bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13848: Establishing an Optogenetic
in vitro
Model to Study Atrial Fibrillation Based on Human Engineered Heart Tissue
Authors: Pan Bangfen , Hansen Julius , Höppner Grit , Stüdemann Tim , Stoter Aaltje Maria Stella , Christ Torsten , Lemoine Marc D. , Foo Roger , Eschenhagen Thomas , Stenzig Justus
Published: April 2022

Introduction:
Atrial fibrillation (AF) is a type of sustained cardiac tachyarrhythmia in which the atrial rate can reach up to 300-600 beats per minute (BPM). The elucidation of the mechanisms of AF and the search for new therapeutic methods is hampered by a lack of suitable
in vitro
models. In previous studies, chronic optical tachypacing induced arrhythmia vulnerability in ventricular-like human engineered heart tissue (EHT). Here, we aimed to optimize an AF
in vitro
model based on optogenetics, EHT and a novel optogenetic pacing platform.

Methods:
Human induced pluripotent stem cells (hiPSC) stably expressing Volvox-Channelrhodopsin-1 (VChR1) were differentiated into atrial-like cardiomyocytes (CM) by treatment with 1 μM retinoic acid (RA) at the cardiac induction stage. CMs were used to cast fibrin-based 24-well format EHTs. The expression of atrial/ventricular markers was validated by qPCR, and action potential (AP) recordings with atrial-specific channel inhibitors were performed on at least one-month-old EHTs. A novel custom-designed circuit board with a programmable microcontroller and 24 RGB addressable light-emitting diodes (LED) was used for optical tachypacing. 25-30 days old EHTs were stimulated by 90 s bursts of blue light pulses (5 Hz), separated by 10 s breaks for 35-40 days. Non-paced and paced EHTs were characterized regarding contractility and gene expression.

Results:
EHTs had a high expression of atrial mRNA markers and displayed atrial-like AP. A flexible and straightforward optogenetic tool was built to make chronic tachypacing feasible. Using this novel platform, EHTs were successfully paced at 5 Hz for up to 40 days. Compared with non-paced EHTs, paced EHTs showed a different spontaneous contractility profile, higher expression of stress genes, and released more troponin I into the medium.

Conclusions:
We have successfully generated an
in vitro
model to mimic the status of atria with a high frequency (300 BPM) during AF. Paced EHTs displayed stress signs, partially resembling the changes of atria in AF. In the future, we could utilize this model to study the underlying mechanisms and assess proarrhythmic and antiarrhythmic drug effects.
Abstract 13861: Cardiac Predictors of Outcomes in Patients With Pulmonary Arterial Hypertension
Authors: Layoun Habib , Kassis Nicholas , Goyal Amit , Dong Tiffany , Saad Anas , Heresi Gustavo A , Tonelli Adriano , Kapadia Samir R , Harb Serge C
Published: April 2022

Introduction:
Pulmonary arterial hypertension (PAH) has significant anatomical, functional, and hemodynamic effects on the right heart. Yet, the prognostic value of these changes remains unclear.

Methods:
From the Cleveland Clinic Pulmonary Hypertension Registry, we included patients diagnosed with PAH between 2007-2013 who had right heart cath (RHC), transthoracic echocardiography (TTE), and cardiac computed tomography (CCT) within six months of each other. Right-sided ventricular and valvular anatomy and function were thoroughly assessed with CCT and TTE, while hemodynamics were determined by RHC. The primary outcome was a composite of all-cause mortality and hospitalization for PAH. The mean follow-up was 45 (+/- 42.4) months.

Results:
A total of 88 patients were included (mean age 55, 79% female). Among CCT, TTE, and RHC variables, RV diastolic pressure was the sole predictor of the primary outcome on multivariable analysis (HR 2.43, p=0.001) (Figure 1). When considering each outcome separately, central venous pressure and RV diastolic pressure were both predictive of death (HR 2.27, p=0.045 and 2.18, p=0.03 respectively), whereas RV diastolic pressure and pulmonary arterial mean pressure were predictors of hospitalization (HR 2.18, p=0.038 and 2.19, p=0.035 respectively) (Table 1). Tricuspid annular anatomy by CCT, and tricuspid regurgitation and RV size and function by TTE were not significantly associated with clinical outcomes.

Conclusions:
Right heart hemodynamics predict clinical outcomes in patients with PAH, while anatomic and functional characteristics do not.
Abstract 13865: Impact of Prior Aortic Aneurysm Diagnosis on Presentation and Outcomes in Stanford Type B Acute Aortic Syndromes
Authors: Barns Briana M , Khairani Candrika D , Rizzo Samantha , Pfeferman Mariana , Snyder Julia , Tristani Anthony , Piazza Gregory , Goldhaber Samuel Z , Campia Umberto
Published: April 2022

Introduction:
Acute aortic syndromes (AAS) involving the descending, but not the ascending, aorta (Stanford type B) are medical emergencies that require multidisciplinary management. Aortic aneurysms are a known risk factor for AAS. We investigated the impact of a history of aortic aneurysm on presentation and outcomes in patients with type B AAS.

Hypothesis:
We hypothesize that patients with a history of aortic aneurysm have higher in-hospital mortality rate and adverse outcomes compared to those without.

Methods:
We performed a retrospective analysis of all patients admitted with AAS to our tertiary medical center between July 2012 and October 2020. Type B AAS presentations included aortic dissection, aortic rupture, intramural hematoma (IMH), penetrating atherosclerotic ulcer, and symptomatic aneurysm. Prior history included presence of a thoracic and/or abdominal aortic aneurysm.

