bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19305: Diabetes Mellitus and Ischemic Heart Disease Susceptibility: Which is the Influence of Genetic Polymorphisms for Katp Channels?
Authors: Severino Paolo , Cinque Alessandra , Salvi Nicolò , Calabrese Giorgio , Armato Alessandra , De Marchis Maria Laura , Palmirotta Raffaele , Mancone Massimo , Fedele Francesco
Published: July 2021

Background:
Evidences show that diabetes mellitus (DM) lead to higher risk for ischemic heart disease (IHD). Recently, we proposed that genetic polymorphisms (SNP) of coronary ion channels might be involved in IHD. We showed that the genotype distribution of SNP rs5215 for Kir6.2 subunit of ATP-dependent potassium (KATP) channels moderately deviated from the HW equilibrium and that rs5215_GG is linked to IHD susceptibility: it might have a ‘‘protective’’ role in IHD genesis. Moreover, previous studies described that SNP rs5215_GG is strongly correlated with DM and hyperinsulinism in human.

Aim and methods:
In the present study, we hypothesized that SNP rs5215_GG for Kir6.2 subunit for KATP channels had some influences in the susceptibility of DM to IHD. We performed a subgroup analysis about the influence of rs5215_GG in diabetic patients on our previous population, i.e. 242 patients candidates to elective or emergency coronary angiography for acute coronary syndrome or chronic angina, of which 155 with CAD, 46 with microvascular dysfunction and 41 with anatomically and functionally normal coronary arteries (control group).

Results:
Among 242 patients, comparing subjects with DM to those without, there was not any significant difference in the prevalence of rs5215_GG. However, among 33 subjects without DM with normal coronary arteries, SNP rs5215_GG had a higher prevalence compared to those in the CAD group (10/33; 30.3%; p= 0.0277) as well as non-diabetic patients in the microvascular dysfunction group (9/33; 27.2%; p= 0.0295).

Discussion and conclusion:
The variant rs5215_GG results in the substitution of isoleucine (I) residue with valine (V) in the Kir6.2 subunit of KATP channels. Our results confirm that rs5215_GG might decrease susceptibility to IHD in patients without DM. In fact, rs5215_GG was confirmed to be present more frequently in patients without DM presenting anatomically and functionally normal coronary arteries. We believe that absence of DM is protective against IHD genesis and it might be improved by coronary KATP channels expressing rs5215_GG. Taken together, our data ratify the possibility that ion channels play a key role in coronary homeostasis and that SNP encoding for ion channels are involved in IHD pathophysiology.
Abstract 19340: Advanced Peripheral Endothelial Dysfunction Correlates with Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Left Ventricular Ejection Fraction in Hypertensive Patients
Authors: Akiyama Eiichi , Sugiyama Seigo , Matsuzawa Yasushi , Suzuki Hiroyuki , Konishi Masaaki , Nakayama Naoki , Kurokawa Hirofumi , Fujisue Kouichirou , Nozaki Toshimitsu , Ohba Keisuke , Matsubara Junichi , Sugamura Koichi , Sumida Hitoshi , Kimura Kazuo , Umemura Satoshi , Ogawa Hisao
Published: July 2021

Background:
Left ventricular (LV) diastolic dysfunction (DD) and vascular functions including peripheral endothelial function play an important role in the pathogenesis of heart failure (HF) with preserved LV ejection fraction (EF) (HFPEF). Hypertension is the most important risk factor in HFPEF and the increased workload caused by hypertension results in LV pathological hypertrophy and LVDD. However, the importance of endothelial function in hypertensive patients with LVDD or HFPEF remains yet undetermined. We investigated the association between peripheral endothelial function, LVDD, and HFPEF in hypertensive patients.

Methods and Results:
We evaluated cardiac function by echocardiography measuring the ratio of early transmitral flow velocity to tissue Doppler early diastolic mitral annular velocity (E/e’) and LVEF. We also noninvasively assessed peripheral endothelial function by reactive hyperemia-peripheral arterial tonometry (RH-PAT) as the RH-PAT index(RHI) in 405 hypertensive patients with preserved LVEF (LVEF>50%), comprising 180 HFPEF and 225 non-HF patients (LVDD; E/e’>15, non-HF with LVDD; n=98, non-HF without LVDD; n=127). RHI negatively correlated with E/e’ (r=-0.24, P<0.001) and B-type natriuretic peptide (r=-0.19, P<0.001). RHI was significantly lower in hypertensive patients with HFPEF than in non-HF hypertensive patients (0.49±0.17 vs. 0.62±0.20, P<0.001). Furthermore, RHI was significantly lower in non-HF hypertensive patients with LVDD than those without LVDD (0.58±0.19 vs. 0.65±0.21, P=0.01). Multivariate logistic regression analysis identified that lower RHI independently correlated with the presence of HFPEF in hypertensive patients with preserved LVEF (odds ratio: 0.65, 95% confidence interval: 0.55-0.77, P<0.001) and with the presence of LVDD in non-HF hypertensive patients (odds ratio: 0.65, 95% confidence interval: 0.71-0.95, P=0.01).

