bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19273: Fibroblast-Derived TSP1, via CD47, Upregulates Connective Tissue Growth Factor to Promote Left Ventricular Fibrosis and Heart Failure
Authors: Sharifi-Sanjani Maryam , Beezhold Kevin , Cook Hallie , Baust Jeffrey , Isenberg Jeffrey
Published: July 2021

Background:
An estimated 5.5 million individuals in the United States have left ventricular heart failure (LV HF). Therapeutics, while relieving symptoms and extending life in some cases, cannot resolve this process. LV HF is characterized by excessive accumulation of the extracellular matrix. The causes of this process remain incompletely understood. Our team has recently described a widely expressed cell surface receptor CD47 that is activated by its high affinity ligand, thrombospondin-1 (TSP1) to promote LV HF. However, the role of TSP1-CD47 signaling in promoting fibrosis, in general, and in the setting of LV HF, in specific, is unknown.

Methods:
Wild type mice expressing CD47 and mutated mice lacking CD47 (CD47 null) were subjected to transverse aortic constriction (TAC) for 4 weeks followed by open chest pressure-volume loop analysis of cardiac hemodynamics. Signal transduction was confirmed in isolated left ventricles (LV) and normal human ventricular fibroblast cell culture systems.

Results:
In biopsy samples from failing human hearts and in pre-clinical model of TAC-driven LV HF, TSP1-CD47 signaling was altered. Post-TAC wild type (CD47+/+) mice developed cardiac fibrosis, associated cardiac stiffness and HF. In contrast, CD47 null mice subjected to TAC showed enhanced cardiac function and decreased fibrosis concordant with suppression of TSP1. In cardiac resident fibroblasts, but not myocytes, hypoxia rapidly induced TSP1 protein, while treating with 7N3, a TSP1-based peptide mimetic that selectively binds CD47, increased connective tissue growth factor (CTGF) protein. Further, treating cardiac fibroblast with 7N3 increased fibroblast collagen production. Finally, CD47 blocking antibody mitigated established TAC-driven LV fibrosis and HF.

Conclusion:
These data identify a proximate role for activated cardiac fibroblast CD47 in promoting LV fibrosis associated with HF and suggest possible therapeutic opportunity.
Abstract 19285: Notch1 Haploinsufficiency Increases Risk of Congenital Heart Defects in the Setting of Maternal Diabetes by an Epigenetic Mechanism
Authors: Basu Madhumita , Bosse Kevin , Garg Vidu
Published: July 2021

Congenital heart disease (CHD) is the most common type of birth defect. Epidemiologic studies have shown the importance of genetic and environmental factors in the multifactorial etiology of CHD. Maternal diabetes mellitus (DM) is one of the non-genetic risk factors that predisposes to CHD predominantly cardiac septation and cardiac outflow tract defects. DM is known to be associated with endothelial cell dysfunction and we recently demonstrated a genetic interaction between endothelial nitric oxide synthase and Notch1, which encodes a receptor that functions in an important cardiac developmental signaling pathway. We hypothesized that maternal DM in the setting of
Notch1
heterozygosity of the developing embryo will predispose to CHD.

Notch1
+/-

embryos (E13.5) exposed to maternal DM demonstrated an increased incidence (86%) of ventricular septal defects compared to wildtype littermates (22%) (Table). Gene expression studies in non-diabetic wildtype, diabetic wildtype and

Notch1
+/-

embryos showed DM was associated with decreased Notch1 mRNA levels and upregulation in Jarid2, a histone H3K9 demethylase known to regulate Notch1. In H9C2 and endocardial-derived cells and chick embryos, we showed that hyperglycemia led to decreased expression of Notch1 and its downstream targets in a dose-dependent manner. Similarly, Jarid2 mRNA levels increased with high glucose. Furthermore, we found reduced luciferase reporter activity in cells transfected with a constitutively active Notch1 intracellular domain with hyperglycemia. Studies demonstrating the relative enrichment of Jarid2 on Notch1 locus with hyperglycemia by ChIP-qPCR will also be presented. Our findings reveal that maternal DM disrupts cardiac development by deregulating the Notch1 signaling pathway and suggest that this gene-environment interaction is mediated by an epigenetic mechanism involving Jarid2 providing the first mechanistic insights for this association.
Abstract 19297: Susceptibility Loci for Clinical CAD Predispose to Subclinical Coronary Atherosclerosis Throughout the Life Course
Authors: Salfati Elias , Nandkeolyar Shuktika , Fortmann Stephen , Sidney Stephen , Hlakty Mark A , Quertermous Thomas , Go Alan S , Iribarren Carlos , Goldstein Benjamin A , Assimes Themistocles L
Published: July 2021

