bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19648: Amino-Terminal Pro-Brain Natriuretic Peptide Improves Risk Stratification in Asymptomatic Individuals at Very High Risk of Future Cardiovascular Events
Authors: Pilbrow Anna P , Frampton Chris M , Richards A M , Troughton Richard W , Cameron Vicky A
Published: July 2021

Background:
In the general population, screening for risk of future cardiovascular events is performed using established risk scores based on traditional risk factors. Previous studies suggest that amino-terminal pro-brain natriuretic peptide (NT-proBNP) may provide additional prognostic information on incident cardiovascular events in the general population.

Aim:
This study investigated whether NT-proBNP could improve risk prediction among asymptomatic individuals with a very high risk of future cardiovascular events (Framingham risk score ≥30%).

Methods:
Middle-age and older participants with no history of cardiovascular disease or heart failure were recruited from the general population (n=1244, mean age 64.9±10.2 years, 69% male). Fatal/non-fatal cardiovascular events were recorded over 5 years follow-up. Associations between plasma NT-proBNP at baseline, Framingham risk score and cardiovascular events were tested with Cox regression and log-rank tests.

Results:
A total of 194 (16%) participants experienced a fatal/non-fatal cardiovascular event within 5 years. For all participants, higher levels of NT-proBNP were strongly associated with fatal/non-fatal cardiovascular events (event rates for NT-proBNP tertiles: 6%, 13%, 27% log-rank p<0.001). This association was independent of the Framingham risk score (p<0.001). The majority of events (117 events, 60%) occurred among participants with a Framingham risk score ≥30% (380 participants), among whom NT-proBNP conferred an even greater prognostic advantage: those with the highest NT-proBNP levels were at markedly increased risk (event rates for NT-proBNP tertiles: 17%, 28%, 38%, log-rank p=0.006, Figure 1).

Conclusions:
These data suggest that plasma NT-proBNP may significantly improve risk stratification among asymptomatic individuals of middle-older age identified as having a very high risk of future cardiovascular events according to established risk scores.
Abstract 19708: Pre-Hospital Initiation of Therapeutic Hypothermia Associated With Better Survival and Neurologic Outcome in a Broad Population of Patients in North Carolina
Authors: Rao Meena P , Dupre Matthew , Hansen Carolina , Milford-Beland Sarah , Monk Lisa , Tyson Clark , Pearson David A , Nelson Robert D , Meyers Brent , Jollis James G , Granger Christopher B
Published: July 2021

Introduction:
Out-of-hospital cardiac arrest (OHCA) has less than 10% hospital survival. While therapeutic hypothermia resulted in a 16%-24% improvement in neurologic outcome in patients with ventricular fibrillation (VF) in prior trials, recent trials have not shown benefit of pre-hospital initiation hypothermia or of hospital cooling to 33 vs 36 degrees.

Methods:
We studied patients who suffered OHCA in North Carolina from 2012-2013 captured in the CARES database as part of the Heart Rescue Project. To limit selection bias, we excluded patients without return of spontaneous circulation after arrest and without intubation in the field as they may have regained consciousness.

Results:
847 patients were included in the analysis of pre-hospital hypothermia. The patients that received pre-hospital hypothermia had more bystander initiated CPR (p-value < 0.45). Pre-hospital hypothermia was associated with a significant increase in survival to hospital discharge (OR 1.55, 95% CI 1.03-2.32) and neurologic outcome at discharge (OR 1.56 95% CI 1.01-2.40). When looking at arrest types, the significant association was seen after VF arrest (figure). 537 patients survived to hospital admission and included in the analysis of in-hospital hypothermia. Patients who received hospital hypothermia were younger, had more VF, more witnessed arrest and more pre-hospital hypothermia. Hypothermia showed a non-significant trend toward better survival to discharge.

Conclusions:
The association between pre-hospital hypothermia after VF arrest and improved survival, in light of randomized data showing no effect, may be due to confounding or to a greater likelihood of in-hospital hypothermia in this group. The trend in better outcome using in-hospital hypothermia is consistent with a benefit from temperature management. These findings suggest the need for ongoing efforts to understand the value of hypothermia in context of other efforts to improve survival from cardiac arrest.
Abstract 19722: Pericardial Mass in a Patient With Rheumatoid Arthritis: A Case Report
Authors: Al-Ani Mohammad A , Weber Michelle H , Lucas Alexandra R , Kosboth Matthew D
Published: July 2021

Introduction:
Rheumatoid arthritis (RA) can affect the heart via either inflammatory or ischemic processes. Pericardial disease is common in RA patients (30-50%) but is usually subclinical and not hemodynamically significant unless accompanied by infiltrative cardiomyopathy which carries a poor prognosis.

Case report:
A 65 year-old Caucasian male presented with long standing RA, severe fatigue and mild arthritis of MCP joints. Physical examination indicated S3, II/VI decrescendo diastolic murmur, and 2+ LL edema. ESR was normal but anti-CCP antibodies were > 250 units. On echocardiogram, a large pericardial mass was detected without atrial nor ventricular collapse and mild-moderate aortic regurgitation. Cardiac MRI defined the mass as a heterogeneous entity attached to the right, anterior, and inferior borders of the heart with compression of the right atrium, left and right ventricles, and the tricuspid valve. CT guided biopsy demonstrated fibrinous material without granulomas nor infection. Fatigue was initially attributed to uncontrolled RA and low dose prednisone and Leflunamide were started. 3 months later, he developed frank heart failure with NYHA class IIIb functional impairment. Cardiac Tamponade was confirmed by heart catheterization demonstrating typical 4-chamber pressure equalization. The mass was surgically excised with partial pericardiectomy. The patient had a dramatic improvement and 4 years later, he remains asymptomatic.

