in TOF, suggesting we should focus on RV mechanical changes rather than RF when managing these patients.
Abstract 16526: Nanoparticle-mediated Targeting of Endothelial mir92a-PPAP2B Signaling Axis in Atherosclerosis
Authors: Wu Congqing , Leon Lorraine , Chung Eun Ji , Tirrell Matthew , Fang Yun
Published: March 2022

Introduction:
Atherosclerosis develops preferentially at arterial sites where endothelia are activated by local disturbed hemodynamics. We have recently demonstrated that disturbed flow suppresses PhosPhatidic-Acid-Phosphatase-type-2B (PPAP2B), an integral membrane protein also known as Lipid Phosphate Phosphatase (LPP3) that inactivates lysophosphatidic acid (LPA) and is implicated in coronary artery disease (CAD) by genome-wide association studies. Reduced PPAP2B was detected in athero-susceptible arterial sites exposed to disturbed flow in mice, swine and humans, resulting from elevated miR-92a. PPAP2B inhibition drives the inflammatory and permeable endothelial phenotype by activating LPA-stimulated signalings. Expression quantitative trait locus (eQTL) mapping demonstrated PPAP2B CAD risk allele is not linked to PPAP2B expression in various human tissues but significantly associated with reduced PPAP2B in human aortic endothelial cells (HAEC).

Hypothesis:
Given the critical role of PPAP2B in mediating the athero-resistant endothelial phenotype, we test the hypothesis that miR-92a inhibition that elevates PPAP2B can promote vascular health and alleviate atherosclerotic burdens. Novel nanoparticles are designed to spatially target dysfunctional endothelia and deliver miR-92a inhibitors.

Methods:
Polyelectrolyte complex micelles were engineered to encapsulate charged nucleic acids (miR-92a inhibitors) forming a core by neutralizing their charge. Valine-Histidine-Proline-Lysine-Glutamine-Histidine-Arginine (VHPKQHR), which was identified via phage display and binds vascular endothelial cells through the vascular cell adhesion molecule-1 (VCAM-1), was incorporated to the miRNA inhibitor-containing polyelectrolyte complex micelles to target inflammatory endothelia and facilitate the cellular uptake.

Results and Conclusions:
We have successfully engineered lesion-targeting polyelectrolyte complex micelles as an innovative delivery system for therapeutic nucleotides and tested their effectiveness in inhibiting miR-92a signaling in vitro in HAEC. Moreover, miR-92a inhibitor-containing micelles significantly reduced the lesion size in ApoE(-/-) mouse model of atherosclerosis in vivo.
Abstract 16543: Concomitant Left Atrial Appendage Closure During Cardiac Surgery: A Meta-analysis
Authors: Aggarwal Saurabh , Akinapelli Abhilash , Kabach Amjad , Ayan Mohamed , Saurav Alok , Bansal Ojas , Smer Aiman , Pandya Jitendra , Kaushik Manu , Alla Venkata
Published: March 2022

Introduction:
Surgical left atrial appendage (LAA) closure is an option in patients undergoing cardiac surgery who have a history of atrial fibrillation. Despite multiple studies, it is not clear whether LAA closure during cardiac surgery results in improved outcomes.

Hypothesis:
We hypothesized that LAA closure is associated with significant decrease in risk of stroke and mortality.

Methods:
We conducted Pubmed, EMBASE and CENTRAL searches for studies comparing cardiac surgery alone or with concomitant LAA closure. Efficacy outcome was future risk of stroke. Safety outcomes were total mortality and postoperative bleeding.

Results:
A total of six studies with 3267 patients fulfilled the inclusion criteria. Primary surgeries were mitral valve surgeries in four studies and coronary artery bypass grafting in 2 studies. Successful LAA closure confirmed by trans-esophageal echocardiography was achieved in 97.8% of patients. Concomitant left atrial appendage closure was not associated with any significant difference in risk of future stroke (Odds ratio (OR) 0.61, 95% Confidence Interval (CI) 0.30 to 1.24, p=0.12) or recurrence of atrial fibrillation (OR 0.92, 95% CI 0.66 to 1.29, p=0.63). However, the combined procedure was associated with lower long-term mortality (OR 0.41, 95% CI 0.22 to 0.77, p=0.005) when compared to cardiac surgery alone.

