bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11287: Trends in Pulmonary Embolism Mortality Rates by Age Group in the United States, 1999-2019
Authors: Cash Ayla , Minhas Abdul , NAZIR SALIK , Ariss Robert W , Gupta Rajesh
Published: March 2022

Introduction:
Acute pulmonary embolism (PE) is a major cause of mortality in the United States. Recent reports indicate that PE-related mortality rates have increased among individuals 25-64 and 65-79 years old and plateaued among individuals ≥80 years old. A narrowly focused and clinically meaningful age group analysis is necessary.

Methods:
Death certificate data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database were examined to determine all-cause PE mortality trends from 1999 to 2019 among adults 25-39, 40-54, 55-69, 70-84, and ≥85 years old. The crude death rates for individual years were calculated by dividing the number of PE-related deaths by the corresponding population. Annual percentage change (APC) was calculated to determine trends.

Results:
Among individuals 25-39 years old, the death rate increased from 1.76 to 2.01 (APC 0.7 [95% confidence interval (CI) 0.2 to 1.1]) between 1999 and 2014 and continued to increase from 2.01 to 2.42 (APC 4.1 [95% CI 1.8 to 6.5]) between 2014 and 2019. Among those 40-54 years old, the death rate increased from 5.7 to 7.46 (APC 2.0 [95% CI 1.6 to 2.5]) between 2007 and 2019. Among those 55-69 years old the death rate increased from 15.64 to 18.53 (APC 2.2 [95% CI 1.9 to 2.5]) between 2010 and 2019. Among those 70-84 years old the death rate decreased from 49.46 to 43.96 (APC -0.7 [95% CI -0.8 to -0.5]) between 1999 and 2019. While death rate among those older than 85 decreased from 112.31 to 100.53 (APC -1.3 [95% CI -1.9 to -0.7]) between 2007 and 2016, the death rate among this cohort increased non-significantly between 2016 and 2019.

Conclusions:
Despite significant improvements in PE risk stratification and clinical management, recent PE related mortality rates increased significantly among those younger than 69 years old. The APC in mortality was highest among those 25-39 years old. Among individuals older than 70 years old, recent death rates decreased or plateaued.
Abstract 11300: Identification of Two Distinct Phenotypes Among Hospitalized Covid-19 Patients Using Latent Class Analysis
Authors: Teng Catherine , Li Pengyang , Liu Qi
Published: March 2022

Introduction:
COVID-19 pneumonia is a heterogeneous disorder with a complex pathogenesis. Underlying subgroups may exist among patients who are admitted to the hospital with COVID-19 infection.

Methods:
We reviewed the charts of adult patients who were hospitalized primarily for COVID-19 at Greenwich Hospital. We performed latent class analysis using variables based on patient demographics (age, sex, race, and body mass index), comorbidities (hypertension, diabetes, coronary artery disease, chronic heart failure, chronic kidney disease, neurological disease, and pre-existing respiratory disease), laboratory results, and treatment information (medications received during hospitalization, hospital length of stay, maximized oxygen requirement, and requirement for intubation).

Results:
Two phenotypes were identified: C1 and C2. C1 (n=193) included older individuals with a higher mortality rate (25.4% vs 8.97%, p<0.001) and more comorbidities such as hypertension (88.6% vs 22.8%, p<0.001), coronary artery disease (32.1% vs 0.0%, p<0.001), chronic heart failure (20.7% vs 0%, p<0.001), diabetes mellitus (38.3% vs 17.6%, p<0.001), chronic kidney disease (25.4% vs 2.8%, p<0.001), pre-existing respiratory disease (24.9% vs 11.0%, p=0.004), and pre-existing neurological disease (32.1% vs 3.5%, p<0.001). C2 (n=290) consisted of individuals who were younger (53.7 years vs 79.5 years, p<0.001), more likely to be obese (40.3% vs. 28.0%, p=0.007), mostly male (70.3% vs 52.3%, p<0.001), and mostly non-white (69.7% vs. 28.5%, p<0.001), with higher levels of inflammatory markers such as C-reactive protein (18.3±43.4 vs. 10.7±13.7 mg/L, p=0.006) and alanine aminotransferase (209±512 vs. 96.2±204 U/L, p=0.001).

Conclusions:
Using latent class analysis, we identified two clinical phenotypes of patients who were admitted to the hospital for COVID-19. Our findings may reflect different pathophysiologic processes that lead to moderate to severe COVID-19 and may be useful in the identification of treatment targets and the selection of patients with severe COVID-19 disease for future clinical trials.
Abstract 11301: Comparing All-Cause to Procedure-Related Mortality in Cardiac Implantable Electronic Device (CIED) Lead Removals: A Systematic Review
Authors: Herman Josh E , Somanader Deborah , Ishaq Laith , Abdelaal Ahmed , Mehra Vrati , Ramendra Rayoun , Morris Andrew
Published: March 2022

Introduction:
Infection is a serious complication in patients with cardiac implantable electronic devices (CIEDs). Infection of the generator pocket, systemic bacteremia and lead-related or suspected endocarditis are absolute indications for device removal. While previous studies have reported infection as a major risk factor for mortality, it is unclear what proportion is related to complications of infection or the CIED lead removal procedure itself.

Objective:
We have conducted a systematic review looking at all-cause in-hospital mortality, intraprocedural, and procedure-related mortality in CIED lead removals and have done a subanalysis specifically exploring removals for infectious indications.

Methods:
A search was performed of studies published between January 1, 2000-August 29, 2019 indexed on Medline, EMBASE and Cochrane. Inclusion criteria were: (a) transvenous removal of ICD, pacemaker or CRT device leads, (b) Age≥18, (c) n>100 patients. Exclusion criteria were: (a) generator only procedures, (b) planned surgical extractions, (c) data prior to 2000. From these studies, we further selected papers containing mortality data in which all subjects had infectious indications for removal, or papers with infectious only cohorts of n>100 with mortality data.

