bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13311: Cyclocreatine Phosphate: A Novel Mechanism for Preventing Development of Heart Failure
Authors: Elgebaly Salwa A , Van Buren Charles , Todd Robert , Poston Robert , Rabie Mostafa A , Mohamed Ahmed F , Ahmed Lamiaa A , El Sayed Nesrine S
Published: May 2021

Introduction:
Demand ischemia causes irreversible myocardial injury (MI) through exhaustion of cellular adenosine triphosphate (ATP). We demonstrated that enhancing myocardial ATP stores during ischemia using Cyclocreatine Phosphate (CCrP), prevents myocardial injury and maintains cardiac contractility in a variety of models. The FDA has granted CCrP Orphan Drug Status with the designation of “
Prevention of Ischemic Injury to Enhance Cardiac Graft Recovery and Survival in Heart Transplantation
”
.

Hypothesis:
CCrP administration will prevent ischemic injury and the subsequent development of heart failure in standard isoproterenol (ISO) rat model.

Methods:
20 male Wistar rats (180-220 g) were used: ISO/saline (n=6), ISO/CCrP 0.8 gm/kg/day (n=5), control/saline (n=5), control/CCrP 0.8 gm/kg/day (n=4). Rats were injected S.C. with ISO for two consecutive days at doses of 85 and 170 mg/kg/day, respectively, then left for 2 weeks. CCrP and saline were injected IP (1 ml) 24 hours and 1 hour before ISO administration, then daily for 2 weeks. Serum CK-MB (U/L) measured 24 hours after last ISO injection. After 14 days, ECHO analysis for Ejection Fraction (EF%) was conducted, as well as heart weight (mg), fibrosis and deposition of collagen. Mean ± S.E.M and one-way ANOVA analysis were used.

Results:
Table I shows evidence of MI after 24 hours by high elevation of CK-MB in ISO rats, while significant protection was seen in ISO/CCrP rats. After 14 days, ISO/CCrP rats showed normal EF% and heart weight, while ISO/saline rats showed significant drop in EF% and an increase in heart weight. Blinded pathology indicated marked increase of fibrin and collagen deposition in ISO/saline rats, which were not seen in ISO/CCrP rats. Healthy rats treated with CCrP for 14 days, showed no toxicity in liver and renal function.

Conclusions:
The bioenergetic Cyclocreatine Phosphate is a promising first-in-class cardio-protective drug that prevents the development of heart failure due to ischemia.
Abstract 13315: Long-term Risk of Cardiovascular Events Following Hospitalization for Sepsis: A Systematic Review and Meta-analysis
Authors: Kosyakovsky Leah B , Angriman Federico , Katz Emma , Adhikari Neill , Godoy Lucas C , Ko Dennis T , Lee Douglas , Marshall John , Rosenson Robert S , Farkouh Michael E , Scales Damon , Detsky Michael , Bibas Lior , Lawler Patrick R
Published: May 2021

Introduction:
Sepsis results in dysregulated inflammation, coagulation, and metabolism, which may contribute to increased cardiovascular disease (CVD) risk. We conducted a systematic review and meta-analysis to determine the association between sepsis and subsequent long-term CVD events.

Methods:
MEDLINE, Embase, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched from inception to May 2020 to identify observational studies of adult sepsis survivors (defined by diagnostic codes or consensus definitions) measuring long-term CV outcomes. The primary outcome was a composite of myocardial infarction, CV death, and stroke. Random-effects models estimated the pooled cumulative incidence and adjusted hazard ratios of CV events relative to hospital or population controls. Odds ratios were included as risk ratios assuming <10% incidence in non-septic controls, and risk ratios were taken as hazard ratios (HR) assuming no censoring. Outcomes were analyzed at maximum follow-up (primary analysis) and stratified by time (<1 year, 1-2 years, and >2 years) since sepsis.

Results:
Of 11,235 abstracts screened, 25 studies (22 cohort studies, 2 case-crossover studies, and 1 case-control) involving 1,949,793 sepsis survivors were included. The pooled cumulative incidence of CVD events was 9% (95% CI; 5-14%). Sepsis was associated with an increased risk (HR 1.59, 95% CI 1.37-1.86) of CVD events at maximum follow-up (
Figure
); between-study heterogeneity was substantial (I
2
=97.3%). There was no significant difference when comparing studies using population and hospital controls. Significantly elevated risk was observed up to 5 years following sepsis.

Conclusions:
Sepsis survivors experience an approximately 50% increased risk of CVD events, which may persist for years following the index episode. These results highlight a potential unmet need for early cardiac risk stratification and optimization in sepsis survivors.
Abstract 13323: Identifying the Culprit Lesion in a Symptomatic Patient With Physiologically Corrected Transposition of the Great Arteries
Authors: Aldweib Nael , Stefanescu Ada , Bhatt Ami , Learn Christopher P , Yeh Doreen D
Published: May 2021

Introduction:
Physiologically corrected transposition of the great arteries [(S,L,L) TGA] is a rare congenital heart disease characterized by atrioventricular and ventriculoarterial discordance.

Case Presentation:
A 28-year-old man with (S,L,L) TGA, pulmonary valve (PV) stenosis, ventricular septal defect (VSD), and history of Kawasaki disease who presented for a gradual decline in exercise tolerance. Oxygen saturation was 96% at rest and dropped to 86% with ambulation. Hemoglobin was 17.7 g/dl, EKG showed no bradyarrhythmias. On stress test, peak heart rate was 159 beats/minute, and peak VO
2
22.6 ml/kg/min (83%, and 57% of predicted value respectively). Spirometry was normal. Transthoracic echocardiogram revealed biventricular hypertrophy with normal systolic function, a bicuspid PV with severe stenosis (peak and mean gradient of 155 and 90 mmHg respectively), large inlet VSD with bidirectional flow and mild systemic TV regurgitation. Coronary CTA showed no coronary artery aneurysms. Cardiac catheterization suggested hypoxia due to pulmonary-to-systemic shunting across the VSD with Q
p
/Q
s
= 0.86 (Figure). Consideration should be given to performing a high-risk surgical repair versus medical management.