Conclusions:
Concomitant left atrial appendage closure is a safe procedure but is not associated with a significant decrease in future risk of stroke. Patients with LAA closure had significantly lower mortality but this may be related to lower long term use of anticoagulants and bleeding events in this group. These findings need to be investigated further in large prospective studies.
Abstract 16620: Enhancing transplanted Cardiac Progenitor Cells homing and survival in Ischemic Heart By CRISPR-dcas9/sgRNA-based Endogenous CXCR4 Promoter Activation
Authors: Li Youngjun , Ma Genshan , Weintraub Neal , Tang Yaoliang
Published: March 2022

Cardiac progenitor cell (CPC) therapy is promising for repairing the damaged heart, limited stem cell survivability post-transplantation has precluded widespread use of this therapy. Recent reports indicate that interactions between the CXC chemokine stromal cell-derived factor 1 and its receptor CXC chemokine receptor 4 (CXCR4) critically mediate the ischemia-induced recruitment of bone marrow-derived circulating stem/progenitor cells, but the expression of CXCR4 in cardiac progenitor cells is very low. Strategies to overexpress CXCR4 genes in CPC have been shown to improve the survival of donor cells within the ischemic myocardium. The CRISPR/dCas9-VP64/sgRNA activation system (CAS), was recently developed as a simple and efficient method in activation of endogenous loci by targeting their promoter region in mammalian cells. With single guide chimeric RNA's (sgRNA) targeting proximal promoter region of CXCR4, we found that the CAS activation system can upregulate protein level of endogenous CXCR4 gene expression about 140 fold by qRT-PCR. The CAS -CXCR4 improves CPC response to SDF-1 induced migration and survival against H2O2 induced oxidative stress. Half million CAS-Control or CAS-CXCR4 CPC were intramyocardially injected into the peri-infarction zone after myocardial infarction (MI) induced by left anterior descending coronary artery (LAD) ligation in mice. The CAS- CXCR4 gene modification improved CPC survival by bioluminescence imaging (BLI), and CAS-CXCR4 CPC also exhibited improved left ventricular (LV) ejection fraction (EF) at 3 wk after MI (n=6, P<0.05). Our results demonstrate that activation of endogenous CXCR4 expression by CRISPR/dCas9-VP64 activation system using sgRNA is very effective in improving homing and survival of donor CPC, and attenuate cardiomyopathy after MI.
Abstract 16636: Superior Vena Caval Occlusion: A Novel Approach to Improve Cardiac Function in Heart Failure
Authors: Kapur Navin K , Paruchuri Vikram , Annamalai Shiva , Buiten Lyanne , Konstam Marvin A , Karas Richard H
Published: March 2022

Cardiac preload is a primary target of drug therapy for heart failure. No device based approaches to limit preload in heart failure exist. The inferior (IVC) and superior vena cava (SVC) provide two-thirds and one-third of venous return, respectively. We hypothesized that mechanical occlusion of the SVC improves biventricular function in heart failure by reducing ventricular preload. Methods and Results: To test this hypothesis, 4 adult swine underwent 60 minutes of left anterior descending artery occlusion followed by 60 minutes of reperfusion. 1 animal expired due to ventricular fibrillation after reperfusion. The acute hemodynamic effects of transient sequential percutaneous balloon occlusion of the SVC or IVC (n=4) were studied using conductance catheters before the onset of left ventricular (LV) injury. Transient IVC occlusion significantly reduced biventricular volumes, reduced LV stroke volume, and reduced LV peak-systolic pressure (Figure). In contrast, transient SVC occlusion reduced biventricular volumes but increased LV stroke volume, without decreasing LV peak-systolic pressure (Figure). IVC occlusion increased renal vein pressure from 10 to 24 mmHg, whereas SVC occlusion did not alter renal vein pressure. One week after LV injury, the hemodynamics of prolonged SVC occlusion were studied (n=3). Full SVC occlusion for 2 hours reduced biventricular volumes, and increased LV stroke volume, without decreasing LV peak-systolic or systemic blood pressure. Conclusions: SVC occlusion represents a novel device based approach that targets cardiac preload. In contrast to IVC occlusion, transient and prolonged full SVC occlusion was well tolerated. SVC occlusion reduces biventricular volume, while increasing cardiac output and sustaining systemic blood pressure, without adversely affecting renal hemodynamics. Future studies will test the clinical utility of continuous and intermittent SVC occlusion in acute and chronic heart failure.
Abstract 16650: The Relationship Between Post Deployment Balloon Dilation and Cerebrovascular Events During Transcatheter Aortic Valve Replacement
Authors: Goel Kashish , Nkomo Vuyisile , Hoffman Scott , Slusser Joshua P , Lennon Ryan , Brown Robert D , Suri Rakesh , Greason Kevin , Holmes David R
Published: March 2022

