bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16304: Readiness for Physical Activity in Patients With Heart Failure
Authors: Marques-Sule Elena , Almenar Luis , Deka Pallav , Pathak Dola , López-Vilella Raquel , Klompstra Leonie
Published: November 2020

Introduction:
Little attention has been given to assessing the physical readiness and psychological readiness (motivation & self-efficacy) in patients with heart failure (HF). The aim of this study is to explore the readiness for PA (physical and psychological) in patients with HF and factors related.

Method:
A cross-sectional study with 163 patients included (mean age 66±16, 50% female, 63% NYHA I, 37% NYHA II) assessing background and clinical data, physical activity (IPAQ-s), depression and anxiety (HADs), quality of life (SF36). Readiness for PA was assessed with physical readiness based on the PA Readiness Questionnaire (PAR-Q) and psychological readiness was measured with the Exercise Self-efficacy Scale (ESES) and motivation with the Motivation for PA and Exercise/ Working Out questionnaire (RM 4-FM). Correlational analyses were done to explore the relationship between physical readiness and psychological readiness and factors related. A multivariate analysis of covariance was done to test the effect of categorical variables on readiness for PA.

Results:
Of the patients, 64% were not physically ready in becoming more physically active (n=105), 80% of the patients reported low self-efficacy (n=129), 45% (n=74) were extrinsically motivated for change and 55% (n=89) had primarily internal factors that motivated. Physical readiness and psychological readiness were highly correlated with each other. There was a statistically significant higher readiness for PA based on lower age (p < 0.01), male gender (p < 0.01), lower time since diagnose (p < 0.01), being married (p < 0.01), higher educational level (p < 0.01), lower NYHA-class (p = 0.04), lower BMI (p < 0.01), not having COPD (p < 0.01), higher quality of life (p < 0.01) and lower experience of anxiety symptoms (p = 0.03).

Conclusions:
A prudent first step in fitness assessments and exercise prescription process is the determination of readiness for PA. Along with screening for any physical limitations, it is also important to screen for psychological readiness for engaging in PA. Our findings may assist healthcare providers who are dealing with patients with HF to modify current and develop new practices related to risk reduction as screening readiness for PA before entering PA programs.
Abstract 16359: Incidence of Fontan Associated Liver Disease and Its Impact on Mortality in Patients With Single Ventricle Physiology
Authors: Guerrero Carlos , Therrien judith , Liu Aihua , Guo Liming , Kodaira Masaki , Bernier Pierre-luc , tchervenkov Christo , Marelli Ariane J
Published: November 2020

Introduction:
Data on the burden of clinically significant Fontan associated liver disease (FALD) and its relationship to mortality is scant. We performed a retrospective cohort study to assess the incidence of FALD and its association with mortality.

Methods:
Data source was the Quebec Congenital Heart Disease (CHD) Database, a population-based cohort of over 100,000 CHD patients followed from 1983-2017. Fontan patients surviving longer than 30 days post-Fontan were identified, each were matched to 20 VSD patients on age and sex. The Fontan-VSD cohort were used to assess the association between Fontan and the risk of developing FALD. The VSD cohort served as “Non-exposed to Fontan” group. FALD was defined as at least one hospitalization due to liver disease. Kaplan-Meier curves were used to estimate and compare the cumulative probability of 1) developing FALD between Fontan and VSD patients; and 2) mortality between Fontan patients w/o FALD.

Results:
A total of 512 Fontan patients and 10,232 VSD patients were included. The cumulative probability of developing FALD at 10 and 25 years of follow-up was higher in Fontan patients (13.0% and 37.1%, respectively), compared to 0.7% and 2.0% for VSD patients respectively
(p-value <0.0001-Logrank test).
In Fontan patients with FALD, the cumulative probability of mortality by 5 years after the diagnosis of FALD was 12.6%, 11 times higher than the risk in Fontan Patients without FALD
(Figure)
. Calendar year of Fontan operation was found to be an important predictor of developing FALD.

Conclusions:
This is the first study documenting the impact of FALD on mortality, using a large cohort with long-term follow up. The findings support the use of well-defined surveillance protocols to identify potential precipitants of FALD before liver disease becomes irreversible.
Abstract 16363: An 18-month Smoking Cessation Intervention Incorporating Pharmacotherapy and Behavioral Counseling Improves Tobacco Abstinence Rates in Adult Smokers With Serious Mental Illness (smi) in Community Mental Health Settings: Results of a Randomized Clinical Trial
Authors: Daumit Gail , Evins A. Eden , Cather Corinne , Dalcin Arlene , Dickerson Faith , Miller Edgar R , Appel Lawrence J , Jerome Gerald J , McCann Una , Charleston Jeanne , Young Deborah , Gennusa Joseph , Goldsholl Stacy , COOK COURTNEY , Fink Tyler , Wang Nae Yuh
Published: November 2020

Introduction:
Tobacco smoking is the largest contributor to markedly elevated CVD and preventable death in persons with SMI. Trials of combined pharmacologic and behavioral treatments improve abstinence rates, but have targeted those ready to quit right away, and evidence-based treatments are rarely used in the community. Weight gain often accompanies abstinence. Our objective was to determine the effectiveness of an 18m smoking cessation pharmacotherapy and behavioral counseling intervention incorporating weight management and physical activity in persons with SMI.

Hypothesis:
The active intervention is more effective than control in achieving biochemically validated, 7-day point prevalence smoking abstinence at 18m.