Results:
A total of 169 patients with type B AAS were included in our analyses. Of these, 54 (32%) had a history of prior aortic aneurysm and 115 (68%) patients did not (Table). Patients with prior aortic aneurysm were significantly older (74.3±14.6 vs. 68.7±14.1 years,
p
<0.0001), had a lower proportion of aortic dissection (33.3% vs. 50.4%,
p
<0.05) and a higher proportion of symptomatic aneurysm (27.8% vs. 8.7%,
p
<0.001) as their presentation. Similar rates of mortality (8.9% vs. 7.4%), AAS related complications, and 30-day hospital readmission were observed between patients with a prior aortic aneurysm and those without.

Conclusions:
Among patients with type B AAS, those with a history of aortic aneurysm have a lower proportion of dissection and a higher proportion of symptomatic aneurysm at presentation. However, their rates of in-hospital mortality and 30-day readmission do not differ compared to those observed in patients without a history of aortic aneurysm.
Abstract 13866: Quantity of Cardiovascular Risk Factors and Associated Outcomes in Young Women With ST-Elevation Myocardial Infarction
Authors: Yildiz Mehmet , Lantz Rebekah H , Mattingly Georgia M , Schmidt Christian W , Sharkey Scott W , Rohm Heather S , Chambers Jenny , Coulson Teresa , Henry Timothy D , Quesada Odayme
Published: April 2022

Introduction:
Despite the remarkable progress in STEMI care, the mortality rates in young women with STEMI remain high. It remains unclear whether this is related to the number of cardiovascular (CV) risk factors.

Methods:
From 2010 to 2020, we evaluated 10,441 consecutive STEMI patients, including 3,150 (30%) women enrolled in prospective Midwest STEMI Consortium registry, constituted of Minneapolis Heart Institute, Minneapolis, MN, The Christ Hospital, Cincinnati, OH, Prairie Heart Institute, Springfield, IL, and Iowa Heart Center, Des Moines, IA. We categorized baseline CV risk factors (hypertension, dyslipidemia, diabetes, smoking, and family history of CAD) in the 477 (15%) women <55 years and without previous history of CAD.

Results:
Smoking was the most common, and diabetes the least common CV risk factor. Of the 477 women, 161 (33.8%) had 0 or 1 CV risk factor, 132 (27.7%) had 2, and 184 (38.6%) had at least 3 CV risk factors. As the number of CV risk factors decreased, non-atherosclerotic STEMI etiologies -SCAD or Takotsubo syndrome- increased, as did the incidences of cardiogenic shock or cardiac arrest. There were no differences in reperfusion strategies or time among patients with 0 or more CV risk factors; however, as the number of CV risk factors decreased, patients were less likely to receive antiplatelet or statin at discharge. There was a trend toward higher death in the hospital with decreasing number of CV risk factors, but it did not reach statistical significance (p=0.075)
(Table).

Conclusions:
Young women with fewer traditional CV risk factors more often presented with non-atherosclerotic causes of STEMI and higher incidences of cardiogenic shock or cardiac arrest and had a trend toward a higher risk of in-hospital death. Thus, future epidemiological studies are needed to determine if sex-specific risk enhancers, in addition to traditional CV risk factors, have a role in risk stratification among young women for future CV events.
Abstract 13867: Performance of the Pooled Cohort Equation and Cohort Specific Approaches to Estimate Atherosclerotic Cardiovascular Disease Risk of Type 2 Diabetic Patients in the Penn Medicine Biobank
Authors: Tsao Noah , Shakt Gabrielle , Judy Renae , Damrauer Scott
Published: April 2022

Introduction:
T2D is a widely-recognized risk factor for CVD, and leads to worse CVD outcomes. However, there remains considerable heterogeneity among individuals with T2D with respect to who will develop CVD. To develop more effective strategies for risk prediction of T2D-associated heart and vascular disease, we leveraged the ASCVD Pooled Cohort Risk Equation (PCE), a cohort optimized approach and polygenic risk scores (PRS) based on various CVD traits to generate 10-year CVD risk.

Hypothesis:
We hypothesize that a cohort optimized approach as well as the addition of PRS to traditional risk factors will allow for improved identification of individuals with T2D who are at risk for CVD.

Methods:
Among our cohort of 1845 T2D patients of African and European ancestries. PRS were derived using ischemic stroke (IS) from the MEGASTROKE consortium and coronary artery disease (CAD) from CardioGRAMplusC4D and calculated in the PMBB dataset using LDPred. A cox proportional hazards model was used for time-to-event analyses within our cohort and we compared model discrimination using AUC.

Results:
The PCE demonstrated an inadequate discrimination for the study population with an AUC of 0.494 (SD = 0.002), 0.41 (SD = 0.002), 0.609 (SD = 0.004) and 0.514 (SD = 0.004) for female and male Africans and Europeans respectively. A cohort optimized approach demonstrated an AUC of 0.598 (SD = 0.002), 0.440 (SD = 0.002), 0.564 (SD = 0.004) and 0.388 (SD = 0.002) for female and male Africans and Europeans respectively.

The addition of CAD and IS PRS to the PCE demonstrated an AUC of 0.519 (SD = 0.002), 0.414 (SD = 0.002), 0.610 (SD = 0.007) and 0.505 (SD = 0.004) for female and male Africans and Europeans respectively. The addition of CAD and IS PRS to the cohort optimized approach demonstrated an AUC of 0.610 (SD = 0.001), 0.478 (SD = 0.001), 0.539 (SD = 0.007) and 0.403 (SD = 0.003) for female and male Africans and Europeans respectively.