Outcomes:
All-cause mortality during index hospitalization, intraprocedural mortality, procedure related mortality.

Results:
2307 abstracts were screened after de-duplication resulting in 164 papers for full text review. Of these 164, 8 papers were selected for analysis based on our inclusion criteria. 7 reported periprocedural/mortality during index hospitalization which ranged from 1.47-7.20%; median 4.98% (IQR 2.74-5.69%). 4 studies reported intraprocedural mortality which ranged from 0-0.69%; median 0.10% (IQR 0.00-0.32%). and 6 reported procedure related death which ranged from 0-0.72%; median 0.50% (IQR 0.10-0.67%).

Conclusions:
Mortality after CIED lead removal is high in patients presenting with infection, however intraprocedural mortality and death directly related to the removal procedure remains low.
Abstract 11307: Meta-Analysis Evaluating Dapagliflozin in Heart Failure Reduced Ejection Fraction: A Focus on Left Ventricular Remodeling
Authors: Prasad Rohan M , Mujer Mark T , Salam Mohammad Fahad , Al-abcha Abdullah , Qutrio Baloch Zulfiqar Q , Abela george
Published: March 2022

Introduction:
Through an unknown mechanism, anti-diabetic sodium-glucose cotransporter-2 inhibitors have been shown to be effective in patients with heart failure reduced ejection fraction (HFrEF). Specifically, dapagliflozin significantly decreased the risk of cardiovascular death and hospitalization for heart failure. However, the effects on left ventricular remodeling have not been well reported or analyzed.

Methods/Results:
We conducted a meta-analysis of all randomized controlled trials that reported left ventricular remodeling outcomes in patients with HFrEF comparing dapagliflozin versus placebo. The outcomes in this study were analyzed as changes in values compared to baseline levels. Statistical analysis was conducted using Review Manager 5.4. Two-sided p values of <0.05 were considered as statistical significance. A total of 254 patients with a median-weighted follow-up duration of 13.13 months were included amongst four RCTs. Heterogeneity was low-high across the trials (0-85%). Stroke volume significantly favored the dapagliflozin arm (mean difference 1.85, 95% confidence interval 0.10 to 3.60, p=0.04, I
2
=0%). However, left ventricular mass index, left atrial volume index, left ventricular end systolic volume, left ventricular end diastolic volume, and E/e’ were determined to be insignificant between the dapagliflozin and placebo arms. The first outcome was assessed by cardiac magnetic resonance imaging, while the former were seen on echocardiograms.

Conclusion:
This meta-analysis illustrates that dapagliflozin significantly increased SV in HFrEF patients, but had an insignificant effect in the other left ventricular remodeling outcomes. One limitation of this meta-analysis is low power due to only a few trials in the literature. Therefore, further trials with larger sample size and longer follow-up periods should be conducted to determine the dapagliflozin’s outcome on left ventricular remodeling in patients with HFrEF.
Abstract 11318: Countering the Impact of Covid-19 on Fellow Transesophageal Echocardiogram Education in a Tertiary Academic Program
Authors: Elhamdani Adee , Doyle Mark , Gajjar Kushani , Pyle Daniel , Hughes-Doichev Rachel A , Biederman Robert W
Published: March 2022

Introduction:
TEE’s are an essential component of cardiology fellowship education. At our institution, COVID peaked twice in 2020. The first peak showed a drop in total fellow TEE’s. To counter this decline, the use of personal protective equipment (PPE) and COVID testing patients requiring TEE’s were implemented to maintain patient care and ensure the safety of health personnel. We analyzed the differences in fellow TEE’s during the second COVID wave compared to the first to determine if these interventions prevented a decline in fellow TEE’s.

Methods:
The monthly number of TEE’s performed by fellows on core TEE rotations was plotted for the year 2019, prior to the COVID pandemic. For the data set, a linear line was fit to account for the variation of studies read over the year. This linear variation was subtracted from the monthly totals to remove seasonal variation. The degree of variation was taken as the standard deviation (SD) for 2019. The 2020 data was processed using the predictions for 2019 and the upper and lower limits of variation were taken as three times the SD of the 2019 data.

Results:
Using the 2019 TEE data (Figure 1A), the linear seasonal variation line was created and used to account for variations in the 2020 TEE data (Figure 1B). After accounting for seasonal variation, a significant decline is noted, indicated by the red dot, in the number of fellow TEE’s during the month of April, the first peak (Figure 1C). Institutional guidelines for PPE and COVID testing were put in place in June 2020 and December 2020. After implementation, fellow TEE numbers improve back to baseline and remain consistent even through the December peak (Figure 1C).

Conclusions:
Our data demonstrates the value of PPE and COVID testing prior to TEE’s can help maintain fellow education during a pandemic while ensuring the safety of fellows, faculty, and technicians. COVID brings uncertainty to the healthcare field and these systems will allow for maintenance of both fellow education and patient care.
Abstract 11322: Role of Centhaquine (lyfaquin
®
) in the Protection of Renal Tissues After Acute Kidney Injury
Authors: Ranjan Amaresh , Briyal Seema , Zhang Zhong , Gulati Anil
Published: March 2022

Background:
Acute Kidney Injury (AKI) is frequently associated with an in-hospital complication of sepsis, heart conditions, hemorrhagic shock, and surgery. However, at present, no specific drug to treat AKI is available. Centhaquine (Lyfaquin
®
) is a safe and effective first-in-class resuscitative agent for hypovolemic shock. We are investigating whether centhaquine could protect kidneys from acute injury during hypovolemic shock.

Hypothesis:
AKI is known to be associated with shock-related morbidity and mortality. We hypothesize that centhaquine would have a direct effect on alleviating the AKI and reducing shock-related mortality.

Methods:
Renal arteries of rats were clamped and de-clamped to induce AKI like ischemia/reperfusion model, and hemorrhage was carried out by withdrawing blood for 30 min from the femoral artery. Rats were resuscitated with centhaquine (0.02 mg/kg) for 10 min. Mean Arterial Pressure (MAP), heart rate (HR), and renal blood flow (RBF) were monitored for 120 min.