Methods:
We conducted an RCT in 4 community mental health settings in 192 smokers with SMI, stratified by readiness to quit within 30d or in 1 to 6m. The active intervention group was offered 18m of 1
st
-line cessation pharmacotherapy, smoking cessation and weight management counseling tailored to readiness to quit, and support for physical activity. Controls received a quit line referral.

Results:
Mean(SD) age was 49.6(11.7); cigarettes/day 12.1(9.5); BMI 32.0(7.6) kg/m
2
; 49% were male, 48% African-American, 62% willing to quit in 30d, 95% completed 18m follow-up. At 18m, 27.8% of active group and 6.3% of controls achieved 7d smoking abstinence (p<0.0001); adjusted odds ratio 6.0 (95% CI: 2.3 –15.6; p=0.0002). There was no significant modification of intervention effect on abstinence by readiness to quit. Mean difference in weight change over 18m between active and control was not significant (3.5 lbs, 95% CI: -3.3 –10.3; p=0.32).

Conclusions:
Offering 18m of evidence-based cessation treatment in the community substantially increased smoking abstinence without significant weight gain in SMI. Implementing best practice guidelines to treat all smokers regardless of readiness to quit should improve CVD health in this high-risk population.
Abstract 16396: The Anti-inflammatory Role of Chronic Maintenance Statin Therapy in Hospitalized Coronavirus Disease 2019 (covid-19) Patients: An Exploratory Assessment
Authors: Mughal Mohsin S , Jaffery Ali R , Kaur Ikwinder P , Wang Chang , Mirza Hasan , Dalmacion Denise , Tawfik Isaac , Usman Mohammed , Granet Kenneth M
Published: November 2020

Introduction:
The role of inflammation in the spectrum of COVID-19 disease is well documented. Statins are one of the most commonly used prescription medications for the treatment of hyperlipidemia. Additionally, statins have been shown to decrease intracellular pro-inflammatory compounds and thus reduce overall inflammation in the vasculature and myocardium. Limited information is available about their anti-inflammatory role in COVID-19.

Hypothesis:
We hypothesize that chronic maintenance statin therapy can prevent cardiac complications (acute cardiac injury) and mitigate the hyper-inflammatory state in COVID-19.

Methods:
In this single-center study, adult patients who were hospitalized from March 1 to April 20, 2020, with RT-PCR confirmed SARS-CoV-2 infection were included. Patients were divided into two cohorts; cohort 1 included the patients who were on maintenance statin therapy (regardless of dosage) and cohort 2 included patients who were not on statins. We retrospectively analyzed lab findings and compared clinical outcomes among the two cohorts. Median two-sample test (for continuous variables), chi-square test, and Fisher's exact test (for categorical variables) were utilized for statistical analysis.

Results:
Out of 120 patients, 44 patients were on statin therapy. Acute cardiac injury, defined as an elevation of cardiac biomarkers, was seen in 13.64% and 2.63% of patients in cohorts 1 and 2, respectively. Median values of peak inflammatory markers (LDH, CRP, Ferritin, and IL-6) were higher in cohort 1.

Conclusion:
Chronic maintenance statin therapy showed no additional benefit in hospitalized COVID-19 patients. We suspect that the higher median age and underlying vascular disease in cohort 1 likely played a significant role in worse clinical outcomes. However, we speculate that statin therapy should be investigated while adjusting for age and comorbidities to understand their anti-inflammatory role in COVID-19.
Abstract 16723: A Machine Learning Approach to Acute Heart Failure Risk Stratification
Authors: Ghandian Sina , Mataraso Samson , Pellegrini Emily , Lynn-Palevsky Anna , Barnes Gina , Green Saxena Abigail , Hoffman Jana , Calvert Jacob , Das Ritankar
Published: November 2020

Introduction:
Acute heart failure (AHF) syndromes are associated with significant morbidity, mortality, and hemodynamic complications. Patients at risk of AHF are likely to experience rehospitalization or death post-discharge. AHF patient risk stratification remains an unmet need.

Hypothesis:
Gradient boosted machine learning can be used to predict likelihood of AHF diagnosis, enabling identification of at-risk patients.

Methods:
A gradient boosted machine learning algorithm was developed on retrospective data from 236,275 total emergency department patients, 807 of whom experienced AHF and were prescribed a vasodilator during their stay. A model was developed using age, sex, and six vital signs (systolic and diastolic blood pressure, heart rate, respiratory rate, peripheral oxygen saturation, and temperature). A second model used these demographics, vitals, and laboratory data (troponin, bicarbonate, and O2 saturation) as available to predict AHF diagnosis, as defined by ICD code and prescription of beta-blocker and angiotensin converting enzyme (ACE) inhibitor vasodilators. Model performance was assessed with regard to area under the receiver operating characteristic (AUROC).

Results:
The algorithm obtained AUROCs of 0.860 and 0.767 for prediction of AHF diagnosis and prescription of vasodilator at discharge with and without laboratory data, respectively (Figure 1). Predictions from the vitals only model were made an average of 38.5 hours prior to AHF diagnosis. Predictions from the model which included labs were made an average of 34 hours prior to AHF diagnosis.

