bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11539: Causes of Thirty Day Readmissions Following Left Atrial Appendage Closure
Authors: Sundhu Murtaza A , Nasir Usama , Waheed Tayyab Ali , Ahuja Keerat Rai , NAZIR SALIK , Kolte Dhaval , Ramanathan P. Kasi
Published: March 2022

Introduction:
Left Atrial Appendage Occlusion (LAAO) devices provide non pharmacological methods of preventing stroke in patients with atrial fibrillation who cannot tolerate anticoagulation. Data on 30-day readmission measures following LAAO is limited.

Methods:
Nationwide Readmissions Database from 2016 to 2018 was utilized to identify patients undergoing LAAO. Incidence, prevalence, and causes of readmission were identified. Predictors of 30-day readmission were also identified using complex sample multivariable regression model.

Results:
Among 29,367 patients receiving LAAO, the average rate of readmission was 9.2%. Readmitted patients were more likely to be females with heart failure, peripheral vascular disease, chronic lung disease, chronic liver disease, and chronic kidney failure especially end stage renal disease (ESRD).The most common overall cause of 30-day readmission was gastrointestinal bleeding (18.5%), followed by heart failure (13.1%), and infection (7.3%) (Figure 1). The odds of readmission were highest in the end stage renal disease patients (OR - 2.75; 95% CI, 2.13 - 3.55; p<0.001) followed by presence of pericardial effusion requiring intervention (OR - 2.13; 95% CI, 1.26 - 3.61; p=0.005) and Stroke/TIA (OR - 1.82; 95% CI, 1.10 - 3.01, p=0.02).

Conclusions:
The highest odds of readmission were associated with ESRD, periprocedural pericardial effusions requiring intervention, and in hospital stroke/TIA. Gastrointestinal bleeding remained the most common overall cause of readmission, followed by heart failure, and infections. To improve 30-day post-procedural outcomes, further studies are warranted to better identify reversible factors.
Abstract 11540: Charlson Comorbidity Index is an Effective Predictor of Hospital Outcomes in Takotsubo Cardiomyopathy
Authors: Aguilar-gallardo Jose S , ROMEO Francisco , Correa Ashish A , Contreras Johanna P
Published: March 2022

Introduction:
The Charlson Comorbidity Index (CCI) is a recognized predictor of clinical outcomes that has been studied in diverse clinical settings. In this study, we evaluate its utility for prediction of outcomes in Takotsubo cardiomyopathy.

Methods:
This is a retrospective cohort study using the 2018 Nationwide Inpatient Sample that included patients admitted with a primary diagnosis of Takotsubo syndrome. Outcomes were mortality, length of stay, total hospitalization charges, and cardiogenic shock. Multivariate regression analysis was performed adjusting for patient age, race, gender, severe sepsis, cardiogenic shock, tobacco use, atrial fibrillation, and other relevant comorbidities with a p-value <0.2 in univariate screen. Statistical analysis was performed using Stata 17.0.

Results:
A total of 7,970 weighted patients were hospitalized with Takotsubo syndrome, with a mean age of 66.5 years. Incidence of primary outcomes was gradually higher with an increasing Charlson Comorbidity Index. On multivariate regression analysis, each one-point increase in Charlson score was associated with 64% increased odds of inpatient mortality (odds ratio 1.64, p= 0.000). The odds of cardiogenic shock was also increased (odds ratio 1.24, p=0.000), as well as the mean length of stay and total hospitalization charges.

Conclusions:
The Charlson Comorbidity Index is an effective predictor of hospital outcomes in Takotsubo cardiomyopathy.
Abstract 11561: Pharmacological Inhibition of Rage/diaph1 Axis Enhances Weight Loss in Diet Induced Obese Mice and Improves Glucose Homeostasis
Authors: Wilson Robin , Arivazhagan Lakshmi , Ruiz Henry , Manigrasso Michaele , Ramasamy Ravichandran , Schmidt Ann Marie
Published: March 2022

Introduction:
The incidence of obesity and its comorbidities has soared at an alarming rate in US and around the world. Our previous studies have shown that the receptor for advanced glycation end products (RAGE) and its ligands contribute to the pathogenesis of obesity and insulin resistance. Both global and adipocyte-specific
Ager
(gene encoding RAGE) deleted mice fed a high fat diet (HFD) showed protection from weight gain and insulin resistance. However, if RAGE deletion/inhibition affects weight loss in mice with established obesity is under investigation. We have discovered novel small molecule antagonists of the interaction between the cytoplasmic domain of RAGE with its intracellular effector Diaphanous 1(DIAPH1). We tested the hypothesis that these chow containing small molecule antagonists vs. vehicle might enhance weight loss and improve metabolic function in obese mice undergoing weight loss.

Methods:
Male mice (C57BL/6, N=78) were fed HFD (60% kcal/fat) for 20 weeks starting at 8 weeks of age to establish obesity; mice were then switched to either low fat RAGE/DIAPH1 inhibitor diet (N=40) or vehicle diet (N=38). Body mass was serially monitored and after six weeks of medicated chow vs. vehicle, glucose and insulin tolerance, body composition, plasma insulin and lipids were measured. Adipocyte size was monitored by histology.

Results:
Six weeks administration of RAGE/DIAPH1 antagonist in mice with established obesity resulted in significantly greater weight loss and fat mass vs. vehicle treatment. Further, metabolic recovery was enhanced, as evidenced by greater improvement in glucose tolerance and reduced plasma insulin and cholesterol levels. Histology revealed that epididymal and subcutaneous adipose tissues displayed smaller mean adipocyte size in mice receiving the RAGE/DIAPH1 antagonists vs. vehicle.

