bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16166: Validation of a of Self-Reported Measure of Physical Capacity in the Context of Chronic Cardiovascular and Pulmonary Diseases
Authors: Gallani Maria-Cecilia , Poirier Paul , Doré Michel , Provencher Steeve , Gagné Camille , Gélinas Céline , Caron-Cantin Sarah-Maude , Myers Jonathan
Published: July 2021

Background:
The assessment of physical capacity (PC) is relevant to estimate prognosis and guide therapeutics for patients with chronic cardiopulmonary disease. The Veterans Specific Activity Questionnaire (VSAQ) is a self-reported tool designed to assess perceived physical capacity in METs according to a given patient’s level of physical activity limited by symptoms. The purpose of this study was to examine the validity of the score of the French-Canadian version of the VSAQ among patients suffering from cardiovascular symptoms and chronic pulmonary diseases.

Methods:
A total of 140 subjects referred for treadmill testing (TT group) and 134 patients with pulmonary hypertension or interstitial lung disease (PD group) were enrolled. Criterion validation was verified in the TT group by level of agreement (Bland-Altman coefficient) between the VSAQ and the workload estimated by the gold standard to assess PC, the maximal treadmill test (MTT). Convergent validation was tested using correlations between the VSAQ score and physical capacity (MTT and 6-min walking test - 6MWT); practice of physical activity (Godin-Shephard Leisure-Time Physical Activity Questionnaire-GSLTPAQ); pulmonary function (forced vital capacity- FVC) and quality of life (Minnesota living with Heart Failure Questionnaire-LHFQ and SF-12). Partial correlation coefficients were adjusted for sex, age, BMI and education.

Results:
The mean bias between VSAQ and estimated METs was -1.54 with limits of agreement (CI 95%) of 3.71 to -6.79 METs, being constant around all MET levels. Significant correlations (p <0.05) between the VSAQ score in the TT sample were 0.65 with MTT, 0.20 with the GSLTPAQ; -0.36; -0.39 and -0.29 with the LHFQ total score, physical and emotional domains. Significant correlations (p <0.05) for the PD sample were: 0.58 with 6MWT; 0.43 with FVC (interstitial lung disease only); 0.31 with GSLTPAQ; and 0.65 and 0.24 with SF-12 physical and emotional components.

Conclusion:
The VSAQ French-Canadian version demonstrated acceptable criterion and convergent validation among two different groups of chronic disease patients. Its utilization by the nurse during routine clinical follow-up of these patients could be helpful to guide functional evaluations and interventions.
Abstract 16175: Total Burden of Out-of-Pocket Costs for Penicillin Prophylaxis for Rheumatic Heart Disease in India: Results From the AIIMS Pediatric RHD Registry
Authors: Mehta Anurag , Saxena Anita , Kazi Dhruv S
Published: July 2021

Introduction:
Out-of-pocket costs are a major barrier to medication adherence in low and middle income countries and an important target for policy-level interventions. The total economic burden for patients receiving secondary penicillin prophylaxis for Rheumatic Heart Disease (RHD) is uncertain.

Methods:
We prospectively collected self-reported out-of-pocket drug, transportation, and provider costs from patients in the AIIMS Pediatric RHD Registry. Monthly costs were estimated by adjusting visit costs for frequency of drug administration. Because adverse drug reactions are rare, we did not collect complication-related costs. Mean (±SD) costs are reported in 2013 Indian Rupee (INR) and International Dollars (INT$).

Results:
In our registry, 230 patients provided cost data over 313 visits. The mean age was 11.8 (±2.9) years, and 83 (36%) were girls. The majority of patients resided in rural areas (n=197, 86%), and were from the lower and upper lower socioeconomic strata (n=160, 70%) on the modified Kuppuswami scale. Nearly all patients hailed from outside Delhi (91%), reflecting the referral population of our tertiary hospital.

The monthly out-of-pocket cost was INR 74.92 (±109.00) or INT$ 4.04 (±5.88), drug cost forming 36% of the total costs (INR 26.71 [±11.6]; INT$ 1.44 [± 0.63]). Provider costs (INR 18.21 [±32.48]) and transportation costs (INR 30.00 [±106.51]) comprised 24% and 40% of total costs respectively. Provider and transportation costs exceeded the drug costs for 38% of the patients. Patients traveled 12 (±38) km round trip to obtain penicillin prophylaxis.

Conclusions:
Drug costs constitute only 36% of the total out-of-pocket cost of penicillin prophylaxis for RHD, with provider costs (24%) and transportation costs (40%) comprising the remainder. Because out-of-pocket costs can be a major barrier to long-term adherence, future efforts must be directed at improving access to and lowering total costs of penicillin prophylaxis for RHD.
Abstract 16201: Combined Treatment of the PI3k/mTOR Inhibitor BEZ235 With Doxorubicin Does Not Increase Cardiotoxicity While Improving Efficacy in Breast Cancer Cells
Authors: Durrant David E , Dyer Samya , Das Anindita , Kukreja Rakesh C
Published: July 2021

Background:
Cardiotoxicity is a major clinical limitation with doxorubicin (DOX). Also, the PI3K/Akt survival pathway is one of the most commonly mutated pathways in cancer. Therefore, the combination of kinase inhibitors and chemotherapy, such as DOX, are necessary for achieving cancer control. The PI3K pathway is also critical for protecting the heart from stress. Therefore, we examined the combined effect of BEZ235 (BEZ), a dual PI3k/mTOR inhibitor, with DOX on cardiac function and killing of breast cancer cells.

Methods and results:
c57 mice were treated with BEZ (40 mg/kg daily oral gavage) and DOX (3 IV injections of 5 mg/kg) either alone or in combination. Systolic function was assessed 12 weeks after initial treatment using echocardiography. Decreased ejection fraction was observed after DOX treatment. Interestingly, the combined treatment with BEZ and DOX did not exacerbate DOX cardiotoxicity (Fig. A). Western blot analysis showed significant increase in AKT (thr 308) and ERK phosphorylation with BEZ and DOX as compared individual treatment with BEZ or DOX in the heart (Fig. B). To address the anti-cancer effects of these drugs, MDA-MB-231 breast cancer cells were treated with BEZ and DOX either alone or in combination for 48 hours. Necrosis, measured using the trypan blue assay, showed a significant increase in dead cells compared to either drug alone (Fig. C).