Recent genome wide association studies (GWAS) have identified 49 single nucleotide polymorphisms (SNPs) associated with clinically significant complications of CAD including myocardial infarction (MI), CABG, PCI, and/or angina. The mechanism by which these loci influence the risk of clinical CAD remains largely unclear. We hypothesized that variants at these loci collectively facilitate the formation of coronary plaque in a monotonic fashion throughout the life course. We used genetic data from dbGAP (SEA, FHS, and MESA) as well as from the Stanford-Kaiser ADVANCE study imputed to the 1000 genomes project to examine the association between a genetic risk score (GRS) of high-risk alleles at these 49 SNPs and the presence of subclinical atherosclerosis. Subclinical atherosclerosis was identified by either pathologic examination of the coronary arteries or by radiographic assessment of coronary artery calcification (CAC). We stratified white/European subjects within each study into one of five age groups (≤30, 31-45, 46-60, 61-75, >75 years) and defined cases as subjects with either any raised lesions in their right coronary artery on autopsy (SEA, 26.7% subjects aged 18 to 30 years at time of unexpected death) or with an age and sex specific CAC score >75th percentile (all other studies, age > 30 years). Among 1561 cases and 5068 controls, we found a one SD increase in the GRS was associated with a 28% increased risk of having advanced subclinical coronary atherosclerosis (p = 3.82 x 10
-16
). This increase in risk was significant in every age stratum (.01 > p > 9.4 x 10
-7
)

and was remarkably similar across all age strata (p test of heterogeneity = 0.99). We obtained near identical results and levels of significance when we restricted the GRS to 33 SNPs not associated with traditional risk factors. Our findings strongly support the notion that susceptibility alleles for clinical CAD uncovered through large-scale meta-analysis of GWAS uniformly promote the development of coronary atherosclerosis from birth. This predisposition is sustained at a constant level throughout one’s lifetime. Given it is observed at the earliest stage of plaque formation, it is unlikely to involve a concurrent predisposition to plaque rupture and/or thrombosis.
Abstract 19354: Management and Outcomes of Acute Type B Dissection in IRAD Treated with Open Surgery, Endovascular Flap Fenestration or TEVAR
Authors: Costin Nathaniel I , Levanovich Peter , Bossone Eduardo , Peterson Mark D , Myrmel Truls , O’Gara Patrick , Suzuki Toru , Hutchison Stuart , Greason Kevin , Abdul-Nour Khaled , Trimarchi Santi , Montgomery Daniel G , Isselbacher Eric M , Nienaber Christoph A , Eagle Kim A , Patel Himanshu J
Published: July 2021

Background:
The debate for the optimal treatment of complicated Type B Acute Aortic Dissection (TBAAD) is primarily focused upon open surgical intervention versus thoracic endovascular aortic repair (TEVAR). The technique of fenestration with stenting has been proposed to resolve malperfusion. This study evaluated post-procedural outcomes of all three approaches for TBAAD.

Methods:
TBAAD patients enrolled in the International Registry of Acute Aortic Dissection were stratified by management type: TEVAR, fenestration and stenting, and surgery.

Results:
Of the 552 patients with TBAAD, 231 (41.8%) underwent TEVAR, 214 (38.8%) standard open surgery, and 107 (19.4%) fenestration and stenting. TEVAR or fenestration and stenting were more likely to be performed in classic double barrel aortic dissection when compared to open surgery (73.2%, 76.6%, 52.8% respectively; p<0.001). Patients treated with open repair were less likely to have distal extension into the abdominal aorta than those with TEVAR or fenestration and stenting (47.7%, 62.7%, 86.4%, respectively; p<0.001). In-hospital mortality was similar between groups (11.7% TEVAR, 14.0% fenestration and stenting, 15.9% surgery). At five years, Kaplan-Meier post-discharge all-cause survival estimates were highest for TEVAR, followed by endovascular fenestration and finally open surgical intervention (85.2%, 78.3%, 67.2%, respectively; p=0.039).