Introduction:
The risk of stroke or transient ischemic attack (TIA) remains increased after transcatheter aortic valve replacement (TAVR), especially in the first 30 days. Limited data is available regarding the impact of procedural characteristics on risk of stroke/TIA.

Hypothesis:
Post deployment balloon dilatation (PD) and total number of balloon dilatations (pre, valve and post insertion) may be associated with increased risk of stroke/TIA in patients undergoing TAVR.

Methods:
We included consecutive patients who underwent balloon-expandable TAVR until June 2014 at Mayo Clinic, Rochester. Patients who died in the operating room, converted to open surgery, or had valve-in-valve, or underwent self-expanding TAVR were excluded. Primary end-point was stroke or TIA at 30 days.

Results:
Mean age was 80.9±8 y, mean STS score was 8.3±5 and 50% underwent transfemoral access. The overall incidence of PD was 14% (n=53). Total number of dilations ranged from 2-7, with 5% (n=19) getting ≥ 4 total dilatations. Out of the 370 patients, 13 patients (3.5%) suffered stroke/TIA (9.4% in PD group vs. 2.2% in non-PD group) in the first 30 days after TAVR. Cox-proportional hazards regression analysis indicated that PD during TAVR was associated with a significantly increased risk of 30-day stroke/TIA (HR, 3.8; 95% CI, 1.2-11.6; p=0.02). There was a trend towards increased stroke/TIA with total number of dilations (HR, 1.5; 95% CI, 0.87-2.6; p=0.14), longer procedural time (HR per 30 minutes, 1.3; 95% CI, 0.96-1.7; p=0.09) and severity of atherosclerosis (moderate-severe - HR, 1.9; 95% CI 0.95- 3.8; p=0.07). PD was not significantly associated with the risk of 30 day death (HR, 1.1; 95% CI, 0.24-4.85; p=0.93).

Conclusions:
In patients undergoing PD after balloon-expandable TAVR, 9.4% suffered a stroke or TIA in the first 30 days. PD was associated with a four-fold increase in 30 day risk of stroke or TIA.
Abstract 16657: MicroRNA-184 is Epigenetically Silenced by CpG Methylation and Contributes to the Pathogenesis of Arrhythmogenic Cardiomyopathy Phenotype
Authors: Chen Xiaofan , Gurha Priyatansh , Lombardi Raffaella , Willerson James T , Marian Ali J
Published: March 2022

Introduction:
A phenotypic characteristic of arrhythmogenic cardiomyopathy (AC) is a gradual replacement of cardiac myocytes by fibro-adipocytes, which leads to cardiac arrhythmias, dysfunction and sudden death.

Hypothesis:
Differentially expressed miRNAs contribute to the pathogenesis of AC

Results:
Control and plakophilin-2 (PKP2)-suppressed HL-1 myocytes (HL-1Pkp2-shRNA) were screened for the expression of 750 miRNA using Taqman low-density microfluidic panels. Thirty-one miRNAs were up- and 28 were down-regulated in the HL-1Pkp2-shRNA myocytes. MiR-184 was the most down-regulated miRNA (~10-fold). It was also down-regulated in the heart of mouse models of AC. MiR-184 was developmentally regulated in the mouse heart as its levels were the highest in cardiac myocytes islated from the newborn mice, the lowest in adult myocytes and intermediate in myocytes isolated from 3-week old mice. Ingenuity pathway analysis of paired miR-184 and mRNA sequencing data identified cell proliferation, differentiation and death as the major affected functions. Knock down of miR-184 by shRNA reduced cellular proliferation/viability, increased apoptosis, and enhanced adipogenesis. Levels of over a dozen regulators of lipid synthesis were increased along with fat droplets. Over-expression of miR-184 had reciprocal effects. Bisulfite sequencing identified differential hypermethylation of the CpG sites at the upstream region of miR-184. Treatment with 5-aza-2’-deoxycytidine, a demethylation agent, partially rescued suppressed miR-184 levels. However, activation or suppression of the Hippo and the canonical Wnt signaling pathways, implicated in the pathogenesis of AC, did not affect miR-184 levels. Likewise, miR-184 over-expression or suppression did not affect the Hippo and Wnt signaling.