Conclusion:
Concurrent treatment with DOX and BEZ did not exacerbate cardiac toxicity as demonstrated by similar level of deficit in ejection fraction between DOX as well as DOX plus BEZ. This could be due to enhanced survival signaling in the combination group. BEZ also sensitized breast cancer cells to DOX resulting in increased cell death. We propose that this combination strategy might lead to improved long term outcomes for patients with breast cancer without additional complications related to cardiac dysfunction.
Abstract 16238: Mortality and Predictors of Appropriate ICD Therapy in Japanese Primary
Prevention
Patients: A 13-year Experience Based on the MADIT2 Criteria
Authors: An Yoshimori , Ando Kenji , Nagashima Michio , Fukunaga Masato , Hiroshima Kenichi , Nobuyoshi Masakiyo
Published: July 2021

Background:
There are still limited data on the mortality for a long-term follow-up and the clinical factors influencing appropriate therapies in Japanese patients with implantable cardioverter-defibrillator (ICD) for primary prevention, who satisfied the criteria in Multicenter Automatic Defibrillator Implantation Trial 2 (MADIT2).

Methods:
Between January 2000 and December 2012, a total of 436 patients without prior ventricular arrhythmic event underwent ICD implantation for primary prevention at our institution. Among these patients, we enrolled consecutive 122 patients (69±10 years, male: 84%, biventricular-pacing: 54%, median follow-up: 1390 days) who met the MADIT2 criteria; left ventricular ejection fraction (LVEF) ≤30% with ischemic heart disease, more than 4 weeks after myocardial infarction.

Results:
At the 3 years of follow-up, the mortality rate (21%) was comparable with that of the original MADIT2 ICD group (20%). The Kaplan-Meier event rate for appropriate ICD therapy (shock and anti-tachycardia pacing therapy) (35%) was also similar to that of the original MADIT2 ICD group (32%). Multivariate analysis by Cox regression model revealed that left ventricular diastolic diameter (LVDd) ≥60mm (Hazard Ratio [HR]: 1.65, 95% Confidence Interval [CI]: 1.16-2.14, P=0.004) and non-sustained ventricular tachycardia (NSVT) (HR: 1.55, 95%CI: 1.13-2.15, P=0.007) were independent predictors for appropriate ICD therapy. On the other hand, LVEF, NYHA class, biventricular-pacing, amiodarone or inducibility of ventricular arrhythmia was not associated with appropriate ICD therapy.

Conclusion:
Appropriate ICD therapy was delivered in Japanese primary prevention patients as often as in the original MADIT2 ICD group and strongly predicted by dilated left ventricle and NSVT.
Abstract 16331: Alcohol Consumption and Its Relation to Obesity in a Population-Based Study in Finland
Authors: Männistö Satu , Kontto Jukka , Borodulin Katja , Kanerva Noora , Laatikainen Tiina , Jousilahti Pekka
Published: July 2021

Introduction:
Alcohol is the second most energy-dense macronutrient and it is metabolized very effectively. The previous results, however, do not conclusively confirm a positive association between alcohol consumption and BMI. In several studies, moderate alcohol consumers have shown lower BMI than abstainers, despite their higher daily energy intake. Our aim was to determine associations of alcohol consumption with energy intake and BMI.

Methods:
The National FINRISK 2012 Health Study consisted of 4776 participants aged 25-74 years. The Study included questionnaires and measured weight and height. A validated food frequency questionnaire was used to assess participants’ whole diet.

Findings:
Of men, 12% were classified as abstainers and 6% as heavy drinkers, while the percentages for women were 25% and 3%, respectively. The mean daily alcohol consumption was 12.9 g among men and 4.4 g among women. Alcohol consumption had a highly skewed distribution; the participants in the highest alcohol quintile consumed about half of all reported alcohol (46% for men and 44% for women). Men consumed 71% of all the reported alcohol.

In men and women, daily energy intake increased with rising alcohol consumption. However, there were no differences in the non-alcoholic energy intake from foods between alcohol consumption categories (p-value was 0.15 for men and 0.74 for women). The U-shaped association between low/moderate alcohol consumption and BMI was observed, especially in women. Moderate female alcohol consumers were 1.5-2 BMI units leaner than the others, whereas the difference was below 1 BMI unit in male.

Conclusions:
Alcohol consumers did not habitually substitute food items with alcohol beverages. The participants with low or moderate alcohol consumption, however, had the lowest BMI. The reasons for moderate drinkers being leaner than abstainers remain an interesting open question. Obesity, however, can partly explain the U-shaped association found between alcohol consumption and the risk of cardiovascular diseases.
Abstract 16349: A Novel Class of Inhibitors That Are Specific to Human NPP1 Prevent Pathologic Mineralization of Valve Interstitial Cells
Authors: Shayhidin Elnur E , Forcellini Elsa , Boulanger Marie-Chloé , Ablajan Mahmut , Dautrey Sébastien , Barbeau Xavier , Lague Patrick , Sévigny Jean , Paquin Jean-François , Mathieu Patrick
Published: July 2021

BACKGROUND:
Ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) is an ectoenzyme, which plays a role into several disorders including calcific aortic valve disease (CAVD). So far, compounds that have been developed as inhibitors of NPP1 lack of potency and specificity. Quinazolin-4-piperidin-4-methyl sulfamide (QPS) derivatives have been described as potent inhibitors of NPP1. However, their mode of inhibition as well as their selectivity and capacity to modify biological processes have not been investigated.