Conclusion:
Patients treated by endovascular approaches, whether with flap fenestration or thoracic endovascular aortic repair, had lower five year mortality when compared to patients who required open repair in the setting of TBAAD. Either endovascular approach may be helpful in the treatment of TBAAD. Further research is needed to determine how much of the observed difference represents patient selection versus differential effects of treatment.
Abstract 19370: Myocardial Extracellular Volume is Elevated in Human Duchenne Muscular Dystrophy
Authors: Soslow Jonathan H , Damon Stephen M , Damon Bruce M , Parra David A , Burnette W B , Sawyer Douglas B , Stein C M , Markham Larry W
Published: July 2021

Introduction:
Duchenne muscular dystrophy (DMD) leads to cardiomyopathy (CM) with variable severity and age of onset. Predicting early CM would alter therapeutic approaches and improve morbidity and mortality. Extracellular volume (ECV) calculated with cardiac MRI (CMR) quantifies extracellular matrix expansion, including myocardial fibrosis, and has never been reported in human DMD. We hypothesized that subjects with DMD would have abnormal ECV and that these values would correlate with other markers of LV function.

Methods:
27 DMD subjects were prospectively studied. CMR included LVEF, late gadolinium enhancement (LGE), circumferential strain (ε
cc
), and modified Look-Locker (MOLLI) sequences to calculate ECV maps (in-house software using Matlab). ECV calculated for each segment in the short axis at mid-ventricle and compared with LVEF and ε
cc
using linear regression. Normal values taken from unmatched cohort of healthy male adults with mean ECV of 0.25 ± 0.015 (range 0.23-0.28).

Results:
Imaging was adequate to calculate ECV maps in 20 DMD subjects. Mean age in years was 14. Mean LVEF was 52% and mean global ε
cc
was -14.6%; 11 subjects had LVEF < 55% and 6 had negative LGE. Mean ECV was 0.33 ± 0.05 (0.25-0.45); there was significant intersubject and intersegment variability (Figure 1). When compared with highest mean control ECV (0.28), only one subject had a normal ECV in every segment. In subjects with LVEF ≥ 55%, the mean ECV was 0.32 ± 0.07 (0.25-0.45). In subjects with negative LGE, the mean ECV was 0.28 ± 0.04 (0.25-0.36). The ECV of the inferolateral and anterolateral segments correlated with LVEF (p=0.025 and p<0.001) and the inferolateral ECV correlated with mean ε
cc
(p=0.025).

Conclusions:
In this cohort, 19/20 DMD subjects have elevated segmental ECV, even with normal LVEF and negative LGE. Segmental ECV correlates with both LVEF and mean ε
cc
. ECV may be a more subtle biomarker of early myocardial disease than standard measures such as LVEF and LGE in human DMD.
Abstract 19387: Angioplasty of Chronic Total Coronary Occlusions is Not Associated with Improved Survival Compared With Elective Medical Therapy: a Propensity Matched Retrospective Cohort Study
Authors: Ladwiniec Andrew , Allgar Victoria , Thackray Simon , Alamgir Farquad , Hoye Angela
Published: July 2021

Introduction:
Although an association between improved survival and successful PCI of chronic total coronary occlusions (CTO) compared with failed PCI has been widely reported, there is little published data reporting outcomes for those found to have a CTO which is electively treated medically versus those treated by PCI; a comparison which is more pertinent to clinical decision making. Our aim was to compare long-term clinical outcomes in a cohort of patients with an identified CTO on angiography between these two treatment groups. We hypothesised there would be a significant difference in all-cause mortality at 5 year follow-up.

Methods:
Patients found to have a CTO on angiography between 2002 and 2008, without prior CABG or important structural heart disease in a single tertiary centre were identified using a dedicated database. Patients undergoing CTO PCI and elective medical therapy to the CTO were propensity matched to adjust for baseline clinical and angiographic differences. Events at follow-up were identified using national death certification records and national registries for myocardial infarction, CABG and PCI. Comparisons were stratified by matched pair.

Results:
In total 1957 patients were identified, a CTO was treated by PCI in 405(20.7%) and medical therapy in 667(34.1%), 885(45.2%) patients underwent CABG. Of those treated by PCI or medical therapy, propensity score matching identified 389 pairs of patients. PCI was successful in 238 patients (61.2%). There was no difference in the primary study objective of 5 year mortality between the propensity matched treatment groups (CTO PCI: 10.8%, medical therapy: 15.7%; HR 0.74; 95% CI 0.49 to 1.11; p=0.146). There remained no difference if only the 238 matched pairs in which CTO PCI was successful were included (HR 0.83; 95% CI 0.48 to 1.42; p=0.493). There was an increase in repeat revascularization associated with CTO PCI (HR 2.18; 95% CI 1.49-3.18; p<0.001). This difference was not present in the successful PCI matched pair subgroup (HR 0.79; 95% CI 0.45-1.37; p=0.397).