Results:
An improved RBF (p<0.003) in centhaquine compared to vehicle rats was observed after resuscitation. While MAP and HR were similar in centhaquine and vehicle groups. At 120 min post-resuscitation, significantly reduced blood lactate level (p=0.0064) in centhaquine than the vehicle was seen. Higher damage in renal tissues in the vehicle than centhaquine was observed by histopathological analysis. Western blots showed higher HIF-1α (p=0.0152) and lower NGAL (p=0.01626) levels in centhaquine vs. vehicle. While significantly higher (p<0.045) expression of HIF-1α and lower expression of Bax (p<0.044) in kidney cortex and medulla of centhaquine rats were observed after immunofluorescence analysis. On the other hand, expression of PHD 3 (p<0.0001) was higher, while the expression of Cytochrome C (p=0.01429) was lower in the cortex of centhaquine than the vehicle. Also, the
in situ
PCR data showed higher mitochondrial biogenesis in centhaquine than in the vehicle.

Conclusions:
Centhaquine (Lyfaquin
®
) increases renal blood flow and augments hypoxia response, which probably helps reduce tissue damage and apoptosis following hemorrhagic shock induced AKI, and hence the potential of centhaquine could be explored further to prevent/treat AKI.
Abstract 11323: Role of Mir-6236 on Skeletal Muscle Angiogenesis
Authors: Mani Arul Murugan , Eigner-Bybee Isaac L , Singh Madhu V , Dokun Ayotunde O
Published: March 2022

Peripheral arterial disease (PAD) affects more than 200 million people worldwide and is characterized by impaired blood flow to the lower extremities. There are no medical treatments available and in severe cases, PAD may lead to critical limb ischemia requiring amputation. The pathophysiology of PAD is characterized by marked changes in gene expression and reduced angiogenesis. Although many studies have investigated the molecular mechanisms involved in PAD, less is known about the role of microRNAs (miRNA) in the pathogenesis of the disease. MiRNAs are important regulators of gene expression that bind to specific target mRNA and repress their expression. Using a mouse model of PAD, we investigated miRNAs induced by ischemia using RNAseq analysis of ischemic and non-ischemic hind limb tissue. Our data showed 77 miRNAs were upregulated and 40 miRNAs were downregulated in ischemic mouse hind limbs versus non-ischemic controls. Among these miRNAs, miR-6236 was significantly upregulated suggesting a possible role in post ischemic adaptation. We validated miR-6236 expression by qPCR (Ischemic 2.04±0.39 vs Non-Ischemic 1.0±0.11; n=5-6; p<0.05). In vitro, using primary mouse microvascular endothelial cells (MVECs), ischemia induced miR-6236 expression in a time dependent manner up to 72 hrs. At the same time, ischemia caused decrease in proliferation (Ischemia (Isch) 0.12±0.03 vs Normoxia (Norm) 0.23±0.02; n=4-6; p<0.05), migration (Isch 46.7±0.52 vs Norm 72.02±2.74; n=6; p<0.05) and tube formation (Isch 31.5±3.58 vs Norm 82.12±6.5; n=8; p<0.05), and increased apoptosis (Isch 0.94±0.05 vs Norm 0.59±0.02; n=4-5; p<0.05). Treatment of mouse MVECs with miR-6236 inhibitor (miRINH, 100 nM) prior to ischemia decreased miR-6236 expression by 50% and improved proliferation (miRINH + Isch 0.21±0.01 vs Isch 0.12±0.03; n= 4; p<0.05), migration (miRINH + Isch 63.71±2.08 vs Isch 46.7±0.52; n=6; p<0.05), tube formation (miRINH + Isch 50±5.92 vs Isch 31.5±3.58; n=8; p<0.05) and decreased ischemia-induced apoptosis (miRINH + Isch 0.64±0.04 vs Isch 0.94±0.05; n=4-5; p<0.05). We conclude that miR-6236 serves as a critical regulator of endothelial cell function in ischemic skeletal muscle and can be a promising target for therapeutic skeletal muscle angiogenesis.
Abstract 11325: Lipidomics Profiling of Risk for Subclinical Atherosclerosis: A Longitudinal Study in American Indians in the Strong Heart Study
Authors: Miao Guanhong , Zeng Wenjie , Roman Mary J , Devereux Richard B , Zhang Ying , Lee Elisa T , Howard Barbara , Fiehn Oliver , Zhao Jinying
Published: March 2022

Background:
Dyslipidemia is an established risk factor for atherosclerotic CVD, but full identification of circulating molecular lipids associated with atherosclerosis is still lacking in any racial/ethnic group.

Objective:
Prospectively identify lipid species associated with risk of atherosclerosis in American Indians.

Methods:
Using an untargeted LC-MS, we repeatedly measured 3,891 paired fasting plasma samples from 1,950 American Indians at two exams (~5.5 year apart) in the Strong Heart Family Study. Carotid atherosclerosis was assessed by carotid ultrasonography. Incident carotid atherosclerosis was identified if plaque was absent at baseline but detected at follow-up. Elastic net model was used to select baseline lipids or change in lipids (baseline to follow-up) associated with risk for atherosclerosis beyond traditional risk factors (TRFs) including age, sex, center, smoking, BMI, hypertension, diabetes, LDL-c and albuminuria. Multivariate analysis was used to identify lipidomic signatures associated with risk for carotid atherosclerosis.