Conclusions:
Natural history, symptoms, and timing of intervention are determined by the associated cardiac anomalies and the progressive dysfunction of the systemic right ventricle (SRV). Anatomic repair to restore the left ventricle as a systemic pump is a very high-risk procedure in adults. Functional repair maintains SRV, repair the VSD, and PV stenosis has a poor late outcome. Medical management ensures iron stores are repleted, provide empirical use of pharmacological heart failure therapy, and referral to heart transplantation when SRV systolic dysfunction ensues. Clinicians need to know the potential complications in both unoperated patients and following various surgical repairs to recommend appropriate treatment options.
Abstract 13346: The Rate of Incomplete Revascularization Following Coronary Artery Bypass Surgery Has Increased Over Time
Authors: Soukup Chase R , Schmidt Christian W , Chan-Tram Carmen , Garberich Ross F , Sun Benjamin , TRAVERSE Jay H
Published: May 2021

Introduction:
Incomplete revascularization following coronary artery bypass surgery (CABG) is associated with increased repeat revascularization, myocardial infarction and death. However, whether the rate of incomplete revascularization is increasing over time has not been previously described.

Methods:
We performed a retrospective review of consecutive patients who underwent elective and isolated CABG for multi-vessel coronary artery disease in 2007 (n=291) and in 2017 (n=290) at a single Institution. All coronary angiograms and CABG operative reports were reviewed and a Revascularization Index Score (RIS) was created to compare rates of incomplete revascularization between the two time periods based on the coronary anatomy and degree of stenosis. Thus a patient with complete revascularization will have an RIS score of 1.0 while a patient who has 3 of 4 eligible vessels bypassed will have an RIS score of 0.75.

Results:
Over a 10 year period, the rate of incomplete revascularization increased from 17.9% to 28.3% (p = 0.003) and was accompanied by a decline in the RIS score from 0.73 to 0.67 (p= 0.005). Mortality significantly increased over time with incomplete compared to complete revascularization in the 2007 cohort.

Conclusions:
The incidence of incomplete revascularization following CABG significantly increased over a 10-year time period between 2007 and 2017. These differences may be attributable to patient factors including more severe coronary artery disease associated with older age, greater incidence of smoking and previous PCI. In line with previous. meta-analyses, the incidence of mortality over time was higher in those patients with incomplete compared to those with complete revascularization. These results suggest that patients with incomplete revascularization represents an important target for the development of novel therapies.
Abstract 13355: Obesity is Associated With Incident Cancer in the Community
Authors: Liu Elizabeth E , Paniagua Samantha M , Lau Emily S , Li Shawn X , Jovani Manol , Takvorian Katherine , Kreger Bernard E , Benjamin Emelia J , Splansky Greta Lee , Ramachandran Vasan S , Larson Martin G , Levy Daniel , Cheng Susan , De Boer Rudolf A , Ho Jennifer E
Published: May 2021

Introduction:
Obesity and cardiometabolic dysfunction may be shared risk factors for development of cancer. We sought to examine the association of obesity and abdominal adiposity with incident cancer.

Methods:
We studied participants of the Framingham Heart Study and Prevention of Renal and Vascular End-Stage Disease study. We examined the association of obesity, body-mass index (BMI), waist circumference (WC), and visceral adiposity (VAT) with future cancer in Cox models. We adjusted for age, sex, diabetes, systolic blood pressure, hypertension treatment, smoking status (current, former, never), and cholesterol ratio.

Results:
Among 20,667 individuals (mean age 50, 53% women) free of cancer at baseline, we observed 2,619 incident cancer events over a mean follow-up of 13.3±3.3 years. Obesity (BMI≥30 kg/m
2
) was associated with 30% increased hazard of future gastrointestinal cancer (HR 1.30, 95% CI 1.05-1.60, P=0.01), 62% increased hazard of gynecologic cancers (HR 1.62, 95% CI 1.08-2.45, P=0.02), and by contrast, 38% lower risk of lung cancer (HR 0.62, 95% CI 0.44-0.87, P=0.006). We found similar associations of future cancer with continuous BMI and WC (
Figure
). Among 3,077 individuals with CT scans, VAT was associated with incident cancer (HR 1.16, 95% CI 1.03-1.31, P=0.01 per 1-SD change in VAT). After adjusting for BMI, higher VAT was associated with greater risk of lung cancer (HR 1.92, 95% CI 1.01-3.65, P=0.045).

Conclusions:
We observed that obesity and abdominal adiposity were associated with future cancer events, including gastrointestinal and gynecologic cancers. Interestingly, obesity was associated with lower risk of lung cancer. However, greater VAT was associated with greater lung cancer risk after adjusting for BMI. These findings highlight the importance of specific obesity-related phenotypes and adipose depots in better understanding the association between obesity and cancer.
Abstract 13362: Socio-ecological Variables Influenced Moderate-to-vigorous Intensity Physical Activity Levels Amongst Hospital-based Nurses: A Multi-site Study
Authors: Law Daniel , chirico daniele , Terada Tasuku , Prince Ware Stephanie , bernick jordan , Reid Robert D , Pipe Andrew , Tulloch Heather , Reed Jennifer L.
Published: May 2021

Introduction:
Previous research has shown that nurses are not meeting recommended moderate-to-vigorous intensity PA (MVPA) guidelines (≥150 minutes/week) for optimal cardiovascular disease risk reduction. Socio-ecological approaches have been used to explore the determinants of PA levels. We examined personal, social and environmental factors associated with the MVPA levels of Canadian nurses.