METHOD:
We have investigated the potency and selectivity of QPS derivatives in inhibiting NPP1 by enzymatic activities. The biological effect of QPS derivatives was documented on the mineralization of valve interstitial cell cultures, apoptosis assay, as well as quantitative polymerase chain reaction.

RESULTS:
We documented that QPS1 derivative is a potent (67.9 ±5.3 nM) and selective non-competitive inhibitor of human NPP1. Moreover, QPS1 also significantly inhibited the K121Q NPP1 gene variant (ki 51.9±9.8 nM), which is prevalent in the general population. QPS1 did not significantly alter the activity of other nucleotide metabolising enzymes expressed at the cell surface, namely NPP3, NTPDases (1-3), ecto-5’-nucleotidase and ALP. Importantly, QPS1 in the low micromolar range (≤10μM) prevented phosphate-induced mineralization of VICs and lowered the rise of osteogenic genes as expected for NPP1 inhibition.

CONCLUSION:
We provide evidence that QPS1 is a potent and selective non-competitive inhibitor of NPP1 that prevents pathologic mineralization in a cellular model.
Abstract 16435: Lifestyle Interventions Reduce Ten-Year Risk of Atherosclerotic Cardiovascular Disease as Predicted by the Pooled Cohort Equations
Authors: Hinderliter Alan , Smith Patrick , Sherwood Andrew , Blumenthal James
Published: July 2021

Introduction:
Lifestyle measures, such as adoption of the DASH diet, weight reduction, and exercise, are effective in lowering blood pressure. The degree to which these behaviors reduce the risk of cardiovascular events is not well-established. We examined the effect of dietary and weight management inventions used in the ENCORE study on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD), as defined by the Pooled Cohort Equations.

Methods:
Participants included 129 overweight or obese men and women between the ages of 40 and 80 years who had blood pressure 130-160/80-99 mmHg and who were not treated with antihypertensive medications. Subjects were randomized to 16 weeks of DASH diet plus behavioral weight management (consisting of nutritional counseling and a behavioral weight management program)(DASH+WM), DASH diet alone (consisting of nutritional counseling without exercise or caloric restriction)(DASH), or usual care (UC).

Results:
The participants averaged 53.5±8.8 years of age; 68% were female, and 60% were white. One had diabetes and 11 (9%) were smokers. Systolic BP averaged 138±9 mmHg; total and HDL cholesterol averaged 203±36 mg/dl and 55±14 mg/dl, respectively. The average estimated 10-year risk of ASCVD for the entire cohort was 5.7%. The baseline characteristics of the subjects randomized to DASH+WM (n=46), DASH (n=39), and UC (n=44) were similar. Participants in the DASH+WM and DASH interventions had significant decreases in systolic blood pressure, and those in the DASH+WM group had a significant decrease in total cholesterol. Post-intervention estimated 10-year ASCVD risk [mean(SE)], adjusted for baseline values, was 4.4(0.2)% for DASH+WM, 5.0(0.3)% for DASH, and 5.7(0.2)% for UC (p<.001 for DASH+WM vs UC; p<.05 for DASH vs UC). The number of untreated subjects with an indication for consideration of statin therapy, as recommended in the 2013 ACC/AHA Guideline for the Treatment of Blood Cholesterol, fell from 11 to 6 in DASH+WM and from 12 to 10 in DASH, while remaining unchanged (11) in UC.

Conclusions:
In overweight or obese men and women with high BP, lifestyle interventions reduce the predicted 10-year risk of ASCVD and decrease the number of individuals in whom statin therapy is recommended.
Abstract 16535: Clinical Significance of Echo-Attenuated Plaque on Intravascular Ultrasound in Patients With Stable Angina Pectoris
Authors: Kimura Shigeki , Yamakami Yosuke , Kojima Keisuke , Sagawa Yuichiro , Ohtani Hirofumi , Hishikari Keiichi , Sugiyama Tomoyo , Hikita Hiroyuki , Takahashi Atsushi , Isobe Mitsuaki
Published: July 2021

Background:
Several studies have reported that echo-attenuated plaque (EA) on intravascular ultrasound (IVUS) was related to poor outcomes after percutaneous coronary intervention (PCI) in acute coronary syndrome. However, its clinical significance and influence on outcomes in patients with stable angina pectoris (SAP) has not been fully clarified. We investigated relationships of EA on IVUS with other plaque morphologies and outcomes after PCI in SAP patients.

Methods:
We investigated 127 de-novo lesions in 127 SAP patients with normal pre-PCI cardiac troponin-T level (cTnT <0.014ng/ml), who underwent pre-PCI IVUS and optical coherence tomography (OCT) examination. All lesions were divided into lesions with and without EA on IVUS. The occurrence of periprocedural myocardial infarction (PMI) was defined by elevation of cTnT level at 24h after PCI ≥5 times the upper limit of normal range. Plaque morphologies on IVUS and OCT were compared between the two groups. Further, we investigated the independent predictors for occurrence of PMI by multivariate analysis.

Results:
EA was observed in 34 (26.8%) lesions. Lesions with EA had greater vessel area (15.8±4.9 vs. 12.7±4.0 mm2, p=0.002), plaque burden (83.9±7.2 vs. 78.6±8.6%, p<0.001) and remodeling index (1.19±0.25 vs. 1.00±0.24, p<0.001) on IVUS than those without EA. OCT analysis showed greater lipid arc (213±80 vs. 155±99 degree, p=0.001), thinner fibrous cap thickness (182±109 vs. 231±114 μm, p=0.03), higher frequency of thin-cap fibroatheroma (23.5 vs. 7.5%, p=0.03), and white thrombus (29.8 vs. 9.7%, p=0.004) in lesions with EA. Lesions with EA had calcified plaques with smaller arc (92.6±45.4 vs. 144±88 degree, p=0.005) and thinner thickness (388±151 vs. 623±265 μm, p<0.001) on OCT than those without EA. Multivariate analysis including clinical, lesion characteristics and procedural results revealed that EA on IVUS remained an independent predictor for PMI (odds ratio 4.49, 95% confidence interval 1.72-11.73, p=0.002).