Discussion:
Our patient presented with uncontrolled RA and a pericardial mass that was not hemodynamically significant per the initial echocardiogram. Despite intensifying immunosuppression, his fatigue progressed with signs of congestive heart failure. Tamponade physiology was diagnosed invasively and the mass was resected with excellent recovery. Microscopically, the lesion consisted of a fibrous and exudative material. The patient likely had multiple asymptomatic episodes of pericarditis, gradually leading to this condition. We demonstrate with this case that RA pericardial disease can cause hemodynamic compromise while sparing myocardium and valves and that surgery is associated with very good prognosis. Physicians should be vigilant about a cardiac cause of fatigue in RA patients.
Abstract 19727: ROCK2 Mediates Browning of White Fat and Protects Against Obesity
Authors: Chen Phetcharat , Park Christina , Karrar Eltayeb , Wang Chaoyung , Liao James
Published: July 2021

Background:
The Rho-activated kinases (ROCK1 and ROCK2) are serine threonine kinases that are ubiquitously expressed with higher levels of ROCK2 compared to ROCK1 in adipocytes. Recent studies suggest that ROCK2 may be an important regulator of energy metabolism and obesity. However, its role in adipocyte development and function is unknown.

Methods and Result:
To determine the role of ROCK2 in adipocyte development and obesity, we generated adipocyte-specific deletion (ROCK2
adipoQ-/-
) and overexpression (CA-ROCK
adipoQ+/+
) of ROCK2 in mice. Compared to control mice, CA-ROCK
adipoQ+/+
mice exhibited increased browning of inguinal white adipose tissue (iWAT). Indeed, immunohistochemical staining of iWAT in CA-ROCK
adipoQ+/+
mice showed that UCP1 was upregulated. Furthermore, CA-ROCK
adipoQ+/+
mice on high fat diet were resistant to weight gain and obesity for up to 18 weeks. This is in contrast to ROCK2
adipoQ-/-
mice, which developed more weight gain or obesity than control mice. To determine the physiological effects of ROCK2 on browning of iWAT, control and ROCK2
adipoQ-/-
mice were exposed to 4°C for 1 week. In control mice, cold exposure increased ROCK2 activity and lead to browning of iWAT. However, the iWAT in ROCK2
adipoQ-/-
mice failed to undergo browning. Analysis of gene expression in iWAT demonstrated increased UCP1 and mitochondria proteins in control but not ROCK2
adipoQ-/-
mice. Thermal imaging revealed that ROCK2
adipoQ-/-
mice were unable to maintain basal body temperature after prolonged cold exposure. In contrast, the heat map of the CA-ROCK
adipoQ+/+
mice showed an elevation of body temperature, particularly in areas of iWAT as compared to that of control littermates.

Conclusions:
ROCK2 mediates the “browning” of white adipocytes and prevents the development of obesity through increased thermogenesis. These findings suggest that the activation of ROCK2 in adipocytes may have therapeutic benefits in preventing diet-induced obesity.
Abstract 19734: Advantages of the Cardiac Isochrone Positioning System for Localization of PVCs to the Endocardium, Epicardium, and Mid-myocardium from a 12 lead ECG
Authors: Gordon Jeffrey P , Laks Michael , Boyle Noel G , van Dam Peter M
Published: July 2021

Introduction:
PVC localization from a 12 lead ECG is an imperfect deduction prone to inaccuracy. The cardiac isochrone positioning system (CIPS) is a non-invasive cardiac imaging method to localize the PVC origin quantitatively to the ventricles using a 12 lead ECG coupled with anatomical imaging data from MRI/CT. The purpose of this study is to: 1) Demonstrate and clarify the limitations of using only the 12 lead ECG to localize a PVC, and 2) Show the advantages of CIPS to localize a PVC, including to the mid-myocardium.

Methods:
9 subjects had successful PVC ablation in the endo- , epi, or mid-myocardium. To demonstrate the limitations of localizing PVCs using only a 12 lead ECG, 8 blinded physicians were asked both to localize the PVC origin to a specific myocardial area using polar map representations of the LV and RV and to specify the PVC as endo- or epicardial in origin. CIPS was used to localize the same PVCs using the MRI derived models and the same 12 lead ECG.

Results:
All 8 blinded reviewers located the PVCs to the correct location with an accuracy of 27%. A qualification of the PVC to an endo- or epicardial surface could not be reliably determined. In contrast, CIPS located the PVCs with an accuracy of 86%. CIPS also successfully localized all 9 PVCs to endo-, epi-, or mid-myocardium.

Conclusions:
Our results confirm the limited capability of using only a 12 lead ECG to localize a PVC origin. Currently, there are no criteria to differentiate the location of the PVC specifically to the mid-myocardium. Coupling the 12 lead ECG and anatomical data, CIPS is able to reliably determine PVC origin. As demonstrated here, it also has the ability to successfully localize PVCs to an epi-, endo-, or mid-myocardial site. CIPS is a promising new technology that could be used to quickly and accurately ascertain an exact PVC location, translating into a direct clinical benefit for patients undergoing ablation.
Abstract 19753: Hdl Cholesterol Efflux Capacity is Inversely Associated With Incident Chd Events Independent of Hdl-c and Apoa-i Concentrations
Authors: Saleheen Danish , Scott Robert , Javad Sunda , Zhao Wei , Rodrigues Amrith , Picataggi Antonino , Lukmanova Daniya , Mucksavage Megan , Luben Robert , Khaw Kay-Tee , Billheimer Jeffery , Wareham Nick , Rader Daniel J
Published: July 2021

Background:
Although plasma HDL-C levels are strongly associated with risk of coronary heart disease (CHD), interventions that raise HDL-C have not been shown to reduce CHD risk. A prototypical measure of HDL function, namely HDL cholesterol efflux capacity, has been shown to be associated with prevalent CHD even after adjusting for HDL-C, but its association with incident CHD events remains uncertain.