Methods:
Secondary analysis of data from a multi-site cross-sectional study was undertaken. Nurses were recruited from 14 hospitals in Ontario, Canada. An accelerometer (ActiGraph GT3X) was used to measure MVPA levels (minutes/day). Socio-ecological variables were derived from sociodemographic, anthropometric and cardiometabolic data, and questionnaires assessing determinants of PA (Table 1). Multivariate generalized estimating equations (GEE) were used to explore associations between socio-ecological variables and MVPA levels while accounting for hospital sites. Variables were selected for multivariate analyses if they were significant (
p
<0.05) in univariate analyses.

Results:
A total of 257 nurses (42±12 years) had complete accelerometer (≥10 hours of wear time for ≥4 days) and questionnaire data. Of these nurses, 54% were overweight/obese and 6% were smokers. Multivariate analyses showed positive associations between MVPA levels and high perceived capability to exercise despite common barriers (e.g. poor weather; β=0.13,
p
=0.02) and feeling connected to their exercise peers (β=1.34,
p
=0.01). Greater shiftwork associated daytime sleepiness and/or insomnia were inversely associated with MVPA levels (β=-4.87,
p
<0.01).

Conclusion:
Future endeavors to accentuate nurses’ PA levels should address modifiable socio-ecological variables such as encouraging exercise despite common barriers, and with peers to whom they feel connected. Nurses should consider increasing time spent engaging in MVPA to minimize the negative effects of shiftwork.
Abstract 13368: Clinical Impact of Heart Rate Change in Early Phase in Patients With Acute Decompensated Heart Failure
Authors: kazama shingo , Kondo Toru , Kimura Yuki , Shibata Naoki , Oishi Hideo , Araki Takashi , Mizutani Takashi , Kuwayama Tasuku , Hiraiwa Hiroaki , Morimoto Ryota , OKUMURA TAKAHIRO , Sawamura Akinori , Shimizu Kiyokazu , Kato Toshiaki , Murohara Toyoaki
Published: May 2021

Introduction:
Several studies have evaluated prognostic value of heart rate (HR) change during hospitalization in patients with acute heart failure (AHF). However, the relationship between HR change in early phase after admission and prognosis have not been fully elucidated.

Hypothesis:
The aim of this study was to evaluate the prognostic value of HR change in early phase in patients with AHF.

Methods:
We used a data of multicenter retrospective registry for the consecutive hospitalized patients due to AHF since January 2012 to March 2019. Patients were divided into three groups according to tertiles of HR at admission: lower tertile, HR <85 bpm; middle tertile, HR 85-108 bpm; higher tertile, HR >108 bpm. And, (HR [at admission] - HR [at 12 hour after admission]) * 100 / HR [at admission] was calculated as HR change (%).

Results:
Total of 1625 patients were analyzed. The median HR at admission was 96 bpm, and HR decreased to 81 bpm at 12 hours after admission (p < 0.001). Larger HR change was observed according to increase in HR at admission (HR change; lower tertile, 1.0%; middle tertile, 12.5%, higher tertile, 38.0%, p < 0.001). In Kaplan-Meier analysis, the cumulative event-free rates in the composite endpoint of death and re-hospitalization due to AHF showed better according to higher HR at admission (p < 0.001, log-rank) (Figure). After dividing the patient into two groups in each tertiles based on the median HR change, the cumulative event-free rates were comparable between higher HR change group and lower HR change group in all tertiles (Figure). Cox proportional hazards analysis showed that HR change was not the independent predictors of composite endpoint adjusted by covariates in each tertile (lower tertile, p = 0.81; middle tertile, p = 0.78; higher tertile, p = 0.90).

Conclusions:
HR decreased significantly until 12 hours after admission. However, HR change in early phase did not have prognostic value in patients with AHF.
Abstract 13369: Sympathovagal Imbalance Decades After Atrial Septal Defect Repair
Authors: Alstrup Mathias , Karunanithi Zarmiga , Hjortdal Vibeke
Published: May 2021

Introduction:
Heart rate variability (HRV), a measure of the autonomic nervous system activity, is a morbidity and mortality predictor. HRV is decreased in children with atrial septal defects (ASD) indicating parasympathetic withdrawal and sympathetic predominance, and increased right atrial end-diastolic pressure is believed to influence the sympathovagal balance. Despite the belief of a benign long-term outcome after closure, ASD patients have increased mortality rates after the age of 30 yrs. This may correlate to HRV, why we study HRV in adults after closure.

Hypothesis:
ASD patients have impaired HRV after closure when compared with controls.

Methods:
Surgically closed ASD patients (n=17, mean age 32±9 yrs., mean time since closure 19±8 yrs.), percutaneously closed ASD patients (n=18, mean age 28±7 yrs., mean time since closure 15±5 yrs.) and age- and gender-matched controls (n=15, mean age 30±9 yrs.) underwent a 48-hr Holter monitoring. Inclusion criteria were an age of minimum 2 yrs. at the time of diagnosis and minimum 3 yrs. must have passed since ASD closure. The following time-domain HRV measures were analyzed: SD of NN intervals (SDNN), SD of the average NN interval for each 5-minute segment, mean of the SDs of all NN intervals for each 5-minute (SDNNi), root mean square of successive RR interval differences (RMSSD), percentage of successive RR intervals that differ by >50 ms (pNN50), and triangular index.

Results:
Surgically closed ASD patients have an impairment of all time-domain parameters, while transcatheter closed patients have an impairment of half the parameters.

Conclusion:
These novel findings demonstrate a cardiac sympathovagal imbalance in adult patients several yrs. after ASD closure and may potentially explain why we observe a long-term morbidity and mortality increase in ASD patients.
Abstract 13400: Patients Less Than or Equal to 2.5kg Have Higher Morbidity and Mortality After Norwood-sano Palliation
Authors: Averin Konstantin , Ryerson Lindsay , Hajihosseini Morteza , Dinu Irina A , Freed Darren H , Bond Gwen , Joffe Ari , jonker viljee , Robertson Charlene M , Atallah Joseph
Published: May 2021

Introduction:
In patients with single ventricle heart disease, prematurity and low weight at the Norwood operation are risk factors for mortality. Reports assessing peri-operative and long-term outcomes of Norwood palliation in patients ≤ 2.5kg are limited.