Conclusions:
This study found that the PCE had an inadequate model discrimination across all race/gender categories, however, was improved by using a cohort specific approach and the incorporation of CAD and IS PRS. These findings support further study into the implementation of cohort specific and PRS based approaches in CVD risk prediction of T2D patients.
Abstract 13872: Atrial Fibrillation and Acute Ischemic Stroke: Evaluation of the Contemporary 2018 National Inpatient Sample Database
Authors: Sidhu Gursukhman D , Nedunchezhian Saihariharan , El Hajjar Abdel Hadi , Dhorepatil Aneesh , Dagher Lilas , Ayoub Tarek , Ferdinand Keith , Marrouche Nassir
Published: April 2022

Aims:
Atrial Fibrillation (AF) treatment in Acute Ischemic Stroke (AIS) is based on thromboembolism prophylaxis regardless AF type, and degree of atrial myopathy. We aim to investigate morbidity and mortality of persistent AF related stroke.

Methods:
Patients admitted with AIS and associated paroxysmal and persistent AF were identified in the 2018 National Inpatient Sample. The study compared in-hospital mortality, stroke-related morbidity, hospital cost, length of stay, and discharge disposition between patients with paroxysmal and persistent AF

Results:
A total of 26,470 patients were admitted for AIS with associated AF. AIS with persistent AF had a longer hospital length of stay (paroxysmal AF Mean(M): 5.7 days, Standard Deviation (SD) 6.8, persistent AF M: 7.4 days, SD 11.9, p<0.001) and in-hospital costs (paroxysmal AF M: $15,449, SD $18,320, persistent AF M: $19,834, SD $23,312, p<0.001). Indirect markers of stroke-related disability, like intracranial hemorrhage (Odds Ratio (OR): 1.9, 95% Confidence Interval (CI): 1.6-2.2), need for gastrostomy (OR: 2.1, 95% CI: 1.8-2.4), and tracheostomy (OR: 3.1, 95% CI: 2.1-4.4) were more associated with AIS and persistent AF (FIGURE 1)

Conclusion:
Persistent AF is associated with poor in-hospital stroke-related outcomes, possibly due to a higher embolic burden. The current recommendation of using only the CHA2DS2-VASc score without AF pattern needs be reevaluated. Further investigation is required to determine the impact of prevention of AF progression on stroke related morbidity.
Abstract 13879: Relationship of Serum Lipid Metabolites and Clonal Hematopoiesis of Indeterminate Potential Among 12,186 Participants of the UK Biobank
Authors: Khetarpal Sumeet A , Uddin Md Mesbah , Koyama Satoshi , Yu Zhi , Pampana Akhil , Niroula Abhishek , Gibson Christopher , Griffin Gabriel , Libby Peter , Ebert Benjamin , Natarajan Pradeep
Published: April 2022

Background:
Clonal hematopoiesis of indeterminate potential (CHIP), the expansion of leukemogenic mutations in hematopoietic stem cells in asymptomatic individuals, is an emerging age-related risk factor for blood cancers and myriad cardio-metabolic diseases. The spectrum of metabolites that may protect from or predispose to development of CHIP remains unknown.

Methods:
We obtained CHIP genotypes and measured serum metabolites among UK Biobank, a population-based study of United Kingdom residents aged 40-70 years. CHIP was also categorized by driver genes
DNMT3A
and
TET2
and presence of large CHIP clones (variant allele fraction or VAF > 10%). 152 lipid and lipoprotein metabolites were performed using NMR from blood samples. The relationship of CHIP to metabolites was assessed by multivariate linear regression adjusting for covariates of age, sex, smoking and principal components 1-10.

Results:
Among the 12,186 included UK Biobank participants with mean (SD) age 57.1 (8.0), we identified CHIP in 701 (5.75%). 313 participants with CHIP had large clones (VAF>10%), and of these, 169 had
DNMT3A
mutations and 75 had
TET2
mutations. Presence of CHIP was nominally associated with multiple measures of HDL and apolipoprotein B-containing lipoprotein metabolites. Among HDL metabolites, CHIP was associated with reductions in the percentage of HDL total cholesterol (ß = -0.09, P = 0.01), free cholesterol (ß = -0.072, P = 0.01) and cholesteryl ester (ß = -0.087, P = 0.01) and increased HDL triglyceride percentage (ß = 0.09, P = 0.01). Similar findings were observed for small, medium and large HDL particles. CHIP was also associated with decreased percentage of small LDL free cholesterol (ß = -0.089, P = 0.016) and phospholipid (ß = -0.106, P = 0.0057) and increased cholesterol ester (ß = 0.105, P = 0.0061). For VLDL, CHIP was associated with increased VLDL particle number (ß = 0.077, P = 0.035) and VLDL phospholipid percentage (ß = 0.085, P = 0.025) in the largest VLDL particles. Similar findings among HDL and VLDL metabolites were seen in those with large CHIP clones due to
TET2
mutations but not with large clones due to
DNMT3A
mutations.

Conclusions:
These results reveal novel relationships of CHIP with lipid and lipoprotein metabolites in a population-based cohort.
Abstract 13882: Increase in Reporting of Coronary Calcium: Is This a Sign of Improved Provider Awareness
Authors: Campbell Blake , Gopalakrishnan Prabhakaran
Published: April 2022

Background:
Coronary calcium (CC) is often demonstrated in Low dose chest CT scans (LDCT) performed for attenuation correction during SPECT myocardial perfusion studies (MPS). Reporting of presence or absence of CC (CC status) during MPS is variable. Absence of coronary calcium signifies lower risk for cardiovascular events.

Methods:
MPS performed in study period 1 (SP1) - first 2 months of 2018 (n=629) and study period 2 (SP2) - first 2 months of 2021 (n=611) were analyzed. Procedures without LDCT and patients with previous surgical or percutaneous revascularization were excluded. Final analysis included 487 studies from SP1 and 475 studies from SP2. LDCT images were analyzed for presence or absence of CC. MPS reports were analyzed for reporting of CC status. Provider level analysis was performed.