Conclusions:
miR-184 is developmentally regulated with the highest levels of expression in the newborn myocytes. It levels are suppressed in the AC models, partially because of hypermethylation of the CpG sites at its genomic regions. MiR-184 by regulating cellular proliferation and differentiation contributes to the pathogenesis of AC.
Abstract 16675: Intraplaque Hemorrhage-induced Atherosclerotic Plaque Progression as the Bridge Between Intact and Ulcerated Plaques: An Imaging-based Natural History Study
Authors: Sun Jie , Liu Jin , Balu Niranjan , Hippe Daniel S , Xu Dongxiang , Canton Gador , Hatsukami Thomas S , Yuan Chun
Published: March 2022

Introduction:
Previous studies have associated intraplaque hemorrhage (IPH) with future ischemic events, of which the mechanisms are less understood.

Hypothesis:
Understanding morphological features and progression behaviors of plaques with and without IPH would allow us to define the role of IPH in the natural history of atherosclerosis.

Methods:
In an ongoing study, asymptomatic subjects with 16-79% stenosis on ultrasound underwent 3-dimensional carotid MRI. Those with carotid plaque(s) on MRI were recruited and a follow-up scan was performed 1-year later using the same protocol. Individual plaques (maximum thickness>1.5 mm) within scan coverage were identified in bilateral carotids, of which morphological data were collected at baseline and plaque progression was determined by comparing both scans while blinded to the time sequence.

Results:
Twenty-nine subjects have completed the study. A total of 64 de novo plaques were identified, of which 15 (23.4%) demonstrated IPH. Plaques with IPH are more likely to have an ulcerated surface than those without IPH (60.0% vs. 8.2%, odds ratio: 16.9 [3.9, 72.3]). Furthermore, there was a stepwise progression in baseline morphological measures from IPH-/ulcer- plaques to IPH+/ulcer- plaques and to ulcer+ plaques (Table), suggesting that IPH+/ulcer- plaques may be at the intermediate stage between IPH-/ulcer- and ulcer+ plaques. During the 1-year period, IPH+/ulcer- plaques had significantly greater increases in mean wall thickness and percent luminal stenosis compared to IPH-/ulcer- plaques, indicating further progression towards ulcer+ plaques. In contrast, ulcer+ plaques, as the most stenotic group, showed little plaque burden change on average.

Conclusions:
Collectively, our data support the conjecture that IPH promotes plaque progression and appears to be an intermediate step toward surface ulceration. IPH could be a critical step in phenotype transition from asymptomatic to symptomatic plaques.
Abstract 16715: Incidence of Atrial Fibrillation After Atrial Flutter Ablation: A Meta-analysis Study
Authors: Pino Maria Isabel , Ayoub Karam , Llanos Oscar L , Nairooz Ramez , Abualsuod Amjad , Hakeem Abdul , Pothineni Naga V , Paydak Hakan , Maskoun Waddah
Published: March 2022

Background:
Atrial Flutter (AFL) is usually initiated with short bursts of Atrial Fibrillation (AF). The incidence rate of AF after AFL ablation is variable. We evaluated the occurrence of AF in patients who underwent successful AFL catheter ablation with documented prior AF versus no prior AF.

Methods:
A meta-analysis was performed by searching online databases from January 1996 to April 2015 for studies describing patients who underwent typical AFL catheter ablation with and without prior AF.