Results:
Of 1,319 participants with no evident plaque at baseline (2001-2003), 270 developed incident carotid atherosclerosis at 5-year follow-up (2006-2009). Of 518 known lipids detected, altered baseline levels of 29 lipid species, largely glycerophospholipids and glycerolipids, were significantly associated with risk of atherosclerosis beyond TRFs (HR: 1.06-1.33 for risk lipids; 0.85-0.93 for protective lipids). A lipid score comprising top 5 baseline lipids improves risk prediction beyond TRFs (ROC increases from 0.79 to 0.80, P = 0.03). Longitudinal changes in 20 lipids, mainly glycerophospholipids, were significantly associated with risk of atherosclerosis after adjusting for TRFs and baseline lipids. Multivariate analysis identified distinct lipidomic signatures associated with atherosclerosis.

Conclusion:
Altered baseline lipids were independently associated with prevalent and incident carotid atherosclerosis in American Indians. Our findings shed light on the mechanisms linking dyslipidemia to atherosclerosis and provide instrumental data for risk stratification and therapeutic targets customized to American Indians.
Abstract 11328: Risk Analytics and Clinical Decision Support System Role in Identifying Elevated Serum Lactate Level for Pediatric Cardiac Patients
Authors: Asfari Ahmed , Hock Kristal , Huskey Jordan , Tomczak Adam , Butler Evan , Borasino Santiago , Zaccagni Hayden
Published: March 2022

Introduction:
Pediatric patients with congenital heart defect are predisposed for low cardiac output syndrome (LCOS). Serum lactate is a well-defined marker of LCOS. To improve the quality and safety of care, new tools that are less invasive, more sensitive and specific are needed.

Hypothesis:
We hypothesize that analytics algorithms can compute risk indices that are associated with elevated lactate.

Methods:
Quality improvement project in tertiary pediatric cardiac intensive care unit. Data used were collected retrospectively throughout 6/2019-8/2020. The risk analytics algorithm uses a model of patient physiology with vitals and lab data to compute probability density curves for various physiologic variables in real-time. These densities are used to calculate the Hyperlactatemia Index (HLA) and Inadequate Delivery of Oxygen Index (IDO2) [Etiometry Inc., Boston, MA]. HLA and IDO2 represent the integrated probabilities that the current lactate is greater than 4 mmol/L and that the current SvO2 is less than 40% respectively. The minimum data required to calculate HLA and IDO2 is heart rate every 60 seconds, oxygen saturation via pulse oximetry, blood pressures every ten minutes, and at least one lactate lab per day (HLA only). The reported lactates were categorized in four groups. We subdivided the preceding three hours period before the lactate into 30 minutes windows. Subsequently, we calculated the mean IDO2 and HLA and compared the positive predictive value (PPV) of lactate > 4 for both.

Results:
We included 484 patients in our analysis, 20% of which were neonates. The median patient age was 7.7 months (IQR:2,46). IDO2 and HLA trended higher when lactate levels were elevated, especially in the 30 minutes immediately preceding the lactate check. When the individual probability > 50%, lactate was > 4 in 44% (
+
10%) for HLA and 3% for IDO2.

Conclusions:
HLA shows a strong association with lactate and is superior to IDO2 across all time points. Performance of the indices was better in the 30min prior to the elevated lactate. Future studies validating this new tool prospectively are critical before its usage in the clinical setting.
Abstract 11329: Prospective Analysis of Vascular Resistance in Patients with Persistent Tachycardia and or Dyspnea on Exertion in the Post Acute Sequela of Covid-19 Syndrome
Authors: landers david , Jamal Sameer , Turi Zoltan , Vandyck-Acquah Marian , Hollenberg Steven , GLotzer Taya , Klinkhammer Brent , Tancredi Jana , Parrillo Joseph E
Published: March 2022

Introduction:
The cause of tachycardia and dyspnea on exertion (DOE) in the Post Acute Sequelae CoV-2 syndrome (PASC) has yet to be identified. While endothelial invasion of the virus is well documented, how that might explain PASC is unknown.

Hypothesis:
Covid induced changes in vascular signaling to autonomic regulatory centers can induce sinus tachycardia and DOE.

Methods:
In a prospective, observational study, we enrolled 18 PASC patients who reported DOE or inappropriate tachycardia. All patients had normal left ventricular function, CXR, Hgb and thyroid studies. None had preexisting autonomic dysfunction. Vascular resistance was assessed by echocardiographic measurement of aortic-vascular impedance (Zva)=(systolic BP + mean Ao valve gradient)/stroke volume index. Ambulatory heart rate monitoring and head-up tilt table testing (HUTT) were performed.

Results:
Consecutively enrolled patients (18) were studied (17 females, ages 27 to 64). None had a significant aortic valve gradient. Zva was elevated in 17 of 18 patients. Ambulatory monitoring revealed episodes of symptomatic sinus tachycardia. Higher average daily heart rates correlated significantly with higher Zva levels (fig1). The 14 patients with DOE trended to higher average Zva levels than the 4 patients without dyspnea (4.13 +- 0.85 vs 3.5 +- 0.24, P=0.14). Of the 17 patients who had HUTT, 16 demonstrated patterns of orthostatic intolerance consistent with excess sympathetic tone including both postural orthostatic tachycardia and neurogenic cardiac syncope.

Conclusions:
PASC associated sinus tachycardia and HUTT abnormalities result from excess sympathetic tone. Covid-19 vascular injury as evidenced by abnormal Zva values may result in abnormal vascular signaling to autonomic regulatory centers. Resultant increases in sympathetic output may produce inappropriate sinus tachycardia, vasomotor dysregulation and DOE via peripheral vasoconstriction.
Abstract 11331: Economic and Social Challenges Faced by People Living with Rheumatic Heart Disease in a Resource Limited Setting
Authors: Pulle Jafesi , ATALA JENIFER , Nalubwama Hadija , Namara Rebecca , Ndagire Emma , Okello Emmy , Sarnacki Rachel , Beaton Andrea Z , Sable Craig A , Watkins David
Published: March 2022

Introduction:
Rheumatic heart disease (RHD) has nearly been eradicated in wealthy nations but remains a significant public health concern in low-resource countries like Uganda. Many people living with RHD (PLWRHD) is these settings have not been diagnosed and many who are diagnosed have late-stage disease.