Methods:
All patients who underwent Norwood-Sano procedure between 2005-2020 were identified. Patients ≤ 2.5kg at the time of the Norwood operation (cases) were matched 1:3 with patients ≥ 3.0 kg (comparisons) for year of surgery and cardiac diagnosis. Demographic and peri-operative characteristics, survival to hospital discharge and 2-year neurodevelopmental outcomes were compared.

Results:
Twenty-seven cases (mean±SD weight 2.2±0.3 kg, mean age 15.6±14.1 days at surgery) and 81 comparisons (mean weight 3.5±0.4 kg, mean age 10.9±7.9 days at surgery) were identified. There was no statistically significant difference in the presence of chromosomal abnormalities (7.4% vs. 12.3%, p=0.485), prenatal diagnosis made (88.9% vs. 75.3%, p=0.141), or duration of cardiopulmonary bypass (140.7±65.6 vs. 121.3±42.3 min, p=0.068) between cases and comparisons, respectively. Cases had a longer time to post-operative lactate < 2 mmol/L (33.1±27.5 vs. 17.9±12.2 hours, p<0.001), longer duration of ventilation (30.5±24.5 vs. 18.6±17.5 days, p=0.005), higher need for dialysis (48.1% vs. 19.8%, p=0.007) and greater need for extracorporeal membrane oxygenation support (29.6% vs. 12.3%, p=0.004). Cases also had significantly higher in-hospital (25.9% vs. 1.2%, p<0.001) and 2-year (59.2% vs. 11.1%, p<0.001) mortality. The 2-year Bayley Scales of Infant and Toddler Development, III, was completed on all living cases (n=11) and most comparisons (n=63; 1 refusal and 8 too young); delay, a score of < 70, showed the following differences between cases vs. comparisons for cognitive (86.9 vs. 91, p=0.363), language (84.9 vs. 88.2, p=0.494) and motor (73.6 vs. 87.3, p=0.013).

Conclusions:
Patients ≤ 2.5kg at the time of Norwood-Sano have significantly higher post-operative morbidity and mortality up to 2-year follow-up, and worse 2-year neurodevelopmental motor outcomes. Additional studies are warranted to assess the outcome of alternative therapeutic options in this patient population.
Abstract 13410: Patient and Family Perspectives of Early Mobilization in Acute Cardiovascular Care
Authors: Najjar Caroline , Goldfarb Michael
Published: May 2021

Introduction:
Early mobilization (EM) is safe, feasible, and associated with good outcomes in people with acute CV disease. While studies have explored the perspectives of care providers on mobilization, little is known about patient and family member perspectives and experience with mobilization.

Methods:
Patient and family member surveys were developed using previously validated surveys (Family Satisfaction with Care in the ICU and the Patient Mobilization Attitudes & Beliefs survey). The survey assessed attitudes toward and knowledge of mobilization, the family member’s role in providing care and the mobilization care they received. Surveys were distributed to patients and their family members in an acute CV unit of a tertiary care centre in Montreal, Canada over a 4-month period.

Results:
102 participants completed the survey (78 patients and 24 family members). Most patients (N=54; 69.2%) agreed or strongly agreed that EM should be routinely performed, although nearly half of the patients (N=37, 47.4%) felt that mobilization soon after admission was potentially dangerous. Out of 64 patients who underwent EM, 60 (93.8%) felt that mobilization helped their recovery (Figure). 35 patients (54.7%) felt that family member participation helped their mobilization. Family members included 12 (50.0%) spouses/partners, 10 (41.7%) children, 1 (4.2%) siblings, and 1 parent (4.2%). Most family members felt that mobilizing their relatives too soon after admission was potentially dangerous (N=17, 70.8%). However, family members were interested in being involved with mobilization (N=22; 91.7%) and only a few felt that mobilization should not be routinely performed (N=2; 8.3%).

Conclusion:
Patients felt that EM helped with their recovery process. Family members were interested in being involved in mobilizing their relatives. Our findings should inform efforts to overcome patient and family-related barriers to mobilization and design an EM program for acute CV care.
Abstract 13429: Echocardiographic Predictors of Mitral Transvalvular Gradients After Mitraclip Insertion
Authors: Hadjadj Sandra , B. Freitas-Ferraz Afonso , Paquin Amélie , Bernier Mathieu , O'Connor Kim , Salaun Erwan , Pibarot Philippe , Clavel Marie-Annick , Rodés-Cabau Josep , Paradis Jean-Michel , Beaudoin Jonathan
Published: May 2021

Introduction:
The MitraClip procedure is a non-surgical alternative for patients with severe mitral regurgitation and high surgical risk. However, the MitraClip may lead to a reduction in the mitral valve orifice area (MVOA) and elevated transmitral mean gradients (TMG). The objectives of this study are to assess the value of baseline MVOA by different imaging methods and explore the value of MVOA indexed for left ventricular (LV) forward stroke volume (SV) to predict postprocedural TMG.

Methods:
Preprocedural echo images were retrospectively reviewed in 76 consecutive patients. MVOA from 2D transthoracic (MVOA
TTE
), 2D transgastric (MVOA
TG
) and 3D transesophageal (MVOA
3D
) echocardiography were measured and then indexed by the SV measured by Doppler in the LV outflow tract (MVOA/SV)
.
Postprocedural TMG was measured at one month and survival rate at one year.