Methods:
We measured HDL cholesterol efflux capacity and assessed its relationship to incident CHD events in a nested case control sample within a prospective study (EPIC-Norfolk) of 25,639 individuals aged 40-79 years examined in 1993-1997 and followed up to 2009. We quantified efflux capacity in 1895 incident CHD cases and 2474 control participants free of any cardiovascular disorders, by using a validated ex-vivo radiotracer assay that involved incubation of J774 macrophages with apoB-depleted serum from the study participants.

Results:
HDL cholesterol efflux capacity was positively correlated with HDL-C levels (r2=0.27; P-value<5x10-5) and apoA-I (r2=0.24;P-value< 5x10-5). In analyses comparing top versus bottom third, cholesterol efflux capacity was significantly inversely associated with incident CHD, independent of age, sex, diabetes, hypertension, smoking and alcohol use, waist-to-hip ratio, BMI, LDL-C levels and even after controlling for HDL-C or apoA-I (OR: 0.75 [0.53, 0.97];P-value:9.1x10-3) (Figure).

Conclusions:
HDL cholesterol efflux capacity is significantly and inversely associated with incident CHD events, independent of established vascular risk factors and after adjusting for HDL-C and apoA-I levels.
Abstract 19772: The Significance of Blood Pressure on Cardiovascular Risk Attributable to Diabetes
Authors: Komi Ryosuke , Tanaka Fumitaka , Makita Shinji , Onoda Toshiyuki , Tanno Kozo , Ohsawa Masaki , Itai Kazuyoshi , Sakata Kiyomi , Omama Shin-iti , Ogasawara Kuniaki , Ishibashi Yasuhiro , Okayama Akira , Nakamura Motoyuki
Published: July 2021

Background:
Diabetes mellitus (DM) is an established risk factor of atherosclerotic cardiovascular events (CVE). Individuals with DM often have elevated levels of blood pressure (BP) which is closely associated with CVE.

Hypothesis:
The risk of DM-related CVE may depend on BP levels.

Methods:
A population-based prospective cohort study was performed in 24,350 subjects aged 40 to 89 years (mean age = 63.0±10.0 years) who did not have a history of CVE. DM was defined as a casual blood glucose level ≥ 200 mg/dl or fasting blood glucose level ≥ 126 mg/dl, a glycated hemoglobin value ≥ 6.5%, and/or current anti-diabetic therapy. BP levels at the baseline examination were classified into three categories including normotension, pre-hypertension, and hypertension according to JNC7. This classification was applied also to subjects with antihypertensive agents use. After adjustment for age, sex, body mass index, eGFR, total and HDL cholesterol, smoking habits, and anti-hypertensive medication use, a multivariate Cox regression analysis was performed to examine an association and contribution of pre-hypertension and hypertension on the risk of CVE in DM and non DM.

Results:
During a mean follow-up period of 5.5 years, 746 subjects developed CVE which was defined as stroke or acute myocardial infarction/sudden cardiac death. In both DM and non DM, the hazard ratios for CVE were increased in pre-hypertensives (HR 1.25, p < 0.05; HR 2.59, p < 0.02, respectively) and in hypertensives (HR 1.82, p < 0.01; HR 3.66, p < 0.01, respectively) in comparison with normotensives. However, the population-attributable fractions (PAFs) of pre-hypertension and hypertension were apparently higher in DM (21.5%, 41.2%, respectively), as these were more than double compared to PAFs in non DM (6.7%, 20.3%, respectively).

Conclusions:
Approximately two-third of excess CVE attributable to DM is estimated to occur among individuals with elevated BP levels.
Abstract 19808: Short Term Outcomes After Use of Bone Marrow Transplantation for Management of Heart Failure: A Meta-analysis
Authors: Loomba Rohit S , Gupta Navdeep , Aggarwal Saurabh , Ismail Imtiaz , Agarwal Anushree , Chugh Atul R , Arora Rohit R , Bolli Roberto
Published: July 2021

The role of bone marrow cell transplant in ischemic heart failure is being increasingly recognized. Multiple studies have been published evaluating their use with varying results. We aimed to perform a meta-analysis of the published literature.

We searched Pubmed, EBSCO and Cochrane databases for terms “bone marrow transplant”, “stem cell transplant”, “heart failure”, “cardiac failure” and their combinations. Only studies comparing bone marrow cell transplantation via intracoronary route to placebo, and those with 6 month follow up data were included. Studies in language other than English were excluded.

Results:
Ejection fraction was significantly increased with the use of bone marrow cell transplant compared to placebo (mean difference 6.16% 95%CI 4.16 to 8.16, p < 0.00001). No significant differences were observed in left ventricular (LV) end-systolic volume (mean difference -1.58 ml 95%CI -4.98 to 1.82, p = 0.36), LV end-diastolic volume (mean difference -0.77 ml 95%CI -3.75 to 2.22, p = 0.61) and mortality (odds ratio 1.08 95%CI 0.26 to 4.56, p = 0.92). Results of heterogeneity analysis showed significant heterogeneity only for ejection fraction endpoint (p = 0.01).