Objectives:
To explore the social and economic challenges faced by PLWRHD in a resource limited setting.

Methods:
This was a qualitative study. We conducted in depth interviews on a sample of 36 RHD patients randomly selected from a computer-generated list from RHD registries in the Northern, Central, and South-western regions. The selected participants were interviewed by trained qualitative research staff. All interviews were tape recorded and transcribed verbatim. Data were analyzed by thematic content analysis and useful codes were generated by both inductive and deductive approaches. Generated codes were collapsed into themes. Coding was done by 3 independent researchers who compared their results and agreed on one codebook which was updated iteratively.

Results:
Of the 36 interviewed participants, 18 had congestive heart and another 18 had no congestive heart failure, a complication of RHD. Economic challenges faced by PLWRHD included financial burdens to family, debts incurred to meet treatment costs, selling off assets and loss of jobs. Social challenges entailed poor support at schools for RHD patients, school drop outs, family instability, poor social relations and poor community perception of RHD.

Conclusion:
Understanding challenges faced will enable designing of interventions that improve the quality of life of PLWRHD and significantly influence future policies on RHD management.
Abstract 11334: Metabolic Labeling and Systemic Tracking of Cardiomyocyte-Derived Exosomal MiRNAs
Authors: Han Chaoshan , Yang Junjie , zhang qinkun , Lal Hind , Zhang Jianyi , Qin Gangjian
Published: March 2022

Background & Hypothesis:
Following acute myocardial infarction (AMI), cardiac exosomes are released into circulation (
PB
Exo), thereby transferring cargo miRNAs (miRs) to remote organs to trigger systemic responses. However, the scope and impact of cardiac miR transfer is largely unknown. Since
T. gondii
uracil phosphoribosyltransferase (UPRT) can convert 4-thiouracil into 4-thiouridine (4TU), then incorporating into nascent RNAs, and the 4TU-labeled RNAs can be identified by thio-linked-biotinylation and streptavidin-affinity isolation, we hypothesize that cardiomyocyte (CM)-specific expression of UPRT (
CM
UPRT) allows labeling and tracking of CM-derived miRs in
PB
Exo and peripheral organs.

Methods & Results:
We generated
CM
UPRT mice by crossing αMHC-Cre and CA-GFPstop
flox
-
UPRT mice. Six hours after 4-thiouracil injection, RNAs were isolated from the heart and
PB
Exo and found to be labeled with high specificity and sensitivity. Then we attempted to isolate representative miRs of different tissue specificities from
PB
Exo and multiple organs; only CM specific miR-208a, but not other-tissue specific miRs, was 4TU labeled, thus isolated, abundantly in
PB
Exo and lung. Among FACS-sorted lung cells, endothelial cells (ECs) have the highest
CM
miR-208a level. Next, we monitored
CM
miR-208a levels after AMI, which peaked in
PB
Exo at 12 h and in the lung at 24 h. Since miR-208a is from the intron 29 of the cardiac α-MHC, we measured α-MHC transcript in the lung, which was barely detectable. To determine the biological effect of
PB
Exo-mediated
CM
miR-208a transfer, we
i.v.
injected
PB
Exo obtained from Sham and AMI mice to intact mice; Sham-Exo and to a greater extent, AMI-Exo, but not Exo from LNA-anti-miR-208a pre-treated mice, downregulated the protein expression of miR-208a target genes (Glyr1, Tmbim6, and NLK) in the lung. Since all the three proteins suppress key effectors in the NF-kB pathway, we examined NF-kB’s classic targets (ICAM-1, VCAM-1 and E-selectin);
PB
Exo-mediated Glyr1, Tmbim6, and NLK downregulation was associated with ICAM-1, VCAM-1 and E-selectin upregulation.

Conclusion:
CM
UPRT expression permits labeling and tracking of
CM
miRs in
PB
Exo and organs; cardiac Exo and
CM
miR-208a may contribute to AMI-associated lung inflammation.
Abstract 11339: Novel Ecg Protocol for Early Detection of Cardiac Amyloidosis
Authors: Gonzalez Laura , Delgado Reynolds , Lamba Harveen
Published: March 2022

Background:
Due to recent improvements in treatment of Cardiac Amyloidosis (CA) early detection of the disease has become important. We present a novel ECG protocol for early detection of CA utilizing a ratio of the P wave amplitude to the R wave amplitude. It is known that the R wave amplitude decreases early in the disease progression, and the P wave amplitude may remain unchanged or increase. By analysis of amplitudes of the waves relative to each other, artifacts may be eliminated, and quantitative cutoff values obtained may accurately detect early disease.

Methods:
Six male patients with a known diagnosis of Transthyretin Amyloidosis were analyzed with lead II ECG. Three had wild type and three had the genetic form. For controls, six patients, matched for age and sex were analyzed. The control patients had no significant cardiac disease, a normal ECG, and normal left ventricle septal wall thickness. All ECGs were examined in a blinded fashion to obtain the quantitative ratio of the P wave amplitude to the R wave amplitude.

Results:
Median age of the two groups was comparable (74 vs 71 years, p=0.6). The CA group had a higher median septal thickness than the control (1.4 vs 1.05 cm, p=0.005) and a higher median ratio of the P wave to R wave amplitude (0.16 vs 0.09, p=0.002). A cut off of 0.11 for P wave to R wave amplitude was significantly associated with the diagnosis of CA (p=0.006).

Conclusion:
Despite the small sample size these data support the hypothesis that a lead II ECG analysis of the P wave to R wave ratio may be effective as an early screening tool for CA. Further large-scale studies are needed for validation and identification of appropriate and generalizable cut off values.
Abstract 11341: Diabetes and Chronic Kidney Disease: Prevalence, Associated Factors and Influence on Optimal Medical Therapy in Patients with Coronary Artery Disease
Authors: Moreira Eduardo M , Trombini Pinesi Henrique , Bolta Paula , Martins Eduardo , Rached Fabiana H , Pitta Fabio G , Favarato Desiderio , Lima Eduardo G , Garzillo Cibele L , Segre Carlos A , Serrano Carlos V
Published: March 2022

Introduction:
Diabetes mellitus (DM) and chronic kidney disease (CKD) are comorbidities of great therapeutic and prognostic importance in patients with coronary artery disease (CAD). Knowledge about their prevalence, associated factors and influence on optimal medical therapy are needed to best manage this population.