Findings:
During SP1, 10 cardiologists and 4 radiologists interpreted the studies. During SP2, 14 cardiologists and 6 radiologists interpreted the studies. In SP1, CC status was reported in 9.4% [cardiology 2.9% (Range: 0% - 13.8%), radiology 12.3% (0% - 26.2%)] of all studies and 16% [cardiology 5.3% (0% - 23.5%), radiology 19% (0% -40%)] of studies with CC. In SP2, CC status was reported in 70.1% [cardiology 71.7% (9.5%-100%), radiology 67.9% (0% - 100%)] of all studies and 74.4% (cardiology 78.9% (25% - 100%), radiology 66.3% (0%-100%)] of studies with CC. CC status reporting increased 7-fold (9.4% → 70.1%,
p
<0.001). The increase was more significant among cardiologists (2.9% → 71.7%,
p
< 0.001), than radiologists (12.3% → 67.9%,
p
= 0.16).

Conclusion:
Reporting of CC status during MPS was low in 2018 but improved significantly in 2021. The 25-fold increase in reporting of CC status among cardiology readers is likely related to increased awareness of significance of coronary calcium in Preventive cardiology. Routine reporting of CC noted during MPS may assist in cardiovascular risk stratification and disease prevention, especially when no perfusion defect is seen in the MPS study.
Abstract 13889: Impact Of Acute Hypoxia On Left Ventricular Relaxation Time In Healthy Men
Authors: Melnikov Vladimir N , Karmakulova Irina V , Komlyagina Tamara G , Krivoschekov Sergey G
Published: April 2022

Introduction:
The oxygen-dependence of myocardial contractility is known but it is not the case for ventricular distension in humans. It has been shown that acute ischemia causes incomplete and retarded relaxation through the decrease in intracellular pH and ATP content.

Purpose:
to verify whether hypoxemia changes the left ventricular relaxation time (LVRT).

Methods:
Overall, 37 physically active normotensive men (age 19-42 years, 20.4±2.3 yrs., M±SD) constituted the study sample. The LVRT was derived from aortic pulse wave analysis (SphygmoCor) and measured as difference between the end of systole (ejection duration point, ED, corresponding to the closure of aortic valve) and the time of peak pressure (T1), generated by LV in the aortic root and corresponding to the first incisura [LVRT,%=(ED-T1)/length of cardiac cycle*100]. Subjects inhaled hypoxic mixture with 10%O2 over 10 min for mean blood SpO2 of 80%. Associations were assessed by partial correlation (age, SBP=const.), multiple linear regression analyses (GLM option in SPSS), and t-test for dependent samples.

Results:
At baseline, the longer length of LVR was associated with lower end systolic blood pressure (r=-0.56, p<0.001). The regression model combining heart rate, augmentation pressure, and aortic-to-radial pulse pressure amplification explained 98.6% of total LVRT variation with significant effects of all covariates. Hypoxia increased LVRT from 19.0±2.8% to 23.1±4.2%, p<0.001. The response of LVRT to hypoxic exposure (range for Δ, -0.7%, +9.1%) was directly correlated with the extent of blood oxygen desaturation (r=0.53, p=0.016).

Conclusion:
The results show that cardiomyocytes retard their relaxation in hypoxic conditions. Cardiomyocytes happened to be quite sensitive to hypoxemia since even 10-min hypoxia was sufficient for elongation of the ventricular relaxation.
Abstract 14008: Three Dimensional Surface Strain Computation From Three Dimensional Echocardiographic Images of the Right Ventricle in Idiopathic Pediatric Pulmonary Hypertension
Authors: Kundu Priyamvada , Jone Pei-ni , Hunter Kendall S
Published: April 2022

Introduction:
Right Ventricular (RV) dysfunction is the primary aspect of acute right ventricular failure, commonly realized in pulmonary arterial hypertensive (PAH) patients. As a standard clinical assessment for PAH, echocardiographic strain provides a mechanical measure of ventricular deformation during RV contraction. Current strain computation via 2D echo is limited in that imaging and strain are confined to a 2D plane, and thus the technique is unable to fully visualize the asymmetrical deformation of the RV. We believe 3D surface (3DS) strain, obtained from 3D echo (3DE) will overcome this limitation and more thoroughly evaluate myocardial mechanics.
In this initial work, we hypothesize that end-systolic 3DS longitudinal and shear freewall strain group means computed from 3DE-cardiac data of the RV will differ between healthy and PAH patient groups.

Methods:
3DS strain (longitudinal, circumferential, shear; principal strains, principal angle, and max shear) was computed on the RV freewall at end-systole with finite element analysis post-processing techniques from RV surface meshes obtained from 3DE from 10 normal children and 43 children with idiopathic PAH.

Results:
3DS longitudinal and circumferential strain group means were significantly different (p<0.0001, p=0.0002, respectively), and the 3DS shear strain mean difference approached significance (p=0.0532). Further, the 3DS max and min principal strain group means were also different (p=0.0001, p<0.001, respectively), as were the max shear strain group means (p=0.0275), while the group mean difference of the principal strain angle approached significance (p=0.1055).

Conclusions:
These results suggest that 3DS strain is a promising approach to strain computation with potential to yield more mechanical knowledge of different segments of RV dysfunction. Future work should be directed in the evaluation of focused regional strain specific towards RV dysfunction and evaluate for prognosis.
Abstract 14012: Trends of Cannabis Use Disorder and Its Impact on Outcomes of Acute Ischemic Stroke: 2007-2018
Authors: Kurra Nithin , Cheriyan Renu , Munonye Ifeanyi , Patel Krupa , Desai Saral , Roy Ntasha , Ali Ahmed M , Theli Abhinay , Patel Achint , Lunagariya Abhishek
Published: April 2022

Background:
Cannabis is one of the most extensively cultivated illicit drugs internationally. Its legalization and decriminalization in some states of the U.S. has increased its usage. Despite its widespread use, cannabinoid-related cerebrovascular disease is underreported. There are contradicting studies regarding the risk of Acute Ischemic Stroke (AIS) and its outcomes among cannabis users.