Conclusion:
As compared to placebo, intracoronary bone marrow cell transplant is associated with improved LV ejection fraction by 6% in ischemic heart failure patients at 6 month follow up.
Abstract 19810: A Significant Decrease in Early Confirmed Left Ventricular Assist Device Pump Thrombosis: Recent Observations from a Large Multi-Institutional Experience
Authors: Stulak John M , Schirger John A , Joyce Lyle D , Aaronson Keith D , Pagani Francis D , Davis Mary E , Haglund Nicholas A , Maltais Simon
Published: July 2021

Introduction:
Recent reports have documented an abrupt increase in 3-month confirmed HeartMate II left ventricular assist device (LVAD) thrombosis beginning in 2011 without a plateau observed to date. Because very little data exist from multi-institutional efforts, we report our experience.

Methods:
From January 2004 to December 2013, 516 pt underwent HeartMate II LVAD implant at three institutions (University of Michigan (n=254), Mayo Clinic Rochester (n=205), and Vanderbilt Heart and Vascular Institute (n=57)). Median age at implant was 60 yr (range, 18-82) and 428 (83%) were male. Confirmed pump thrombosis at 3 months was defined as thrombus found in the blood-contacting surfaces of the pump at the time of urgent transplant, device exchange or autopsy. Pt without at least 3 months of follow-up were excluded.

Results:
Confirmed pump thrombosis occurred in 9 pt within 3 months post implant. The incidence was greatest in the year 2012 (5.3%). Following this peak, the incidence of 3-month confirmed pump thrombosis decreased significantly to 2.9% (Figure). Significant differences in preoperative characteristics between patients with pump thrombosis and without thrombosis included female sex (36% vs. 16%, p=0.01), bridge to transplant (77% vs. 54%, p=0.03), atrial fibrillation (55% vs. 32%, p=0.04), and preop platelet count (231,000 vs. 172,000, p<0.001). Follow-up was available in all for a total of 857 patient years of support. At a median follow-up of 1.2 years (max., 9.8 years), a similar proportion of patients were alive (73% vs. 74%, p=0.9).

Conclusions:
We report a recent decrease in early, confirmed HeartMate II LVAD thrombosis to historically observed levels, which is disparate to recent reports. While we identified several differences in clinical characteristics between patient groups, the issue of pump thrombosis is complex and multifactorial. Most importantly, our findings demonstrate the need for more granular analyses from collaborative efforts.
Abstract 19836: Lipid Metabolism is Modified by the Interaction Between Cholesteryl Ester Transfer Protein Gene Polymorphism and Mediterranean Diet in Patients in Secondary Prevention for Cardiovascular Disease
Authors: Garcia Rios Antonio , Gomez-Delgado Francisco , Perez Caballero Ana Isabel , Corina-Baba Andreea , Navarro-Martos Vanesa , Marin-Hinojosa Carmen , Lopez-Miranda Jose , Perez-Martinez Pablo
Published: July 2021

Introduction:
Cholesteryl ester transfer protein (CETP) gene has been implicated in lipid metabolism. However, little is known about the impact of this gene on coronary heart disease (CHD) patients and its interaction with diet.

Hypothesis:
To evaluate whether the chronic consumption of a Mediterranean diet enriched in olive oil, compared with a Low fat diet, interacts with the
rs3764261
SNP at CETP locus in order to modify lipid metabolism among MetS patients from the CORDIOPREV clinical trial

Methods:
Plasma lipid concentrations and
rs3764261
genotypes were determined in 424 MetS subjects participating in the CORDIOPREV clinical trial. Gene-diet interactions were analyzed after a year of dietary intervention (Mediterranean diet (35% fat, 22% MUFA) vs Low fat

diet (28% fat, 12% MUFA))

Results:
We found significant gene-diet interactions between
rs3764261
SNP and the dietary pattern for HDL-C (
P=0.006
) and triglyceride concentrations (
P=0.040
). Specifically, after 12 months of Mediterranean diet intervention, subjects who were carriers of the minor T allele (TT+TG) displayed higher plasma HDL-C concentrations (
P=0.021
) and lower triglycerides (
P=0.020
) compared with homozygous for the major allele (GG). In contrast, in the Low fat intervention group no significant differences were found between CETP genotypes after 12 months of dietary treatment.

Conclusions:
Our data support the notion that a chronic consumption of a Mediterranean diet may play a contributing role in triggering lipid metabolism by interacting with the
rs3764261
SNP at CETP gene locus in MetS patients
Abstract 20069: Serum-Free Culture Conditions Support Human Cardiac Stem Cell Outgrowth
Authors: Mount Seth , Etoubashi Nesma , Davis Darryl R
Published: July 2021

Introduction:
Autologous cardiac stem cell (CSC) therapies represent an emerging treatment option for patients with congestive heart failure. Unfortunately, straightforward translation to the clinic is limited by traditional culture conditions that are supplemented by ill-defined or xenobiotic components such as fetal bovine serum. As such, overcoming these barriers is the next critical step in developing next generation CSC therapies for clinical use.

Methods/Results:
Transition of CSC culture methods to serum-free, xeno-free culture conditions demonstrated negligible effects on the overall numbers of cells cultured with equivalent cardiac (c-Kit+; 7.8±0.2 %, p=0.34) and mesenchymal (CD90+; 32±7 %, p=0.57) progenitor content as compared to standard culture conditions. Flow cytometry morphometry demonstrated that serum free cells provide a smaller, more homogeneous cell product. Exposure to hypoxic stress conditions demonstrated equivalent secretion of SDF-1α, SCF, HGF, and VEGF-A with reduced production of the pro-inflammatory cytokine IL-6 from serum-free cells (7±2 fold less; p=0.005). Despite differences in cytokine production, conditioned media from serum-free CSCs promoted similar new vessel formation (37±5 vs. 41±7 % of positive control within a HUVEC tube formation assay; p=0.69) and circulating stem cell recruitment (39±9 vs. 47±12% of the positive control within a transwell assay, p=0.64) when compared to media conditioned by standard cultures. Storage of cell suspensions at 4°C had negligible effects on 12 hour viability (95.3±1.6%, p=0.50), suggesting a shelf life sufficient for transport between institutions. Finally, injection of CSCs through a clinically approved coronary artery perfusion catheter did not alter cell viability (99.2±1.7 % after delivery, p=0.77) while ensuring successful product delivery to the peri-infarct zone.