Conclusion:
Machine learning is a useful method for predicting AHF diagnosis. Patient risk stratification enabled by the tool may serve to reduce duration of hospital stay for patients at low risk of developing AHF. Identification of high risk patient populations may also allow for earlier diagnosis and treatment, preventing development of chronic heart failure and other sequelae of AHF.
Abstract 16730: Computerized Prediction of Avoidable Serum Potassium Testing in Critically Ill Cardiac Patients
Authors: Sperotto Francesca , Patel Bhaven B , Molina Mathieu , Kimura Satoshi , Delgado Marlon , Santillana Mauricio , Kheir John
Published: November 2020

Introduction:
Electrolytes are frequently monitored among critically ill patients, especially among cardiac patients due to higher risk of arrhythmias. However, a percentage of these blood draws may potentially be saved. To date, no studies have investigated strategies to safely reduce the density of electrolyte monitoring in critically ill patients.

Hypothesis:
We hypothesized that machine learning models can identify potentially avoidable blood draws for serum potassium (K) among pediatric patients following cardiac surgery.

Methods:
We retrospectively reviewed data of all patients admitted to the CICU at Boston Children’s Hospital during 2010-2018, having a length of stay ≥4 days and ≥2 recorded serum K measurements. We collected variables related to K homeostasis, including serum chemistry, hourly K intake, diuretics, and urine output. Using established machine learning techniques (Random Forest classifiers and hyperparameters) we created models predicting whether a patient’s K would be normal or abnormal based on the most recent K level, medications administered, urine output, and markers of renal function. We developed multiple models based on different age categories and temporal proximity of the most recent K measurement. We assessed the predictive performance of the models using an independent test set.

Results:
Of the 7,269 admissions (6,196 patients) included, 95,674 serum K was measured on average of 1 (IQR 0-1) time per day. 96% of patients received at least one dose of IV diuretic and 83% received a form of K supplementation. Our models predicted a normal K value with a median positive predictive value of 0.90. A median percentage of 2.1% measurements (mean 2.5%, IQR 1.3%-3.7%) were incorrectly predicted as normal when they were abnormal. A median percentage of 0.0% (IQR 0.0%-0.4%) were incorrectly predicted as normal while being critically low or high. A median of 27.2% (IQR 7.8%-32.4%) of samples were correctly predicted to be normal and could have been potentially avoided.

Conclusions:
Machine-learning methods can be used to accurately predict avoidable blood tests for serum K in critically ill pediatric patients. A median of 27.2% of samples could have been saved, with decreased costs and risk of infection or anemia.
Abstract 16762: Post-Operative Prognostic Prediction of Different Myocardial Fibrosis Measures in Severe Aortic Valvular Heart Disease
Authors: Pires Lucas J , Rosa Vitor E , MORAIS THAMARA C , de Santis Antonio S , Fernandes Joao Ricardo C , boer berta p , rossi eduardo , Lavitola Paulo d , Rochitte Carlos E , Nomura Cesar H , Pomerantzeff Pablo M , Tarasoutchi Flavio
Published: November 2020

Introduction:
Aortic stenosis (AS) and aortic regurgitation (AR) patients develop myocardial remodeling characterized by hypertrophia and fibrosis. Cardiac magnetic resonance (CMR) imaging can detect the presence of replacement myocardial fibrosis, by using late gadolinium enhancement (LGE), and diffuse myocardial fibrosis, by using extracellular volume (ECV) based measures (relative - ECV fraction - and absolute - indexed ECV) calculated from T1 mapping. There are only few studies with AS patients and scarce data with AR patients showing an association between fibrosis and post-operative clinical outcomes.

Hypothesis:
There is an association between preoperative myocardial fibrosis measures and post-operative clinical outcomes in severe aortic valvular heart disease (VHD) patients submitted to surgical intervention.

Methods:
Patients with isolated severe AS or AR were prospectively recruited to be submitted to CMR before indicated surgery, including LGE and ECV measures quantifications. All patients were submitted to conventional surgery and were followed during post-operative period.

Results:
The study population included 99 patients, 67 with AS and 32 with AR. After a median post-operative follow up of 12.3 (3.2-24.4) months, the presence of LGE areas, found in 32 patients (32.3%), independently predicted post-operative combined events (global mortality or STS morbidity events or persistent NYHA functional class III-IV) during follow up in univariate and multivariate Cox regression analyses (HR 3.96, 95%CI 1.76-8.91, p<0.01). Kaplan-Meier curve is presented in Figure 1. ECV fraction (HR 1.02, 95%CI 0.96-1.09, p=0.55) or indexed ECV (HR 1.00, 95%CI 0.97-1.03, p=0.86) did not predict post-operative combined events.

Conclusions:
Presence of replacement myocardial fibrosis, but not diffuse myocardial fibrosis, in preoperative CMR predicts post-operative combined clinical events in severe VHD patients submitted to surgery.
Abstract 16774: Adverse Childhood Experiences Reported by Adults With Congenital Heart Disease
Authors: Taunton Marshall A , Levy Sheldon , Kovacs Adrienne H , Khan Abigail M
Published: November 2020

Introduction:
Adverse childhood experiences (ACEs), such as witnessing domestic abuse or experiencing physical/sexual abuse, are associated with poorer long-term health outcomes, including acquired cardiovascular disease. This study offers the first investigation of ACEs in adults with congenital heart disease (CHD).

Methods:
In this cross-sectional study, adult CHD outpatients completed the ACE Questionnaire, the Relationship Scales Questionnaire, the Perceived Stress Scale, and a 0 - 100 linear analogue scale of quality of life. Total scores on the ACE Questionnaire range from 0 - 10 (a point for each ACE reported) and scores ≥ 4 are associated with poorest health outcomes. We performed correlations, t-tests, and analyses of variance to explore relationships between ACE Questionnaire scores and demographics, medical variables, and other survey scores.