Hypothesis:
Our analysis estimates concurrent Cannabis Usage Disorder (CUD) trends among AIS patients and its impact on AIS outcomes.

Methods:
Study cohort was derived from the Nationwide Inpatient Sample (NIS) for the years 2007-2018. Hospitalizations due to AIS in the age group of 18-49 were identified using previously validated ICD-9-CM/ICD-10-CM codes. Cochran Armitage trend test and multivariable survey logistic regression modeling were then utilized to analyze temporal trends, predictors, and outcomes.

Results:
Out of a total 406,987 hospitalizations due to AIS from 2007-2018, 19,614 (4.82%) had concurrent CUD. AIS hospitalizations with concurrent CUD have increased from 3.3% in 2007 to 6.6% in 2018 with a yearly increase of 10% (OR 1.1; 95%CI 1.1-1.1; p<0.01). In multivariable regression analysis, age group 18-34 (OR 2.5; 95% CI 2.3-2.7; p< 0.01); male (OR 1.5; 95%CI 1.4-1.6; p<0.01), African American (OR 2.1; 95% CI 1.9 -2.2, p<0.01), lower socio-economic group (OR 1.3; 95% CI 1.2-1.5, p<0.01), West region (OR 1.5; 95% CI 1.3-1.7, p<0.01), Weight loss (OR 1.3; 95% CI 1.1-1.6, p=0.01), Depression (OR 1.2; 95% CI 1.1-1.3, p =0.001) and other psychiatric disorders were associated with concurrent CUD among AIS patients. After adjusting with confounding factors, CUD was not associated with higher in-hospital mortality (OR 1.0; 95% CI 0.9-1.1, p=0.21) and discharge to facility.

Conclusion:
Our results show that between 2007 and 2018, hospitalizations due to AIS with concurrent CUD has doubled. This association is significantly higher among 18-34 age group, males, African American, Western US and with concomitant psychiatric disorders. However, CUD was not associated with poor outcomes in AIS. Our study highlights underlying demographic trends and emphasizes the need for further studies to identify the causal association of cannabis use and AIS.
Abstract 14016: Sex-Related Differences in Type A Acute Aortic Syndromes
Authors: Khairani Candrika D , Barns Briana , Rizzo Samantha , Snyder Julia , Pfeferman Mariana , Piazza Gregory , Goldhaber Samuel Z , Campia Umberto
Published: April 2022

Introduction:
Acute aortic syndromes (AAS) involving the ascending aorta (Stanford type A) are medical emergencies that require multidisciplinary management. Limited data exist on sex differences in presentation, management, and outcomes of patients with type A AAS. We aimed to assess sex-related differences in patients with type A AAS.

Methods:
Retrospective analysis of all patients admitted with AAS to our tertiary academic medical center between July 2012 and October 2020. Type A AAS presentations included aortic dissection, intramural hematoma, and aortic rupture.

Results:
Of 159 patients presenting with type A AAS, 55 (34.6%) were women and 104 were men (65.4%). Women were older than men (74.3±13.4 vs. 60.4±14.9 years, p<0.001). The most common cardiovascular risk factor both in men and women was diagnosed or self-reported hypertension (76.0% and 89.1%, respectively). Aortic rupture occurred at higher rates in women (16.4% vs. 5.0%, p=0.02), whereas aortic dissection occurred at higher rates in men (88.1% vs. 69.1%, p=0.004). Women were less likely to undergo surgical intervention than men (63.6% vs. 87.1% p=0.001). In-hospital complications and surgical mortality occurred at similar rates in both sexes. In-hospital mortality was higher in women than in men (30.9% vs. 15.8%, p=0.03). After adjusting for age, sex was not independently associated with mortality (unadjusted OR 2.35, 95% CI 1.07-5.14 vs. adjusted OR 1.08, 95% CI 0.44-2.67) (Table).

Conclusions:
While women with type A AAS had higher rates of aortic rupture and in-hospital mortality than men, sex was not independently associated with mortality. Further investigation is needed to better understand the impact of sex differences in type A AAS.
Abstract 14017: Use of Cephalothin Prophylaxis in Artificial Cardiac Stimulation Procedures
Authors: Sa Isabella , Sa Joceline , Sa Gabriella , Melo Sylton
Published: April 2022

Introduction:
Antibiotic prophylaxis for artificial cardiac stimulation procedures is already established in clinical studies, however, it can be used in different prophylactic schemes and with different costs.

Objective:
To evaluate the effectiveness of cephalothin as a prophylactic antibiotic in artificial cardiac stimulation procedures. Secondly, to compare the cost of cephalothin with other well-established prophylaxis antibiotics in these procedures.

Material and Methods:
We assigned patients between 18 to 103 years old who had clinical recommendations for pacemaker implantation. In this retrospective study, we included all permanent artificial cardiac stimulation procedures with cephalothin prophylaxis realized between January 2011 and December 2020 at Hospital do Coração in Natal, Brazil. The prophylactic scheme was an intravenous infusion of cephalothin 2g administered 30 minutes before single-chamber, double-chamber implantation, and replacement pacemakers.

Results:
We performed 2,162 procedures and registered seven cases of postoperative infections (0.32%) after procedures. Besides, cephalothin is less expensive (U$1.35/1g - total U$5,887.81), compared to other well-established and commonly used antibiotics prophylaxis as cefazolin (U$2.91/1g - total U$12,596.00) or cefuroxime (U$7.24/750mg - total U$31,310.54).