Conclusions:
RHI was independently associated with the presence of HFPEF and LVDD in hypertensive patients with preserved LVEF. Endothelial dysfunction in microcirculation could play a crucial role in the pathogenesis of LVDD and HFPEF in hypertensive patients.
Abstract 19342: Bilateral Phlegmasia Cerulea Dolens: More Than Meets the IVC
Authors: Metkus Thomas , Yevich Steven , Maleki Zahra
Published: July 2021

A 40 year-old woman presented with edema, discoloration and severe pain of the lower extremities. Four weeks prior, she noted chest pain with pain and swelling of the right arm and both legs. Imaging demonstrated sub-segmental pulmonary embolism (PE) with bilateral deep venous thrombi (DVT) of the legs and thrombus of the right brachial vein. She was treated with warfarin however despite anticoagulation, had progressive dyspnea. Repeat imaging demonstrated new PE and progression of bilateral DVT. Anticoagulation was transitioned to argatroban, and an IVC [[Unable to Display Character: ﬁ]]lter was placed. Subsequently, she had worsened edema and discoloration of the lower extremities, weakness, and severe pain. On physical examination, the lower extremities were cold and deeply violaceous with 2/5 strength at the bilateral hips and 0/5 strength below. Pulses were absent. Ultrasound examination demonstrated complete thrombosis of the lower extremity venous system to the level of the IVC. The clinical triad of limb swelling, ischemic pain, and blue color change suggested bilateral phlegmasia cerulea dolens (PCD). She was referred emergently for catheter based thrombolysis, however despite restoration of venous patency, she had progressive lower limb ischemia. She underwent bilateral above-the-knee amputation on hospital day 4. Given her profound thrombotic state, she underwent evaluation for inherited and acquired thrombophilia. To evaluate for malignancy, whole-body PET/CT was performed demonstrating FDG avidity of the gallbladder, multiple liver lesions, and adenopathy at the porta hepatis concerning for metastatic gallbladder carcinoma. Fine-needle biopsy of a liver lesion demonstrated poorly differentiated adenocarcinoma. Given poor prognosis, the patient elected not to pursue further therapy and passed away at home. This patient presented with bilateral PCD as a [[Unable to Display Character: ﬁ]]rst manifestation of metastatic gallbladder carcinoma. PCD is a rare cause of limb ischemia characterized by the clinical triad of limb swelling, ischemic pain, and blue color change. Early attention to restoring venous patency is critical to avoid life and limb loss, and thrombophilia evaluation including evaluation for malignancy should be included in the diagnostic evaluation.
Abstract 19346: Peak Oxygen Consumption Predicts Outcome in Hypertrophic Cardiomyopathy
Authors: Contaldi Carla , Lombardi Raffaella , Giamundo Alessandra , Betocchi Sandro
Published: July 2021

Introduction:
Peak oxygen consumption (VO
2
) has a strong and independent prognostic value in systolic heart failure; in contrast no data support its prognostic role in hypertrophic cardiomyopathy (HCM).

Hypothesis:
We assess if peak VO
2
is a long-term predictor of outcome in HCM.

Methods:
We studied 92 HCM patients (40±15 years). Peak VO
2
was expressed as percentage (%) of the predicted value. Follow up was 76±57 months. The primary composite endpoint (CE) was atrial fibrillation, progression to NYHA class III or IV, myotomy-myectomy (MM), heart transplantation (HT) and cardiac death. An ancillary endpoint (HFE) included markers of heart failure (progression to NYHA class III or IV, MM and HT).

Results:
At baseline, 62% of patients were asymptomatic, 35% NYHA class II and 3% NYHA class III; 26% had left ventricular outflow tract obstruction. During follow up, 30 patients met CE with 43 events. By multivariate Cox survival analysis, we analyzed 2 models, using the CE, and in turn HFE. For CE, maximal left atrial diameter (LAD) (HR: 1.12; 95% CI: 1.04 to 1.22), maximal wall thickness (MWT) (HR: 0.14; 95% CI: 1.04 to 1.23) and % predicted peak VO
2
(HR: -0.03; 95% CI: 0.95 to 0.99) independently predicted outcome (overall, p<0.0001). For HFE, maximal LAD (HR:0.31; 95% CI: 1.09 to 1.70), MWT (HR: 0.35; 95% CI: 1.08 to 1.84) and % predicted peak VO
2
(HR: -0.06; 95% CI: 0.89 to 0.98) independently predicted outcome (overall, p<0.0001). Only 19% of mildly symptomatic or asymptomatic patients with % predicted peak VO
2
>80% had events, as opposed to 53% of them with % predicted peak VO
2
< 55% (p= 0.04). Event-free survival for both endpoints was significantly lower in patients with % predicted peak VO
2
< 55% as compared to those with it between 55 and 80 and >80% , Figure.

Conclusion:
In mildly or asymptomatic patients severe exercise intolerance may precede clinical deterioration. In HCM, peak VO
2
provides excellent risk stratification with a high event rate in patients with % predicted value <55%.
Abstract 19350: Ventricular Functional Response During Exercise in Patients After Fontan
Authors: Cifra Barbara , Mertens Luc , Slorach Cameron , Friedberg Mark K , Dragulescu Andreea
Published: July 2021

Background:
Patients with a functionally univentricular heart after Fontan are at risk for long-term complications. The influence of ventricular systolic and diastolic function and functional reserve on exercise performance has not been well established in this population. The aim of the current study was to assess ventricular systolic and diastolic response during exercise in children after Fontan completion using semi-supine cycle ergometry stress echocardiography (SSCE).

Materials and Methods:
Sixteen Fontan patients (11 RV dominant, 5 LV dominant), mean age 14.2±2.1y and 16 age and gender matched controls were included. A stepwise SSCE protocol was used. TDI peak systolic (s’), early diastolic (e’) velocities and myocardial acceleration during isovolumic contraction (IVA) were measured in the free wall of the dominant ventricle at rest and at incremental heart rates (HR) and compared to control results at the LV lateral wall. IVA was used to evaluate the force-frequency relationship (FFR).