Conclusion:
Pharmacological inhibition of RAGE/DIAPH1 axis in mice with established obesity enhances weight loss, and improves metabolic recovery.
Abstract 11564: Epicardial Adipose Tissue Thickness as a Mortality Risk Marker in Covid-19
Authors: Salguero Lopez Douglas , Ferri-Guerra Juliana , Porras Angel , Friedman Jonathan , Donatelle Marissa A , Rogers Everett , Seifer Lee , Porudominsky Ruben , Ujueta Francisco , Olayiwola Ayoola , Loescher Viky , Burke William F. , Mihos Christos G. , Tuda Claudio
Published: March 2022

Intro:
Cardiac involvement in COVID-19 infection is common. Epicardial adipose tissue functions as an inflammatory depot, and a thickness (EAT-T) >5mm is associated with increased cardiovascular risk. The present study assessed the significance of increased EAT-T in patients with COVID-19.

Methods:
A retrospective cohort study of 149 consecutive patients diagnosed with COVID-19 between March 2020 to January 2021 was performed. Inclusion criteria were lab-confirmed COVID-19 infection and having a Chest CT scan without contrast during hospitalization. EAT-T was measure in right ventricle free wall (Figure 1). Characteristic of patients and comparisons were analyzed by T-Test and Chi-square. Log-linear analysis and cumulative logistic regression was carried out to predict effect between EAT-T and mortality

Results:
The mean age was 67 ± 15 years, 65% were male, and time from onset of symptoms was 7 ± 5 days. Forty-seven (31.5%) patients required mechanical ventilation, and 34 (22.8%) required vasopressors. Medical therapy included convalescent plasma (36%), Remdesivir (28%), Tocilizumab (46%), Enoxaparin (64%), and Dexamethasone (39%). There were 36 (24.2%) in-hospital deaths, with a greater incidence amongst patients with an EAT-T > 5 mm versus ≤ 5 mm (95 vs 5%, p=.001). Notably, age was not significantly different on patients with in-hospital mortality (69 vs 66 years, p=0.5), and higher EAT-T by 2.17 mm on patient with acute respiratory distress syndrome (p=.001) and 10.9 mm in myocardial infarction (p=.02). In multivariable analysis an EAT-T >5mm was associated with an increased risk of mortality (OR 12.3, 95% CI 3-55, p=.001). In the presence of EAT-T > 5 mm, no effect was observed by chronic kidney disease, hypertension, coronary artery disease, dyslipidemia, or body mass index (p >0.5).

Conclusions:
In patients with COVID-19, an EAT-T > 5 mm is associated with increased risk of in-hospital mortality and may provide important risk stratification.
Abstract 11579: In-Hospital Characteristics and Outcomes Among Patients Who Received an Off-Label Tricuspid Clip
Authors: Donatelle Marissa A , Torres Christian , Vedantam Karthik , Beohar Nirat
Published: March 2022

Intro:
Tricuspid regurgitation has high morbidity & mortality, leading to recurrent hospitalization preventing surgery. Tricuspid valve transcatheter edge-to-edge repair with an off-label clip (TVc) are becoming more common, but data are limited. We examined the National Inpatient Sample (NIS) database to describe demographics & in-hospital outcomes among TVc patients.

Methods:
The NIS database was queried from 2016-2018 to identify patients that received TVc using ICD-10 codes. Weights were applied to obtain national estimates.

Results:
All P values were <.05. A total of 485 patients received TVc, 94% at large academic medical centers as elective procedures (73%). Patients were older (78±9 Vs 58±20 yrs) with an equal proportion of males & females (45% vs 55%). They were more likely to have comorbidities, like congestive heart failure (88.6% vs 15%), chronic kidney disease (45.3% Vs 16%), hypertension (72.1% vs 52%), atrial fibrillation (85.5% vs 13%) & pulmonary hypertension (47.4% vs 3%). Concomitant mitral regurgitation was the most common valve disorder (7.2% vs. 0.1%). The most common complication was acute kidney injury (32.9% vs 13%), followed by pericardiocentesis (4% vs 0.06%) & cardiac arrest (1% vs 0.01%). Hospital costs rose by six-fold ($303,222 vs $53.5270) & length of stay (LOS) was longer by 3.5 days in those with a TVc. Half of patients were discharged home (54.6%) but 23% required home health & 19% a skilled nursing facility.

Conclusions:
TVc patients are more likely to be white, older, with an even division in gender & a significant number of chronic comorbidities. Overall mortality is low & complications are rare. Both hospitalization costs & LOS were higher.
Abstract 11586: Diagnostic Tests Used to Identify Transthyretin Amyloid Cardiomyopathy (ATTR-CM) in the United States
Authors: Brown Sarah , Chung Wei Yen , Deemer James , Melinis Niya , Wright Devon
Published: March 2022

Introduction:
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed, progressive disease characterized by amyloid protein deposits building in the left ventricle. The deposition of transthyretin (TTR) amyloid causes the heart walls to weaken and specialized tests are needed to identify ATTR-CM.

Hypothesis:
This paper examines the tests used to identify ATTR-CM in the US.

Methods:
Ipsos’ ATTR-CM Therapy Monitor was fielded monthly between February 2021 and April 2021, with ~100 treating doctors providing data online on >200 ATTR-CM patients seen in consultation per wave. Ipsos analyzed information provided on the diagnostic tests ordered for the total 665 patients to understand how ATTR-CM is diagnosed and tracked the order in which the tests were conducted, across four batteries, to understand the flow of the diagnostic procedures.

Results:
The patients in our study went through 5 diagnostic tests on average before receiving a confirmed ATTR-CM diagnosis via Echocardiogram (ECHO) with strain imaging (91%), Genetic tests (75%), Scintigraphy tests (60%), Cardiac Magnetic Resonance Imaging (MRI) (55%), Laboratory tests (51%), and Biopsy tests (30%) as the top tests ordered. Overall, 19% of the reported patients had an unknown order of tests. ECHOs were most ordered in the 1st battery of tests (92%), Cardiac MRIs in the 2nd battery (39%), and Scintigraphy tests in the 2nd (33%) and 3rd batteries (26%). Biopsy tests were ordered in the 3rd battery (18%) and Genetic tests in the 4th+ battery (25%), while laboratory tests were ordered throughout the batteries (1st: 19%, 2nd: 14%, 3rd: 19%, 4th+: 11%). Patients experienced a delay of 3.7 weeks between the 1
st
and 2
nd
batteries of tests on average, and 3.8 weeks between the 2
nd
and 3
rd
batteries. Once ATTR-CM was suspected, it took physicians 6.5 weeks on average to run all necessary tests and arrive at a confirmed ATTR-CM diagnosis.