Methods:
This is a unicentric cross-sectional analysis of 869 patients enrolled in a CAD registry in Brazil. To be included, patients needed to have a previous coronary artery revascularization procedure (either percutaneous or surgical), documented previous acute coronary syndrome, or known coronary stenosis greater than 50%. CKD was defined as creatinine clearance < 60 mL/min. DM was defined as prescription of glucose-lowering drugs or a HbA1c > 6.5%.

Results:
Overall, mean age was 64.7 years, 261 (30%) were women, 528 (61%) had previous myocardial infarction, and 547 (63.4%) had a previous revascularization procedure. DM was prevalent in 449 (51.7%) patients and CKD in 280 (32.2%). Both comorbidities were concomitant in 151 (17.4%) patients. On multivariate analysis, CKD was correlated to female sex (OR 2.94; 95%CI 1.88-4.67), age (OR 1.20; 95%CI 1.16-1.23), BMI (OR 0.80, 95%CI 0.76-0.84), and HDL-cholesterol (OR 0.97; 95%CI 0.96-0.99). DM was associated with age (OR 1.02, 95%CI 1.00-1.04), BMI (OR 1.05, 95%CI 1.01-1.08), high blood pressure (OR 2.1, 95%CI 1.39-3.21), and heart rate (OR 1.02, 95%CI 1.00-1.03). Concomitant presence of CKD and DM was associated with age (OR 1.09, 95%CI 1.06-1.13) and left ventricular ejection fraction (OR 0.97, 95%CI 0.95-0.98). Patients with DM were more likely to receive ACE inhibitors or ARBs (79.3% x 67.1%, p< 0.001) and calcium channel blockers (41.9% x 31.2%, p=0.001). Patients with DM and CKD had higher use of nitrates (38.4% x 25.6%, p=0.002). There was no difference in the prescription of antithrombotic drugs, beta-blockers or statins between groups.

Conclusion:
DM and CKD are both very prevalent comorbidities in patients with CAD. They are associated with age and risk markers such as high blood pressure and lower left ventricular ejection fraction. Although typically these populations are undertreated in others registries, this fact was not observed in our study.
Abstract 11342: Contemporary in-hospital Outcomes of Chronic Total Occlusion Interventions: Update from the Progress-cto (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) International Registry
Authors: Kostantinis Spyridon , Alaswad Khaldoon , Karmpaliotis Dimitrios , Krestyaninov Oleg , Khelimskii Dmitrii , Choi James , Jaffer Farouc A , Poommipanit Paul , Karacsonyi Judit , Vemmou Evangelia , Nikolakopoulos Ilias , Gorgulu Sevket , Koutouzis Michael , Tsiafoutis Ioannis , Riley Robert , Elbarouni Basem , Jaber Wissam , Samady Habib , Tammam Khalid , Elguindy Ahmed M , GOKTEKIN OMER , Abi-Rafeh Nidal , Rangan Bavana V , Burke M Nicholas , Brilakis Emmanouil S
Published: March 2022

Introduction:
Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is an evolving field.

Methods:
We examined the clinical and angiographic characteristics and procedural outcomes of 8,666 CTO PCIs performed at 36 centers between 2012 and 2021.

Results:
Mean age was 64±10 years and 82% of the patients were men. The prevalence of prior PCI (62%) and diabetes mellitus (43%) was high. Median ejection fraction was 54% (42%, 60%). Radial access was used in 50%. The most common target vessel was the right coronary artery (52%), followed by the left anterior descending artery (26%). The target CTOs were highly complex with mean J-CTO score of 2.4 ±1.3 and PROGRESS score of (1.3 ±1). Technical and procedural success rates were high (86% and 85% respectively) with a relatively low percentage of in-hospital major adverse cardiac events (Figure 1). The final successful crossing strategy was antegrade wire escalation in 62%, retrograde in 22%, and antegrade dissection re-entry in 16%. Median contrast volume, air kerma radiation dose and procedure time were 220 (155, 300) ml, 2.2 (1.2, 3.8) Gray and 116 (75, 172) minutes, respectively.

Conclusions:
High success and acceptable complication rates can currently be achieved in CTO PCI among high-volume, experienced centers.
Abstract 11344: Association of Canonical Pathways with Length of Survival in Pulmonary Arterial Hypertension
Authors: Webb Amy , An Hyoin , Correa-Jaque Priscilla , Lin Shili , Liu Zilu , Tiwari Hemant K , Wiener Howard , Benza Raymond L
Published: March 2022

Introduction:
Pulmonary arterial hypertension (PAH) is a chronic, progressive disease without cure. Treatment can improve outcome, but informed predictions with clinical and genomic measurements can guide treatment and therapy choices. Previous research has focused on identifying clinical variables that could predict future outcomes. The current research aims to find genomic variants that can predict survival time.

Hypothesis:

Methods:
Whole genome sequencing was performed on stored samples from 221 PAH patients. Samples were included with Long survival greater than 7 years and Short survival with mortality less than 5. Variants were filtered for quality, assigned to genes, and filtered for function and population frequency. Genes are grouped based on Canonical Pathways defined in Ingenuity Pathway Analysis

Results:
Patient were 50% IPAH, 81% female, 97% european decent with a mean age of 54 at sample acquisition. Mean Follow-up post sample acquisition was 5 years. Mean long and short survival was 8.3 and 2.1 years, respectively. Of pathways containing more than one gene mutated in 3 or more samples, 29 pathways were associated with survival length. Biologically relevant pathways include Pentose Phosphate (p=0.005), IL-22 (p=0.006), Phospholipase C signaling (p=0.007), Endocannabinoid related pathways (p=0.01), and Thioredoxin pathway (p=0.015). A Neural network model based on the top pathways was constructed (figure) that predicted Long/Short survival.