Results:
Systolic function was qualitatively good in all patients and there was no more than mild valvar regurgitation. Resting HR was not significantly different between patients and controls but peak HR was lower in the Fontan group vs controls (p=0.003). Systolic and diastolic TDI velocities, but not IVA values, were lower at rest in Fontan patients (s’ 3.5±1.2 vs. 7.5±2.5 cm/sec; e’ 5.9±1.9 vs. 12.9±3.0 cm/sec, p<0.001). At peak exercise all parameters were lower in the Fontan group (s’ 6.4±1.3 vs. 14.4±4 cm/sec; e’ 9.4±2.8 vs. 18.2±3.7 cm/sec, p<0.001; IVA 2.9±1.1 vs. 5.6±1.6 m/sec2, p=0.001). During increasing HR, TDI velocities and FFR showed a blunted response in Fontan patients compared to controls (see figure).

Conclusions:
Our results suggest significantly reduced systolic and diastolic myocardial response to exercise in Fontan patients compared to normal controls. The mechanism and clinical implications of these findings require further investigation.
Abstract 19512: Right Ventricular Global Longitudinal Strain Improves Diagnostic and Prognostic Assessment in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Onishi Tetsuari , Yoshii Kosuke , Tsuru Masato , Shimane Akira , Okajima Katunori , Yamada Shinichiro , Taniguchi Yasuyo , Yasaka Yoshinori , Kawai Hiroya
Published: July 2021

Introduction:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiomyopathy characterized by right ventricular (RV) myocardium dysfunction leading to RV failure and fatal arrhythmias.

Hypothesis:
RV global longitudinal strain (GLS) derived from two-dimensional speckle-tracking echocardiography (2DSTE) contributes to diagnostic and prognostic assessment in ARVC.

Methods:
We retrospectively evaluated the echocardiographic data of 67 patients referred with suspected ARVC and 27 age- and gender-matched healthy controls (Group C). Of 67 suspected ARVC patients, 34 patients (Group A) were diagnosed as ARVC, while remaining 33 patients (Group B) were not diagnosed due to not meeting criteria. Tricuspid annular plane systolic excursion (TAPSE), RV end-diastolic and end-systolic area (RVEDA, RVESA), RV fractional area change (RVFAC) and GLS were measured to assess the RV function. Outcome was assessed according to death and hospitalization with heart failure, fatal arrhythmia and appropriate defibrillator shock.

Results:
Patients in Group A had significantly reduced values of TAPSE, RVFAC and GLS, and significantly greater vales of RVEDA and RVESA in comparison among 3 groups. In Group A, 11 adverse cardiac events were observed during averaged 718 follow-up days. Multivariate Cox’s regression analysis showed that GLS was an independent prognostic factor. Kaplan-Meier survival analysis revealed there was a significant difference in outcome between patient groups divided by the median value (11%) of GLS in Group A.

Conclusions:
GLS in RV may be a tool to assist in diagnosis of ARVC, and be a superior prognostic factor in ARVC patients.
Abstract 19570: Diastolic Anterior Leaflet Tethering Contributes to Functional Mitral Stenosis after Restrictive Mitral Valve Annuloplasty
Authors: Bertrand Philippe B , Verhaert David , Smeets Christophe J , Verbrugge Frederik H , Grieten Lars , Mullens Wilfried , Gutermann Herbert , Dion Robert A , Levine Robert A , Vandervoort Pieter M
Published: July 2021

Introduction:
Restrictive mitral valve annuloplasty (RMA) for secondary mitral regurgitation (MR) might cause functional (mitral) stenosis, yet underlying pathophysiological mechanisms remain debated.

Hypothesis:
Diastolic restriction of the anterior leaflet (AL) opening, due to papillary muscle tethering, plays a key role in the inflow obstruction after RMA. Increasing AL opening during exercise is associated with greater mitral valve area (MVA).

Methods:
Consecutive RMA patients (n=39, 63±11 years, 77% male) performed a symptom-limited (supine) bicycle exercise test with stepwise Doppler echocardiography and respiratory gas analysis. Diastolic AL opening angle (3-chamber view, Figure A), transmitral flow rate, mean transmitral gradient, and effective MVA were assessed at rest and during peak exercise.

Results:
At rest, effective MVA (1.5±0.4cm2) correlated moderately to the AL opening angle (68±10°) (r=0.4, p=0.014; Figure B). During exercise, effective MVA increased significantly to 2.0±0.5cm2 (p<0.001), with a stronger correlation to AL opening angle (r=0.6, p<0.001; Figure B). After stratification of the population into tertiles according to increase in AL opening angle during exercise (<=0°, 0-4° and >4° AL angle increase, respectively), a higher increase was significantly associated with greater effective MVA during exercise (p=0.013, Figure C). Patients with AL opening angle <69° at rest (median) and without dynamic AL angle increase of >4° (n=13) had a significantly lower maximal oxygen uptake compared to patients with AL opening angle at rest above the median or a greater dynamic AL angle increase with exercise (n=22) (VO2max 12.5±2.8 versus 16.4±4.7 mL/kg/min, p=0.005).

Conclusions:
Diastolic restriction of AL opening plays a key role in functional mitral stenosis after RMA for secondary MR. Increasing AL opening at rest, or better AL opening reserve during exercise, are associated with higher MVA and improved exercise capacity.
Abstract 19601: Differential Patient Perceptions of Limitations to Quality of Life in a Large Ambulatory Heart Failure Population
Authors: Joyce Emer , Badloe Sabrina , Stevenson Lynne W , Desai Akshay , Chung Christine , Young Michelle , Weintraub Joanne , Givertz Michael , Lewis Eldrin F
Published: July 2021

Introduction:
Clinical assessment of quality of life (QOL) is being increasingly adopted in the ambulatory management of heart failure (HF). Little is known about the impact of other conditions on QOL in clinical practice.