Conclusions:
Transitioning CSCs to clinically acceptable protocols provides a more uniform cell product ready for clinical delivery. These findings represent the first published evidence that altered serum-free xeno-free culture conditions can provide a superior CSC cell product with the potential for ready translation to clinical use.
Abstract 20129: Polyunsaturated Fat Intake Estimated by Circulating Biomarkers is Inversely Associated with Cardiovascular Disease and All-Cause Mortality in a Large Population-Based Cohort of Swedish Women and Men
Authors: Marklund Matti , Laguzzi Federica , Vikström Max , Alsharari Zayed , Sjögren Per , Gigante Bruna , Cederholm Tommy , Leander Karin , Hellenius Mai-Lis , De Faire Ulf , Risérus Ulf
Published: July 2021

Increased intake of certain polyunsaturated fatty acids (PUFA) in place of saturated fatty acids has shown beneficial effects on cardiovascular disease (CVD) risk, although results are inconsistent. This may partly be explained by sex differences and shortcomings with self-reported intake data.

The objective was to evaluate associations between markers of PUFA intake, from vegetable oils and fish, with CVD incidence and mortality (all-cause).

In a representative population-based prospective cohort study including 2193 women and 2039 men (all aged 60 y) in Stockholm County, Sweden, PUFA were measured in serum cholesteryl esters by gas chromatography at baseline (1997-1998). Using national registers, 484 first CVD events (male, n=294; female, n=190) and 456 deaths (n=265; n=191) were identified during follow-up (median 14.5y), in individuals without prior CVD events at baseline. Associations between PUFA intake (assessed by circulating PUFA [linoleic acid, LA; α-linolenic acid, ALA; eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA]) and risk of CVD and mortality were evaluated in men and women separately and together, by Cox proportional hazard models. Hazard ratios (HR) with 95% confidence interval (95%CI) were estimated in crude models and after adjusting for BMI, sex, education, smoking, physical activity, alcohol intake, diabetes, hypertension, and hypercholesterolemia.

In the whole population, EPA and DHA were inversely associated with mortality risk in adjusted model; 1 SD increment in EPA and DHA decreased the risk of mortality by 21% (HR 0.79 [95%CI 0.65-0.96]) and 22% (0.78 [0.66, 0.93]), respectively. Among women, EPA and DHA were associated with reduced CVD risk (HR 0.79 [95% CI 0.64-0.97] and 0.74 [0.61-0.89], respectively), whereas women with high ALA levels had moderately increased risk of CVD (1.16 [1.02-1.32]). High LA levels were associated with reduced mortality in men (0.73 [0.64-0.83]).

In line with some previous studies, circulating PUFA reflecting dietary n-3 and n-6 PUFA intake were in general inversely linked with CVD and/or mortality. Sex specific relations between PUFA and CVD/mortality motivate further investigations and may partly explain previous inconsistencies regarding dietary PUFA in CVD prevention.
Abstract 20144: Aortic Arch Plaque Deteriorates With Advancing Chronic Kidney Disease Stage
Authors: Nishiyama Satoshi , Watanabe Tetsu , Sasaki Shintaro , Wanezaki Masahiro , Yamaura Gensai , Takahashi Hiroki , Arimoto Takanori , Shishido Tetsuro , Miyamoto Takuya , Kubota Isao
Published: July 2021

Introduction:
The patients with chronic kidney disease (CKD) are likely to suffer from cardiovascular diseases as well as end stage renal disease. CKD plays a role in development of atherothrombotic stroke. In the present study, we investigated the impact of advancing CKD stage on aortic arch plaque and carotid atherosclerosis which are important causes of atherothrombotic stroke.

Methods:
We enrolled 368 subjects (255 males, 66 ± 12 years) who underwent transesophageal echocardiography and carotid ultrasonography, and measured estimated glomerular filtration rate (eGFR). We defined arch plaque as wall thickness ≥4 mm and the presence of ulceration or mobile plaque in aortic arch. The common carotid artery maximum intima-media thickness (IMT-C max) and carotid artery plaque score was used as parameters of carotid atherosclerosis.

Results:
There were 31 patients with the history of atherothrombotic stroke. The eGFR correlated with IMT-C max, carotid plaque score and arch wall thickness. IMT-C max, carotid plaque score and arch wall thickness were increased with advancing CKD stage. An increase in IMT-C max was observed even in stage 2 and 3 while carotid plaque was frequently observed in stage 3b or higher. An increase in arch plaque was observed in stage 3a or higher. The patients with atherothrombotic stroke had significantly lower eGFR than those without. The prevalence of atherothrombotic stroke was increased in stage 3b or higher.

Conclusions:
Aortic arch plaque and carotid plaque deteriorated with advancing chronic kidney disease stage. Aortic arch plaque and carotid plaque were observed even in early stages of CKD.
Abstract 20149: Effect of Mitral Valve Area Following Surgical Repair for Degenerative Mitral Regurgitation on Exercise Hemodynamics and Functional Consequences
Authors: Chan Kwan , Mesana Thierry , Lam Buu-Khanh
Published: July 2021

Introduction:
Mitral valve (MV) area is the key measure of mitral stenosis (MS) in rheumatic MV disease, but its role in the follow-up of patients who had MV repair for degenerative mitral regurgitation (MR) remains uncertain. Our objective is to evaluate the relationships of MV area with hemodynamic effects at rest and during exercise, and with functional measures in patients following MV repair for degenerative MR.