Results:
A total of 36 articles were included, describing 6567 patients with typical AFL (2753 with prior AF and 3814 with no prior AF) who underwent ablation with 95% average success rate (bidirectional block). The overall incidence of AF after ablation was 35.3% (41% prior to ablation) during mean weighted follow-up (f/u) duration of 29.4 months. AF incidence after AFL ablation was 23% in patients with no prior AF and 52% in those with prior AF (OR 3.96, 95% CI [3.174.95] ; p<0.00001). Subgroup analysis based on duration of f/u showed a significant variation of this probability (p=0.0003) between the group with < 2 years f/u, compared to > 2 years f/u due to an increase of AF incidence rate in patients with no prior AF. In studies with < 2 years f/u duration, AF weighted average incidence rate after AFL ablation was 53.6 % in patients with prior AF and 14.3% in those with no prior AF (OR 6.90, 95% CI [4.5410.48] ; p<0.00001). In studies with > 2 years f/u duration, post-ablation AF developed in 51.3% of those with prior AF and in 26.3% of those with no prior AF (OR 2.93, 95% CI [2.423.56] ; p<0.00001). Figure 1

Conclusions:
Patients with prior history of AF have a higher incidence of AF after AFL ablation when compared to patients with no prior history of AF. However, this significantly decreases with extended follow-up duration due to an increase of detected AF in patients with no prior history of AF. This finding is important for decisions regarding anticoagulation plan after successful AFL ablation.
Abstract 16750: Access to Alcohol and Heart Disease Among Hospitalized Patients: A Natural Experiment
Authors: Dukes Jonathan W , Dewland Thomas A , Vittinghoff Eric , Olgin Jeffrey E , Pletcher Mark J , Hahn Judith A , Marcus Gregory M
Published: March 2022

Background:
Alcohol may have important effects on heart disease, but studies have generally relied on self-reported alcohol consumption and have yielded conflicting results. We utilized differences in county-level alcohol sales laws as a natural experiment to investigate the relationship between alcohol consumption and heart disease.

Hypothesis:
Wet counties residents have higher rates of atrial fibrillation (AF) and lower rates of myocardial infarction (MI) and congestive heart failure (CHF) related admissions.

Methods:
All counties in Texas with no restriction (“wet”) or complete prohibition (“dry”) of alcohol sales or a change in such laws between 2005 and 2010 were identified. Data from the Texas Inpatient Research Data File was used to characterize the hospitalizations of adult residents of those counties. Differences in alcohol use rates were validated using alcohol abuse and alcoholic liver disease outcomes. Adjustment covariates included age, race, ethnicity, sex, diabetes, hypertension, obesity, CHF, CAD, lung disease, and valvular disease.

Results:
Among 1,106,968 patients; wet county residents had a greater incidence of alcohol abuse (HR 1.36, 95% CI 1.23-1.50, p <0.001) and alcoholic liver disease (HR of 1.81, 95% CI 1.51-2.16, p <0.001). After adjustment, wet county residents exhibited a greater incidence of AF (HR 1.07, 95% CI 1.01-1.13, p 0.013) and a lower incidence of MI (HR 0.89, 95% CI 0.84-0.96, p 0.001). There was no statistically significance difference in CHF rates (HR 0.96, 95% CI 0.92-1.01, p 0.072). Among the seven counties that converted from dry to wet during the study period, statistically significantly higher rates of alcohol abuse, alcoholic liver disease, AF and CHF were observed after the conversion (Figure).

Conclusions:
Greater access to alcohol is associated with more alcohol abuse, alcoholic liver disease and AF, and less MI and CHF, though there is an increased risk of CHF shortly after alcohol sales are liberalized.
Abstract 16771: Feasibility of Noninvasive Assessment of Tissue Property in the Fibrotic Infarcted Myocardium Using Speckle Tracking Echocardiography
Authors: Hotta Yu , Asanuma Toshihiko , Masuda Kasumi , Nakatani Satoshi
Published: March 2022

Background:
Early systolic lengthening (ESL) and post-systolic shortening (PSS) is subtle myocardial deformation that occurs in the ischemic myocardium and is easily assessed by spekle tracking echocardiography. Because ESL and PSS in the ischemic region is caused by tension from the surrounding nonischemic region, such deformation may be attenuated in the infarcted myocardium with advanced fibrosis, which is less stretched by tension. We investigated whether the echocardiographic assessment of ESL and PSS can estimate tissue property in the fibrotic infarcted myocardium.