Conclusions:
Using an alternative approach to much of the existing literature, we did not demonstrate an associated difference in survival between patients with a CTO treated by PCI versus those in whom the CTO was treated medically.
Abstract 19392: A Landmark Analysis of 30-day Mortality after Coronary Artery Bypass Surgery in Patients with Ischemic Heart Failure: Results of the Surgical Treatment for Ischemic Heart Failure (STICH) Trial
Authors: Wrobel Krzysztof , Stevens Susanna R , Jones Robert H , Selzman Craig H , Lamy Andre , Beaver Thomas M , Djokovic Ljubomir T , Wang Nan , Velazquez Eric J , Sopko George , Kron Irving L , DiMaio Micheal J , Michler Robert E , Lee Kerry L , Yii Michael , Chua Yeow Leng , Zembala Marian , Rouleau Jean L , Al-Khalidi Hussein , Daly Richard
Published: July 2021

Background:
Among patients (pts) with coronary artery disease (CAD) who are candidates for coronary artery bypass graft surgery (CABG), a reduced ejection fraction (EF) identifies a high-risk group. The profile of pre-operative, intra-operative and post-operative factors contributing to 30 day (d) mortality in pts with low EF undergoing CABG has not been well characterized.

Methods:
The STICH trial enrolled 2136 pts with CAD amenable to CABG with an LVEF < 35% who were treated with medical therapy (MED) alone, MED with CABG, or with MED plus CABG and surgical ventricular resconstruction (SVR). Multivariable logistic regression models utilizing extensive baseline, intra-operative and post-operative care variables were developed to determine factors associated with mortality at 30d in a landmark analysis among pts surviving the first 36 hours (h).

Results:
Among those enrolled, 1460 pts received CABG; 673 (46.1%) on pump, 160 (11.0%) off pump, 132 (9.0%) with a mitral valve procedure (MVR), 393 (26.9%) with SVR, and 102 (7.0%) received CABG with SVR and MVR. Mortality in the operating room (OR) was 0.3 %, within the first 36h was 1.0%, and at 30d was 5.1%. The rate of in-hospital acute myocardial infarction was 0.8%, stroke 1.6%, mediastinitis 1.7%, worsening renal insufficiency 8.4%, and return to OR was 6.9%. Inotropes were used in 43.6% and intra-aortic balloon pump in 18.6%. At 36h, 148 pts (10.2%) remained intubated. Among pts who survived to 36h, a robust multivariable model (Table, c-statistic 0.89) was developed to predict 30d mortality. A prolonged intubation time (>36h) was the strongest marker of 30d mortality (odds ratio 7.4, 95% CI 3.8, 14.5, p<0.0001).

Conclusions:
Among pts with ischemic heart failure, CABG can be performed with a low rate of complications and intra-operative mortality. Prolonged intubation time (>36h) after CABG is an integrated clincal marker that may serve to identify those pts with the least likelihood of survival to 30d.
Abstract 19483: Assessment of Outcome in Patients With Acute Minor Ischemic Stroke Treated With Intravenous TPA
Authors: Sharma Sameer , Afzal Umair , Pervez Mubashir , Clark Rochele , Latorre Julius G , El-Zammar Ziad
Published: July 2021

Introduction:
Minor acute stroke (NIHSS≤4) within 4.5 hours from symptom onset is a common reason for withholding intravenous (iv) Thrombolysis (TPA), due to potential risk of major bleeding with such treatment and assumed good outcome without intervention. This subgroup of patients was excluded from the landmark NINDS iv tPA trial as per the prespecified protocol and also from various recent clinical trials involving acute stroke. In a recent study of patients with Rapid Improving symptoms and Minor stroke who did not receive IV tPA, 28.3% could not be discharged home and 28.5% could not ambulate independently at the time of discharge (Smith et al 2011). The efficacy of iv TPA in Minor stroke has not been previously studied.

Method:
Retrospective review of consecutive patients with Minor stroke (NIHSS ≤4) arriving within 4.5 hours between January 2009-July 2013 was done. Outcome in patients who received IV TPA was compared with patients who did not receive any IV tPA. Good outcome was defined as mRS ≤2.