Conclusions:
In SAP lesions, presence of EA on IVUS may suggest the existence of unstable plaque compositions and may predict for occurrence of PMI.
Abstract 16555: Angiotensin II Directly Induces Mitochondrial Dysfunction and Atrophy in the Skeletal Muscle
Authors: Kadoguchi Tomoyasu , Kinugawa Shintaro , Fukushima Arata , Furihata Takaaki , Suga Tadashi , Takada Shingo , Mizushima Wataru , Kudo Masato , Matsumoto Junichi , Tsuda Masaya , Nishikawa Mikito , Yokota Takashi , Matsushima Shoji , Okita Koichi , Tsutsui Hiroyuki
Published: July 2021

Background:
Skeletal muscle abnormalities such as mitochondrial dysfunction, fiber type transition, and atrophy are the main cause of reduced exercise capacity observed in various diseases such as diabetes mellitus and heart failure. Renin-angiotensin system (RAS) was activated in the skeletal muscle in these conditions. We thus hypothesized that angiotensin II (Ang II) could directly induce skeletal muscle abnormalities.

Methods and Results:
Ang II (1000ng/kg/min, n=8) or vehicle (saline, n=8) was administrated into male C57BL/6J mice (10-12 week of age) via subcutaneously implanted osmotic minipumps for 4 weeks. Ang II significantly decreased body weight (26.6±0.3 vs. 27.6±0.3 g, p<0.05) and hind limb skeletal muscle weight compared with vehicle at 4 weeks (159±2 vs. 166±2 mg, p<0.05). It also decreased myocyte cross-sectional area in the skeletal muscle at 4 weeks (1869±29 vs. 2233±46 μm2, p<0.05). Muscle RING finger-1 and atrogin-1, the markers of protein degradation, were significantly increased in the skeletal muscle tissue from Ang II at 4 weeks by 133% and 102%, respectively (p<0.05). In addition, cleaved caspase-3 and TUNEL positive cells were significantly increased in Ang II at 4 weeks by 2.5 and 1.4-folds, respectively (p<0.05). Citrate synthase (1 week, 121±4 vs. 162±9; 4 weeks, 117±7 vs. 152±4 nmol/min/mg protein), complex I (1 week, 264±27 vs. 396±30; 4 weeks, 281±21 vs. 400±30 nmol/min/mg protein) and complex III (1 week, 321±33 vs. 508±49; 4 weeks, 347±30 vs. 503±43 nmol/min/mg protein) activities were significantly decreased in mitochondria isolated from skeletal muscle from Ang II at 1 and 4 weeks (all p<0.05). NADH staining revealed that type I fiber decreased by 31% and type IIb fiber increased by 38% in Ang II at 1 week. The work (16±1 vs. 27±3 J, p<0.05) and run distance (359±18 vs. 589±59 m, p<0.05) evaluated by treadmill test significantly decreased in Ang II at 4 weeks. An administration of Ang II for 1 week also induced mitochondrial dysfunction, fiber type shift, and protein degradation, but did not skeletal muscle atrophy.

Conclusion:
Ang II could directly induce the reduction of exercise tolerance in association with the abnormalities in skeletal muscle function and structure.
Abstract 16564: Analysis of the Mechanisms of Intravenous Immunoglobulin-Resistant Kawasaki Disease Using iPS Cell Technology
Authors: Ikeda Kazuyuki , Ameku Tomonaga , Nomiya Yui , Nakamura Masahiro , Matsui Satoshi , Yahata Tomoyo , Okamoto-Hamaoka Akiko , Suzuki Chinatsu , Kuchitsu Yuki , Watanabe Akira , Osafune Kenji , Hamaoka Kenji
Published: July 2021

Introduction:
Kawasaki disease (KD) is a systemic vasculitis of unknown origin. Although the treatment of intravenous immunoglobulin (IVIG) significantly resolves inflammation, 10-20% of KD patients have persistent or recurrent fever after the administration of IVIG, and IVIG-resistant patients have a particularly high risk of developing coronary artery abnormalities.

Hypothesis:
The mechanisms of IVIG-resistant KD have been analyzed using the patients’ leukocyte samples. However, vascular endothelial cells (ECs), closely related to the vasculitis of KD, have not been examined in the previous reports. We propose a hypothesis that ECs are mainly involved in the etiology of IVIG-resistance.

Methods:
The purpose of this study is to establish new in vitro disease models of vasculitis using induced pluripotent stem cell (iPSC) technology, and clarify the mechanisms of IVIG-resistance in KD. Dermal fibroblasts or T cells from 2 IVIG-resistant and 2 IVIG-responsive KD patients were reprogrammed by episomal vectors encoding Oct3/4, Sox2, Klf4, L-Myc, LIN28, and p53 shRNA. The iPSC lines were then differentiated into ECs by using a previously-reported differentiation method, and the EC samples were subjected to the microarray analyses.

Results:
The KD patient-derived iPSCs could be differentiated into ECs. The gene expression profiles were compared between iPS-derived ECs (iPS-ECs) generated from IVIG-resistant and IVIG-responsive KD patients. We found that 107 genes were at least two fold up-regulated and 101 genes were at least two fold down-regulated in iPS-ECs from IVIG-resistant KD patients compared with those from IVIG-responsive patients. The Principle Component Analysis (PCA) was performed, but the gene expression levels showed no significant differences between the groups. The Gene Set Enrichment Analysis (GSEA) revealed that the gene sets related to IL-6, NRAS (a member of the RAS oncogene family) and breast cancer were up-regulated in iPS-ECs from IVIG-resistant KD patients.