Conclusion:
Our data indicate that, patients go through a long journey before receiving a confirmed ATTR-CM diagnosis, taking 6.5 weeks on average once ATTR-CM is suspected and requiring many tests over 4+ batteries. Further research is needed to figure out how to encourage early suspicion of ATTR-CM and increase the speed of the diagnostic process.
Abstract 11601: Single-Volume Quantitative CT Myocardial Perfusion Measurement - Validation in a Swine Model
Authors: Hubbard Logan C , Molloi Sabee
Published: March 2022

Introduction:
Dynamic CT myocardial perfusion imaging enables accurate assessment of coronary artery disease (CAD). However, it is limited by the high radiation dose of serial acquisition of 10 or more volume scans per exam.

Hypothesis:
A single-volume quantitative CT myocardial perfusion technique can accurately measure perfusion in mL/min/g at a low radiation dose, as compared to microsphere perfusion measurement.

Methods:
The single-volume quantitative CT perfusion technique was validated in 6 swine (37 ± 8 kg). In each swine, several intermediate severity stenoses were induced in the left anterior descending (LAD) coronary artery using a balloon under intracoronary adenosine stress. Contrast-enhanced imaging was performed at 100 kVp and 200 mA with a 320-slice CT scanner, where 20 consecutive volume scans were acquired to capture the entire aortic enhancement curve. The image data were then used retrospectively to simulate prospective 2-mm-slice dynamic bolus tracking with aortic triggering at 150 HU followed by “acquisition” of a single volume scan at approximately the peak of the aortic enhancement: identical to a coronary CT angiogram. The dynamic bolus tracking, trigger, and single volume scan data were then used as analytical inputs into a novel first-pass analysis model to derive perfusion in mL/min/g. The accuracy versus microsphere perfusion was assessed via regression analysis.

Results:
Single-volume quantitative CT perfusion measurements (P
CT
) were related to microsphere perfusion measurements (P
MICRO
) by P
CT
= 1.00 P
MICRO
- 0.05 (Pearson’s r = 0.96; RMSE = 0.48 mL/min/g). The average CT dose index of the technique was only 5.4 mGy.

Conclusions:
The single-volume quantitative CT perfusion technique provides accurate, low-dose, myocardial perfusion measurement in mL/min/g using only bolus tracking images and a single volume scan. The technique can also provide simultaneous CT angiography when acquired at an appropriate radiation dose.
Abstract 11618: Serum and Glucocorticoid Inducible Kinase-1 (SGK-1) Activity is Upregulated in Hypertension and Promotes IL-6 Expression to Drive Aortic Macrophage Accumulation
Authors: Brown Adam , Hall SarahRose , xiong Ying , Mukherjee Rupak , Jones Jeffrey A , Ruddy Jean
Published: March 2022

Introduction:
The serum and glucocorticoid inducible kinase-1 (SGK-1) is a mechanosensitive kinase and it is hypothesized that SGK-1 activity is upregulated with elevated aortic tension to augment pro-inflammatory cytokine expression and promote macrophage accumulation to drive hypertensive remodeling.

Methods:
Hypertension (HTN) was induced in C57Bl/6 mice with AngiotensinII (AngII) infusion (1.46mg/kg/day x21days, n=4). Terminal procedure included blood pressure (SBP) quantification, aortic diameter (AoD) assessment, and harvest of infrarenal aorta. Abundance of SGK-1, pSGK-1, and the mature macrophage marker F4/80 was determined by immunoblot. The spontaneously hypertensive BPH/2 mice were also utilized and assessed for SBP, AoD, and target proteins (n=4). A subset of animals had systemic infusion of EMD638683, a selective SGK-1 inhibitor (2.5mg/kg/day x 21 days, n=4). Aortic VSMCs were subjected to 12% biaxial cyclic stretch for 3 and 12 hours +/- EMD638683 (10μM) with subsequent QPCR for IL-6 and MCP-1 expression. Statistical analysis included two-way ANOVA across treatment groups with significance at p<0.05.

Results:
C57Bl/6+AngII mice and BPH/2 mice had significant elevation in SBP (p<0.05) without change in AoD. The pSGK-1/SGK-1 and abundance F4/80 were increased in both models of HTN (p<0.05) and decreased with systemic EMD638683 (p<0.05), with no change in SBP. IL-6 expression was upregulated in VSMC that had Stretch for 3hrs (1.64
+
0.22 fold; p<0.05) or 12hrs (1.99
+
0.33 fold; p<0.05), and at both timepoints EMD638683 significantly inhibited IL-6 expression (p<0.05 vs respective Stretch). MCP-1 expression was unchanged after 3hr Stretch, but it was significantly elevated following 12hr Stretch (2.05
+
0.38 fold; p<0.05), and inhibited by EMD638683 (p<0.05). This data suggests a biomechanical link between aortic VSMC mechanotransduction and cytokine production to promote macrophage accumulation, mediated in-part by SGK-1 activation.

Conclusions:
Mechanical stimuli can elevate SGK-1 activity and increase pro-inflammatory cytokine production to accumulate macrophages, which may lead to proteolytic aortic remodeling. Therefore, SGK-1 may represent a novel target to abrogate hypertensive aortic inflammation.
Abstract 11620: Long-Term Outcomes and Cost for Impella Compared to Intra-Aortic Balloon Pump in Patients Presenting with Acute Myocardial Infarction Complicated by Cardiogenic Shock
Authors: Miller Elliott , Bromfield Samantha G , Ma Qinli , Crawford Geoffrey , Whitney John , Devries Andrea , Desai Nihar R
Published: March 2022

Introduction:
Recent reports have demonstrated an association between Impella compared to IABP use with increased risk for short-term clinical outcomes, including stroke, bleeding, and mortality among patients with AMI and cardiogenic shock (CS) undergoing PCI. Data on long-term outcomes and cost are limited.