Methods:
Patients routinely presenting to the HF clinic completed a self-administered 1-page questionnaire prior to the visit that assessed QOL, functional status, and degree to which their HF, as well as other conditions, affected their QOL. Visual analog scales (VAS) were used to assess a) overall QOL, b) ease of breathing, and c) energy > fatigue. Scores ranged from 0 to 100 (higher scores representing better health status). Patients were asked if their QOL was affected more, equally, or less by their HF compared to other medical conditions. Data was analyzed with Pearson’s correlation coefficients, ANOVA and Chi-square tests.

Results:
A total of 1069 patients completed baseline QOL (mean age 57±16 years, 56% left ventricular ejection fraction [LVEF] ≥40%, 41% female). Mean QOL score was 63±28. Only 48% of patients felt that HF affected their QOL most while 20% felt HF was equal to other illnesses, 18% cited other medical problems and 14% non-medical problems as most important for their QOL. Patients reporting HF as the primary factor influencing QOL had significantly lower scores on all 3 VAS measures, the highest proportion of patients with low LVEF and the strongest correlation between QOL and VAS Breathing (R=0.68) (Table).

Conclusions:
Patients describing HF as their major limitation had the lowest QOL score and were most affected by dyspnea and fatigue. However, over half of ambulatory HF patients rate other medical and/or non-medical factors as equal or greater limitations to their QOL, suggesting this important clinical outcome will be difficult to impact by therapies targeted at HF alone, particularly in those with LVEF ≥40%.
Abstract 19663: Failed Delayed Sternal Closure Following Neonatal Cardiac Surgery Predicted by High Mean Airway Pressure and Associated with Increased Post-operative Mortality
Authors: Massey Dashiell , Williams Kathryn A , Thiagarajan Ravi R , Pigula Frank , Allan Catherine K
Published: July 2021

Background:
Myocardial edema, increased lung water, and anasarca are common following neonatal cardiac surgery with cardiopulmonary bypass and amplify the risk of hemodynamic instability and inadequate ventilation following sternal closure. Delayed sternal closure (DSC) in the intensive care unit one or more days following surgery is a common strategy to mitigate this risk, but has been associated with increased risk of infection. In addition, failed DSC has previously been identified as a risk factor for mortality. This study sought to identify predictor variables and determine impact of failed DSC.

Methods:
Records of all neonates undergoing DSC in the cardiac intensive care unit (CICU) following surgery with cardiopulmonary bypass between January 2008 and May 2013 were reviewed. Pre-operative, intra-operative and post-operative variables were compared for those patients who failed DSC versus those who did not. Continuous variables were compared utilizing Wilcoxon’s test and categorical variables using Fisher’s exact test.

Results:
Of 256 neonates undergoing DSC in the CICU, 22 failed first attempt at DSC. No significant difference between the two groups was appreciated in age, weight, or bypass (cross clamp, circulatory arrest, and total) times. Comparing DSC failures to successes, significantly more failures: followed Stage I palliation (63% vs. 31%); occurred later (post-operative day 4.7 vs. 2.8, p = 0.009); and were proceeded by higher mean airway pressures (9 vs. 8 cm H2O, p = 0.04), peak inspiratory pressure (27 vs. 24, p = 0.002), and inotrope score (12.1 vs. 9.6, p = 0.06). There was no association with systolic blood pressure or lactate prior to DSC. Failed DSC was associated with increased duration of mechanical ventilation (41.6 vs 7.4 days, p < 0.001), length of ICU stay (44.3 vs 12.0 days, p < 0.001), and mortality (38 vs 3%, p < 0.001).

Conclusions:
Mortality for patients who fail the first ICU attempt at delayed sternal closure is significantly higher than for those with successful sternal closure. Ventilatory pressures but not hemodynamic variables prior to DSC differed significantly between the two groups. First attempt at DSC was later in those who failed, suggesting that clinicians had a priori identified these patients as higher risk.
Abstract 19768: Does Frailty Predispose Patients to Increased Adverse Events after Left Ventricular Assist Device Implantation for Destination Therapy?
Authors: Stulak John M , Maltais Simon , Schirger John A , Daly Richard C , Joyce David L , Joyce Lyle D , Dunlay Shannon
Published: July 2021

Introduction:
Frailty has recently been shown to be associated with increased risk of death after continuous-flow left ventricular assist device (CF-LVAD) implantation as destination therapy (DT), but no data exists specifically analyzing its association with specific early and late adverse events.

Methods:
Between February 2007 and May 2014, 251 patients (205 male) underwent primary implantation of CF-LVAD at our institution; 157 (63%) were implanted as DT and preoperative frailty assessment was available in 96 pt. Frailty was identified in 58/96 (60%) patients according to the deficit index (31 impairments, disabilities and comorbidities) and defined as > 25% deficits. Age (67 vs. 64 years, p=0.12), male sex (79% vs. 87%, 0.63), chronic kidney disease (64% vs. 63%, p=0.74), creatinine (1.7 vs. 1.5, p=0.1), hemoglobin (11.6 vs. 11.5, p=0.98), and albumin levels (3.7 vs. 3.8, p=0.53) were similar between frail and non-frail pt, while diabetes (59% vs. 13%, p<0.001), ischemic etiology (64% vs. 45%, p=0.04), and preop balloon pump (50% vs. 26%, p=0.01) were significantly different.

Results:
All patients underwent CF-LVAD implantation and cardiopulmonary bypass time was similar between groups (102 vs. 111 min., p=0.3). There were no significant differences in early adverse events between frail and non-frail pt, including inotrope duration (120 vs. 96 hr., p=0.11), right ventricular failure (19% vs. 13%, p=0.44), respiratory failure (26% vs. 18%, p=0.34), acute renal failure (16% vs. 13%, p=0.69), and hepatic dysfunction (16% vs. 13%, p=0.69). Median length of stay (20 vs. 16 days, p=0.25) and early mortality (12% vs. 8%, p=0.48) were also similar. During a median follow up of 2 years with 224 patient/years of support, any GI bleed (43% vs. 42%, p=0.79), any thromboembolic event (34% vs. 39%, p=0.74), and driveline infection (10% vs. 26%, p=0.052).