Conclusions:
Taking into account that the concentration of IL-6 has been reported to be elevated in acute phase of IVIG-resistant KD, our results suggest that the up-regulation of IL-6 related genes in ECs might be involved in the pathogenesis of IVIG-resistant KD.
Abstract 16584: Abnormal Right Ventricular Strain by Cardiac Magnetic Resonance in Preclinical Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Vigneault Davis , te Riele Anneline S , James Cynthia A , Zimmerman Stefan L , Calkins Hugh , Tandri Harikrishna , Bluemke David A
Published: July 2021

Introduction:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by regional wall motion abnormalities of the right ventricle (RV) that have not previously been quantified, resulting in challenges / errors in diagnosis of the disease. RV strain is poorly assessed with tagged cardiac magnetic resonance (CMR) due to the thin RV wall. We applied novel feature tracking analysis to assess RV strain in patients with ARVC.

Methods:
106 subjects (30 controls, 37 preclinical ARVC [mutation+], and 39 overt ARVC [mutation+, Task Force+] patients) underwent 4 chamber and axial cine imaging using SSFP sequences. The RV was divided into subtricuspid (ST), anterior wall (AW), and apical (Ap) regions. Each region was analyzed to determine peak longitudinal strain and strain-rate using Multimodality Tissue Tracking (MTT) software (MTT Version 6.0.4725, Toshiba Medical Systems Corporation, Tokyo, Japan).

Results:
Average age was 33.6 ± 16.1 years (48.2% women); there were no differences between groups. In the 4 chamber view, mean global and segmental strain and strain rates decreased in magnitude from control (-37.7% ± 11.2) to preclinical (-32.2% ± 11.5) to overt ARVC (mean -22.2% ± 11.9). Differences between groups most pronounced in the subtricuspid segment, and reached statistical significance between overt ARVC and both control and preclinical ARVC (p < 0.01). A similar trend was observed in longitudinal strain measured in the axial view, but these trends were inconsistent; statistical significance was met globally, but most individual segments did not reach statistical significance.

Conclusions:
Longitudinal RV strain as measured by CMR feature tracking in ARVC appears able to quantify wall motion abnormalities in overt ARVC, as well as define subtle abnormalities in patients with preclinical ARVC.
Abstract 16608: Building of a Right Ventricular Conduit in Native Outflow Tract in Preparation of Edwards Sapien Valve Implantation
Authors: Gagliardi M. Giulia , Pilati Mara , Cristofaletti Alessandra , Giannico Salvatore , Secinaro Aurelio , Pongiglione Giacomo
Published: July 2021

Background:
Percutaneous valve implantation (PPVI) is now considered feasible and safe especially in patients with conduit between the right ventricle and the pulmonary arteries. However there are still no clear indications on valvolization in native outflow tract (RVOT), traditionally considered at risk because of the dynamic characteristics of the RVOT

Aim:
The aim of this study is to demonstrate the feasibility and safety of building a percutaneous conduit using a stent in the native RVOT before valve implant performing PPVI two months after stent implant, on the basis of previous animal studies, where endotelitation of the stent was shown to be reached within 60 days.

Methods:
From October 2010 to April 2014, 19 pts, with tetralogy of Fallot, (mean age 15 ± 6 yrs) previously corrected by transannular patch technique, underwent a cardiac catheterization in order to build a stent-conduit in the native RVOT. After a complete right catheterization a balloon was inserted through a long sheath in the RVOT. During the inflation of the balloon a right ventricular angiography and a left coronary artery angiography are performed. In the presence of a complete occlusion of the RVOT and no coronary compression, a stent was deployed in the RVOT. Two months later an Edwards Sapien Pulmonary valve was implanted.

Results:
Twenty two stents were implanted in 19 pts. The mean time of the procedures was 185 ± 89 min with a mean fluoroscopy time of 72 ± 33 min. Two main complications occurred: in 1 pt the stent partially occluded the right pulmonary artery and in a second pt the stent was dislocated in RVOT. In both cases the patients were treated surgically. In all other patients the procedure was successful and patients were discharged home two days later, on Aspirin therapy. The correct position of the stent was confirmed at the 1 month of follow-up by echocardiographic examination. Among the 19 pts , 152 underwent implantation of Edwards Sapien Pulmonary Valve, two months later. No complications occurred during the procedure and during the FU. Two patients are still waiting PPVI procedure

Conclusions:
A two-step procedure approach increases the safety of PPVI with no impact on clinical conditions or complications
Abstract 16619: The Role of Capillary Disorder in Coronary Ischemic Congestive Heart Failure in Rats
Authors: Chen Jiqiu ,   Elisa-Yaniz Galende, Heather J. Kagan. Lifan Liang, Roger Hajjar
Published: July 2021

The aim of present study is to explore the role of capillary disorder in coronary ischemic congestive heart failure (CHF).

Methods:
CHF was induced in rats by aortic banding plus ischemia/reperfusion followed by aortic de-banding. Coronary arteries were perfused with plastic polymer containing fluorescent dye. Multiple fluorescent images of casted heart sections and scanning electric microscope of coronary vessels were conducted to characterize changes in the heart. Cardiac function was assessed by echocardiography and in vivo hemodynamics.

Results:
Stenosis was found in all levels of coronary artery in CHF. Coronary vasculature volume and capillary density in remote myocardium were significantly increased in CHF compared with control. This occurred largely in micro-vessels with diameter ≤ 3 μm. Capillaries in CHF had a tortuous structure, while normal capillaries were linear. Capillaries in CHF had inconsistent diameters, with assortments of narrowed and bulged segments. Their surfaces appeared rough, likely indicating endothelial dysfunction in CHF. Segments of main capillaries between bifurcations were significantly shorter in CHF than in control. Transiently increasing preload by injecting 50 μl of 30% NaCl demonstrated that the CHF heart has lower functional reserve; this is likely associated with congestion in coronary microcirculation.