Conclusion:
Cephalothin is effective in preventing postoperative infections in artificial cardiac stimulation procedures and has a better cost/dose than other well-established prophylaxis antibiotics.
Abstract 14037: A Shorter Myosin Light Chain Kinase 3 Isoform Maintains Myosin Light Chain 2 Phosphorylation but Does Not Attenuate the Dilated Cardiomyopathy Seen in C57BL/6N Mice
Authors: Williams Jack , paudyal anju , Stewart Michelle , Cutillas Pedro , Cox Roger D , Tinker Andrew , Metherell Lou
Published: April 2022

Introduction:
The C57BL/6J and C57BL/6N are two of the most commonly used mouse strains in biological research. We recently discovered C57BL/6N males develop a modest dilated cardiomyopathy (DCM) by 12 months, which is absent from the closely related C57BL/6J. We identified a variant (Chr8:85365179A>T, c.-5T>A) in myosin light chain kinase 3 (
Mylk3
) in the 5’ UTR of the primary isoform resident to C57BL/6N substrains, which abolishes translation of this isoform. Myosin light chain 2 (MYL2) is the primary target of MYLK3, and its phosphorylation is vital for survival.

Hypothesis:
Loss of MYLK3 expression alters phosphorylation of key cardiac proteins.

Results:
Surprisingly, we found no difference in MYL2 phosphorylation by western blot between C57BL/6N and C57BL/6J hearts, at any of the reported target residues. Phosphoproteomics corroborated this, but highlighted significantly different phosphorylation at a number of phosphosites in other proteins linked to cardiomyopathies and cardiac development, particularly a reduction of a number of residues in ACTN2. We also detected peptide sequences that mapped to the C-terminus and middle of MYLK3 in the C57BL/6N. Western blotting with a C-terminal specific antibody revealed expression of a shorter isoform, present at lower levels in both strains, that is unaffected by the variant due to a distinct N-terminus. Using this antibody in IHC showed similar spatial expression of MYLK3 in hearts from both strains, localizing to the Z-disc, although the expression was much lower in the C57BL/6N presumed to be due to lack of the more abundant full-length isoform. Using immunoprecipitation, we found both isoforms bound to MYL2
in vivo
and
in vitro
, and both were capable of phosphorylating MYL2
in vitro.
However, the shorter isoform was not as readily bound to alpha-actinin-2 (ACTN2), a key sarcomeric protein that is reported to bind full-length MYLK3 isoform by its N-terminus.

Conclusions:
This data indicates loss of full-length MYLK3 causes DCM via a MYL2-independent mechanism, possibly due to lack of phosphorylation of alternative target(s), such as ACTN2. The expression of the shorter MYLK3 isoform in C57BL/6N mice may explain the persistence of MYL2 phosphorylation in these mice and enable their survival.
Abstract 14039: Myocardial Work Efficiency is Reduced in Nonobstructive Hypertrophic Cardiomyopathy Patients With Exercise-Induced Symptoms
Authors: Mital Rohit , Fohtung Raymond B , Lu Dai-Yin , Ramsis Ramsis K , Bibby Dwight , Schiller Nelson B , Beutner Katherine , Abraham M. R , Abraham Theodore
Published: April 2022

Introduction:
Despite normal ejection fraction, nonobstructive hypertrophic cardiomyopathy (nHCM; rest and provoked gradients <30 mmHg) is associated with high rates of angina, arrhythmias and heart failure symptoms, as well as abnormalities of echo-based myocardial strain. Using Myocardial Work (MW) analysis, we investigated the potential mechanisms contributing to exercise-induced symptoms in nHCM.

Methods and Results:
Using validated methods (EchoPAC), longitudinal strain and non-invasive blood pressure were integrated to generate normalized left ventricular pressure curves and pressure-strain loops to derive global and segmental MW data in 14 nHCM patients with normal ejection fraction (>55%) who underwent treadmill stress testing. Global myocardial work efficiency was expressed as the ratio of global constructive work over the sum of global constructive and wasted work. A total of 9 of 14 patients reported symptoms during exercise (chest pain, dyspnea, and palpitations) and this group had reduced global myocardial work efficiency compared to those without exercise-induced symptoms (85% vs 90%, respectively, p = 0.04, Figure 1). No statistical differences were noted in age, % men, maximal wall thickness, ejection fraction, E/e’ ratio, resting blood pressure, resting global strain and exercise performance between symptomatic and asymptomatic patients.

Conclusions:
Despite similar ventricular morphology, resting mechanics and exercise performance, nHCM patients with symptoms during exercise have worse myocardial work efficiency. Our data suggest that mechanisms potentially impacting global strain may be distinct from those affecting myocardial work efficiency. Understanding these differences may offer insights into management of exercise-induced symptoms.
Abstract 14040: Hospital Volume-Outcome Relationship After Primary Percutaneous Coronary Intervention: A Contemporary Nationwide Analysis
Authors: Elbadawi Ayman , Elgendy Islam Y , Omer Mohamed , PANIAGUA DAVID , DENKTAS ALI E , Jneid Hani
Published: April 2022

Introduction:
There is paucity of data on the relationship between hospital procedural volume and outcomes of primary percutaneous coronary intervention (PCI) procedures in the past decade.

Methods:
We queried the National Inpatient Sample database (2010-2016) for hospitalizations undergoing primary PCI for STEMI. Hospitals were divided into 3 groups: low-volume (<36 primary PCI/ year), moderate-volume (36-72 primary PCI/year) and high-volume (>72 primary PCI/ year). The main outcome was in-hospital mortality.