Results:
A total of 100 patients were enrolled in the study (40 ± 13 years; 60% female). Ninety percent had defects of moderate or great complexity and 79% were categorized as American Heart Association anatomy + physiology stage B, C or D (i.e., some degree of symptoms and/or functional impairment). Total scores on the ACE Questionnaire ranged from 0 - 9, with a mean of 2.6 ± 2.5; 30% reported ≥ 4 ACEs. The most frequently reported ACEs were parental divorce (46%), emotional abuse (42%), and parental substance abuse problem (32%). ACE Questionnaire scores did not differ as a function of age, sex, defect complexity, or anatomy + physiology stage. However, total ACE score was significantly correlated with all 4 relationship styles (secure, preoccupied, dismissive and fearful; p-values < 0.05). Quality of life scores were lower among those with elevated ACEs, although this did not reach statistical significance (69 vs. 76, p = 0.07).

Conclusion:
It is well accepted that adults with CHD face many health-related challenges throughout their lives. This study serves as an important reminder to providers that many patients will also experience other significant (and potentially traumatic) stressors in childhood. Further research is needed to determine whether the impact of ACEs on adults with CHD extends beyond relationship and stress outcomes and also includes cardiac morbidity and mortality.
Abstract 17114: Whose Work is It? Patient Perspectives on Challenges in Heart Failure Self-Management
Authors: Leverty Renee , Chang Leslie , Barcenas Jose , James Campbell James , Dahlgren Kirsten , Piltzer William , Rich Clayburn , Roark Judy , Sude Barry , Williams Fredonia , Devore Adam D , Hernandez Adrian F , Granger Bradi B
Published: November 2020

Introduction:
The importance of self-care behaviors in successful heart failure (HF) management is widely recognized. And yet, patient perspectives on strategies to effective carry out the work of behavior change remain relatively unexplored.

Methods:
From March 2017 to May 2017, we conducted semi-structured, in-depth interviews with 8 HF patients involved in the CONNECT-HF clinical trial and 7 of their respective caregivers. Interviews were audio-recorded and transcriptions were imported to NVivo 11 (Version 11.4.0) for coding and analysis. We used content analysis and a mixed inductive and deductive approach for interpretation of coded text.

Results:
Patients (n=8) and caregivers (n=7) reported numerous strategies (n=28) for each guideline-based self-care behavior. The over-arching theme contributing to successful, effective behavior change was the value of social support and social interactions in the work of “sticking with it.” Predominant sub-themes included the idea that “knowledge is necessary but not sufficient” for behavior change, and “ building a routine” was critical for life-long self-care to be effective (Table 1).

Conclusions:
Many of the behavior change barriers and strategies proposed by patients are concepts that are consistent with findings in the field of behavioral economics and have the potential to inform development of effective behavior change tools.
Abstract 17115: Age-Related Outcomes for Takotsubo Syndrome Differ by Sex
Authors: Pattisapu Varun , HAO HUA , Nguyen Trevor Trung , Merz Noel B , Cheng Susan
Published: November 2020

Background:
Takotsubo syndrome (TTS) is an uncommon but increasingly recognized cause of myocardial infarction in both women and men across the age spectrum. Emerging data suggest that outcomes are worse in younger compared to older adults, and the extent to which this trend differs by sex is unclear.

Methods:
Using the National Inpatient Sample data from years 2006 to 2014, we identified hospitalizations with either a primary or secondary diagnosis of TTS. We analyzed these data stratified by age and sex. Outcomes measured include in-hospital mortality and in-hospital complications of cardiac arrest, cardiogenic shock, any type of shock, vasopressor use, intra-aortic balloon pump use, and mechanical ventilation.

Results:
We identified a total of N=18,051 TTS cases over the study period, most of which were experienced by women (89%). Despite the majority cases occurring in patients over age 50 years (89%), younger patients hospitalized with TTS were consistently more likely to suffer almost all major types of in-hospital complications except for in-hospital mortality (

Figure

). These apparently paradoxical age-based trends were observed in women more so than in men.

Conclusion:
Our results demonstrate that while individuals age 50 years and older continue to be more frequently hospitalized with TTS than younger patients, younger patients present with greater complications. This age-based finding is seen predominantly in women and much less so in men, potentially related to sex differences in sympathetic regulation of cardiovascular responses to stress. Further research is needed to validate and investigate the potential mechanisms underlying our findings.
Abstract 17217: Brown Adipose Tissue Promotes Exercise Capacity Through Sirtuin-3
Authors: Oydanich Marko , Zhang Jie , Vatner Dorothy E , Vatner Stephen F
Published: November 2020