Conclusions:
In this select cohort of patients, frailty did not portend higher risk of adverse events after CF-LVAD implantation for DT despite prior observation that late survival is reduced in these patients. These findings are extremely important in patient selection and counseling of patients prior to LVAD implantation.
Abstract 19813: Sleep Disturbance, Heart Failure, and Cognitive Function in Older Individuals: The Aging Demographics, and Memory Study (ADAMS)
Authors: Moon Chooza , Yoon Ju Young , Lauver Diane R , Bratzke Lisa
Published: July 2021

Introduction:
Approximately 50% of heart failure (HF) patients experience cognitive decline. In the general population, sleep disturbance is associated with cognitive decline. Sleep disturbance may alter the cellular or chemical homeostasis triggering cognitive decline. Up to 70% of individuals with HF report sleep disturbance. Although the etiology of cognitive decline in HF is unknown, sleep fragmentation and short sleep duration from sleep disturbance may partially explain cognitive decline among individuals with HF. This study investigates the possible mediating role of sleep disturbance on the relationship between HF and cognition.

Methods:
This cross-sectional study examined 856 older adults’ (mean age: 81.6 years, SD: 7.1, male: 355 (41%), Caucasian: 658 (77 %), HF: 100 (11.7%)) data from Aging, Demographics, and Memory Study. To explore the possibility of meditating effects of sleep disturbance on relationship between HF and cognition, we used a structural equation model. Cognition was measured by neuropyshological tests. Sleep disturbance was determined if a subject was positive on one of the following three questions: 1) “Do you have problem falling asleep?”, 2) “Do you wake frequently during sleep?”, and 3) “Do you wake up too early?”

Results:
Individuals with HF were likely to have a higher degree of sleep disturbance (β=0.229,p=0.003). Sleep disturbance was a significant predictor of cognitive decline (β=-6.52,p=0.028). However, there was no significant mediating effect of sleep disturbance on the relationship between HF and cognition (β=-0.011,p=0.978) after controlling for age, sex, and comorbidities.

Conclusion:
Findings from this study suggest that HF can exacerbate sleep disturbance and sleep disturbance can deteriorate cognition. However, the mediating role of sleep disturbance on the relationship between HF and cognitive decline remains questionable. Future studies using objective measures and longitudinal design would enhance our knowledge related to the relationship between heart failure, sleep disturbance, and cognition.
Abstract 19859: Reducing Radiation Exposure for Patients also Improves Staff Radiation Exposure in the Cardiac Catheterization Laboratory
Authors: Robert Alina M , Ver Lee Peter N , Lilieholm Barbara , Morgan Kevin , Cunningham Robert , Qazi Amina , Jansujwicz Alan , McKay Matthew S , Fincke Rupert , Crespo Guillermo J , Rowe Matthew W , vom Eigen Paul R , Wiseman Alan H , Malenka David J
Published: July 2021

Introduction:
As the availability and use of medical imaging has increased, ionizing radiation has become a significant occupational exposure. Staff in the cardiac catheterization laboratory are among those with the highest exposures.

Hypothesis:
Changing equipment defaults to decrease patient radiation exposure would also decrease staff radiation exposure.

Methods:
In October 2013 we made equipment adjustments to decrease patient radiation exposure in all 3 cardiac catheterization laboratories at Eastern Maine Medical Center. We changed fluoroscopy defaults to low dose option and low frame rate (7.5 frames/sec from 15 frames/sec) while maintaining the option for operators to use higher settings as needed. We analyzed staff radiation exposure for 8 physicians and 14 nurses by comparing total collar dosimeter dose (in mRem) between the 3 months before and 3 months after the intervention controlling for procedural volume using standard statistical methods.

Results:
For physician operators, mean dosimeter dose decreased by 41.6% (346.8 ± 264.8 pre vs 202.5 ± 135.9 post intervention, p=0.042). For nurses whose roles are to assist during procedures or to circulate in the room, the mean dosimeter dose decreased by 25% (65.9 ± 49.4 pre vs 50.2 ± 53.5 post intervention, p=0.038). There was no significant difference between the number of cases performed by physicians (p=0.598) and nurses (p= 0.866) before and after the intervention. Procedural success did not decline post-intervention. Compliance with wearing collar dosimeter is required and reported as excellent at our institution.

Conclusions:
Setting fluoroscopy defaults to low dose and low frame rate to improve patient radiation exposure also significantly decreased radiation exposure for both physician and ancillary staff working in the cardiac catheterization laboratory. If widely adopted this intervention would help to mitigate the long term adverse effects of occupational exposure to ionizing radiation.
Abstract 19863: Impact of Coronary Artery Fixed Lesion on 3-years Clinical Outcomes in Vasospastic Angina Patients with Myocardial Bridge
Authors: Rha Seung Woon , Lee Se-Whan , Shin Won-Yong , Lee Seung-Jin , Jin Dong-Kyu , Choi Byoung Geol , Choi Se Yeon , Lee Sunki , Kim Ji Bak , Na Jin Oh , Choi Cheol Ung , Lim Hong Euy , Kim Jin Won , Kim Eung Ju , Park Chang Gyu , Seo Hong Seog , Oh Dong Joo
Published: July 2021

Background:
It is not known whether the presence of angiographic fixed coronary lesion (FCL) can negatively impact on long-term major clinical outcomes in vasospastic angina patients (pts) with myocardial bridge (MB).