Results:
186 patients were identified out of which 20 received iv tPA. The baseline median NIHSS was 2 in the non-intervention group vs 3 in the intervention group (p =0.001), more cardioembolic, cryptogenic and lacunar stroke in tPA group (40% vs 35.53%, 20% vs 14.46% and 30% vs 22.89% respectively) there was no other statistically significant difference between the baseline characteristics of the two groups. Median change in NIHSS from admission to discharge was 1 for non-tPA vs 2.5 for tPA(p<0.001) and good outcome at discharge was seen in 80% patients in tPA vs 69.28% in non-tpa group (p =0.321). 8-12 week follow up data was available for 100 patients (12 tPA patients). Mean mRS was 1.34 in non-tPA vs 1 in tPA group (p=0.430)

Conclusion:
Acute intervention in Minor stroke appears to be safe. We did not find any statistically significant difference in clinical outcome between the two groups; this is likely due to small sample size, short follow-up period, and other confounding factors that we cannot fully account for in a retrospective study. A prospective randomized control study is warranted to clearly delineate the effect of iv TPA in patients with Minor stroke.
Abstract 19569: High-sensitive Troponin T Cut-off Value for Myocardial Infarction After Vascular Surgery
Authors: Gualandro Danielle M , Llobet Gisela B , Yu Pai C , Calderaro Daniela , Marques Andre C , Pastana Adriana F , Caramelli Bruno
Published: July 2021

Introduction:
Isolated high sensitive cardiac troponin T (hsTnT) elevations after vascular surgery are frequent and may lead to over diagnosis of myocardial infarction (MI). The aim of our study was to determine the accuracy of the current hsTnT cut-off value in the setting of acute coronary syndrome (ACS) after vascular surgery.

Methods:
Between August 2012 and March 2014, we included 337 consecutive patients submitted to arterial vascular surgery for which cardiac perioperative evaluation was requested. Perioperative surveillance included 12-lead electrocardiogram and hsTnT measurements on the three days following surgery. Patients were followed-up by cardiologists until hospital discharge and monitored for ACS. A receiver operating characteristics (ROC) curve analysis was performed to determine the hsTnT cut-off value with better accuracy for the diagnosis of perioperative ACS.

Results:
Of the 337 patients included, 240 (71.2%) presented hsTnT elevation above the manufacturer-provided cut-off value (0.014 ng/ml), whereas 22 (6.5%) fulfilled criteria for ACS. Median post-operative peak hsTnT of ACS patients were 0.215 ng/ml (IQR 0.043-0.493 ng/ml), versus 0.02 ng/ml (IQR 0.012-0.038 ng/ml) in patients that did not have events (P<0.001). After performing a ROC curve analysis (AUC = 0.876), we found that the manufacture-provided cutoff hsTnT value yielded a sensitivity of 100% and specificity of only 35% for diagnosis of perioperative ACS. A new hsTnT cutoff value of 0.0415 ng/ml was obtained with 86.4% sensitivity and 77% specificity for the diagnosis of perioperative ACS. Ninety-two patients (27.3%) had hsTnT elevations above the proposed new cutoff.

Conclusion:
A different hsTnT cutoff value of 0.0415 ng/ml is proposed and could be more useful for the diagnosis of perioperative ACS.
Abstract 19626: Muscle Weakness Induces Left Ventricular Hypertrophy via Frequent Elevation of Functional Arterial Stiffness During Exercise in Patients With Hypertension
Authors: Kamada Yumi , Masuda Takashi , Kamekawa Daisuke , Tanaka Shinya , Aoyama Akihiro , Itoh Yoko , Moriguchi Ibuki , Kobayashi Naoyuki , Okubo Michihito , Maekawa Emi , Ako Junya
Published: July 2021

Background:
Hypertension (HT) characterized by autonomic imbalance, is well known to induce an inappropriate elevation of arterial stiffness resulting in left ventricular hypertrophy (LVH). On the other hand, decreased muscle strength enhances autonomic imbalance by stimulating muscle sympathetic activity during exercise even at low- or moderate-intensity. However, it is unclear whether muscle weakness induces LVH via frequent elevation of functional arterial stiffness during exercise in patients with HT. The aim of this study was to investigate the relationships among muscle strength, autonomic activity during exercise, functional arterial stiffness and LVH in them.

Methods:
Fifty-five patients with HT aged 68±9 years, 32 males and 23 females, participated in this study. We measured plasma brain natriuretic peptide (BNP) and LV mass index (LVMI) on echocardiogram as parameters of LV overload and LVH, respectively, and knee extension muscle strength. Patients performed a treadmill exercise test to examine heart rate recovery (HRR). We assessed the changes from baseline values of plasma noradrenalin (NA) and brachial-ankle pulse wave velocity (PWV) to those measured just after a cycle ergometer exercise test that was performed at moderate-intensity ([[Unable to Display Character: ⊿]]NA and [[Unable to Display Character: ⊿]]PWV, respectively). The HRR, [[Unable to Display Character: ⊿]]NA and [[Unable to Display Character: ⊿]]PWV were used as parameters of parasympathetic and sympathetic activities and functional arterial stiffness, respectively. We analyzed the relationships among muscle strength, HRR, [[Unable to Display Character: ⊿]]NA, [[Unable to Display Character: ⊿]]PWV, BNP and LVMI.