Methods:
We prospectively assessed 110 patients who had MV repair for degenerative MR and no more than mild residual MR. Patients with aortic valve disease and ventricular dysfunction were excluded. The patients underwent comprehensive echo assessment at rest and during supine bicycle exercise. Brain natriuretic peptide (BNP) levels and SF36 questionnaires were also performed. MV area was calculated using the continuity equation. The patients were divided into 2 groups for comparison (MV area < 1.5 cm
2
vs > 1.5 cm
2
).

Results:
22 patients (20%) had MV area
<
1.5 cm
2
. The 2 groups were similar in age. Patients with MVR < 1.5 cm
2
had worse resting and exercise hemodynamics, more limited exercise capacity and higher BNP levels compared to those with larger MV area (Table). These patients also had lower scores in physical functioning, vitality (p=0.01) and social function (p=0.04), based on the SF36 questionnaires. Multivariate analysis showed that MV area is an independent predictor of exercise capacity (p=0.003).

Conclusion:
In patients following MV repair for degenerative MR, MV area is a useful measure of MS severity because it is associated with resting and exercise hemodynamics and functional consequences. MV area should be routinely measured in this clinical setting, and refinement in MV repair techniques is needed to optimize MV area in addition to eliminate MR.
Abstract 20157: Circulating Endothelial Progenitor Cells Predict Cardiovascular Outcomes in Patients with Aortic Valve Stenosis
Authors: Shimoni Sarah , Bar Iris , Meledin Valery , Gandelman Gera , George Jacob
Published: July 2021

Introduction:
Degenerative aortic stenosis (AS) is the most common valvular disease. Endothelial progenitor cells (EPCs) have a role in the repair of endothelial surfaces after injury. The aim of this study was to assess EPC number in pts with AS and to study the predictive value of circulating EPC levels on prognosis in pts with AS.

Methods:
The number of EPCs was determined by flow cytometry in 244 consecutive pts with AS and a control group of 75 pts. Thirty eight pts had mild AS, 52 pts had moderate AS and 154 pts presented with severe AS. We evaluated the association between baseline levels of EPCs and functional improvement after an intervention and death from cardiovascular causes.

Results:
The EPC number was significantly higher in pts with AS compared to the control group (p=0.026). There was no difference in EPC number among pts with mild, moderate or severe AS. Two hundred and six pts with moderate and severe AS were followed for a median of 20 months for the occurrence of cardiovascular events. One hundred and twenty pts underwent an intervention. Sixty-two percent showed improvement in functional class after the intervention and 38% did not improve. The EPC number was significantly higher in pts with functional improvement compared to those that did not improve (p=0.01). Forty one pts died during follow up, 21 pts died due to cardiac causes. Advanced age, the presence of CAD, high NYHA class, low aortic valve area, elevated pulmonary artery pressure and low EPC number were found to be predictors of cardiac death in the univariant analysis. Multivariant logistic regression model identified only low EPC number as associated with cardiac death during follow up (p= 0.025, Figure 1).

Conclusions:
EPC number is increased in pts with AS. However, in pts with moderate or severe AS a relatively low number of EPCs is associated with lack of functional improvement after intervention and with cardiac death at follow up. These results may help to identify AS pts at increased cardiovascular risk.
Abstract 20158: Long-Term Device-Related Adverse Events After Implantable Cardioverter-Defibrillator Therapy
Authors: Ranasinghe Isuru , Parzynski Craig , Freeman James V , Dreyer Rachel P , Ross Joseph S , Akar Joseph G , Krumholz Harlan M , Curtis Jeptha P
Published: July 2021

Background:
Long-term implantable cardioverter-defibrillator (ICD) adverse events are poorly documented. In the NCDR ICD Registry™, a nationally representative cohort, we calculated the rate of long-term post-discharge device related adverse events.

Methods:
We included first-time ICD implants from 2006-2010 that could be matched with Medicare fee-for-service claims data to identify outcomes. We excluded patients if they had a previous ICD or pacemaker, CABG during their procedure, or were not discharged alive. The primary outcome was device reoperation (involving the generator, leads, pocket, or a combination) for device malfunction, infection, other complications (wound disruption, cardiac perforation, etc.), or reoperation for battery end-of-life and/or device upgrade. Analysis was performed using unadjusted cumulative incidence functions taking into consideration the competing risk of death.

Results:
We identified 185,263 ICD implants of which 114,649 (19.7% single-chamber, 41.3% dual-chamber, 38.8% CRT-D) could be matched to Medicare data (mean age 74.8±6.2 years, 72.5% male).Of these, 83.5% were for primary prevention of sudden cardiac death. The median follow up was 2.7 yrs (max follow-up 6 yrs). At least 1 reoperation occurred in 15.5% of patients by 6 yrs and more than 80% of these reoperations occurred after the early (>90 days) post-implantation period (Figure). Reoperation rates for specific complications (per 1000 patient yrs) were device malfunction (14.3), infection (5.1), other device related complications (18.4) and reoperation for generator battery end-of-life and/or device upgrade (12.9). The crude reoperation rate (for any cause) was similar among device types (P=0.19).