Methods:
A total 5,882 patients (pts) underwent coronary angiography with acetylcholine (Ach) provocation test from Nov 2004 to Oct 2010. Among them, total 563 pts who had MB and documented significant coronary artery spasm (CAS) by Ach provocation test were enrolled. Study populations were categorized into two groups; the fixed coronary lesion (FCL) group (n=216) and the non-FCL group (n=347). Cumulative major clinical outcomes were compared between the two groups up to 3 years.

Results:
Baseline characteristics were similar between the two groups except the incidence of elderly, hypertension, diabetes, and dyslipidemia were higher in the FCL group. In univariate analysis, only the composite end-point consisted of cardiac death, de Novo percutaneous coronary intervention (PCI), myocardial infarction (MI), and cerebrovascular accident (CVA) was higher in FCL group (Table). However, in multivariate regression analysis, the incidences of cardiac death, PCI, MI, CVA, recurrent chest pain, and other composite end-points were similar between the two groups up to 3 years.

Conclusions:
In our study, the presence of angiographic fixed coronary lesion in vasospastic angina pts with MB was not a predictor of adverse long-term clinical outcomes.
Abstract 20006: RNA Sequencing of Human Hypertrophic Cardiomyopathy Tissue Reveals Diverse Pathways Modulating the Myocardial Tissue Microenvironment
Authors: de Feria Alejandro , Maltais Simon , Absi Tarek S , Su Yan R , Stricker Thomas P , Becker Jason R
Published: July 2021

Introduction:
Hypertrophic Cardiomyopathy (HCM) is a common inherited cardiac disease and cause of sudden death in adolescents and young adults. Despite significant advances in understanding the genetic underpinnings of HCM, there remains an incomplete understanding of how myofilament mutation carriers and non-carriers ultimately develop myocardial hypertrophy.

Hypothesis:
Human hypertrophic cardiomyopathy tissue differentially regulates gene expression involved in cellular growth.

Methods:
RNA was extracted from 5 control human septal tissue samples and 8 HCM septal tissue samples. The HCM tissue samples were from both myofilament mutation positive and negative patients. RNA sequencing was performed using Illumina HiSeq 2500 at a depth of 30 million paired-end reads per sample. Sequencing data was aligned to the hg19 genome using TopHat (splice-aware aligner). Cufflinks was used to estimate transcript abundance and differential expression. Pathway enrichment analysis was carried out on significant genes (q<0.05) using DAVID (v6.7). Only pathways with an enrichment score greater than 2 were evaluated.

Results:
Cluster and principal component analysis showed highly distinct RNA expression signatures between control and HCM tissues. There were 1500 differentially expressed sequences (q<0.05), which included 1286 annotated genes, 168 novel isoforms, and 46 long noncoding RNA sequences. Gene functional classification revealed 40 differentially regulated gene clusters in HCM tissue compared to controls. The most enriched gene clusters induced in human HCM tissue were associated with secreted peptides involved in promoting cell growth and modulation of extracellular structure (enrichment scores > 10). Highly enriched gene clusters that were suppressed in human HCM tissue were associated with secreted peptides involved in regulating inflammation and immune defense response (enrichment scores > 5).

Conclusion:
Our data reveals human HCM tissue differentially regulates a diverse array of genes involved in regulation of the myocardial tissue microenvironment. The strong similarity in gene expression across HCM samples suggests shared pathophysiological mechanisms independent of the underlying genetic etiology.
Abstract 20120: Protease-activated Receptor 4 Deficiency Reduces Atherosclerosis
Authors: Owens A. Phillip , Howatt Deborah A , Daugherty Alan , Mackman Nigel
Published: July 2021

Objective:
Platelet activation is emerging as a critical process in both the formation and propagation of atherosclerosis. The coagulation protease thrombin activates platelets by cleavage of protease-activated receptor 4 (PAR4) in mice. Recent studies have demonstrated direct thrombin inhibitors reduce atherosclerosis in hypercholesterolemic mice. However, PAR4 deficiency had no effect on atherosclerosis in the apolipoprotein E (Apoe-/-) mouse model. The objective of this study was to re-examine the role of PAR4 deficiency in atherosclerosis using the alternative low-density lipoprotein receptor deficient mouse model.

Methods and Results:
To examine the effects of PAR4 deficiency on early atherosclerotic formation, low-density lipoprotein receptor deficient (Ldlr-/-) mice that were either PAR4+/+ (n = 11) or PAR4-/- (n = 12) were fed a fat-enriched diet (21% milk fat) and infused with angiotensin II (AngII; 1,000 ng/kg/min) for 28 days. PAR4 deficiency reduced AngII-induced aortic root atherosclerosis (+/+: 107 ± 22.1; -/-: 28.3 ± 7.50 μm2; P = 0.007). Bone marrow transplantation experiments were performed to determine the cellular source of PAR4 in atherosclerosis. Preliminary results demonstrate this reduction is dependent upon hematopoietic-derived PAR4 (+/+ into +/+: 230 ± 41; +/+ into -/-: 194 ± 23; -/- into +/+: 78 ± 18; and -/- into -/-: 68 ± 13 μm2; n = 4 each group; P < 0.02 +/+ hematopoietic versus -/- hematopoietic). PAR4 deficiency had no effects on total plasma cholesterol concentrations, lipoprotein-cholesterol distributions, or AngII increased systolic blood pressure. To determine the effects of a longer interval of diet-induced atherosclerosis, Ldlr-/-/PAR4+/+ (n = 12) or Ldlr-/-/PAR4-/- (n = 12) were fed a fat-enriched diet for 12 weeks. PAR4 deficiency attenuated aortic root atherosclerosis (+/+: 299 ± 15; -/-: 188 ± 18 μm2; P = 0.001) with no effects on total plasma cholesterol concentrations or lipoprotein distributions.