Methods:
This retrospective study analyzed administrative claims data from a large commercially insured population from 14 states. Patients undergoing PCI for AMI complicated by CS from 7/1/14 to 4/30/20 were included. Those who had both devices or other mechanical circulatory support were excluded. We performed a 1:1 propensity score-matched analysis in patients receiving an Impella versus IABP. The primary outcome was mortality, and secondary outcomes were stroke, bleeding, repeat revascularization, incident dialysis, and cost at 30-days and 1-year follow-up.

Results:
Of the 3,347 patients undergoing PCI for AMI complicated by CS, the mean (SD) age was 65.4 (12.5) years, 71% were men, and 32% had a cardiac arrest. Among 820 propensity-matched pairs, at 30-days use of the Impella was associated with a significantly higher mortality (Odds ratio [OR] 1.91; 95% Confidence interval [CI]: 1.54-2.37,
P
<0.001), incident dialysis (OR 1.55; 95% CI:1.10-2.18,
P
=0.01), and mean difference in cost ($40,869, Interquartile range: $20,829-$64,200,
P
<0.001) compared to IABP (
Figure
). Incident stroke, bleeding, and repeat revascularization were not different between groups (
P
>0.05). At 1-year, mortality (Hazard ratio [HR] 1.58, 95% CI: 1.33-1.87,
P
<0.001) and incident dialysis (HR 1.70, 95% CI: 1.25-2.30,
P
=0.001) remained higher in Impella.

Conclusions:
In patients undergoing PCI for AMI complicated by CS, use of Impella was associated with an increased 30-day and 1-year mortality, dialysis, and cost compared to IABP. There is need for additional evidence surrounding the optimal management of patients with AMI and CS undergoing PCI.
Abstract 11621: Effect of Genotype Guided Oral P2y12 Inhibitor Selection After Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Gupta Rahul , malik aaqib , Chaturvedi Abhishek , Chakraborty Sandipan , mahajan pranav , Mehta Sanjay , Aronow Wilbert S , Vyas Apurva , Patel Nainesh , AHMAD HASAN
Published: March 2022

Introduction:
Clopidogrel is the most frequently used P2Y12 inhibitor as a component of the dual antiplatelet regimen in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Prior studies have shown the variable efficacy of clopidogrel due to genotypic differences in the CYP2C19 enzyme function, which converts clopidogrel to its active metabolite.

Hypothesis:
The aim of this meta-analysis is to evaluate the effectiveness of genotype testing-guided P2Y12 inhibitor prescription therapy to patients after PCI for ACS compared to non-genotype guided conventional treatment.

Methods:
A comprehensive literature search was performed in PubMed, Embase, and Cochrane to identify relevant trials. Summary effects were calculated using a DerSimonian and Laird random-effects model as odds ratio with 95% confidence intervals for all the clinical endpoints.

Results:
Seven studies with 9617 patients were included. Genotype-guided strategy arm included prasugrel or ticagrelor prescription to patients with loss of function (LOF) of CYP219 alleles (most commonly alleles being *2 and *3) and clopidogrel prescription to those without the LOF allele. The conventional arm included patients treated with clopidogrel without genotype testing. Comparison of genotype arm with conventional arm showed decreased major adverse cardiovascular events (MACE) (RR 0.72, 95% CI 0.55-0.95; p=0.02, I
2
=23), improved cardiovascular (CV) mortality (RR 0.62, 95% CI 0.43-0.90; p=0.01, I
2
=0) and reduced incidence of myocardial infarction (MI) (RR 0.57, 95% CI 0.41-0.97; p< 0.01), and a similar stroke incidence (RR 0.65, 95% CI 0.35-1.21; p= 0.18). Regarding adverse events, the incidence of stent thrombosis was lower in the genotype arm than the conventional arm (RR 0.52, 95% CI 0.28-0.96; p=0.04).

Conclusions:
Our analysis illustrates the possible advantages of genotype-guided P2Y12 inhibitor prescription strategy compared to non-genotype-guided strategy with reductions in MACE, CV mortality, MI, and stent thrombosis. This analysis can be used as a stepping stone to conducting further trials determining the efficacy of this treatment strategy in various ACS subtypes.
Abstract 11633: Three-Dimensional Speckle-Tracking Echocardiographic Assessment of Ventricular Dyssynchrony and Arrhythmic Risk in Mitral Valve Prolapse
Authors: Capotosto Lidia , Nguyen Bich Lien L , Tanzilli Gaetano , Ciardi Maria , Mangieri Enrico , Muscaritoli Maurizio , Miraldi Fabio , Vitarelli Antonio
Published: March 2022

Introduction:
Dyssynchrony indices based on two-dimensional speckle tracking echocardiography have demonstrated added value in identifying patients with mitral valve prolapse (MVP) with a higher prevalence of arrhythmic complications and the potential for sudden cardiac death, but measurements are restricted to a single plane, and complex left ventricular (LV) dyssynchrony patterns may be overlooked.

Hypothesis:
The purpose of this study was to investigate whether three-dimensional speckle-tracking echocardiography helps in detecting MVP at higher arrhythmic risk.

Methods:
We studied 21 arrhythmic MVP patients (group 1) with a history of complex ventricular ectopy on holter and/or event monitor (n=17) or defibrillator implant (n=2), 21 MVPs with no arrhythmic complications (group 2) and 21 healthy controls (group 3). 3D LV longitudinal strain (3DE-LVLS) and area strain (3DE-LVAS) were determined (17 segments). 3D LV dyssynchrony index (3DE-LVDI) was obtained as the standard deviation of the times to peak area strain in 17 segments, normalized to RR interval.