Conclusions:
Ischemic coronary vascular disorder is not limited to main arteries, but also occurs in arterioles and capillaries. Capillary disorder in CHF included stenosis, deformed structure, proliferation and roughened surfaces, and is perhaps a primary contributor to the energy starvation which leads to reduction of myocyte intrinsic contractility.
Abstract 16673: Framingham Risk Trajectories Predict Left Ventricular Dyssynchrony as a Measure of Subclinical Myocardial Dysfunction: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Sharma Ravi , Kishi Satoru , Ambale-Venkatesh Bharath , Colangelo Laura , Reis Jared , Lloyd-Jones Donald , Lewis Cora , Sidney Stephen , Jacobs David , Liu Kiang , Gidding Samuel , Lima João A
Published: July 2021

Background:
Left ventricular (LV) dyssynchrony is a measure of myocardial dysfunction in heart failure patients. However, its significance as a marker of incipient myocardial dysfunction in response to cumulative risk burden among asymptomatic individuals is not known. Our objective was to evaluate the extent of LV dyssynchrony in relationship to longitudinal changes in cardiovascular risk in otherwise healthy middle age individuals.

Methods & Results:
We defined five distinct Framingham risk score (FRS, D’Agostino Circulation 2008) (excluding age) trajectories in the CARDIA cohort (n=4634) to estimate the pattern of cumulative cardiovascular risk exposure over 25 year. Standard deviation of time to peak systolic circumferential strain (SD-TPS) among 6 mid-ventricular segments using 2-dimensional speckle-tracking echocardiography determined the extent of LV dyssynchrony in 2718 participant (54.3% women). Using multivariate linear regression after adjustment for demographics and LV ejection fraction, we found that among women in comparison to the low-stablegroup (reference trajectory), increased burden of cardiovascular risk was associated with progressively higher values of SD-TPS; B-coefficients were 3.50msec (95%CI, 0.23 - 6.77, p=0.04) for the moderate-stable, 7.32msec (2.56 - 12.09, p=0.003) for the elevated-stable, 8.79msec (3.49 - 14.10, p=0.001) for the moderate-increasing, and 9.54msec (0.09 - 18.99, p=0.048) for the elevated-increasing groups. There was attenuation of parameter estimates after further adjustment for cumulative body-mass-index (BMI) with loss of statistical significance. These associations were not statistically significant in men.

Conclusions:
Women had higher values of subclinical LV dyssynchrony in response to incremental cumulative cardiovascular risk burden over 25 years. Such relationships were absent in men. Cumulative BMI was the strongest predictor of LV dyssynchrony.
Abstract 16695: Rapid Activation Patterns Identified by Computational Analysis of Multielectrode Endocardial Recordings During Atrial Fibrillation in Humans
Authors: Hummel John D , Zeidan Ziad , Kalbfleisch Steven J , Houmsse Mahmoud , Augostini Ralph , Weiss Raul , Daoud Emile
Published: July 2021

Introduction:
Computational analysis of 64-electrode basket catheter (BC) recordings of atrial fibrillation (AF) have been used to generate visually-identified electrical rotors and focal sources that are then targeted for radiofrequency ablation (RFA).

Hypothesis:
The purpose of this study was to assess BC maps of right (RA) and left (LA) atria during AF in humans using a novel software, CartoFinder™ (CF) (Biosense Webster, CA, USA), which was developed to identify rapid activation patterns (RAP) and incorporate them into a 3D mapping system, CARTO.

Methods:
20 patients who were undergoing RFA AF utilizing CARTO mapping and who consented were enrolled. 1 minute BC maps of the RA and LA were obtained after creation of a 3D virtual anatomic shell prior to and after RFA around the pulmonary veins (PV). There were no complications. BC maps were analyzed by CF post procedure. CF annotates the leading edge of RAP with red color (see figure).

Results:
Of these 20 patients, CF recordings were complete in 14 pts (mean age 59; 12 persistent AF). There were 2.8 RAP / pt. The RA RAP were located septum (n = 9), anterolateral (n=5), and posterior (n = 3) walls. The LA RAP were located anterior (n = 8), roof (n=7), and posterior (n = 7) walls. RFA was delivered on top of (n=10), within 5mm (n = 4), or distant (n=10) from any RAP. Post PV isolation, there was a 45% reduction in RAP vs pre-RFA; and, 11 pts converted to sinus (n=7) or transitioned to flutter (n=4).

Conclusions:
CF is a novel software algorithm incorporated into CARTO that identifies RAP in the RA and LA. RFA around the PV only results in 45% reduction of RAP, suggesting that RFA beyond traditional PV isolation is required to eliminate the bulk of RAP.
Abstract 16725: Family History of Cardiovascular Disease is an Independent Predictor of Gestational Hypertensive Disease and Diabetes: The Korean Nurses’ Survey
Authors: Lee Heesun , Yoon Chang-Hwan , Park Hyun-Young , Lee Hea Young , Choi Dong-Ju , Cho Myeong Chan
Published: July 2021

Background:
Gestational hypertensive disorders and diabetes are well-known to increase the risk of cardiovascular disease (CVD) and diabetes later in life. However, there were few researches to evaluate the association between family history of cardiovascular disease and the occurrence of pregnancy-related medical disorders. We aimed to investigate whether family history of CVD could predict gestational hypertensive disorders and diabetes.

Methods:
The Korean Nurses’ Survey was conducted through web-based computer-assisted self-administered questionnaires, which were compiled by consultation to cardiologists, gynecologists, and statisticians, from October to December 2011. We enrolled a total of 9,989 female registered nurses who could answer reliably the questionnaires based on their medical knowledge. Multivariate logistic regression analysis was used to clarify the effect of family history of CVD on pregnancy-related medical disorders.