It is well recognized that increased white adipose tissue impairs exercise performance. However, little is known about regulation of exercise performance by brown adipose tissue (BAT). The Regulator of G Protein Signaling 14 (RGS 14) knockout (KO) mouse is a model of enhanced longevity and improved metabolism through a novel BAT mechanism. The RGS14 KO mice also exhibit enhanced exercise performance. Accordingly, the goal of this investigation was to determine if BAT from RGS14 KO mice transplanted into their wild type littermates (WTL) recapitulated the enhanced exercise performance of the RGS14 KO mice. To accomplish this, BAT was extracted from the RGS14 KO mice and transplanted into their WTL and exercise was performed 3 days later. When BAT was transplanted from the RGS14 KO mice to WTL, a reversal of phenotype was observed, i.e., WTL with the transplanted BAT ran for a longer distance (565 ± 18m vs. 386 ± 17m) and performed 52% more work to exhaustion, p<0.05, and showed significant increases in maximum VO
2
(21%), VCO
2
(27%), and energy expenditure (23%), and hind limb blood flow (62%), measured ultrasonically with the Vevo 3100, than was observed in the RGS14 KO BAT donor mice. Interestingly, BAT transplanted from WTL to other WTL also recapitulated the enhanced exercise performance, but not at 3 days after transplantation, but rather after 8 weeks of transplantation. Since mitochondrial numbers and cross sectional area were enhanced both in RGS14 KO and BAT recipients, we examined whether blocking Sirtuin-3 (SIRT3), a master regulator of mitochondria, would eliminate the improved exercise performance in the mice with BAT transplants. To accomplish this, we crossed the mice with BAT transplants from RGS14 KO mice with SIRT3 KO mice, which abolished the enhanced exercise capacity in mice with BAT transplants. In conclusion, in contrast to increased white adipose tissue, which impairs exercise performance, brown adipose tissue enhances exercise performance, through a SIRT3 mechanism, suggesting that brown adipose tissue could be a potential mechanism for improving exercise capacity in patients with exercise intolerance.
Abstract 17228: Gender Differences in Treatment and Outcomes of Patients With COVID-19 Respiratory Failure
Authors: Feroze Rafey A , Azam Tariq , Shadid Husam , Pan Michael , Berlin Hanna , Meloche Chelsea , Leya Jeff , O'Hayer Patrick , Anderson Elizabeth , Kaakati Rayan , bitar abbas , Padalia Kishan , Perry Daniel , Blakely Pennelope , Zhao Peiyao , Zhao Lili , Hayek Salim
Published: November 2020

Introduction:
The COVID-19 pandemic has spread across the globe and claimed many lives. Initial studies suggest that there are gender-based differences in severity of disease and mortality, with male patients having worse outcomes. We sought to further characterize gender differences to COVID-19 infection.

Hypothesis:
Male patients have a higher severity of illness from COVID-19.

Methods:
The Michigan Medicine COVID-19 Cohort (M2C2) is an ongoing prospective observational study in which detailed clinical, laboratory and outcomes data were collected from chart review of consecutive adult patients hospitalized for COVID-19. Patients who were positive for SARS-CoV-2 infection but without symptoms of COVID-19 were not included in this cohort. The M2C2registry consists of 553 patients with 491 included in this analysis. There were 282 male patients and 208 female patients. Baseline characteristics, comorbidities, and characteristics of in-patient management were compared among male and female patients. The primary outcomes analyzed were in-hospital death of any cause including dismissal to hospice, need for renal replacement therapy (RRT), need for mechanical ventilation, and hospital length of stay.

Results:
Significant differences were observed among various patient characteristics and outcomes across gender. While no mortality difference was present between males and females, 43.8% of male patients were diagnosed with ARDS compared to 35.1% of female patients. The average days on mechanical ventilation were greater for male ICU patients (4.1 ± 5.91 vs. 3.4 ± 5.75) and the length of stay (days) was also longer for males (13.6 ± 11.94 vs. 12.2 ± 12.29). Admission creatinine was higher in males compared to females (2.95 ± 12.97 vs. 1.31 ± 1.33) and more male patients required RRT during their ICU admission (19.5% vs. 10.6%).

Conclusions:
While no difference in in hospital mortality was observed across gender, the severity of disease was greater among male patients in regards to ARDS, the need for ventilatory support, and kidney injury with requirement for RRT.
Abstract 17239: miRNAs Secreted by Exosomes Derived From Adipose Tissue Mesenchymal Stem Cells Overexpressing GATA-4 Increase Endothelial Cell Survival and Promote Angiogenesis
Authors: Xu Jie , Wang Jiapeng , Liu Min , Wang Yigang , Ashraf Muhammad , Xu Meifeng
Published: November 2020

Exosomes (EXO) secreted from stem cells play a critical role in cell based therapy and appear to have greater salutary therapeutic effects than whole cells. Our previous study showed that EXO produced by GATA-4-overexpressing mesenchymal stem cells (MSCs) significantly promoted angiogenesis and protected cardiomyocytes resulting in improved ischemic myocardial function. In the present studies, we compared the miR expression pattern and determined whether Exo
GATA-4
delivered miRs particularly promoted angiogenesis.

Methods and Results:
EXO were collected from conditioned medium of adipose tissue derived MSCs that were transfected with GATA-4 (Exo
GATA-4
) or with vector-empty (Exo
null
) using ultracentrifugation (
Fig A
). Functional analysis showed that Exo
GATA-4
significantly increased tube formation, migration, and proliferation of human umbilical vein endothelial cells (HUVECs) compared to Exo
null
. MicroRNA-seq data showed that 7 of the 230 miRs found in EXO, were significantly upregulated in Exo
GATA-4
(
Fig B
). To determine the effect of upregulated miRs on Exo
GATA-4
mediated angiogenesis, miR-155 and miR-6240 mimic, inhibitor, and negative control were directly transferred into HUVECs. After 48 hours, HUVECs were harvested for measuring endothelial cell behavior. Transfection of miR-6240-mimic significantly increased HUVECs proliferation, tolerance against H
2
O
2
induced injury (
Fig C
), tube-like structure formation (
Fig D
) and cell migration (
Fig E
) compared to those transfected with negative control. Concurrently, no significant differences were found in proliferation, survival, and tube-like structure formation among the cells transfected with miR-155-mimic and negative control, although miR-155-mimic significantly increased cell migration.