Results:
MVP patients had significantly higher LV dyssynchrony index compared to controls (9.4±3.9% vs 4.3±2.5%, p=0.002) although they had similar LV ejection fraction (64% vs 61%, p=0.51). Group 1 and group 2 had similar LV ejection fraction and clinical data (p>0.05). Bileaflet prolapse was more frequent in group 1 pts (52% vs 24%, p=0.03). Moderate mitral regurgitation was present in 9/21 group 1 pts and 3/21 group 2 pts (p=0.04). Group 1 pts had greater LV dyssynchrony index when compared with group 2 (10.7±4.1% vs 5.1±2.9%, p=0.0001). By ROC (receiver operating characteristics) curves, 3DE-LVDI and 3DE-LVAS cutoff values of 10.2% and -23.8%, respectively, had 89% and 85% sensitivity and 79% and 76% specificity in identifying the presence of significant arrhythmias with areas under the curve 0.87 and 0.84.

Conclusions:
Impairment of LV deformation parameters determined by three-dimensional speckle tracking echocardiography may help detect increased arrhythmic risk in patients with MVP.
Abstract 11636: Association Between Troponin Elevation and Adverse Outcomes: Effects of Cardiac, Non-Cardiac, Acute Coronary Syndrome and Non-Acute Coronary Syndrome Causes
Authors: Rodriguez Guerra Miguel , Omar Alaa , Miranda Jeirym , Dileep Arundhati , Garcia Alvaro , Ali Nisha , Jadhav Preeti , Sklyar Eduard , Vittorio Timothy , Bella Jonathan N
Published: March 2022

Introduction:
The role of high sensitivity troponin (HsTn) is clear in patients with acute coronary syndrome (ACS), however, its role in non-ACS positive HsTn is not. Accordingly, we studied the heterogeneity of outcomes as related to cardiac and non-cardiac causes of positive HsTn.

Methods and Results:
Retrospectively, 288 consecutive patients [60±17 years, 143 (49%) females, EF:59±14%] who had HsTn measured to exclude ACS were included and followed for a median of 4.9 months. Compared to negative HsTn, patients with positive HsTn were older (64±15 vs 57±16 year), with worse EF (55±16 vs 65±8%), left atrial volume index (43±15 vs 26±11 ml/m
2
, all p<0.001), E/e’ ratio (11.6±5.5 vs 9.4±2.7, p=0.002) Tricuspid regurgitation velocity (TRV, 2.8±0.5 vs 2.6±0.4, p=0.015). and pro-BNP (4625±12657 vs 166±228 pg/ml, p=0.003). Survival curves (figure 1) showed that composite of mortality and rehospitalization were not different between both groups at follow-up (p=0.789). Patients with positive HsTn were classified according to the cause of HsTn rise non-cardiac, cardiac non-coronary, coronary non-ACS, and ACS, figure 1). Admission and follow-up HsTn were highest in the non-cardiac group and comparable to the ACS group. Furthermore, the worst EF and diastolic dysfunction were found in ACS and cardiac non-coronary groups, while. Survival curves suggested that the composite outcomes were worst in non-cardiac and cardiac non coronary groups, best in coronary non-ACS group and intermediate in the ACS groups (p=0.05).

Conclusion:
Stratifying causes of HsTn elevation differentiated phenotypes of cardiac function and risk. Patients with non-cardiac or cardiac non-coronary causes had worse outcomes than ACS, while patients with non-ACS coronary causes approach the negative HsTn in terms of outcomes which may explain the lack of significant difference in composite outcomes between positive and negative admission HsTn.
Abstract 11644: Left Ventricular Hypertrophy and Hypertrophic Cardiomyopathy in Adult Solid Organ Transplant Recipients
Authors: Reza Nosheen , De Feria Alejandro , Wang Teresa , Chowns Jessica , Hoffman-Andrews Lily , Kim Jessica , Hornsby Nicole , Marzolf Amy , Atluri Pavan , Herrmann Howard C , Owens Anjali T
Published: March 2022

Introduction:
Data on the incidence and prevalence of HCM in adult post-transplant patients are limited. We describe the characteristics of adult solid organ transplant recipients diagnosed with HCM at a single center.

Methods:
Solid organ transplant recipients with LV wall thickness > 13 mm on TTE were included in this retrospective analysis. Clinical characteristics and outcomes were abstracted. Categorical variables were described as n (%). Continuous variables were described with medians and interquartile ranges (IQR) and compared using the Wilcoxon Rank Sum test. A 2-sided p value < 0.05 was considered statistically significant.

Results:
Twelve transplant recipients — 3 (25%) lung, 5 (42%) kidney, 4 (33%) liver — were identified. Half (50%) were women, and 42% were non-White. One kidney transplant patient had a pathogenic variant in Myosin Binding Protein C (MYBPC3 c.3190+1G>A), and one kidney transplant patient had a likely pathogenic variant in Myosin Heavy Chain 7 (MYH7 c.5561C>T). Most (75%) had NYHA II-III symptoms. Five (42%) had hypertension. 10 (83%) were treated with tacrolimus and 2 (17%) with cyclosporine for a median 11.5 years (IQR 5.0,17.5). All had normal to hyperdynamic LVEF on first TTE (median LVEF 72.5% [IQR 60,75]). Median septal thickness at diagnosis was significantly greater than LV posterior wall thickness (17 vs. 13 mm,
p
<0.001). Seven had resting LVOT gradients >50 mm Hg. Nine (75%) were on beta-blocker, and 3 (25%) were concomitantly on calcium channel blocker. Four patients underwent successful septal reduction therapy: 2 (kidney) with septal myectomy and 2 (lung, kidney) with alcohol septal ablation.

Conclusions:
We report the largest series of adult solid organ transplant recipients with HCM. Symptomatic HCM with dynamic LVOT obstruction can develop in solid organ transplant recipients. Medical management and septal reduction therapy are options for severe symptomatic disease. Prospective study of LVH in these patients is needed.
Abstract 11647: Influence of Hypercoagulability and Impaired Fibrinolysis on Occurrence of Acute Myocardial Infarction and Prognostic Implication Following Percutaneous Coronary Intervention
Authors: Kim Hyun Kuk , Lee Seung Hun , Park Yongwhi , Jeong Young-hoon , Hwang Jinyong , Ahn Jong-Hwa , Tantry Udaya , Gurbel Paul A
Published: March 2022

Introduction:
Although a plaque damage such as rupture is quite commonly observed, catastrophic event with clinical symptoms is not common in real practice.