Results:
Muscle strength was negatively correlated with [[Unable to Display Character: ⊿]]NA (r=-0.23, P<0.05), [[Unable to Display Character: ⊿]]PWV (r=-0.24, P<0.05), BNP (r=-0.23, P<0.05) and LVMI (r=-0.23, P<0.05). No significant relationship was observed between muscle strength and HRR. LVMI was positively correlated with [[Unable to Display Character: ⊿]]PWV (r=0.28, P<0.05).

Conclusion:
Muscle weakness induced LVH via frequent elevation of functional arterial stiffness caused by autonomic imbalance during exercise in patients with HT.
Abstract 19664: Molecular Mechanisms of Gα12 Regulated E-cadherin Shedding in Epithelial Cells
Authors: Xu Jen , Wu Yong , Li Suyang , Lim Kenneth , Kong Tianqing , Lu Tzongshi
Published: July 2021

Introduction and hypothesis:
E-cadherin plays an important role in maintaining the integrity of cell polarity and cell junctions. It is one of the major proteins that forms part of the polycystin-1 (PC1) complex in renal epithelial cells. We previously showed that deletion of the PC1-regulated protein, Gα12, protected kidneys from development of kidney cysts induced by Pkd1 inactivation and activation of Gα12 increased the shedding of E-cadherin in autosomal dominant polycystic kidney disease (ADPKD). The objective of this study was to determine the molecular mechanisms by which Gα12 regulates E-cadherin shedding.

Methods:
We analyzed polycystic kidneys from human and from Pkd1 knock-out mice. Using Madin-Darby canine kidney (MDCK) cells, we developed a Pkd1 deletion in vitro model using Pkd1 siRNA.

Results:
Our data shows that Pkd1 deletion caused accumulation of cleaved E-cadherin fragment in renal cystic fluid in both human polycystic kidneys and in our mice model. In addition, we found that activation of Gα12 increased the active form of ADAM10, the cleavage protein for E-cadherin in both human and mice polycystic kidneys, in vivo. In our MDCK cellular three-dimensional culture system, Gα12 activation promoted cyst formation and this phenomenon was inhibited by ADAM10 knockdown. Furthermore, knockdown of ADAM10 abolished the shedding of E-cadherin caused by Gα12 activation. These data indicate that ADAM10 is the major sheddase for cleavage of E-cadherin caused by Gα12 activation.

Conclusion:
Our results demonstrate that Gα12 activation increases ADAM10 activity and promotes the ectodomain shedding of E-cadherin, which is an important mechanism in the development of kidney cysts induced by Pkd1 deletion in ADPKD.
Abstract 19675: Testing Strategies and Poor Outcomes of Syncope among Medicare Beneficiaries
Authors: Rao Meena P , McCoy Lisa A , Stafford Judith , Curtis Lesley H , Al-Khatib Sana , Hernandez Adrian F
Published: July 2021

Background:
Syncope is a common problem among older patients in the United States and national guidelines recommend a variety of tests to determine the etiology. However, few data are available regarding how tests are used nationwide and outcomes of patients presenting with syncope.

Methods:
Using the nationally representative 5% sample of Medicare beneficiaries 65 years or older, we identified patients who had at least 1 inpatient or 2 outpatient claims for syncope between 2001 and 2010. We excluded beneficiaries with a pacemaker or implantable cardioverter defibrillator in situ prior to the incident syncope encounter that required no prior claim of syncope in the prior 365 days.

Results:
The overall incidence of syncope in 2001 was 11.8 per 1000 person years and remained stable over time ranging from 10.3 to 14.6 per 1000 person years. The average age of beneficiaries with syncope was 79, with the majority being women (63.3%) and white (87.5%). Hypertension was the most common comorbid condition (84%) followed by coronary heart disease (46.5%). When considering the tests ordered within 90 days of the incident encounter, the most frequently ordered tests were CT head (57%) and echocardiogram (50%). Holter monitors were ordered for 18% of beneficiaries, implantable loop recorders for 0.2%, tilt table testing for 4% and electrophysiology study for 2.7% of beneficiaries. From 2001 to 2010, the frequency of these tests did not significantly vary. Mortality at one year was 13% overall (17% for inpatients and 6% for outpatients). All cause readmission at one year was 44% with readmissions for syncope 9% (figure).