Result:
In this survey, 3900 subjects had more than 1 pregnancy. Among them, 247 interviewees (6.3%) had experienced hypertensive disorders during pregnancy, which included preeclampsia (n = 160, 4.1%) and transient hypertension (n = 144, 3.7%), and 120 (3.1%) had experienced gestational diabetes. And, 2872 subjects (73.6%) answered that they had at least 1 family history of CVD. Having family history of CVD increased the risk of gestational hypertensive disorders (adjusted RR 1.51, 95% CI 1.08-2.11,
p
= 0.015) and diabetes (adjusted RR 2.40, 95% CI 1.38-4.17,
p
= 0.002). In particular, family history of hypertension was significantly associated with gestational hypertensive disorders (adjusted RR 2.00, 95% CI 1.47-2.50,
p
<0.001), and diabetes was highly related with gestational diabetes (adjusted RR 3.37, 95% CI 2.35-4.83,
p
<0.001), respectively. Furthermore, this relationship was observed regardless of maternal parity.

Conclusion:
Family history of CVD was a significant predictor of pregnancy-related medical disorders in this survey. Meticulous history taking for family history of CVD can provide the risk of gestational hypertensive disease and diabetes. Thus, special attention should be paid to women with family history of CVD during pregnancy.
Abstract 16765: Cyclophilin-D: A Regulator of Mitochondrial Gene Expression
Authors: Radhakrishnan Jeejabai , Gazmuri Raúl J
Published: July 2021

Background:
Cyclophilin-D (Cyp-D) is a peptidyl-prolyl isomerase resident in the mitochondrial matrix; and like other cyclophilins it can catalyze conformational changes of proteins. Cyp-D is best known for its role in lowering the threshold for opening of the mitochondrial permeability transition pore. However, a serendipitous observation by us, whereby Cyp-D silencing halted cell proliferation, and reports by others that Cyp-D could interact with nuclear transcription factors that have translocated to mitochondria, prompted us to hypothesize that Cyp-D could interact with native mitochondrial transcription factors (mTFs; TFB1M, TFB2M, and TFAM) and therefore be a key regulator of mitochondrial gene expression. Given that all 13 mitochondrial-encoded proteins are components of respiratory chain complexes, our hypothesis would support a central role of Cyp-D in cellular respiration.

Methods and Results:
We first analyzed the interaction of Cyp-D with mTFs by co-immunoprecipitation (co-IP) and reverse co-IP after transfection of constructs expressing FLAG-tagged Cyp-D and V5-tagged mTFs in HEK 293T cells, showing specific interactions of Cyp-D with TFB1M and with TFB2M but not with TFAM. We then quantitated by real time qPCR mitochondrial-encoded respiratory chain transcripts in HEK 293T cells at day 8 post-infection with lentiviruses encoding shRNA against Cyp-D, showing striking reductions in transcripts ND1, COX1, and ATP6 (initiated from the heavy strand promoter 2) but not in transcript ND6 (initiated from the light strand promoter). Finally, we measured cellular oxygen consumption, also on post-infection day 8, and found it reduced without improvement after uncoupling of electron transport from ATP synthesis with FCCP, consistent with the aforementioned reductions in mitochondrial transcripts of electron transport complexes. At the same time, mitochondrial mass, expression of nuclear genes, and cell viability were all preserved.

Conclusion:
In HEK 293 T cells, Cyp-D is required for mitochondrial gene expression modulating transcription possibly through the heavy strand promoter 2 suggesting a novel Cyp-D function as regulator of oxidative phosphorylation and thus of the fundamental process of cellular respiration.
Abstract 16866: Blood Pressure Control and Stroke or Bleeding Risk in Patients with Atrial Fibrillation: Results from the ROCKET AF Trial
Authors: Vemulapalli Sreekanth , Hellkamp Anne S , Jones W. Schuyler , Piccini Jonathan P , Mahaffey Kenneth W , Becker Richard C , Hankey Graeme J , Berkowitz Scott D , Breithardt Guenter , Singer Daniel E , Fox Keith A , Califf Robert M , Patel Manesh R
Published: July 2021

Background:
Hypertension (HTN) is a risk factor for stroke and bleeding in atrial fibrillation (AF). Yet, the association between HTN stage and stroke and bleeding risk in AF is unknown.

Methods:
The study population included 14,256 of the patients randomized in the ROCKET AF trial. Baseline systolic blood pressure (SBP) and history of HTN were determined and categorized as follows: (1) no history of HTN, (2) controlled HTN (SBP <140), (3) stage 1 HTN (SBP 140-159), and (4) stage 2 HTN (SBP ≥160). Cox proportional hazards models were used to compare event rates for stroke or systemic embolism (SE) and major bleeding.

Results:
Of the 90.5% of patients in ROCKET AF with HTN, 55.9% were controlled and 34.6% had stage 1 or 2 HTN. Compared with those with HTN, those without HTN had lower mean CHADS
2
scores (2.8 vs. 3.5), lower rates of prior myocardial infarction (11% vs. 18%), and lower mean age (69 vs. 73 years). Compared with those with no history of HTN, there was a trend towards an increased adjusted risk of stroke or SE in patients with controlled HTN (HR 1.22, 95% CI 0.89-1.66) and stage 1 or 2 HTN (HR 1.42, 95% CI 1.03-1.95) (p=0.06). A similar trend in adjusted risk of hemorrhagic stroke (controlled HTN: HR 2.50, 95% CI 0.89-7.05; stage 1 or 2 HTN: HR 3.04, 95% CI 1.06-8.71) (p=0.11) was observed. The effect of HTN stage on stroke risk did not vary by baseline CHADS
2
score (p interaction=0.70). The adjusted risk of major bleeding was not different between groups (HR 0.96, 95% CI 0.74-1.23; HR 1.00, 95% CI 0.77-1.30) (p=0.84). The benefit of rivaroxaban versus warfarin in preventing stroke or SE was consistent among patients regardless of baseline SBP (p interaction=0.69).