Results:
Patients with postprocedural TMG >5 mmHg (18/76, 24%) had significantly smaller preprocedural MVOA
3D
(3.9±0.9 vs 5.2±1.3 cm
2
, p<0.01) and MVOA
TTE
(4.9±1.1 vs 5.9±1.5 cm
2
, p=0.02). No significant difference was found for MVOA
TG
(5.5±1.4 vs 5.9±1.4 cm
2
, p=0.2). Best threshold values for MVOA
3D
and MVOA
TTE
to predict postprocedural TMG >5 mmHg were respectively 3.9 cm
2
(AUC=0.80, IC95%: 0.67-0.94, p<0.01; sensitivity (Se) 62%, specificity (Sp) 87%) and 4,6 cm
2
(AUC=0.69, IC95%: 0.54-0.83, p=0.02; Se 50%, Sp 84%). MVOA/SV from each echocardiographic modality were smaller in patients with postprocedural TMG >5 mmHg (3D: 80 [62-95] vs 113 [99-129] cm
2
/L; TTE: 92 [81-105] vs 130 [100-166] cm
2
/L; TG: 104 [83-123] vs 135 [104-166] cm
2
/L; p<0.01 for all). MVOA/SV
3D
was overall the best predictor of postprocedural TMG >5 mmHg, with an optimal threshold of 96 cm
2
/L (AUC=0.86, IC95%: 0.76-0.97, p<0.001; Se 84%, Sp 81%). Patients with MVOA
3D
<3.9 cm
2
and MVOA/SV
3D
<96 cm
2
/L tend to be at higher risk for mortality at one-year follow-up (69% vs 84%, p=0.14 and 67% vs 87%, p=0.11 respectively).

Conclusion:
Unlike preprocedural MVOAs assessed by 3D echocardiography, preprocedural MVOAs measured by 2D echocardiographic modalities were poor predictors of high TMG after MitraClip. Preprocedural MVOA
3D
<3.9 cm
2
and MVOA/SV
3D
<96 cm
2
/L were found to be the best cut-off values to predict postprocedural TMG >5 mmHg.
Abstract 13434: Improved Diagnostic Performance of Contemporary Transesophageal Echocardiography With Three-dimensional Imaging for Infective Endocarditis
Authors: Chahine Johnny , Montane Bryce , Alzubi Jafar , Alnajjar Hanan , Fiore Andrew , mutti jasmine , Verma Beni , Gad Mohamed M , Reznicek Emily , Grimm Richard A , Griffin Brian P , Xu Bo
Published: May 2021

Introduction:
Infective endocarditis (IE) is associated with high morbidity and mortality. Conventionally, a repeat transesophageal echocardiogram (TEE) is necessary if the first TEE is negative, and there is high clinical suspicion. We aimed to investigate the diagnostic performance of contemporary TEE for IE.

Hypothesis:
We hypothesize that with advancements in TEE imaging, including three-dimensional (3D) imaging, the diagnostic performance of TEE for IE would be improved.

Methods:
Patients who had two or more TEEs at our center, within 6 months, for evaluation of IE in 2011 (pre-3D imaging) and 2019 (post-3D imaging) were included. Patients not meeting the Duke criteria for IE (n=899) were excluded. The primary endpoint was the sensitivity of TEE to detect IE. TEE sensitivity was also compared among the different subtypes of IE (native valve, prosthetic valve, device-related, central line-related, and aortic prosthetic graft-related).

Results:
242 patients were included: 70 in 2011 and 172 in 2019. In 2011, there were more smokers and a lower rate of pacing devices; otherwise, there were no significant differences in baseline characteristics, including intravenous drug use. The sensitivity of the initial TEE for IE was 85.7% in 2011, improving significantly to 95.3% in 2019 (p=0.01). The improved diagnostic performance in 2019 was mainly driven by the improved detection of prosthetic valve IE (70.8% vs. 93.7%, p=0.009). There were no significant differences for the other subtypes of IE
(Figure).
In 2019, patients had a higher rate of IE diagnosis within 15 days of index admission, which did not reach statistical significance (n=161, 93.6% vs. n=62, 88.6% in 2011, p=0.19). Kaplan Meier analysis demonstrated that patients in 2019 had a higher rate of procedures for endocarditis (p=0.01).

Conclusions:
Contemporary TEE imaging including 3D technology improved the detection of IE on the initial TEE, mainly driven by improved detection of prosthetic valve IE.
Abstract 13453: Estrogen Regulates Expression of Fibrotic Markers in Ips-derived Cardiac Fibroblasts and Cardiomyocytes
Authors: Argenziano Mariana A , Burgos Angulo Mariana , yang jiajia , Bertalovitz Alexander , McDonald Thomas
Published: May 2021

Introduction:
Cardiovascular disease (CVD) is the leading cause of death among women. Epidemiologic studies indicate that pre-menopausal women are protected against the development of CVD when compared to age-matched men. Women show less cardiac remodeling, with downregulation in fibrosis and inflammation pathways. Remodeling is manifested by morphology and electrophysiological changes including hypertrophy, apoptosis, fibroblast proliferation, fibrosis and accumulation of fibrillar collagens.

Hypothesis:
We hypothesize that female protection against CVD is associated with estrogen levels as the incidence and severity of CVD increases after menopause.

Methods:
Induced pluripotent stem cells (IPSC) from male (M) and female (F) controls were differentiated to cardiomyocytes (IPSC-CMs) and cardiac fibroblasts (IPSC-CFs). Samples were cultured for 30 days and collected for analysis before and after 48 hs incubation with 1uM of 17-b-estradiol (EST). In IPSC-CMs we analyzed gene expression, morphology and beating frequency. Gene expression, morphology and wound healing were analyzed in IPSC-CFs.

Results:
Expression of
ESR1
, and
MYH7
was higher in female IPSC-CMs with upregulation after EST treatment in females but not males. Male IPSC-CMs showed higher expression of
COL1A1
,
CX43
,
MYH6
and
RYR2
;
MYH6
,
RYR2
and
COL1A1
were downregulated after EST treatment. No differences were observed in morphology or beating frequency before or after EST treatment (F:27.5±4.5 bpm vs M:22±2.5 bpm). In IPSC-CFs, males showed higher expression of the fibrotic markers
COL1A1
,
POSTN, SMAD2
and
CCL2
; EST treatment decreased the expression of
POSTN
and
SMAD2
. Wound healing assays showed a decrease of the wound healing % in women after EST treatment (CT F:86.4±19.7% vs EST F:57.43±10.1%, at 8 hs, *p<0.05). Male wound healing rate was slower than women in control and treated groups, with no changes after EST treatment (CT F: 86.4±19.7% vs CT M: 51.65±18.4%, at 8 hs, *p<0.05).