Results:
The analysis included 694,505 hospitalizations for primary PCI. There were 329,878 (47.5%) primary PCI procedures performed at low-volume hospitals, 224,317 (32.3%) at moderate-volume, and 140,223 (20.2%) at high-volume hospitals. Compared with high-volume hospitals, low-volume hospitals were associated with higher in-hospital mortality in the unadjusted model (5.3% vs. 4.8%, odds ratio [OR] 1.10; 95% confidence interval-CI 1.02-1.18, p=0.01) and on multivariable analysis (adjusted-OR 1.15; 95%CI 1.04-1.27, p=0.01). There was no difference between moderate-volume and high-volume hospital in unadjusted analysis (5.1% vs. 4.8%, OR 1.07; 95%CI 0.99-1.15, p=0.11) and on multivariable analysis (adjusted-OR 1.08; 95%CI 0.97-1.20, p=0.17).

Conclusions:
This nationwide analysis showed that low-volume hospitals are associated with higher in-hospital mortality after primary PCI compared with high-volume hospitals even in recent years. The current threshold set by national guidelines for primary PCI hospitals remains valid in contemporary practice.
Abstract 14044: Virtual Teaching Kitchen: A Feasibility Study of a Nutrition Intervention for Patients With Food Insecurity and Metabolic Disease
Authors: Rajendran Iniya , Weinstein Olivia , Patel Preya , Lambert Paige , Quintiliani Lisa M , Hamburg Naomi
Published: April 2022

Introduction:
Food insecurity is a well-established risk factor for cardiometabolic conditions. The objective of this study is to examine the feasibility and acceptability of a virtual teaching kitchen-based intervention to promote healthful food intake, cooking skills, and motivation to make dietary changes.

Method:
We conducted a single-group study among patients with metabolic syndrome and food insecurity. The intervention consisted of four classes delivering dietary education promoting healthy food intake, diet strategies, and practical cooking skills, facilitated by a physician and a registered dietician chef. An internet-capable tablet was provided for remote participation via the zoom platform. Interviewer-administered surveys measured food intake and internal motivation via Likert scale screeners at baseline and at immediate post-intervention time points. Interviews were conducted to explore acceptability.

Results:
Of 100 participants invited, 22 were recruited and 10 attended the intervention. Mean age was 61.2 years, nine were female, nine self-identified as Black, and two were Hispanic. Mean BMI was 32.7, all ten participants had hypertension, eight had both diabetes and obesity and seven had hyperlipidemia. Mean attendance per class was seven and five attended all four sessions. From baseline to post-intervention, there was a significant increase in consumption of low-fat milk (0.14 to 0.50, p=0.02), whole grains (0.28 to 0.99, p=0.01), breakfast (0.37 to 1.60, p=0.002) and home cooking (1.09 to 1.88, p=0.04). Internal motivation score was high at baseline and unchanged at follow-up (5.6 to 5.9, p=0.9). Qualitative analysis revealed the following themes: Increase in knowledge of healthy recipes; Barriers to healthy eating including competing household and childcare responsibilities; and Convenience of a virtual group while interacting with group members.

Conclusions:
Our virtual nutrition education intervention addressing cardiometabolic disease in a safety net hospital was deemed feasible and acceptable. Participants made modest changes to their diet. Future directions include measuring health outcomes and primary and secondary prevention of cardiovascular disease.
Abstract 14046: Psychosocial Impact of Risk Mitigation Strategies and Shielding From COVID-19 in Adults and Children With Early-Onset Neuromuscular Disease and Their Families
Authors: Spurr Lydia , Tan Hui-leng , Wakeman Ruth , Chatwin Michelle , Simonds Anita
Published: April 2022

Introduction:
Patients with early-onset neuromuscular diseases (NMDs) were considered clinically vulnerable to COVID-19 due to assumptions that treatments e.g. corticosteroids, or complications e.g. pre-existing respiratory failure or cardiac disease would increase risk. In the UK, most were advised to ‘shield’ and strictly limit social contact, however it is poorly understood how patients and families approached and responded to this.

Methods:
In-depth questionnaires specifically designed to meet research aims were completed by telephone between September 17
th
and December 31
st
2020 by NMD patients or their parent. Open and closed questions enabled a) quantitative analysis and b) thematic analysis to evaluate reasoning and psychosocial impact.

Results:
40 questionnaires were completed: patients were 70% male, aged 2 to 48 years with NMDs e.g. muscular dystrophies, spinal muscular atrophy. 80% (n=32) had long-term non-invasive or tracheostomy ventilation; 20% (n=8) had cardiac involvement. Strict adherence to shielding was initially reported: this included temporary cessation or reduction in external care support in 68% (n=27), leading to increased parental care. Shielding measures were often relaxed due to 1) official guidance, 2) evidence of less severe outcomes in children and NMDs, and 3) unsustainability of limited social contact. Anxiety, fear and worry were the most frequently reported emotions, but level and pervasiveness fluctuated. 75% (n=30) remained “extremely” or “very” worried about risk of COVID-19 to the patient’s health. Concern about hospital attendance during the pandemic and anxiety regarding perceived lack of capacity or access to Intensive care were common. Virtual healthcare access, experienced by 97.5% (n=39), was seen as positive, largely as an interim measure, but was less useful where examination or tests were required.

Conclusions:
Measures to reduce transmission of COVID-19 have disproportionately affected NMD patients and their families. For most, negative psychosocial impacts have and will continue to improve, particularly due to the success of the vaccination programme. Patients and carers require access to support and up-to-date information to minimise risk of infection and psychological burden.
Abstract 14050: Characteristics of Extracellular Vesicle miRNAs in the Breast Milk
Authors: Cho Young-eun , Vorn Rany , Crouch Keith , Narayanaswamy Janhavi , Chang Changgee
Published: April 2022

Introduction:
An increasing number of obese mothers is a rising issue that may negatively impact the overall benefit of breastfeeding. Extracellular vesicles (EVs) in breast milk are important mediators transferring biological molecules of mothers to children, because EV-miRNAs can survive in the stomach and then might be internalized into gut epithelial cells. In this study, we examined breast milk EV-miRNAs to determine the impact of the mother’s pre-pregnancy BMI on the EV-miRNA profiles.