Conclusion:
Syncope is a common condition and is associated with a high mortality and hospitalization within 1 year of initial presentation. Guideline recommended diagnostic tests are ordered infrequently and represent an opportunity to improve care by developing a structured approach for the evaluation of syncope.
Abstract 19710: Causes for Increased Cardiac Troponin I Using Gender-Specific 99th Percentiles From a High Sensitivity Assay in a US Population
Authors: Sandoval Yader , Smith Stephen W , Schulz Karen M , Murakami MaryAnn M , Apple Fred S
Published: July 2021

Introduction:
High-sensitivity cardiac troponin (hs-cTn) assays have not yet been FDA cleared for clinical use in the United States (US). Pending expected approval of hs-cTn assays, which will use gender-specific cutoffs (GSC), it is relevant to recognize the causes of cTn increases using hs-cTnI assays in a US population. Our purpose was to describe the frequency of distinct etiologies of hs-cTnI assay increases using GSC.

Methods:
Retrospective study of 310 patients with serial hs-cTnI (Abbott ARCHITECT, 99th percentiles: F:16 ng/L; M:34 ng/L) measurements. Patients with an increased hs-cTnI were adjudicated into categories according to the 3rd Universal Definition of MI. Categories included, A: primary myocardial ischemia (i.e. plaque rupture); B: injury secondary to supply/demand imbalance; C: injury not related to myocardial ischemia (i.e. cardiac contusion, ablation, shock, surgery); D: multifactorial or indeterminate myocardial injury (i.e. heart failure, critically ill, pulmonary HTN, sepsis, stroke, renal failure, pulmonary embolism); E: Unknown.

Results:
127 (41%) had an increased hs-cTnI above the GSC 99th percentile, whereas 183 (59%) had a normal hs-cTnI. The most common causes of hs-cTnI increases were: a) multifactorial or indeterminate injury - 43% among all patients and 52% in males, and b) supply/demand imbalance - 39% in women (Table). Injury related to primary myocardial ischemia was present in 10% (n=13). Females had more injury related to supply/demand ischemia than males (39% vs. 18%, p=0.01), whereas males had more multifactorial or indeterminate injury (52% vs. 33%, p=0.05).

Conclusions:
Most increased hs-cTnI values were explained by non-plaque rupture conditions. Males tended to have hs-cTnI increases due to multifactorial/indeterminate causes, whereas in women supply/demand imbalance was the most common etiology. Investigations are needed to better understand if etiologies of myocardial injury have gender differences.
Abstract 19735: Temporal Trends in Sample Size of RCTs in Published Cardiology Literature from 1970-2013
Authors: Jain Sonia , Luis Sushil A , Coelho Vivien , Ilan Bushari Limor , Holm Hilma , Subramanian Arun
Published: July 2021

Background:
It is generally perceived that sample sizes of randomized clinical trials (RCTs) have increased over the years, particularly in specialties such as cardiology, with a robust evidence base. The aim of this study was to analyze temporal trends in sample sizes of RCTs in cardiology journals compared to other specialties.

Methods:
Abstracts of RCTs involving humans from PubMed for 1970-2013 were analyzed using a digital search algorithm. Sample sizes of studies were extracted from each abstract. Date of publication and journal name were collected. Journals from several medical subspecialties were selected for comparison, using the journal impact factor as a measure of clinical relevance. Sample sizes of studies in 1990 were compared to 2010 for each of the journals using the Mann-Whitney U test. Graphical comparisons of sample size trends are presented.

Results:
272,054 abstracts of human RCTs were identified. Median sample sizes for the years 1990 and 2010 is shown in table 1. The median sample size for all RCTs published in Circulation was 99 subjects per study in 1990, increasing to 630 subjects per study in 2010 (p < 0.01). All cardiology journals had a significant increase in study sample size over the 20 year period, as did the multispecialty journals (JAMA, NEJM, Lancet). In contrast, only a few non-cardiology specialty journals published studies with increasing sample sizes (table 1). Figure 1 shows the sample size trend for 1970-2013.

Conclusions:
Our study demonstrates a dramatic temporal trend of increasing sample sizes in RCTs in cardiology compared to other specialties. Since sample size is estimated based on the effect size studied, one explanation for this observation is that the more obvious larger effects have been previously elucidated, leaving only smaller associations to be studied. This requires increasing resources, highlighting the importance of alternate study designs and collaborative registries to develop a cost effective evidence base.
Abstract 19798: Should Downsizing Still Be the Gold Standard for Treatment of Ischemic Mitral Regurgitation?
Authors: Robic Boris , Van De Bruaene Alexander , Cools Thijs , Verwerft Jan , Yilmaz Alaaddin , Mees Urbain , Hendrikx Marc
Published: July 2021

Background:
Mitral valve annuloplasty (MVA) or replacement (MVR) are common strategies in the treatment of functional ischemic mitral regurgitation (FIMR). However, the issue of functional stenosis during exercise in MVA patients was raised. This study aims to compare exercise hemodynamics of MVA and MVR patients.