Conclusion:
The upregulated miRs in Exo
GATA-4
may variably regulate endothelial cell behavior and the role of various miRs needs to be investigated individually.
Abstract 17277: Holistic Health-Related Quality of Life in Older Adults Undergoing Transcatheter Aortic Valve Replacement
Authors: Huroy Menal , Rodighiero Julia , Afilalo Jonathan
Published: November 2020

Introduction:
Health-related quality of life (HRQoL) is a prioritized outcome for older adults undergoing transcatheter aortic valve replacement (TAVR). Previous studies have used the Kansas City Cardiomyopathy Questionnaire (KCCQ) to evaluate HRQoL, which is heavily weighted on heart failure symptoms with only one question on mental wellbeing. We sought to determine the incidence and determinants of poor HRQoL using a novel holistic scale.

Methods:
The FRAILTY-AVR prospective multi-centre cohort study of older adults undergoing TAVR was used to develop a holistic HRQoL scale. Construct validity was evaluated using the Spearman’s rank correlation with the 12-item KCCQ, and clinically meaningful change was evaluated using the anchor-based method. The primary endpoint was “poor outcome” defined as all-cause mortality or clinically meaningful decrease in HRQoL at 1 year.

Results:
The cohort consisted of 693 patients with a mean age of 82.9 years and 47% females. A 23-item HRQoL scale was developed, with the total score ranging from 0 (worst) to 40 (best) across 5 domains: disease burden (3 items), general health (1 item), physical (6 items), mental (5 items), and social (8 items) functioning. This scale was correlated with the KCCQ (Spearman’s rho 0.56, P<0.0001) and a 3-unit change was found to be clinically meaningful in longitudinal follow-up. A total of 269 (39%) patients experienced a poor outcome at 1 year post-TAVR, including 144 (21%) deaths. The predictors of poor outcome were Essential Frailty Toolset score >=3 [OR 1.88; 95% CI 1.28, 2.76], mean aortic gradient <40 mmHg [OR 1.83; 95% CI 1.27, 2.63] and Charlson comorbidity index [OR 1.09; 95% CI 1.01, 1.18].

Conclusions:
Two of five patients had a poor outcome 1 year post-TAVR, despite a procedure success rate of 95%. The incidence and determinants of poor outcome using our holistic HRQoL scale, notably the impact of frailty, are highly consistent with previous studies using the KCCQ. These determinants should be integrated in patient-centered decision making and optimized to improve HRQoL post-procedure.
Mitochondrial Reversible Changes Determine Diastolic Function Adaptations During Myocardial (Reverse) Remodeling
Authors: Miranda-Silva Daniela , G. Rodrigues Patrícia , Alves Estela , Rizo David , Fonseca Ana Catarina R.G. , Lima Tânia , Baganha Fabiana , Conceição Gloria , Sousa Cláudia , Gonçalves Alexandre , Miranda Isabel , Vasques-Nóvoa Francisco , Magalhães José , Leite-Moreira Adelino , Falcão-Pires Inês
Published: November 2020

Background:

Often, pressure overload–induced myocardial remodeling does not undergo complete reverse remodeling after decreasing afterload. Recently, mitochondrial abnormalities and oxidative stress have been successively implicated in the pathogenesis of several chronic pressure overload cardiac diseases. Therefore, we aim to clarify the myocardial energetic dysregulation in (reverse) remodeling, mainly focusing on the mitochondria.

Methods:

Thirty-five Wistar Han male rats randomly underwent sham or ascending (supravalvular) aortic banding procedure. Echocardiography revealed that banding induced concentric hypertrophy and diastolic dysfunction (early diastolic transmitral flow velocity to peak early-diastolic annular velocity ratio, E/E′: sham, 13.6±2.1, banding, 18.5±4.1,
P
=0.014) accompanied by increased oxidative stress (dihydroethidium fluorescence: sham, 1.6×10
8
±6.1×10
7
, banding, 2.6×10
8
±4.5×10
7
,
P
<0.001) and augmented mitochondrial function. After 8 to 9 weeks, half of the banding animals underwent overload relief by an aortic debanding surgery (n=10).

Results:

Two weeks later, hypertrophy decreased with the decline of oxidative stress (dihydroethidium fluorescence: banding, 2.6×10
8
±4.5×10
7
, debanding, 1.96×10
8
±6.8×10
7
,
P
<0.001) and diastolic dysfunction improved simultaneously (E/E′: banding, 18.5±4.1, debanding, 15.1±1.8,
P
=0.029). The reduction of energetic demands imposed by overload relief allowed the mitochondria to reduce its activity and myocardial levels of phosphocreatine, phosphocreatine/ATP, and ATP/ADP to normalize in debanding towards sham values (phosphocreatine: sham, 38.4±7.4, debanding, 35.6±8.7,
P
=0.71; phosphocreatine/ATP: sham, 1.22±0.23 debanding, 1.11±0.24,
P
=0.59; ATP/ADP: sham, 6.2±0.9, debanding, 5.6±1.6,
P
=0.66). Despite the decreased mitochondrial area, complex III and V expression increased in debanding compared with sham or banding. Autophagy and mitophagy-related markers increased in banding and remained higher in debanding rats.