Conclusion:
Patients continue to have adverse outcomes in the years post ICD implantation, predominately from device malfunction. Our next steps are to identify patient, device, and provider factors associated with these long-term adverse events.
Abstract 20178: Short Chain Acyl-CoA Intermediates in the Failing Heart: Further Evidence of an Energy Starved State
Authors: Snyder Nathaniel , Bedi Kenneth C , Javaheri Ali , Mesaros Clementina , Margulies Ken , Blair Ian , Rame J E
Published: July 2021

Introduction:
Several studies have implicated energetic deficits in chronic heart failure. Recently, our group has described a state of myocardial substrate deficiency across a broad spectrum of lipid species in non-diabetic end-stage heart failure. We hypothesized that lipid substrate depletion in end-stage heart failure would be associated with dysregulation of short chain acyl-CoA intermediates implicated in important metabolic pathways.

Methods:
Left ventricular samples were obtained at the time of orthotopic heart transplantation for failing cases with idiopathic dilated cardiomyopathy (DCM) n=16, and brain-dead organ donors without a history of heart failure (NF) n=18. Samples were snap frozen at -80°C for further analysis with liquid chromatography in tandem mass spec LC MS/MS. Stable isotope labeled essential nutrient in cell culture (SILEC) internal standards for acyl-CoAs were generated using
13
C
3
15
N
1
pantotheonate in Hepa1c1c7 cells.

Results:
In the myocardium of failing as compared to NF, we identified a significant decrease in Succinyl-CoA (Avg 10.5 versus 17.7 pmol/mg, p = 0.004 ), Propionyl-CoA (0.9 versus 1.8 pmol/mg, p=0.004) and a concomitant increase in β-hydroxybutyryl -CoA (BHB-CoA Avg 0.57 versus 0.29 pmol/mg, p =0.008 ). The ratio of myocardial Succinyl-CoA to Acetyl-CoA, a potential marker of tricarboxylic acid cycling, is significantly decreased in end-stage heart failure ( 0.84 versus 1.93, p= 0.005 ). The figure depicts the levels of myocardial acyl-CoA species in the non-diabetic cohort.

Conclusion:
We have identified important differences in myocardial acyl CoA species—an increase in the ketogenic BHB-CoA and decreased Succinyl-CoA and Propionyl-CoA in end-stage human heart failure. These data, along with the recently identified state of myocardial lipodeficiency, are strongly supporting the concept of a bio-energetic deficit in end-stage heart failure.
Abstract 202: The Use of Bispectral Index EEG Monitoring as a Screening Tool for the Reliable Detection of Epileptic Activity in Post--Cardiac Arrest Patients
Authors: Haesen Jolien , Desteghe Lien , Meex Ingrid , Genbrugge Cornelia , Demeestere Jelle , Ernon Ludovic , Dens Jo , De Deyne Cathy
Published: July 2021

Background:
Assessment of prognosis in post[[Unable to Display Character: –]]cardiac arrest (CA) patients became very challenging since the introduction of therapeutic hypothermia (TH). Continuous EEG monitoring has been proposed to improve prognostication; however, its use is limited due to difficulties in readily interpretation. This emerges the need for a simple EEG montage. The bispectral index (BIS) monitor is a simplified EEG system, mainly calculating an index ranging from 0 (isoelectric EEG) to 100 (full consciousness) to provide information on hypnotic depth of anesthesia. The aim of the study was to validate the accuracy of simplified EEG monitoring in a CA - setting.

Methods:
BIS monitoring (BIS VISTA
TM
) was applied to collect frontotemporal data in TH-treated CA patients. A standard 19 [[Unable to Display Character: –]] channel EEG was performed after return to normothermia. Afterwards, small EEG frames coincident with the time of full EEG registration were extracted from the BIS monitor. We asked 2 neurologists to indicate the presence of status epilepticus (SE), cerebral inactivity (CI), burst suppression (BS) or a diffuse slowing pattern (DS). In addition, these samples were analyzed by 2 inexperienced physicians, who were asked to indicate the presence of SE.

Results:
Thirty simplified EEG samples were analyzed. According to standard EEG, 11 patients showed a DS pattern, 3 had CI, 6 showed BS and 10 had an SE. Neurologists interpreted all samples with a high accuracy (sensitivity: 82% and specificity: 92%). Only 1 SE was missed by one neurologist. Interobserver reliability was high (kappa=0.843). High correlations were found for the comparison of full and simplified EEG for both neurologists (r=0.809). Further, the 2 inexperienced physicians identified SE with a sensitivity of 85% and specificity of 98%.

Conclusion:
Simplified EEG monitoring, using BIS, resulted in high accuracy of a simple classification system in post [[Unable to Display Character: –]] CA patients. Not only neurologists, but also treating physicians were capable to identify SE, which may play an important role in the early detection of SE. We suggest using BIS as a screening tool in post [[Unable to Display Character: –]] CA patients to save valuable time in the detection of SE, without replacing the need of full EEG monitoring for confirmation.
Abstract 20202: Pharmacodynamic Interactions Between Nebivolol and Valsartan in Healthy Volunteers
Authors: Chen Chun Lin , Desai-Krieger Daksha , Ortiz Stephan , Kerolous Majid , Wright Harold M
Published: July 2021

Introduction:
Combining different classes of antihypertensive drugs is more effective for achieving blood pressure (BP) control than increasing the dose of monotherapies. An aim of this study was to investigate pharmacodynamic (PD) interactions between nebivolol, a β1 selective, vasodilatory beta blocker and valsartan, an angiotensin II type 1 receptor blocker.

Methods:
This was a single-center, randomized, open-label, multiple-dose, three-way crossover trial in 30 healthy adults aged 18-45 years. Participants were randomized into one of six treatment sequences (1:1:1:1:1:1) consisting of three 7-day treatment periods followed by a 7-day washout. Once-daily oral treatments comprised nebivolol 20 mg, valsartan 320 mg, or nebivolol 20 mg plus valsartan 320 mg. Outcomes included changes in BP, heart rate (HR), plasma angiotensin II, plasma renin activity (PRA), and 24-hour urinary aldosterone.