Conclusions:
Estrogen treatment exerts an effect on gene expression in female and male IPSC-CMs and IPSC-CFs with men showing higher expression of fibrotic markers, which are down-regulated by EST. Further functional studies will shed light on the phenotypic effects of gene expression changes.
Abstract 13474: Rivaroxaban Reduces Major Cardiovascular and Limb Events in Patients With the High-risk Triad of Chronic Kidney Disease, Peripheral Artery Disease and Recent Lower Extremity Revascularization: Insights From VOYAGER PAD
Authors: Hsia Judith A , Anand Sonia , Nehler Mark R , Bauersachs Rupert , Patel Manesh R , Debus Sebastian , Hess Connie N , Capell Warren , Diao Lihong , Berkowitz Scott D , Muehlhofer Eva , Haskell Lloyd P , Hiatt William R , Bonaca Marc P
Published: May 2021

Introduction:
Chronic kidney disease (CKD) is common among patients undergoing lower extremity revascularization (LER) for peripheral artery disease (PAD) and identifies a population at high risk for adverse outcomes. The VOYAGER PAD trial demonstrated the efficacy of rivaroxaban in PAD patients after LER on a composite of cardiovascular (CV) and limb ischemic events (HR 0.85 vs placebo, 95% CI 0.76-0.96; p=0.009); this analysis examines the prespecified subgroup of patients with CKD.

Methods:
VOYAGER PAD (NCT02504216) was a double-blind, placebo-controlled trial which randomized PAD patients with recent LER to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily. The primary endpoint was a composite of acute limb ischemia, major amputation for vascular cause, myocardial infarction, ischemic stroke or CV death. The primary safety endpoint was TIMI major bleeding. Analysis of the intention-to-treat population utilized Kaplan Meier estimates and Cox proportional-hazards models.

Results:
Among 6319 VOYAGER patients with baseline estimated glomerular filtration rate (eGFR), 21% were <60 (mostly CKD stage 3) and 79% were ≥60 ml/min/1.73m
2
. During 28-month (median) follow up, patients with CKD had a higher rate of major CV and limb events: placebo group 10.0 events/100 patient-years (95% CI 8.5, 11.8) for eGFR <60 vs 7.4 (95% CI 6.7, 8.2) for eGFR ≥60. Rivaroxaban reduced primary outcome events with no heterogeneity by eGFR category (Figure, p for interaction 0.62). Acute limb ischemia and major amputation were significantly reduced among patients with eGFR<60 (HR 0.55, 95% CI 0.36, 0.86) as well as ≥60 (HR 0.77, 95% CI 0.63, 0.94). TIMI major bleeding was numerically more frequent among patients with CKD with no heterogeneity by treatment group (Figure, p for interaction 0.37).

Conclusions:
Rivaroxaban reduced major CV and limb events in patients with PAD undergoing LER, including those with CKD, a particularly high-risk population.
Abstract 13481: South Asian-specific
MYBPC3 25bp
Intronic Deletion Carriers Demonstrate Hypercontractility and Impaired Diastolic Function Under Exercise Stress
Authors: Bazrafshan Kondori Sholeh , Sibilia Robert , Girgla Saavia , Viswanathan Shiv K , Puckelwartz Megan , McNally Elizabeth M , Sangha Kiranpal S , Singh Rohit , Kakroo Mashhood , Jandarov Roman , Harris David , Rubinstein Jack , BECKER Richard C , sadayappan Sakthivel
Published: May 2021

Introduction:
A 25bp intronic deletion in
MYBPC3
(
Δ25bp
), present in 6% of US South Asians, is a risk allele for late onset left ventricular (LV) dysfunction and hypertrophy.

Hypothesis:
Asymptomatic
Δ25bp
carriers have detectable subclinical pathology to development of LV hypercontractility and impaired relaxation.

Methods:
To evaluate
Δ25bp
carriers for changes in cardiac function with bicycle exercise stress echocardiography and continuous cardiac monitoring, 16
Δ25bp
male carriers (51±2 years) and 10 age- and sex-matched non-carrier (NCs) controls (50±3 years) participated in this pilot study. Of 16
Δ25bp
carriers, six carried an additional pathogenic variant D389V in
MYBPC3
. Included subjects had no uncontrolled comorbidities. Regression analysis and two-way ANOVA were performed, and 95% confidence interval (CI) and p values were reported.

Results:
Baseline echocardiographic parameters as well as baseline and monitored exercise heart rate and blood pressure were similar in both groups. The estimated effect of exercise stress and genotype showed that
Δ25bp
carriers had significantly higher ejection fraction (%) (CI: 4.03±1.64; p<0.0001) and higher LV outflow tract peak velocity (m/s) (CI: 0.15±0.06; p<0.0001) in comparison to NCs. Additionally, stress-induced LV end diastolic diameter did not increase in
Δ25bp
carriers as compared to NCs with a significant difference between the groups (CI: 0.22±0.11; p=0.0002). E/A ratio, a marker of diastolic function, significantly decreased with exercise in
Δ25bp
carriers (slope: -0.002; p=0.005) but showed non-significant change in the NCs (slope: -0.0006; p=0.428). Right ventricular systolic excursion velocity s' (m/s) as a marker of right ventricle function increased similarly in both groups, although tricuspid annular plane systolic excursion (cm) increased more dramatically in carriers (slope: 0.004; p=0.0002). Sub-analysis of
Δ25bp
vs
Δ25bp + D389V
did not reveal any differences.