Conclusion:
One-third of patients in a clinical trial of AF had uncontrolled SBP at baseline. Uncontrolled SBP showed a trend towards a higher risk of stroke or SE, but not bleeding. Uncontrolled SBP may be an important factor in reducing the overall risk of stroke, and specifically hemorrhagic stroke, in patients with AF.
Abstract 16877: Correlation of Antibody Binding Strength to Complement Fixation
Authors: Parikh Vishal Y , Reinsmoen Nancy , Patel Jignesh , Yu Zhe , Liou Frank , Yabuno Jamie , Kittleson Michelle , Azarbal Babak , Chang David H , Czer Lawrence , Kobashigawa Jon
Published: July 2021

Background:
In patients (pts) who are highly sensitized, desensitization therapy is commonly applied to reduce antibody (Abs) load and to reduce potential morbidity and mortality following heart transplant (HTx). It is not known as to what level of antibody binding is needed to initiate desensitization therapy. It is believed that high binding Abs may have the ability to fix complement and lead to cytotoxicity.

Methods:
Between 2011 and 2012 we assessed 13 highly sensitized pts who were noted to have standardized fluorescence intensity (SFI) >100,000 pretransplant.

A complement binding assay (C1q binding assay) was then applied to these Abs to assess for a correlation of binding to cytotoxicity. Correlation statistics were used to derive significance between higher antibody binding and capacity to bind complement.

Results:
There seems to be no correlation between the different binding strength and C1q positivity. However, when evaluating Luminex 1:8 test, there seems to be correlation between class I binding strength with C1q positivity. There was C1q positive rate of 10.8% in SFI 200,000 range.

Conclusions:
Undiluted antibodies do not correlate to C1q binding ability. However the 1:8 dilution test seems to provide an better prediction of complement binding. 1:8 dilutions should be performed to accurately assess the ability for antibodies to bind complement.
Abstract 16922: Feasibility of Family Sodium Watcher Program to Improve Adherence to Low Sodium Diet in Patients with Heart Failure and Caregivers
Authors: Chung Misook L , Moser Debra K , Lennie Terry A
Published: July 2021

Introduction:
Poor adherence to the low sodium diet (LSD), common in patients with heart failure (HF), is a major predictor of hospitalization for exacerbation of HF. When family member’s consume the same LSD recommended for patients, patient adherence is increased. The Sodium Watcher Program (SWAP) was developed to improve adherence to LSD using a gradual adaptation strategy and an electronic salt monitoring device that allows detection of sodium content in food. The purpose of this study was to examine whether the SWAP was feasible and if it resulted in reduction in sodium intake for patients with HF and their caregivers.

Method:
In this 2-group randomized controlled trial, 15 patient-caregiver dyads completed 24-hour urine collection for sodium excretion level (24h UNa) at baseline and 3 months follow up. Dyads in the SWAP intervention (n=8) received 12 weeks of self-care education for HF and LSD with gradual adaptation strategies in salt intake via 2 home visits and 4 calls. Paired t-test was used to compare adherence to LSD at two data collection times. Only intervention group evaluated use of the electronic salt monitoring devices and the intervention program at 3 months.

Results:
The intervention group had a significant reduction in 24h UNa (Patients 3894mg vs. 3604mg, p=.02; caregivers 4123mg vs. 3380mg, p<.05). They also reported significant increased level of enjoying eating LSD (M =5.4 on 10-point rating scale vs. M=7.9 p <.01) and 90% noticed a change in their ability to taste salt in their food at the 3-month follow up. They reported that use of the electronic monitoring devices was easy (M=8.3 on 10-point rating scale) and helpful in supporting LSD adherence (M=8.8 on 10-point rating scale). Caregivers in the intervention reported no significant changes in burden levels. The usual care control group had no change in 24h UNa (patients 4369 mg vs. 4434 mg; caregivers 3301 mg vs. 4826mg).

Conclusion:
The findings demonstrated that the SWaP is feasible and efficacious for following LSD by dyads. The intervention was feasible for caregivers and did not increase caregiver burden. This family intervention may have potential for promoting long-term adherence and needs to be tested in a larger clinical trial.
Abstract 16953: Role of the Fast Transient Outward Current Ito,f in Shaping Action Potential Waveforms in Human iPSC-derived Cardiomyocytes
Authors: Marrus Scott , Springer Steven , Martinez Rita , Dranoff Edward , Mellor Rebecca , Zhang Anna , Kanter Evelyn , Yamada Kathryn , Nerbonne Jeanne
Published: July 2021

Abnormalities of a key repolarizing cardiac potassium current, the fast transient outward potassium current,

I
to,f

, are associated with both heart failure and congenital arrhythmia syndromes. However, the precise role of

I
to,f

in shaping action potential waveforms remains unclear. This study was designed to define the functional role of the fast transient outward potassium current,

I
to,f

, in shaping action potentials in human iPSC-derived cardiomyocytes (iPSC-CMs). Most iPSC-CMs (29 of 43 cells) demonstrated spontaneous electrical activity, slow upstroke velocity (63±71 V/s), a wide range of action potential durations (APD90 = 860±722 ms) and heterogeneous action potential waveforms. Using dynamic current clamp, a modeled human ventricular inwardly rectifying K
+
current,

I
K1

, was introduced into iPSC-CMs, resulting in silencing of spontaneous activity, hyperpolarization of the resting membrane potential (RMP = -90±3 mV), increased peak upstroke velocity (dV/dt = 346±71 V/s) and decreased APD90 (420±211 ms) to values similar to those recorded in isolated adult human ventricular myocytes (RMP = -84±3 mV, dV/dt = 348±101 V/s and APD90 = 468±133 ms, all p>0.05). Importantly, a ventricular-like action potential waveform was observed in 25 of the 26 cells studied following the dynamic clamp addition of

I
K1

. Using these cells as a model of human ventricular myocytes, further dynamic current clamp experiments introduced a modeled human fast transient outward K
+
current,

I
to,f

, and revealed that increasing in the amplitude of

I
to,f

results in an increase in the phase 1 notch and a progressive shortening of the action potential duration in iPSC-CMs. Together, the experiments here demonstrate that combining human iPSC-CMs with the power of the dynamic current clamp technique to modulate directly and precisely the “expression” of individual ionic currents provides a novel and quantitative approach to defining the roles of specific ionic conductances in regulating the excitability of human cardiomyocytes.