Conclusions:

During compensatory and maladaptive hypertrophy, mitochondria become more active. However, as the disease progresses, the myocardial energetic demands increase and the myocardium becomes energy deficient. During reverse remodeling, the concomitant attenuation of cardiac hypertrophy and oxidative stress allowed myocardial energetics, left ventricle hypertrophy, and diastolic dysfunction to recover. Autophagy and mitophagy are probably involved in the myocardial adaptation to overload and to unload. We conclude that these mitochondrial reversible changes underlie diastolic function adaptations during myocardial (reverse) remodeling.
Heart Failure and Shared Decision-Making: Patients Open to Medication-Related Cost Discussions
Authors: Rao Birju R. , Dickert Neal W. , Morris Alanna A. , Speight Candace D. , Smith Graham H. , Shore Supriya , Moore Miranda A.
Published: November 2020

Background:

Discussions of medication costs between patients and clinicians are infrequent and often suboptimal. In the context of recently introduced drugs that are effective but expensive, patients with heart failure with reduced ejection fraction provide an ideal population to understand the perspectives of patients with chronic illness on medication cost and cost discussions.

Methods:

To explore patients’ perspectives on discussing out-of-pocket medication costs with clinicians, 49 adults, aged 44 to 70 years, with heart failure with reduced ejection fraction were recruited from outpatient heart failure clinics. Descriptive qualitative analysis was performed on open-ended text data.

Results:

Participants who had prior medication-related cost discussions described their experience as generally positive, but about half of the participants had never had a cost discussion with their clinician. Most participants were open to cost discussions with clinicians and preferred that the clinician initiate discussions regarding medication cost. Importantly, these preferences held constant across reported levels of financial burden.

Conclusions:

These data suggest a substantial willingness on the part of patients with heart failure with reduced ejection fraction to incorporate cost discussions into their care and identify important aspects of these discussions for clinicians to consider when engaging in conversations where cost is relevant. Improving understanding about how to integrate patient preferences regarding cost discussions into clinical encounters is an important priority for advancing patient-centered care.
Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy
Authors: Ammirati Enrico , Frigerio Maria , Adler Eric D. , Basso Cristina , Birnie David H. , Brambatti Michela , Friedrich Matthias G. , Klingel Karin , Lehtonen Jukka , Moslehi Javid J. , Pedrotti Patrizia , Rimoldi Ornella E. , Schultheiss Heinz-Peter , Tschöpe Carsten , Cooper Leslie T. , Camici Paolo G.
Published: November 2020

Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally <1 month). In contrast, chronic inflammatory cardiomyopathy indicates myocardial inflammation with established dilated cardiomyopathy or hypokinetic nondilated phenotype, which in the advanced stages evolves into fibrosis without detectable inflammation. Suggested diagnostic and treatment recommendations for AM and chronic inflammatory cardiomyopathy are mainly based on expert opinion given the lack of well-designed contemporary clinical studies in the field. We will provide a shared and practical approach to patient diagnosis and management, underlying differences between the European and US scientific statements on this topic. We explain the role of histology that defines subtypes of myocarditis and its prognostic and therapeutic implications.
Effects of Omecamtiv Mecarbil on Symptoms and Health-Related Quality of Life in Patients With Chronic Heart Failure
Authors: Felker G. Michael , Solomon Scott D. , McMurray John J.V. , Cleland John G.F. , Abbasi Siddique A. , Malik Fady I. , Zhang Hanze , Globe Gary , Teerlink John R. ,   for the COSMIC-HF Investigators
Published: November 2020

Background:

Chronic heart failure with reduced ejection fraction impairs health-related quality of life (HRQL). Omecamtiv mecarbil (OM)—a novel activator of cardiac myosin—improves left ventricular systolic function and remodeling and reduces natriuretic peptides. We sought to evaluate the effect of OM on symptoms and HRQL in patients with chronic heart failure with reduced ejection fraction and elevated natriuretic peptides enrolled in the COSMIC-HF trial (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure).

Methods:

Patients (n=448) were randomized 1:1:1 to placebo, 25 mg of OM BID, or to pharmacokinetically guided dose titration (OM-PK) for 20 weeks. The Kansas City Cardiomyopathy Questionnaire was administered to assess HRQL at baseline, 16 weeks, and 20 weeks. The primary scores of interest were the Total Symptom Score, Physical Limitation Scale, and Clinical Summary Score.

Results:

Mean change in score from baseline to 20 weeks for the Total Symptom Score was 5.0 (95% CI, 1.8–8.1) for placebo, 6.6 (95% CI, 3.4–9.8) for OM 25 mg (
P
=0.32 versus placebo), and 9.9 (95% CI, 6.7–13.0) for OM-PK (
P
=0.03 versus placebo); for the Physical Limitation Scale, it was 3.1 for placebo (95% CI, −0.3 to 6.6), 6.0 (95% CI, 3.1–8.9) for OM 25 mg (
P
=0.12), and 4.3 (95% CI, 0.7–7.9) for OM-PK (
P
=0.42); for the Clinical Summary Score, it was 4.1 (95% CI, 1.4–6.9) for placebo, 6.3 (95% CI, 3.6–9.0) for OM 25 mg (
P
=0.19), and 7.0 (95% CI, 4.1–10.0) for OM-PK (
P
=0.14). Differences between OM and placebo were greater in patients who were more symptomatic at baseline.

Conclusions:

HRQL as measured by the Total Symptom Score improved in patients with heart failure with reduced ejection fraction assigned to the OM-PK group relative to placebo. Ongoing trials are prospectively testing whether OM improves symptoms and HRQL in heart failure with reduced ejection fraction.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01786512.
Determinants of Value in Coronary Artery Bypass Grafting
Authors: Brescia Alexander A. , Vu Joceline V. , He Chang , Li Jun , Harrington Steven D. , Thompson Michael P. , Norton Edward C. , Regenbogen Scott E. , Syrjamaki John D. , Prager Richard L. , Likosky Donald S. ,   on behalf of the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative (MSTCVS-QC) and the Michigan Value Collaborative (MVC)
Published: November 2020

Background

Over 180 000 coronary artery bypass grafting (CABG) procedures are performed annually, accounting for $7 to $10 billion in episode expenditures. Assessing tradeoffs between spending and quality contributing to value during 90-day episodes has not been conducted but is essential for success in bundled reimbursement models. We, therefore, identified determinants of variability in hospital 90-day episode value for CABG.