Conclusions:
LV hypercontractility under exercise stress conditions with evidence of diastolic impairment at high workloads is evident among asymptomatic carriers of
MYBPC3 Δ25bp
allele,

suggesting
MYBPC3 Δ25bp
as a risk allele with sub-clinical pathology prior to late onset LV dysfunction in South Asians

.
Abstract 13482: The Size of Circulating Microparticles and Cardiac Function in Patients With Cardiac Surgery
Authors: Ou Jingsong , Ma Jian , Chen Ya-Ting , Chen Chao , Li Yu-Quan , Yuan Hao-Xiang , OU Zhijun
Published: May 2021

Introduction:
We previously demonstrated that circulating microparticles (MPs) from cardiac surgery impaired vasodilation. The usages of positive inotropic drugs and the NT-proBNP levels are the important parameters representing cardiac function after cardiac surgery. However, the relationship between the size of MPs and the usages of positive inotropic drugs and the NT-proBNP levels in patients with cardiac surgery remains unknown.

Hypothesize:
The size of circulating MPs may correct with the usages of positive inotropic drugs and the NT-proBNP levels in patients with cardiac surgery.

Methods:
103 patients undergone cardiac surgery and 56 healthy subjects were enrolled. The blood was collected from healthy subjects and patients before (pre-op) and after operation 12h (post-op 12h) and 72 h (post-op 72h). The MPs were isolated by differential centrifugation. The concentration and size distribution of MPs were detected by nanoparticle tracking analysis system. The clinical data were collected and the correlation was performed between the MPs and the clinical data.

Results:
The level of MPs was increased in patients compared with healthy subjects. There was no significant difference of MPs concentration among the different time points (per-op, post-op 12h and post-op 72h) in patients. The MPs were divided into four groups according to the size (0-100nm, 100-200nm, 200-300nm and 300-400nm). The levels of “100-200nm” MPs were decreased in post-op 12h and post-op 72h groups compared with per-op group, but the levels of “200-300nm” MPs were increased after operation. In post-op12h group, the concentration of “0-100nm” MPs was negatively correlated with the NT-proBNP levels, the dose of dopamine, norepinephrine and milrinone, and the level of “200-300nm” MPs were positively correlated with NT-proBNP levels. In post-op72h group, the level of “0-100nm” MPs was negatively correlated with NT-proBNP levels, and the concentration of “200-300nm” MPs was negatively correlated with the dose of dobutamine.

Conclusion:
Our data demonstrated that the size of circulating MPs is corrected with the usages of positive inotropic drugs and the NT-proBNP levels in patients with cardiac surgery, and may predict the cardiac function after cardiac surgery.
Abstract 13501: Patent Ductus Arteriosus Catheterization Closure in Preterm Infants: A Descriptive Study of an Institutional Experience
Authors: Kim Heidi , Yallapragada Sushmita , Savani Rashmin C , Dariya Vedanta , Ullah Sana , Mangona Kate , Pirolli Timothy , Brown Larry , Reddy Surendranath V
Published: May 2021

Introduction:
A patent ductus arteriosus (PDA) in a preterm infant can lead to respiratory insufficiency and chronic lung disease as well as necrotizing enterocolitis due to systemic hypoperfusion. Recently, catheter-based PDA closure has emerged as an appealing alternative to invasive surgical ligation in preterm infants; however, evidence to support this procedure in infancy, particularly in the premature population, is still evolving.

Methods:
A retrospective chart review was conducted to collect information regarding demographics, neonatal and maternal clinical characteristics, and procedural and post-catheterization data. Inclusion criteria included infants born at <32 weeks gestational age whose PDAs were closed via catheterization at our institution between January 2017 and August 2019. Infants with critical congenital heart disease and/or lethal congenital anomalies were excluded from this study.

Results:
Twenty-seven patients were included in our study. Indications for PDA closure in our patient population included hemodynamically significant PDA on echocardiogram, difficulty weaning respiratory support, poor feeding and weight gain, and development of NEC. Median gestational age and weight were 26 weeks and 820 g (ranging from 23 to 30 weeks and 400 to 1540 g, respectively). Most infants tolerated the procedure well and without serious adverse outcomes. One infant developed an intimal flap post-catheterization that resolved without invasive intervention, and 1 infant developed a PAH crisis after PDA closure with resolution of PAH prior to discharge. Statistically significant associations were found between PDA plug closures and decreased oxygen requirements, decreased pulmonary artery hypertension, decreased diuretic requirements, and decreased vasodilator requirements by time of discharge.

Conclusions:
Successful device closures of PDAs are feasible and safe, and preliminary findings show promising outcomes without mortality or long-term morbidity following transcatheter PDA closure.
Abstract 13503: Relative Efficacy of Alirocumab, Bempedoic Acid, Evolocumab, Ezetimibe and Inclisiran Added to Statins for Reduction of Low Density Lipoprotein Cholesterol - A Network Meta-Analysis of Randomized Clinical Trials
Authors: Toth Peter P , Bray Sarah , Worth Gavin
Published: May 2021

Background:
Many patients with hypercholesterolemia and/or cardiovascular disease are unable to achieve sufficient low-density lipoprotein cholesterol (LDL-C) reduction with statins alone (or are statin intolerant). This is increasingly the case with clinical guidelines recommending that lower LDL-C levels are beneficial for patients. This network meta-analysis (NMA) assessed the relative efficacy of lipid lowering therapies (LLTs) added to statins for reducing LDL-C.

Methods:
A systematic review of randomized controlled clinical trials to May 2020 identified 48 studies for inclusion in the primary NMA. The primary NMA included studies ≥12 weeks duration in which alirocumab, bempedoic acid, evolocumab, ezetimibe, or inclisiran were added to moderate-high intensity statins (or lower intensity / no statin in statin intolerant patients). Random effects NMA was used to analyse % change in LDL-C to compare the treatment effects indirectly.