Methods:
In 20 rats, the left anterior descending coronary artery was occluded and short-axis images were acquired at 1 day (1D, n = 7), 1 week (1W, n = 5), and 4 weeks (4W, n = 8) after the occlusion using GE Vivid 7 (frame rate = 235.4 fps). Circumferential strains were analyzed in the ischemic and nonischemic regions, and amplitudes of ESL (ε
ESL
) and PSS (ε
PSS
), and the sum of ε
ESL
and ε
PSS
(ε
ESL+PSS
) were measured. At the end of the protocol, Masson’s trichrome staining was performed on excised hearts to measure the area of fibrous tissue within the infarcted myocardium.

Results:
The fibrous areas in the 1W and 4W were significantly larger than the 1D (1D vs. 1W vs. 4W: 3.7 ± 5.5% vs. 66.5 ± 12.8% vs. 69.5 ± 17.1%). Although there was no significant difference in the fibrous areas between the 1W and 4W, more dense staining of fibers was observed in all of the 4W. In the ischemic region, ε
ESL
, ε
PSS
, and ε
ESL+PSS
did not significantly change between the 1D and 1W. However, ε
PSS
and ε
ESL+PSS
significantly decreased and ε
ESL
tended to decrease in the 4W compared to the 1W (1W vs. 4W: ε
PSS
3.4 ± 1.1% vs. 1.4 ± 1.3%, ε
ESL+PSS
5.9 ± 1.8% vs. 2.4 ± 1.9%, p<0.05, respectively) (figure).

Conclusions:
ESL and PSS was attenuated in the infarcted myocardium with advanced fibrosis. The assessment of such subtle deformation by speckle tracking echocardiography may estimate tissue property in the fibrotic infarcted myocardium.
Abstract 16803: Relationships Between Invasive and Non-invasive Measures of Cardiac Function During Exercise in Heart Failure With Preserved or Reduced Ejection Fraction
Authors: Van Iterson Erik H , Snyder Eric M , Borlaug Barry A , Olson Thomas P
Published: March 2022

Introduction:
Assessment of cardiac function during exercise is critical in the clinical evaluation of patients with heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction. Direct invasive measurement of cardiac power (CP) and stroke work (SW) are robust measures of cardiac function. Non-invasive gas exchange based surrogates may provide practical means of assessing cardiac function in clinical and research settings; however, the relationship between invasive and non-invasive measurement of CP or SW during exercise is unclear in HFpEF and HFrEF. We aimed to assess relationships between invasive and non-invasive measures of CP and SW during exercise in HFpEF and HFrEF.

Methods:
HFpEF (n=47) and HFrEF (n=29) (age 71±10 vs 55±10 yrs; EF% 62±8 vs 21±6%; BSA 2.1±0.3 vs 2.1±0.2 m
2
; weight 99±22 vs 87±15 kg; peak work 36±14 vs 37±13 watts (W), respectively; all p<0.05, except peak work) underwent peak exercise testing during right heart catheterization. Invasive measurement of cardiac pressures, hemodynamics, and arterial pressures were recorded at rest, 20 W, and peak work. Continuous measurement of HR and VO
2
occurred from rest to peak work via 12-lead ECG and metabolic measurement system, respectively. Invasive measurements were calculated as, CP=(MAP–RAP) x Q x 2.22х10
-3
; SW=(MAP–PCWP) x SV
I
x 0.133; and non-invasive as, CP=VO
2
x MAP; SW=VO
2
/HR x MAP. All indices adjusted for body surface area.

Results:
At rest, there were moderate relationships between invasive and non-invasive measures of CP and SW in HFpEF (r=0.56 and 0.48) and HFrEF (0.57 and 0.73), respectively (all p<0.05). At 20 W, relationships between invasive and non-invasive measures of CP and SW strengthened in HFpEF (r=0.74 and 0.69) and HFrEF (0.74 and 0.72), respectively (all p<0.05). The relationships noted between invasive and non-invasive measures of CP and SW at 20 W persisted at peak work in HFpEF (r=0.74 and 0.67) and HFrEF (0.78 and 0.69), respectively (all p<0.05).

Conclusion:
These data suggest that non-invasive estimates of CP and SW correlate closely with invasive measures and may be reasonable surrogates for these indices during peak exercise testing in both HFpEF and HFrEF patients.
Abstract 16816: Association of Exhaled Carbon Monoxide With Stroke Incidence and Subclinical Vascular Brain Injury: The Framingham Study
Authors: Nayor Matthew , Enserro Danielle , Beiser Alexa S , Cheng Susan , DeCarli Charles , Vasan Ramachandran S , Seshadri Sudha
Published: March 2022

Introduction:
Exhaled carbon monoxide (CO) is associated with cardiometabolic traits, subclinical atherosclerosis, and cardiovascular disease, but its specific relations with stroke have not been explored.