Results:
The drop in least square mean values of systolic and diastolic BP was significantly greater following the concomitant administration of nebivolol and valsartan than either monotherapy alone. The mean HR after treatment with nebivolol alone, as well as after the combined treatment, was consistently lower than valsartan monotherapy. A sharp increase in mean Day 7 PRA and plasma angiotensin II occurred in subjects receiving valsartan alone and this was significantly attenuated with concomitant nebivolol administration. Mean 24-hour urine aldosterone at Day 7 was substantially decreased after combined treatment, as compared to either monotherapy treatment. All treatments were safe and well tolerated.

Conclusions:
Nebivolol and valsartan co-administration led to greater reductions in BP compared to either monotherapy. Nebivolol attenuated valsartan-induced increases in angiotensin II levels and PRA and reduced urinary aldosterone levels. Hence, these mechanisms for BP lowering are complementary and provide a rationale for further investigation of this combination in patients with essential hypertension.
Abstract 20232: Haploinsufficiency of MYBPC3 in the Development of Hypertrophic Cardiomyopathy
Authors: Barefield David , Kumar Mohit , Gorham Joshua , Seidman Jonathan , Seidman Christine , de Tombe Pieter , Sadayappan Sakthivel
Published: July 2021

Introduction:
Mutations in MYBPC3, encoding cardiac myosin binding protein-C (cMyBP-C), account for ~40% of hypertrophic cardiomyopathy (HCM) cases. MYBPC3 mutations are usually encode truncated proteins and are not found in tissue and are typically heterozygous (Het) in humans. Reduced protein levels occur in human HCM patients with these mutations, suggesting haploinsufficiency. However, it is unknown if cMyBP-C reduction causes or results from hypertrophy.

Hypothesis:
To test whether haploinsufficiency occurs following cardiac stress and if heterozygous MYBPC3 mice had worsened disease progression.

Methods & Results:
Transverse aortic constriction (TAC) was performed on 3 month old wild type (WT) and Het MYBPC3 truncation mutant mice which were allowed to hypertrophy for 4 or 12 weeks. Het TAC mice showed increased hypertrophy 12 weeks post-TAC compared to WT TAC controls. Het TAC hearts showed reduced ejection fraction compared to WT TAC at 4 and 12 weeks. MYBPC3 transcript levels were significantly reduced in sham and TAC Het hearts. cMyBP-C levels decreased in Het sham and TAC at 4 weeks but returned to baseline levels at 12 weeks. Het TAC myocytes showed higher Ca2+ sensitivity at 4 weeks, and impaired maximal force development. Het sham and TAC skinned cardiomyocytes showed reduced length dependent increases in Ca2+ sensitivity and maximal force development. RNA-Seq shows no alterations in proteasome of RNA-degradation pathways which have been suggested to play a role in the pathology of these mutations. Overexpression of WT cMyBP-C in the presence of truncated MYBPC3 rescued the decline in force observed in Het myocytes in the absence of stress.

Conclusions:
Heterozygous MYBPC3 truncation mutant carriers develop more profound hypertrophy and dysfunction following stress. Also, increased MYBPC3 expression reverses myocyte deficits in force generation in the presence of truncated alleles.
Abstract 20233: Does Evidence Influence Practice in the Real World? Secular Trends in Indication for PCI and Use of Drug-Eluting vs. Bare-Metal Stents From 2006-2012
Authors: Pathak Elizabeth B , Salemi Jason L , Pathak Amit P
Published: July 2021

Introduction:
In this study, we examined the real-world impact of research evidence on the use of and indications for percutaneous coronary intervention (PCI) (before and after COURAGE Trial publication) and the choice of drug eluting stents (DES) vs. bare metal stents (BMS) (before and after FDA warnings about risk of DES thrombosis).

Methods:
We used hospital discharge data from Florida to calculate the distribution of primary indication for PCI and the % of PCI patients who received DES, BMS, or no stent on a quarterly basis from Jan 2006 - Jun 2012. We plotted stent trends separately for patients with principal diagnosis of STEMI (n=66,054), NSTEMI/ICS (n=140,886), and stable CHD (n=117,307).

Results:
Since 2006, the % of PCIs with a primary indication of either STEMI or NSTEMI has steadily increased, while the % with an indication of stable CHD declined from 45% to 28%. In early 2006, DES were used in 86.9% of NSTEMI patients, 87.5% of stable CHD patients, and 81.4% of STEMI patients. DES use first declined in all diagnosis groups in Q3 2006, coinciding with the release of meta-analysis results showing higher risk of late stent thrombosis for DES vs. BMS. The lowest rate of DES usage was reached in Q1 2008 (45% for STEMI, 63% for NSTEMI, 67% for stable CHD). However, by Q2 2012, DES use had increased to 60% in STEMI cases, 75% in NSTEMI cases, and 76% in stable CHD cases. The percent of PCI patients who received no stent has remained stable at < 9% since 2006, regardless of diagnosis.

Conclusions:
The COURAGE Trial showed no benefit of PCI over medical treatment in stable coronary heart disease (CHD). From 2006-2012, the proportion of PCIs with an indication of stable CHD declined from 45% to 28%, indicating a real-world response to evidence. Similarly, following controversy about long-term effects of DES, off-label use, and patient compliance with thienopyridines which began in late 2006, there was an immediate resurgence in use of BMS, especially for STEMI. However, the proportion of patients receiving DES has steadily increased since early 2008, regardless of primary indication. More research on the influence of provider and hospital characteristics on response to evidence is needed.