Hypothesis:
Hypercoagulability and impaired fibrinolysis can be associated with the risk of coronary thrombosis and long-term clinical prognosis in patients with coronary artery disease (CAD).

Methods:
CAD patients who underwent percutaneous coronary intervention (PCI) (n=2,705) were enrolled (presented with acute myocardial infarction [AMI], 47.8%). Global hemostatic properties were evaluated with thromboelastographic assay (TEG
®
) showing hypercoagulability (maximal amplitude [MA]: platelet-fibrin clot strength) and impaired fibrinolysis (LY
30
: percent lysis 30 minutes after maximal clot strength). Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, myocardial infarction, or stroke.

Results:
Patients presented with AMI showed higher MA (66.5±7.8 vs. 65.3±7.2 mm, P<0.001) and lower LY
30
levels (1.0±2.5% vs. 1.2±2.2%, P=0.009) compared with non-AMI patients. Combined criteria of ‘MA≥68 mm’ and ‘LY
30
<0.2%’ increased the risk of AMI occurrence by 1.7-fold. During 4-year follow-up, MACE was associated with ‘MA≥68 mm’ (hazard ratio [HR] 1.447, 95% confidential interval [CI] 1.051-1.992, P=0.024) and ‘LY
30
<0.2%’ (HR 1.328, 95% CI 0.965-1.828, P=0.081), respectively. In multivariate analysis, patients with ‘MA≥68 mm’ and ‘LY
30
<0.2%’ showed an increased risk of MACE compared to those with ‘MA<68 mm’ and ‘LY
30
≥0.2%’ (adjusted HR 1.863, 95% CI 1.191-2.913, P=0.006) (Figure 1). Subgroup analysis showed that this trend was consistent irrespective of baseline demographics and lesional characteristics.

Conclusions:
Hypercoagulability and impaired fibrinolysis were more frequently observed in AMI patients. In addition, these properties were significantly associated with post-PCI clinical prognosis.
Abstract 11648: Bleeding in Patients Receiving Inhaled Pulmonary Vasodilators for Heart Failure Operations
Authors: Lorenzana-Saldivar Erick D , Cooter Mary , Parikh Jhana , Milano Carmelo A , Poisson Jessica , Rajagopal Sudarshan , Levy Jerrold , Ghadimi Kamrouz ,   INSPIRE-FLO Investigators
Published: March 2022

Introduction:
Inhaled pulmonary vasodilators (iPVD) are initiated after CPB during advanced HF operations to reduce RV failure development from high PVR. While inhaled nitric oxide (iNO) is the prototype, its high cost has led to inhaled epoprostenol (iEPO) use. While intravenous epoprostenol contributes to bleeding by platelet inhibition, bleeding and iEPO use has not been compared with iNO in this population.

Hypothesis:
No differences will be seen in perioperative bleeding between iEPO and iNO groups.

Methods:
A secondary analysis of a blinded RCT of 232 patients who underwent LVAD placement or orthotopic heart transplantation (HT), to receive either iEPO or iNO (NCT03081052). Bleeding outcomes were classified through POD 7 as blood product units transfused, delayed sternal closure for bleeding, need for re-exploration due to bleeding/tamponade, and chest tube output volume 12-hours immediately after surgery. Three-level ordinal primary outcome for bleeding was determined and compared between groups via univariable and multivariable proportional odds models. A priori bleeding risk factors were used to adjust for a multivariable model. RBC units transfused were compared univariably by negative binomial regression modeling.

Results:
Of 232 patients, 220 met inclusion criteria: 113 (51%) received iEPO and 107 (49%) received iNO. Of 220, 99 (45%) had LVAD placement while 121 (55%) had HT. Duration of use was similar between groups. Bleeding was common with mild-moderate bleeding in 49 % of the iEPO group v 46 % in iNO group, and severe-massive bleeding in 44% of iEPO group v 47% of iNO group. No differences for bleeding classes were seen in either univariable (OR 1.08, 95% CI: 0.65, 1.81) or multivariable (OR 1.14, 95% CI: 0.60, 2.17) proportional odds models. Modeling showed no differences in RBC transfusion between groups (mean ratio 1.16, 95% CI: 0.82, 1.64).

Conclusion:
No differences were seen in perioperative bleeding between iEPO v iNO for advanced HF operations.
Abstract 11653: Intravascular Targeted Photoactivation Guided by Optical Coherence Tomography-Near Infrared Fluorescence (OCT-NIRF) Imaging Promotes Stabilization of Atherosclerotic Plaques
Authors: Song Joon , Kim Yeon Hoon , Ahn Jae Won , Nam Hyeong Soo , KIM JIN HYUK , Kim Hyun Jung , Kim Ryeong Hyun , Kang Dong , Park Ye Hee , Song Jeonggeun , Park Kyeongsoon , Yoo Hongki , Jin Won Kim
Published: March 2022

Introduction and Hypothesis:
Photoactivation has emerged as an innovative therapeutic strategy for coronary high-risk plaque without metallic remnants, however, limited targetable ability of photoactivator and lack of imaging guidance hinders its application to clinics. To solve these unmet needs, we developed intravascular photoactivation strategy guided by dual-modal OCT-NIRF structural-molecular imaging using a novel theranostic NIRF-emitting photoactivator.

Methods and Results:
Photoactivatable NIRF-emitting theranostic agent targeting scavenger receptors on macrophages was newly synthesized. The intravascular photoactivation system based on fiber type cylindrical diffuser was newly fabricated for the therapeutic light delivery to the plaques. Forty-eight hours after intravenous injection of scale-up NIRF-emitting photoactivator (equivalent Ce6 dose of 2 mg/kg), OCT-NIRF imaging was able to exactly identify the highly inflamed targets in OCT-delineated plaques of rabbit arteries. Two weeks after therapeutic light irradiation through the catheter to the NIRF enhanced macrophages, the inflammatory NIRF signals of targeted atheroma markedly decreased as compared to the controls (Figure). By comprehensive immunofluorescence analysis, photoactivation produced a prominent increase in macrophage-associated apoptotic bodies and also induced autophagy with an enhanced efferocytosis, resulting in stabilization of the atheroma.