Results:
Over 12 weeks, all non-statin LLTs significantly reduced LDL-C from baseline versus placebo. Evolocumab 140 mg Q2W / 420 mg QM and alirocumab 150 mg Q2W were associated with largest LDL-C reductions, which were greater than those achieved with lower/alternative doses of alirocumab, bempedoic acid (± ezetimibe), ezetimibe and inclisiran (Table). Consistent results were observed in sensitivity analyses to address heterogeneity (excluding familial hypercholesterolemia and east Asian studies), in the subgroup NMA of studies in predominantly atherosclerotic cardiovascular disease patients, and in the statin intolerant subgroup NMA.

Conclusions:
All agents reduced LDL-C, however, the PCSK9 inhibitors evolocumab 140 mg Q2W / 420 mg QM and alirocumab 150 mg Q2W were the most effective LLT regimens for reducing LDL-C when added to statins.
Abstract 13506: Reduced Mortality After Implementation of a Multidisciplinary Pulmonary Embolism Response Team
Authors: Wright Colin M , Goldenberg Ilan , Schleede Susan , McNitt Scott , Gosev Igor , Pietropaoli Anthony , Barrus Bryan , Elbadawi Ayman , Chen Yu Lin , Mazillo Justin , Acquisto Nicole , Van Galen Joseph , Hamer Annelise , Marinescu Mark , Delehanty Joseph M , CAMERON Scott J
Published: May 2021

Introduction:
Multidisciplinary Pulmonary Embolism Response Teams (PERTs) improve the care of patients with high risk pulmonary embolism (PE). The effect of a PERT on long-term mortality has never been evaluated.

Hypothesis:
We assessed the hypothesis that PERT would improve mortality of patients with high risk PE.

Methods:
An observational analysis was conducted of patients before PERT (pre-PERT, N = 137, between 2014 and 2015) after PERT (post-PERT, N = 231, from 2016 to 2019) presenting to the emergency department of a large academic medical center with submassive and massive PE. The primary outcome was six-month mortality with univariate and multivariate analyses.

Results:
PERT was associated with a sustained reduction in Kaplan-Meier mortality estimates (Figure) through six months (six-month mortality rates of 14% post-PERT vs. 24% pre-PERT, unadjusted HR of 0.57, RRR of 43%, NNT of 10, log-rank p=0.025). A Cox proportional hazards model demonstrated no difference in mortality from diagnosis through 1 month after presentation (HR 1.11 vs pre-PERT, 95% CI 0.55-2.26, p=0.766), but confirmed a reduction in mortality 1-6 months after diagnosis post-PERT (HR 0.42 vs pre-PERT, 95% CI 0.19-0.95, p=0.037). There was a reduced length of stay post-PERT (9.1± 10.8 vs 6.5 ± 9.8 days pre-PERT, P=0.007). Time from triage to diagnosis of PE was independently predictive of mortality, and the risk of mortality was reduced by 4.6% for each hour earlier that the diagnosis was made.

Conclusions:
In conclusion, this study is the first to demonstrate an association between PERT implementation and reduction in 6-month mortality in patients with high risk PE. This effect of reduced time to PE diagnosis associated with a multidisciplinary PERT may be a mechanism for the reduction in mortality.
Abstract 13527: Inhibition of With-No-Lysine Kinase Improves Right Ventricular Function by Blunting Excess Protein O-GlcNAcylation
Authors: Prisco Sasha Z , Eklund Megan , Prins Kurt W
Published: May 2021

Introduction:
Pulmonary arterial hypertension (PAH) is caused by obstructive remodeling of the pulmonary arteries which ultimately causes right ventricle (RV) failure and death. Increased expression of the glucose membrane transporters Glut1 and Glut4 occurs in the failing RV, but the upstream regulators of these proteins are unknown. The With-no-Lysine (WNK) kinase-1, a kinase activated in low chloride conditions, promotes expression of Glut1/4 in skeletal muscle, but its regulation in the RV in PAH is unexplored. Furthermore, the relationship between WNK1 and protein O-GlcNAcylation, a glucose based post-translational modification, has not been examined.

Methods:
Immunoblots quantified the abundance of WNK1, Glut1, Glut4, and total protein O-GlcNAcylation in the RV of control, monocrotaline (MCT) rats, and MCT rats treated with a WNK inhibitor two weeks after MCT injection. Echocardiography and pressure-volume loop analysis assessed RV function and pulmonary vascular disease severity.

Results:
Treatment with WNK inhibitor improved TAPSE (2.4±0.1 vs 1.8±0.1 mm,
p
=0.0007), cardiac output (86.0±9.1 vs 52.5±5.6 ml/min,
p
=0.02), and cardiac output normalized body weight (0.26±0.03 vs 0.15±0.02 ml/min/g,
p
=0.0032). Importantly, the WNK inhibitor did not alter pulmonary vascular disease severity as there were no differences in pulmonary artery acceleration time (18.2±1.5 vs 14.2±0.9 sec,
p
=0.22), Ea (0.58±0.07 vs 0.58±0.08 mmHg/μL, p=1.00), or right ventricular systolic pressure (71.8±7.6 vs 72.0±4.0 mmHg,
p
=1.00) compared to MCT. At the molecular level, WNK1 inhibition decreased expression of WNK1 (MCT: 1.3±0.2 fold increase, MCT-WNK: 3.4±2.2 fold decrease), Glut1 (MCT: 2.7±0.9 fold increase, MCT-WNK: 1.2±0.2 fold increase), Glut4 (MCT: 1.7±0.4 fold increase, MCT-WNK: 1.0±0.2 fold increase), and protein O-GlcNAcylation (MCT: 2.4±0.7 fold increase, MCT-WNK: 1.1±0.1 fold increase).

Conclusions:
WNK inhibition normalized Glut1/4 expression and protein O-GlcNAcylation in the RV. These molecular changes resulted in improved RV function without a change in pulmonary vascular disease burden.