Methods

Medicare and private payor admissions for isolated CABG from 2014 to 2016 were retrospectively linked to clinical registry data for 33 nonfederal hospitals in Michigan. Hospital composite risk-adjusted complication rates (≥1 National Quality Forum-endorsed, Society of Thoracic Surgeons measure: deep sternal wound infection, renal failure, prolonged ventilation >24 hours, stroke, re-exploration, and operative mortality) and 90-day risk-adjusted, price-standardized episode payments were used to categorize hospitals by value by defining the intersection between complications and spending.

Results

Among 2573 total patients, those at low- versus high-value hospitals had a higher percentage of prolonged length of stay >14 days (9.3% versus 2.4%,
P
=0.006), prolonged ventilation (17.6% versus 4.8%,
P
<0.001), and operative mortality (4.8% versus 0.6%,
P
=0.001). Mean total episode payments were $51 509 at low-compared with $45 526 at high-value hospitals (
P
<0.001), driven by higher readmission ($3675 versus $2177,
P
=0.005), professional ($7462 versus $6090,
P
<0.001), postacute care ($7315 versus $5947,
P
=0.031), and index hospitalization payments ($33 474 versus $30 800,
P
<0.001). Among patients not experiencing a complication or 30-day readmission (1923/2573, 74.7%), low-value hospitals had higher inpatient evaluation and management payments ($1405 versus $752,
P
<0.001) and higher utilization of inpatient rehabilitation (7% versus 2%,
P
<0.001), but lower utilization of home health (66% versus 73%,
P
=0.016) and emergency department services (13% versus 17%,
P
=0.034).

Conclusions

To succeed in emerging bundled reimbursement programs for CABG, hospitals and physicians should identify strategies to minimize complications while optimizing inpatient evaluation and management spending and use of inpatient rehabilitation, home health, and emergency department services.
What God Does Not Possess: Moses Mendelssohn’s Philosophy of Imperfection
Authors: Atlas Dustin Noah
Published: November 2020

This paper proposes that Moses Mendelssohn’s Morning Hours be viewed as the final chapter in a philosophy of imperfection that Mendelssohn had been developing over the course of his life. It is further argued that this philosophy of imperfection is still of philosophical interest. After demonstrating that the concept of imperfection animates Mendelssohn’s early work, this paper turns towards the specific arguments about imperfection Mendelssohn made in the midst of the pantheism controversy—in particular, the claim that human imperfection attests to an independent existence. Simply put: God knows human imperfection, but does not possess it. Therefore, there is a sense in which humans, because of our imperfections, are distinct from God. It is shown that, at least in part, Mendelssohn’s entry into the pantheism controversy, and his willingness to engage even his recently departed friend Lessing in argument, is part of his strategy to preserve his philosophy of imperfection.
On the Legitimacy of National Interests of Sponsoring States: A Deep Sea Mining Conundrum
Authors: Willaert Klaas
Published: November 2020

Beyond national jurisdiction, the deep seabed and its mineral resources are designated as the ‘common heritage of mankind’. Nevertheless, the governing legal framework does not only consist of international instruments, as domestic legislation issued by sponsoring States also plays a decisive role. The legitimacy of certain national provisions can be questioned though, taking into account the duty to carry out activities in the Area for the benefit of mankind as a whole. For instance, can a sponsoring state demand that the proposed mining activities are in the public interest of the State? Are they allowed to generate revenue by introducing a recovery fee or other taxes? Should developing States enjoy more leeway, given the particular consideration for their interests and needs in the Law of the Sea Convention? This article analyses to what extent creeping national interests in domestic legislation on deep sea mining are in accordance with international law.
From Angel to the Shekhina: The Influence of Kabbalah on the Late Work of R. B. Kitaj
Authors: Knotter Mirjam
Published: November 2020

After a lifelong career as a central figure in the London art scene, the American-Jewish artist R. B. Kitaj (1932–2007) left England in 1997 for Los Angeles to be “in exile,” as he named it, following a series of tragic events that he believed had caused the sudden death of his beloved wife and muse, artist Sandra Fisher (1947–1994). In Los Angeles, he continued the mission he had assigned himself long before: to create a meaningful, new Jewish art. For Kitaj, Jewish art was a “Diasporist” art—that is, a modernist, universal art whose core lies in the experience of the artist living and working in multiple societies simultaneously, and a response to being Heimatlos (“homeless”). He formulated his thoughts in two manifestos (1988/1989 and 2007), which were followed in 2017 by his posthumously published autobiography, Confessions of an Old Jewish Painter. Around 2003, Kitaj’s perception of Sandra Fisher attained a more mystical level: in addition to angelic qualities, he began to assign divine qualities to her as the personification of the Shekhina, the feminine aspect of God, to whom he could cleave as a mystic through his art while painting his Los Angeles series. In his final years, his personal devotion focused entirely on his reunion with Sandra. In this, mystical ideas about the Shekhina offered Kitaj a vehicle for his thought and art as well as a means of transition from earthly existence to death.