Conclusions:
Intravascular photoactivation using targeted NIRF emitting photosensitizer could stabilize the inflamed plaque under the guidance of OCT-NIRF imaging. This imaging guided therapeutic innovation will be a promising theranostic strategy for the high-risk coronary plaques.
Abstract 11657: Cannabis Use is Associated With Abnormal P-wave Axis
Authors: Patel Nikhil , Skipina Travis , Upadhya Bharathi , Soliman Elsayed
Published: March 2022

Introduction:
Cannabis use has been linked to incident ischemic cerebrovascular disease (CVA) and atrial arrhythmias in various case series and population studies.

Hypothesis:
Cannabis is independently associated with abnormal p-wave axis (aPWA), a marker of atrial myopathy.

Methods:
This analysis included 3,600 (age 48.2 ± 5.9 years, 47.6% male, 69.1% whites) participants from the Third National Health and Nutrition Examination Survey. Cannabis use was defined by self-report. aPWA was defined as p-wave axis outside of 0-75 degrees. Multivariable logistic regression was used to examine the association between cannabis use and aPWA. The consistency of this association was tested among subgroups stratified by demographic and comorbid covariates.

Results:
About 24.3% (n = 875) of participants were ever-cannabis users and 20.4% (n = 735) had aPWA. In multivariable and logistic regression analysis, ever- and former cannabis users had increased odds of aPWA compared to never users [OR (95% CI): 1.27 (1.03-1.56) and 1.28 (1.03-1.59), respectively]. Those reporting ≥10 lifetime uses had 40% increased odds of aPWA [OR (95% CI): 1.40 (1.07-1.84)]. This effect was stronger among ever-users with a history of cardiovascular (CV) disease versus those without [OR (95% CI): 4.11, 95% CI: 1.35 - 12.52, interaction p-value 0.03].

Conclusion:
Cannabis use is associated with atrial myopathy reflected as aPWA. This association is stronger among participants with a history of CV disease. These findings underscore a potential mechanism by which cannabis use increases the risk for ischemic CVA/atrial arrhythmias and highlights the need for personalized cannabis risk assessment.
Abstract 11662: Extracellular Vesicle (EV)-Derived PiRNA, ImEX-Pi, is Protective in a Rat Model of Ischemia/Reperfusion Injury
Authors: Ciullo Alessandra , Li Liang , Li Chang , Marban Eduardo , Ibrahim Ahmed G
Published: March 2022

Introduction:
Cardiosphere-derived cells (CDCs ) are a population of heart-derived progenitors with demonstrated therapeutic efficacy in preclinical and clinical settings. CDCs exert their effect through the secretion of EVs, lipid-bilayer nanoparticles laden with bioactive molecules. Among the bioactive cargo identified in these immortalized CDC (imCDC)-derived EVs (imCDC-EV) are piwi RNAs (PiRNAs). PiRNAs bind Piwi proteins (members of the argonaute family) and regulate both the epigenome and transcriptome. The role of piRNAs (in particular EV-derived piRNAs) in modulating gene expression remains undescribed. Here we describe the role of a PiRNA highly enriched in imCDC-EVs (imEX-Pi).

Methods:
EVs were prepared by 24 hours hypoxic conditioning followed by normoxic recovery for three cycles. EVs were isolated from conditioned media using ultrafiltration. Fractions were analyzed for particle size, concentration and piRNA content. In vitro, bone marrow derived-macrophages (BMDM) were exposed to imCDC-EV, imEX-Pi and vehicle for transcriptomic analysis. In vivo, myocardial ischemia-reperfusion (I/R) injury was induced in 8-10-week-old Wistar-Kyoto female rats by LAD coronary ligation for 45 minutes followed by reperfusion. Twenty minutes later, imCDC-EV, imEX-Pi, scramble or vehicle were injected into the left ventricle with an aortic cross-clamp. Cardiac Troponin I levels, infarct size and circulating monocytes were assessed at 24 and 48 hrs post I/R.

Results:
RNA sequencing showed that piRNAs are enriched in both CDC-EV and imCDC-EV. ImEX-Pi was one of the most highly-expressed non-coding RNAs.
In vitro
, imEX-Pi altered the transcriptome of BMDMs compared to vehicle. This included upregulation of inflammatory and cell death pathways. In a rat model of I/R injury, imEX-Pi reduced infarct size and cardiac troponin levels compared to vehicle- and scrambled- treated animals. ImEX-Pi also significantly decreased circulating monocytes at 24 hours followed by a significant increase at 48hrs.

Conclusions:
We show that imEX-Pi is a key mediator of imCDC-EV therapeutic efficacy and that the principle target cells may be macrophages. This is further rationalized by the critical role that macrophages play in the injury and resolution response.
Abstract 11682: Race, Sex, and Socioeconomic Disparities in Hospitalization With Ventricular Tachycardia or Cardiac Arrest in a National Medicare Cohort
Authors: Kipp Ryan T , Kalscheur Matthew , Sheehy Ann , Bartels Christie , Kind Amy J , Powell Ryan
Published: March 2022

Introduction:
Significant disparities by race, sex, and socioeconomic status exist in cardiovascular care. Yet little is known regarding the disparities in patients hospitalized with life-threatening arrhythmias.

Hypothesis:
We hypothesize that there are differences in race, sex, and socioeconomic status between patients who develop ventricular tachycardia (VT) or cardiac arrest (CA).

Methods:
Using the national 100% U.S. Medicare inpatient dataset of fee-for-service beneficiaries admitted with VT or CA from January 1, 2014 through November 30, 2014, multivariable logistic regression was constructed to examine the characteristics associated with hospitalization with VT compared to those with CA. Neighborhood-level socioeconomic disadvantage for each patient was measured by the Area Deprivation Index which reflects 17 dimensions related to education, income, housing, and employment factors.