Conclusion:
We demonstrated that PAR4 deficiency resulted in an early (AngII: 74%) and late (Diet-induced: 37%) reduction in aortic root atherosclerosis. These results suggest that thrombin activation of PAR4 on platelets contributes to atherosclerosis in the Ldlr-/- model, but not the Apoe-/- model.
Abstract 20130: Permanent Pacemaker Implantation Following Heart Surgery: In-Hospital and Postoperative Retrospective Multicentre Evaluation in 1,156 Implants
Authors: Lorusso Roberto , Barili Fabio , Miceli Antonio , Parolari Alessandro , Alamanni Francesco , De Vincentiis Carlo , Aimè Ezio , Nicolini Francesco , Gherli Tiziano , Colli Andrea , De Bonis Michele , Paglino Gabriele , Della Bella Paolo , Actis Dato Guglielmo , Casabona Riccardo , Sponga Sandro , Livi Ugolino , Mariscalco Giovanni , Beghi Cesare , Scrofani Roberto , Antona Carlo , Tritto Francesco P , Gerosa Gino , Piazza Luigi , Villa Emanuel , Troise Gianni , Serraino Filibertio , Renzulli Attilio , Rosato Francesco , Grossi Claudio , Paparella Domenico , Amorese Lillà , Vizzardi Enrico , Solinas Marco , Glauber Mattia
Published: July 2021

Introduction:
Permanent pacemaker (PPM) implantation represents a potential event after cardiac surgery. However, comprehensive investigation of robust patient cohorts in this respect is unavailable.

Hypothesis:
A multicenter retrospective study was undertaken to assess in-hospital and long-term postoperative outcome of a large patient population undergoing PPM soon after cardiac surgery procedures.

Methods:
Among 94.693 patients submitted to cardiac surgery procedures in 16 centers from 2000 to 2013, there were 1.156 patients (1.2 %) with PPM implantation during hospitalization postoperatively. Preoperative, in-hospital, and follow-up data were collected with a common dataset and analyzed. Follow-up was performed by direct visit, and PPM dependency was assessed by electrocardiogram and pacemaker check during periodic examinations. The identification of potential predictors of PPM dependency at follow-up was evaluated with a multivariate logistic regression.

Results:
Patient mean age was 69 years (range 17-92 years) and 53.4% were male. Preoperative electrocardiogram showed first degree atrio/ventricular block in 11.0% of patients, left bundle branch block in 11.1%, right bundle branch block in 11.0%, and atrial fibrillation in 22.8%, respectively. Most of the patients had had isolated aortic valve replacement (25.8%). Pacemakers were implanted after a median of 11 days after surgery. At follow-up, 43.6% of the patients did not show a PPM dependency with restoration of sinus rhythm. The multivariate logistic regression demonstrated that only preoperative right bundle branch block (p-value 0.031) and mitral valve repair (p-value 0.032) were independent risk factor for PPM dependency at follow-up.

Conclusions:
More than 40% of patients with PPM implantation shortly after cardiac surgery show recovery of sinus rhythm at follow-up. Wide variability of strategies and PM implant timing are currently applied in routine practice. Refinement of current guidelines in this setting based also on predictors of permanent conduction defects postoperatively are warranted.
Abstract 20218: Comparative Effectiveness of Dabigatran and Rivaroxaban versus Warfarin in Patients With Non-Valvular Atrial Fibrillation
Authors: Bengtson Lindsay , Chen Lin , MacLehose Richard , Lutsey Pamela , Alonso Alvaro
Published: July 2021

Background:
In randomized trials, the new oral anticoagulants (NOAC) dabigatran and rivaroxaban have been at least as efficacious as warfarin in the prevention of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Information on the effectiveness of NOACs versus warfarin in real-world populations in the US is more limited.

Methods:
We used data from the US MarketScan Commercial and Medicare Supplemental databases in the period 2010-12. We selected patients initiating oral anticoagulants after NVAF diagnosis, and with at least 6 months of enrollment before first anticoagulant use. Patients initiating dabigatran or rivaroxaban were matched with up to 5 warfarin users by age, sex, and time in the database. Outcomes of interest (ischemic stroke, intracranial bleeding, and gastrointestinal [GI] bleeding) were defined according to validated algorithms. Information on other comorbidities and medication use was obtained from inpatient, outpatient, and pharmacy claims. High-dimensional propensity score-adjusted Cox proportional hazards regression was used to estimate the association of NOACs vs warfarin with each outcome of interest.

Results:
The analysis included 32,918 dabigatran, 3,301 rivaroxaban and 92,633 warfarin users with NVAF. During an average 13-month follow-up (6 for rivaroxaban, 15 for dabigatran), 1035 ischemic strokes, 225 intracranial bleeds, and 1842 GI bleeds were identified. Rate of ischemic stroke was similar in patients initiating NOACs compared to those on warfarin. However, rate of intracranial bleeding was lower in patients using NOACs compared to warfarin users, while GI bleeding rate was higher in dabigatran users than warfarin users (Table).

Conclusion:
In this large real-world patient population, effectiveness of NOACs (compared to warfarin) for diverse outcomes was comparable to efficacy reported in the RE-LY and ROCKET-AF trials.
Abstract 20267: Diminished Levels of Circulating Bone Morphogenetic Protein 9 Identify Pulmonary Arterial Hypertension Associated With Liver Disease
Authors: Nikolic Ivana , Paskin-Flerlage Samuel D , Malhotra Rajeev , Yung Lai-Ming , Chung Raymond T , Channick Richard N , Roberts Kari E , Yu Paul B
Published: July 2021

Background:
Dysregulated bone morphogenetic protein (BMP) signaling is thought to contribute to the pathogenesis of pulmonary arterial hypertension (PAH). BMP9 can be detected in the circulation at physiologically active concentrations, and is thought to serve as a vascular endothelial quiescence factor.