Hypothesis:
We hypothesized that exhaled CO is related to MRI measures of subclinical cerebrovascular disease cross-sectionally, and to incident stroke/ transient ischemic attack (TIA) prospectively in the Framingham Offspring Study.

Methods:
We measured exhaled CO in 3313 participants (age 59±10 years, 53% women) and Brain MRI imaging was available in 1982 individuals (age 58±10, 54% women). Participants were analyzed according to tertiles of exhaled CO concentration.

Results:
In age- and sex-adjusted models, the highest tertile of exhaled CO was associated with lower total cerebral brain volumes (TCBV), higher white matter hyperintensity volumes (WMHV), and greater prevalence of silent cerebral infarcts (p <0.05 for all). The results for TCBV and WMHV were consistent after removing smokers from the sample, and the association with WMHV persisted after multivariable adjustment (p=0.04). In prospective analyses (mean follow-up 12.9 years), higher exhaled CO was associated with 67% (second tertile) and 97% (top tertile) increased incidence of stroke/TIA relative to the first tertile that served as referent (p <0.01 for both), Table. These results were consistent in nonsmokers, and were partially attenuated upon adjustment for vascular risk factors, but were maintained after adjusting for circulating biomarkers B-type natriuretic peptide and C-reactive protein, Table.

Conclusion:
In this large, community-based sample of individuals free of clinical stroke/TIA at baseline, higher exhaled CO was associated with a greater burden of subclinical cerebrovascular disease cross-sectionally, and with increased risk of stroke/TIA prospectively. Further investigation is necessary to explore the biological mechanisms linking CO with stroke.
Abstract 16838: Circulating miRNAs Can Predict Cardiac Allograft Vasculopathy in Pediatric Heart Transplant Recipients in a Sex-dependent Manner
Authors: Auerbach Scott R , Miyamoto Shelley D , Karimpour-Fard Anis , Gralla Jane , Stauffer Brian L , Sucharov Carmen C
Published: March 2022

Introduction:
MicroRNAs (miRs) are small noncoding ~22 nucleotide RNAs capable of modulating the expression of many genes. Our hypothesis was that circulating miRs are useful biomarkers of cardiac allograft vasculopathy (CAV) in pediatric heart transplant recipients (PHTR).

Methods:
An array for 765 miRs was performed using the Applied Biosystems technology normalized by a global normalization method as determined by the Expression Suite Software. Serum was obtained from 132 PHTR at the time of routine surveillance catheterization with coronary evaluation (intravascular ultrasound [IVUS] performed if ≥ 25 kg). Rejection free CAV+ patients were matched by age at transplant and time since transplant to CAV- controls. Statistical analysis was performed using the Wilcoxon test.

Results:
Samples were analyzed from 32 CAV+ PHTR matched to 17 CAV-controls. There were no significant differences between expression of miRs between CAV+ and CAV- PHTR alone, but differences in expression were found when PHTR were separated by sex. miRs significantly upregulated in females (F) included miRs-636 (F with both IVUS and angiographic CAV; p=0.008), -636 and -523 (F with a maximal intimal thickness [MIT] of ≥ 0.5mm; p=0.008 and 0.01, respectively), and -509 and -636 (F with any diagnosis of CAV; p=0.01 and p=0.01, respectively). miRs significantly upregulated in males (M) included miRs-422a (M with both IVUS and angiographic CAV; p=0.007), -422a and let-7e (M with a MIT of ≥ 0.5mm; p=0.003 and p=0.01, respectively), and -422a (M with any diagnosis of CAV; p=0.002). miR-19a was significantly downregulated in in M with any diagnosis of CAV (p=0.04). Boxplots highlighting differential expression of miRs by sex in CAV are shown in Figure 1.

Conclusions:
miRs are differentially expressed between PHTR with CAV on the basis of sex. A unique biomarker signature of miRs that are specific to PHTR with CAV would be valuable in the risk stratification of this challenging patient population.