Results:
Of 195,806 patients admitted with VT or CA, 117,930 (60%) were admitted with VT and 77,876 (40%) with CA. Those residing in the most disadvantaged neighborhoods had a significantly lower rate of hospitalization with VT, and a higher rate of hospitalization with CA (Figure 1). After adjustment for baseline demographics, comorbidities, and hospital characteristics, living in one of the top 20% most disadvantaged US neighborhoods (OR 1.09, 95% CI 1.05-1.12), female sex (OR 1.27, 95% CI 1.24-1.29), non-White race (OR 1.16, 95% CI 1.12-1.20), and non-urban residence (OR 1.10, 95% CI 1.06-1.14) were associated with greater odds of hospitalization with CA.

Conclusion:
Significant differences exist in the race, sex, and neighborhood socioeconomic characteristics for patients hospitalized with VT compared to those with CA. Possible etiologies for these differences include geographic or economic barriers in accessing acute medical care or trust in the medical system. Further studies are needed to investigate the drivers and solutions to this difference.
Abstract 11688: Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation and Cancer
Authors: Shabtaie Samuel A , Tan Nicholas Y , Ward Robert C , Herrmann Joerg
Published: March 2022

Introduction:
Prevention of stroke in patients with atrial fibrillation and cancer is challenging as patients are at increased bleeding and thrombotic risk. Left atrial appendage occlusion (LAAO) has evolved as a promising strategy for stroke prevention with protentional to reduce bleeding risk, though no data exists on its efficacy in patients with cancer.

Hypothesis:
LAAO is a safe and effective strategy for reducing stroke and bleeding risk in cancer patients with atrial fibrillation.

Methods:
We retrospectively reviewed all patients with nonvalvular atrial fibrillation who underwent LAAO at all Mayo Clinic sites from 2017-2020 and identified those who had undergone prior or current treatment for cancer. Baseline demographics, malignancy history, atrial fibrillation parameters, procedural success/complications, stroke and bleeding incidence and major adverse cardiac events were ascertained.

Results:
55 patients were included in the study; 44 (80.0%) were male and mean age was 79.0 ± 6.1 years. Most common primary malignancies included prostate cancer (29.1%), oropharyngeal cancer (12.7%), and melanoma (10.9%) with 15 (27.3%) having metastatic disease and 14 (25.5%) patients having active malignancy at device implant. Mean CHA2DS2-Vasc score was 4.9 ± 1.3, with 47 (85.5%) patients having a prior bleeding event. Acute procedural success was achieved in all patients with 30-day complications including 4 (7.3%) with vascular access site bleeding, 1 (1.8%) with pericarditis and 1 (1.8%) with a seizure. At a follow up of 1.8 ± 1.1 years, ischemic stroke occurred in 2 (3.6%) patients with bleeding complications in 5 (9.1%) patients. Device related complications occurred in 6 (10.9%) patients with 4 (7.3%) with device thrombosis and 2 (3.6%) with a peri-device leak. Death occurred in 14 (25.5%) patients most commonly due to malignancy progression (9.1%) and infection (7.3%).

Conclusions:
In our study cohort, LAAO in patients with cancer was achieved with excellent procedural success and offered reasonable reduction in stroke and bleeding risk. Mortality was high likely due to the age of the patients studied, underlying malignancy and comorbidities. Further studies are needed to investigate the prevalence of device thrombosis in cancer patients.
Abstract 11692: High-Sensitivity Cardiac Troponin and the Efficacy of Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction: An Analysis of the DAPA-HF Trial
Authors: Berg David D , Sabatine Marc S , Sattar Naveed , Jarolim Petr , WELSH Paul , Jhund Pardeep S , Anand Inder , De Boer Rudolf A , Kosiborod Mikhail , O'Meara Eileen , Hammarstedt Ann , Langkilde Anna Maria , Lindholm Daniel , Sjöstrand Mikaela , McMurray John J , Morrow David
Published: March 2022

Introduction:
Circulating high-sensitivity cardiac troponin T (hsTnT) reflects myocardial injury, and higher levels are associated with an increased risk of worsening heart failure (HF) and death in patients with HF with reduced ejection fraction (HFrEF). Dapagliflozin reduces the rate of worsening HF or cardiovascular death in patients with HFrEF. The effect of dapagliflozin on the risk of worsening HF or CV death in relation to baseline concentration of hsTnT in patients with HFrEF is unknown.

Methods:
DAPA-HF was a randomized, double-blind, placebo-controlled trial of dapagliflozin (10 mg once daily) in patients with New York Heart Association class II, III, or IV HF and a left ventricular ejection fraction ≤40%. We measured hsTnT (Roche Diagnostics) at baseline in 3,138 patients randomized in DAPA-HF and at one year among 2,500 survivors. The primary outcome was adjudicated worsening HF or cardiovascular death. Secondary outcomes included each component individually, hospitalization for HF, and death from any cause. The median follow-up was 18.2 months.

Results:
By the time of this presentation, data will be available for presentation of the distribution of baseline hsTnT concentration and the clinical characteristics associated with strata of hsTnT concentration. The association between baseline hsTnT and 2-year outcomes will be presented and adjusted for potential confounders, including age, sex, eGFR, history of diabetes mellitus, and principal cause of HF (ischemic or non-ischemic). The effect of dapagliflozin on the change in hsTnT concentration from baseline to one year will be presented. The effect of dapagliflozin on the primary and secondary outcomes (both absolute and relative risk reductions) stratified by baseline hsTnT concentration will be analyzed.

Conclusions:
Biomarkers of myocardial injury identify patients with HFrEF at heightened risk of adverse outcomes. This analysis from a large, international, randomized, placebo-controlled trial will provide a robust assessment of the effect of dapagliflozin on hsTnT and the ability of dapagliflozin to improve outcomes in relation to baseline hsTnT concentration.