Conclusions:
We identified biologically relevant pathways associated with a Long/Short survival time in PAH patients. Our neural network model for predicting Long/Short survival using the 29 ident ified pathways and has achieved excellent performance.
Abstract 11349: Substance Use and Associated Risk of Incident Atrial Fibrillation
Authors: Lin Anthony , nah gregory , Vittinghoff Eric , Marcus Gregory M
Published: March 2022

Introduction:
Atrial fibrillation (AF) is a common arrythmia associated with high morbidity and mortality. Understanding modifiable risk factors that contribute to AF could have a broad impact on patient outcomes. While work has been done to understand the association between alcohol use and AF, there is limited understanding in the relationship between non-alcohol substance use and new-onset AF. Our study sought to investigate the associations of methamphetamine, cocaine, opiate, and cannabis use with incident AF.

Methods:
This is a retrospective observational study of 23,561,844 adult inpatient hospitalizations and ED visits from January 1, 2005 to September 30, 2015 in California’s Office of Statewide Health Planning and Development (OSHPD) database. International Classification of Disease (ICD) codes were used to document AF and methamphetamine, cocaine, opiate, or cannabis use disorders. All patients with prevalent AF were excluded from analysis.

Results:
Methamphetamine use (n=98,271), cocaine use (n=48,700), opiate use (n=10,032), and cannabis use (n=132,834) disorders were coded as part of routine clinical care. In multivariate analysis adjusting for age, race, sex, income, and cardiovascular risk factors, methamphetamine, cocaine, opiate, and cannabis use were associated with higher incidence of AF (
Table
). The cumulative probability of incident AF increased over time with all four substances (
Figure
).

Conclusion:
Patients with documented methamphetamine, cocaine, opiate, or cannabis use disorders had an increased risk of incident AF that was independent of the risk already portended by established cardiovascular risk factors.
Abstract 11350: DNP-PhD Collaboration in NIH-funded Physical Activity Trials for Women at Risk for Cardiovascular Disease: A Team Science Approach
Authors: Halloway Shannon , Buchholz Susan W , Daniel Manju , Lemke Sally , Bavis Margaret , odiaga janice A , Pelt Phyllis , Braun Lynne T , Tafini Susan , Kalensky Melissa , Opdycke Anita , Knudson Krista , Cygan Heide R , Wilbur Joellen
Published: March 2022

Doctorally prepared nurse scholars with the doctor of nursing practice (DNP) and the doctor of philosophy (PhD) degrees are equally well suited to engage in scholarship to advance cardiovascular nursing and health outcomes. Collaboration between DNP and PhD scholars is crucial to develop interventions to improve cardiovascular outcomes and encourage efficient translation of research findings into practice. The purpose of this paper is to (1) provide a targeted review of the current state of literature on examples of DNP-PhD collaboration, and (2) describe ongoing DNP-PhD collaborations across three NIH-funded trials (1 completed, 2 ongoing) testing physical activity interventions for women at risk for cardiovascular disease. First, a targeted review was conducted to identify examples of DNP-PhD collaboration, and identified 12 published articles. Articles described the DNP-PhD collaborations in research/scholarship (
n
= 8) and education (
n
= 5). Of the research articles, there was evidence of collaboration in evidence-based practice projects for various health outcomes. However, none of the articles described DNP-PhD collaboration in NIH-funded clinical trials, including behavioral interventions for cardiovascular health. Three physical activity interventions for women at risk for cardiovascular disease were or are being tested in three trials (NCT01700894, NCT03558828, NCT04556305). Examples of DNP-PhD collaboration are categorized according to the four Team Science Phases. Research teams are led by PhD nurse scholars who oversee design and implementation (Development, Conceptualization, Implementation, Translation). DNP scholars provide clinical feedback in advisory panels and focus groups (Development, Conceptualization), provide training to intervention teams, lead personal call and group interventions (Implementation), facilitate patient referrals for participation (Implementation), oversee intervention safety (Implementation, Translation), and contribute to dissemination (Translation). DNP-PhD collaboration is important for all phases of NIH behavioral trials to optimize outcomes. There is a need for additional publications to detail applicable DNP-PhD collaborations in NIH-funded nursing research.
Abstract 11351: Efficacy of Catheter Ablation for Atrial Fibrillation Across Race-Ethnicity
Authors: Al-azzam Bahaa , Diaz Annette , Tso Taylor , Barney Miles , Sreepathy Pranati , Ali Mustafa , Aggarwal Ishita , Perez Miguel , Qiao Victor , Ongtengco Ana , Konda Sreenivas , Wissner Erik , Darbar Dawood
Published: March 2022

Introduction:
Catheter ablation (CA) is now an established therapy for symptomatic atrial fibrillation (AF). Although the procedural success rate is high, the role of race-ethnicity and clinical predictors in preventing recurrence of AF remains unclear.

Methods:
Patients prospectively enrolled in an AF clinical-DNA biorepository and treated with CA for AF were included in the study. Recurrence of AF was assessed with symptom assessment, ECG, Holter, and event recorder evaluations in all patients during follow-up visits and Holter recordings were done when appropriate. Recurrence of AF was defined as AF detected <12 months after CA.