Aim:
We hypothesized that circulating levels of BMP9 might be associated with altered endothelial homeostasis, and could help predict the presence of PAH or distinguish between PAH of distinct etiologies.

Methods:
Circulating levels of BMP9, and its biological inhibitor, soluble Endoglin (sEng), were measured in the plasma of 96 patients with various etiologies of pulmonary hypertension and 28 healthy individuals using enzyme-linked immunoassays.

Results:
Patients with Group I PAH (n=44) had significantly lower levels of BMP9 compared to healthy individuals (188 ± 22 pg/mL vs 254 ± 17 pg/mL, mean ± SEM, p=0.001). BMP9 was significantly decreased in PAH associated with connective tissue disease (p=0.02), but was most profoundly decreased in patients with portopulmonary hypertension (82 ± 27 pg/mL, p<0.0001 vs controls). BMP9 was a strong predictor of concomitant liver disease (ROC AUC=0.920), correlating positively with serum albumin and platelet counts, and negatively with INR, total bilirubin, cardiac index and MELD score among Group I PAH patients (
Abstract 20416: Ttc39b Deficiency Has a Beneficial Role on Cholesterol and Triglyceride Absorption in Enterocytes
Authors: Koseki Masahiro , Hsieh Joanne , Yakushiji Emi , Welch Carrie , Iqbal Jahangir , Hussain Mahmood M , Tall Alan R , Sakata Yasushi , Yamashita Shizuya
Published: July 2021

Background:
TTC39B
, encoding tetratricopeptide repeat domain 39B, was identified in genome wide association studies (GWAS) as a novel gene influencing HDL-cholesterol (HDL-C) levels. Since
Ttc39b
had not been previously implicated in lipoprotein metabolism at all and nothing was known about the functions of
Ttc39b
, we investigated animal models.

Method and Results:
We have found that on a chow diet there were increases in LXR protein but not mRNA, increased expression of
Abca1
mRNA and protein and 22% increased HDL-C levels in
Ttc39b
-/-
mice.

Experiments using primary enterocytes isolated from
Ttc39b
-/-
mice revealed that secretion of particles containing apoA-1 increased by approximately twofold. When mice were fed with a high fat/high cholesterol/bile salt diet, primary enterocytes secreted 50% less particles not containing apoA-1, as well as particles containing apoA-1 by twofold. In the cholesterol absorption study by gavaging [
3
H]-cholesterol total cholesterol absorption were decreased by 50%
Ttc39b
-/-
mice. As a result, hepatic cholesterol and TG after mice were fed with a high fat/high cholesterol/bile salt diet for eighteen week were dramatically decreased in
Ttc39b
-/-
by 42 and 50% respectively. In addition, external oxysterols, such as 7b-hydroxycholesterol and 7-ketocholesterol were also parallel decreased.

Conclusion:
These studies show that
Ttc39b
deficiency results in increased LXR primarily in enterocytes, beneficial lipoprotein changes and reduced atherosclerosis. Moreover,
Ttc39b
-/-
mice were protected from fatty liver, indicating that
Ttc39b
inhibition could be an effective strategy for reducing atherosclerosis and fatty liver.
Abstract 20439: Novel Long Intergenic Noncoding RNAs Modulate Adipose Functions in Human
Authors: Zhang Xuan , Ballantyne Rachel , Xue Chenyi , Ferguson Jane F , Gregory Brian , Li Mingyao , Reilly Muredach P
Published: July 2021

Recently long intergenic noncoding RNAs (lincRNAs) have emerged as key mediators of cellular differentiation and functions in a variety of cell systems critical to cardiovascular and metabolic disorders. To identify and investigate novel functional lincRNAs in human adipose, we performed deep high-throughput RNAseq (>200 million reads/sample) in subcutaneous adiposes of 13 health volunteers. Of an integrated dataset of 54,944 human lincRNAs, 6,558 lincRNAs were detected.

Here we report 2 cytoplasmic adipose lincRNAs, linc-DMRT2 and linc-NFE2L3-1, were detected in human adipocytes but not monocytes or macrophages. Linc-DMRT2, one of the most abundant adipose lincRNAs, was markedly induced during in vitro human adipocyte differentiation. Notably, single molecule RNA FISH (fluorescence in situ hybridization) demonstrated that linc-DMRT2 were exclusively present in adipocyte cytoplasma and co-localized with processing bodies (P-bodies) marker, GW182, suggesting its potential role in modulating turnover of certain RNA species. In addition, linc-NFE2L3-1, predominantly detected in adipose and skeleton muscle, is localized near an established GWAS locus associated with waist-hip ratio adjusted BMI. We identified 4 SNPs in linc-NFE2L3-1 reaching genome wide significance for BMI (lead SNP rs10267498, P=2.73х10
-8
). Linkage disequilibrium analysis confirmed linc-NFE2L3-1 harbors stronger GWAS signals than protein-coding genes in the locus, suggesting lincRNA might be causal for GWAS association with BMI. Bioinformatic prediction algorithms identified potential binding sites in linc-DMRT2 and linc-NFE2L3-1 for multiple microRNAs that have been demonstrated to regulate adipogenesis (e.g. miR-15 a/b and let-7) or adipocyte functions (e.g. miR-320).

In summary, our data suggest that cytoplasmic linc-DMRT2 and linc-NFE2L3-1 may play important roles in adipocyte biology by functioning as competing endogenous RNAs and binding specific microRNAs that mediate adipocyte cellular functions. Genetic variation in such human linRNAs may contribute to cardiometabolic traits.