Methods:
We recruited healthy nursing mothers who delivered a singleton baby in the past 6 months. Mothers pumped breast milk after 1-hour fasting and froze them. EVs were isolated from breast milk with ultracentrifugation. EV characteristics were examined by flow cytometry using 39 different EV markers. A total of 800 miRNAs were screened using a human miRNA panel (NanoString diagnostics, WA). Differential expression analysis was performed using DESEQ2.

Results:
We included 27 nursing mothers; the mean age was 31.1±7.6 years old, and 92% were Caucasian. All mothers breastfed their children and 22% of mothers supplemented with formula. Mean pre-pregnancy BMI was 21.6±2.0 kg/m
2
in the lean group (BMI<25kg/m
2
, n=17), and 29.1±4.5 kg/m
2
in the overweight/obese group (BMI≥25kg/m
2
, n=10). Besides BMI, all other demographics were not significantly different between groups. Breast milk EVs expressed not only general EV markers including CD9, CD63, and CD81, but also CD14, CD24, CD133/1, HLA-DRDPDQ and CD326. The most highly expressed marker is CD326 showing more than 2 times higher intensity than the general EV markers. Marker profiles were not different between groups. After normalization with housekeeping genes and spike-in controls, we obtained 10 differentially expressed miRNAs in the overweight/obese group (p<0.05 cut-off). Among those, miR-490-5p, miR-139-3p, and miR-291a-3p were the top 3 deregulated miRNAs downregulated in the overweight/obese group with a fold change >1.5.

Conclusion:
We found (1) CD326 as a breast milk EV marker, and (2) deregulated miRNAs in the overweight/obese mothers’ breast milk. Our findings will provide the opportunity to improve the quality of breast milk which ultimately promotes the children’s growth and health.
Abstract 14056: Evaluation Of A Non-invasive Left Ventricular Pressure-volume Loop Approximation Method Based On Arterial Blood Pressure Values And Cardiac MRI
Authors: Liu Jing , Pahlevan Niema M
Published: April 2022

Introduction:
Left ventricle (LV) pressure-volume loop (LVPVL) is an informative manifestation of LV mechanical dynamics. Seemann et al. (Circulation: Cardiovascular Imaging. 2019;12(1): e008493) proposed a novel non-invasive LVPVL approximation method using brachial blood pressure and cardiac MRI with the double-Hill model characterizing the time-varying LV elastance. However, their clinical validation was performed on a small population with a significant age difference between the control and HF groups.

Methods:
We evaluated the noninvasive LVPVL method on the iPhone-HMRI study cohort that includes non-HF (N = 102) and HF (N =25) participants. (Pahlevan et al. Critical Care Medicine ,2017 PMID: 28441235) Mean[range] of age (years) were 53[20-92] and 55[26-88] for the non-HF and the HF groups, respectively. Stroke work, potential energy, external power, energy per ejected volume, contractility, and LV efficiency from the estimated loops were compared between the non-HF and HF groups.

Results:
The estimated LVPVLs for HF group yielded significantly higher mechanical potential energy and energy per ejected volume, but significantly lower ventricular efficiency and contractility (p<0.0001). There were no significant differences between groups for stroke work (p=0.09) and mean external power (p=0.86).

Conclusions:
Our results with an age-matching control group agree with the previously reported results. However, since this method uses a fixed guesses of LV end-diastolic pressure, it is suspected that the resultant estimated LVPVL cannot effectively characterize the variation along the pressure axis and the loop-area for features such as stroke work and mean external power. Improvements are needed to leverage hemodynamic information in arterial pressure waveforms (i.e., carotid) to enhance the sensitivity of such non-invasive LVPVL determination based on time-varying LV elastance model and arterial waveforms measured using tonometry.
Abstract 14059: Lycopene Reduces Formation of Cholesterol Crystals and Accelerates Their Dissolution
Authors: Petyaev Ivan M
Published: April 2022

Introduction:
Cholesterol crystals are one of the main culprits behind the rupture of atherosclerotic plaque and resultant thrombosis, the process responsible for the development of heart attack and ischemic stroke, the world’s leading causes of mortality. Today there are no drugs or treatment able to target these crystals.

Hypothesis/Objectives and Methods:
Effect of lycopene on the growth of cholesterol crystals was investigated. A study was also made on the effect of this carotenoid on the dissolution of already formed cholesterol crystals
in vitro
and in human atherosclerotic plaques.

Results:
It was found that lycopene was directly able to disrupt, slow down and facilitate the reversal of the cholesterol crystallisation process. In
in vitro
experiments, lycopene delayed the time of the beginning of the process by 8 fold and its rate of this process itself by 5 fold. In addition it was able to reduce the cholesterol mass involved into crystallisation by 60%, fig. 1. Even when the cholesterol crystals were formed in the presence of lycopene their size was significantly smaller than when the crystals grew undisrupted, fig. 2. This effect could be observed in a ratio of 1 molecule of lycopene to 1,000-10,000 molecules of cholesterol, which indicates that these two molecules can create a thermodynamically favourable complex, which triggers a long-range ordering transition in their folding.

Conclusion:
The presented findings provide a sound rationale for future studies of lycopene on its potential prevention of cholesterol crystal formation and facilitation of their disassembly in patients with clinical complications of atherosclerosis.