Results:
Of the 238 enrolled, 84 (35.3%) were European American (EAs), 106 (44.5%) were African American (AA) and 48 (20.2%) were Hispanic American (HA). Baseline clinical characteristics were similar across the groups. Eighty-eight (37%) patients had AF recurrence within 12 months of CA. Multivariate analysis showed that compared to EAs, AAs (odds ratio [OR] 0.48, 95% confidence interval [CI]: 0.24-0.96, P+0.048) and HAs (OR 0.42, 95% CI: 0.18 - 0.94, P+0.048) are less likely to experience AF recurrence after CA (Table 1). Other clinical predictors included left atrial dilatation (OR 1.88, 95% 1.04 - 3.44, P+0.036), persistent AF (OR] 1.94, 95% [CI]: 1.04-3.64, P+0.074), valvular heart disease (VHD) (OR 2.66, 95% CI: 1.02-7.20; P=0.046) and history of smoking (OR 2.16, 95% CI: 1.18-3.99; P=0.012).

Conclusion:
We showed that clinical predictors of recurrence of AF after CA included left atrial dilatation, VHD, persistent AF and a history of smoking. Surprisingly, we found that AAs and HAs were less likely to experience AF recurrence than EAs and reasons for this differential response remains unclear.
Abstract 11354: Registry Based Mid-Term Mortality After Stenting of Distal Left Main Stenosis with Regular, Third Generation Drug Eluting Stent or Dedicated Bifurcation Stent or Surgery
Authors: Vassilev Dobrin , Zlatancheva Galina , Shumkova Monika , Nikolov Pavel , Karamfiloff Kiril , Gil Robert
Published: March 2022

Background:
The aim of the current study was to identify predictors of cardiac mortality at mid-term follow up after PCI (DES vs. dedicated bifurcation stent) or CABG.

Methods:
All patients with distal LM stenosis≥50% were included in prospective registry starting from 01.2015.The exclusion criteria for registry are cardiogenic shock,a priory life expectancy duration < 1 year,lack of inform consent.All patients were prospectively followed about the alive status through the national security number data base.

Results:
For three year follow up period (median 35 months, IQR 18-50) 303 patients were included.220 patients were stented with 3
rd
generation DES, 43 with dedicated bifurcation stent BiOSS (Balton, Poland),and rest were sent for CABG.The mean age was 67 ± 10 years,72% were males,37% diabetics,all with hypertension, 97% dyslipidemia,15% PAD,9% COPD,16% carotid artery disease,previous MI 28%,previous PCI 50% - without significant difference between three groups.The frequency of acute coronary syndrome during admission was 11%-without difference in frequency between groups.The patient referred to CABG had significantly lower left ventricular EDV and ESV,more severe mitral regurgitation and kinetic disturbances,higher SYNTAX score and longer lesion length.On univariate COX regression analysis, the following factors were associated with mortality:age, NYHA class,GFR,baseline troponin,hemoglobin,LV EF,mitral regurgitation,kinetics disturbances,treatment with beta blockers,ACE inhibitors,statin,atrial fibrillation,SYNTAX score,lesion length.The type of treatment was not associated with differences in mortality.On COX multiple regression survival analysis independent predictors of survival were:age (HR=1.036, CI 1.005-1.068, p= .023);COPD (HR= 2.313, CI 1.170-4.572, p= .016);GFR (HR= .988, CI .978-1.000, p= .048);hemoglobin(HR= .970, CI .955- .986, p= .000);left ventricular EF (HR= .958, CI .832- .985, p= .003).

Conclusions:
The type of treatment was not associated with mid-term mortality.Our data demonstrate that dedicated bifurcation stent could be used safely for distal LM stenosis treatment with similar safety as 3
rd
generation DES.
Abstract 11355: Contemporary Patterns of Lipoprotein(a) Testing and Associated Clinical Care and Outcomes
Authors: Kelsey Michelle D , Mulder Hillary , Chiswell Karen , Lampron Zachary M , Nilles Ester K. K , Kulinski Jacquelyn P , Joshi Parag H , Jones William S , Chamberlain Alanna M , Leucker Thorsten M , Hwang Wenke , Milks Michael W , Paranjape Anuradha , McTigue Kathleen M , Obeid Jihad , Linton Macrae F , Kent Shia , OBrien Emily C , Pagidipati Neha J
Published: March 2022

Introduction:
Elevated lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease (ASCVD), yet little is known about Lp(a) testing patterns in real-world practice. We hypothesized that Lp(a) testing occurs in a different population than calculated low density lipoprotein (LDL-C) testing alone, and that elevated Lp(a) is associated with greater lipid-lowering therapy (LLT) initiation and cardiovascular (CV) events.

Methods:
We used data from 11 health systems participating in the National Patient-Centered Clinical Research Network. We created two cohorts based on lab tests from Jan 1, 2015 to Dec 31, 2019: 1) the Lp(a) cohort, of adults with an Lp(a) test and 2) the LDL-C cohort, of 4:1 date- and site-matched adults with an LDL-C test, but no Lp(a) test. We used logistic regression to assess the relationship between Lp(a) levels (< 50, 50-100, and > 100mg/dL) and initiation of LLT within 3 months; and cox proportional hazards to evaluate Lp(a) levels and time to all-cause hospitalization and the composite of MI, revascularization and ischemic stroke hospitalization.

Results:
Overall, 20,551 patients (0.06% per year) had Lp(a) tests, with median Lp(a) value 17.5mg/dL (Q1, Q3: 7.0, 56.0). Compared with the LDL-C cohort (N=82,204), the Lp(a) cohort more frequently had ASCVD (24.3% vs. 8.5%) or multiple prior CV events (8.6% vs. 2.6%). Elevated Lp(a) was associated with greater odds of LLT initiation (Figure 1). Elevated Lp(a) was not significantly associated with all-cause hospitalization; however, Lp(a) > 100mg/dL was correlated with composite CV hospitalization compared with Lp(a) < 50mg/dL [adj HR (95% CI): 1.24 (1.06-1.44), p=0.006].

Conclusions:
Lp(a) testing occurs more often in adults with ASCVD and multiple CV events, but testing is infrequent. Elevated Lp(a) was associated with LLT initiation, including niacin, despite lack of evidence of CV benefit. There was an association between elevated Lp(a) and CV hospitalization outcomes.