Methods:
Thirty patients (23 MVA, 66.8±8.8 y at repair, and 7 MVR, 66.1±5.5y) underwent exercise echocardiography. Stroke volume, ejection fraction, cardiac index, mitral valve gradient, mitral valve area and pulmonary artery pressures were evaluated at rest and at peak exercise.

Results:
Both patient groups had comparable exercise capacity (65±16 vs 67±15 %predicted; P=0.760). In MVA patients, stroke volume (38±14 to 39±14 mL; P=0.707) and ejection fraction (51±15 to 55±14%; P=0.123) did not change, whereas cardiac index (2.9±1.1 to 4.2±1.2 L/min.m
2
; P<0.0001), mitral valve gradient (peak 11.8±4.6 to 21.3±7.6 mmHg; mean 5.2±2.2 to 11.3±4.9 mmHg; both P<0.0001) and pulmonary artery pressure (33±10 to 51±16 mmHg; P<0.0001) increased during exercise. In MVR patients, stroke volume (29±7 to 35±7 ml; P=0.006), ejection fraction (52±12 to 61±14%; P=0.009), cardiac index (2.0±0.4 to 3.1±0.9 L/min.m
2
; P=0.006), mitral valve gradient (peak 9.8±3.8 to 22.0±7.5 mmHg; mean 4.8±1.8 to 12.3±4.3 mmHg; both P<0.05) and pulmonary artery pressure (32±5 to 45±9 mmHg; P=0.006) all increased during exercise. Cardiac index at rest (P=0.040) and at peak exercise (P=0.038) was slightly higher in the MVA group, whereas pulmonary artery pressures at rest (P=0.750) and at peak exercise (P=0.293) were not statistically different. Total pulmonary resistance did not change during exercise (P=0.115 and P=0.546 for MVA and PVR respectively). In MVA, there was a relation between peak mitral valve gradient at rest and pulmonary artery pressure at rest (R=0.525, P=0.017) and at peak exercise (R=0.508; P=0.022).

Conclusions:
Surgical repair achieves leaflet coaptation at the expense of raised transmitral gradients. Even after successful MVA, patients had worse exercise hemodynamics and lack of mitral valve opening reserve. Therefore we should question downsizing as the gold standard for treatment of FIMR and look for a more patient tailored approach.
Abstract 19949: Attainment of Lipid Levels in Patients at High Cardiovascular Risk: Results from a U.S. Managed Care Population Study
Authors: Steen Dylan , Khan Irfan , Becker Laura K , Gorcyca Katherine M , Foody JoAnne
Published: July 2021

Background:
Current, generalizable data on low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) as well as triglyceride (TG) levels are necessary to guide health policy decisions, guideline recommendations and treatment innovation. While LDL-C and non-HDL-C are established targets, TG elevations of 150-500 mg/dL and >500 mg/dL can contribute to CV disease and pancreatitis risk, respectively. We evaluated attainment of these lipid measures in a large, managed care population in the US.

Methods:
The analysis included patients from the Optum Research Database meeting the following criteria: a valid lipid profile measurement in 2012 (i.e. “index date”); ≥20 years of age; continuous enrollment for≥ 2 years; and ≥1 high risk CV condition. Each patient was categorized into a mutually-exclusive category in the following hierarchy: acute coronary syndrome (ACS) within 12 months; stable coronary heart disease (CHD); ischemic stroke; peripheral arterial disease (PAD); and diabetes mellitus. Patients covered by a prescription on the index date or within 30 days were considered to be on treatment.

Results:
In total, 217,516 patients met the inclusion criteria. Median (Q1 to Q3) age was 61 (53 to 70) years, 51.6% were male, 10.7% were treated with intensive statins, 34.8% with less-intensive statins and 5.8% with nonstatin lipid-modifying therapy. Median LDL-C was 92 (72 to 116) mg/dL, non-HDL-C was 118 (96 to 145) mg/dL and TG was 120 (85 to 169) mg/dL in the overall cohort. The frequency of lipid level achievement is displayed by hierarchical disease state (TABLE).

Conclusions:
This study is the largest analysis of LDL-C, non-HDL-C and TG levels in a contemporary US managed care high risk population. Statins were underutilized, reflected by inadequate achievement of optimal LDL-C and non-HDL-C levels. While very high TG levels were infrequent, more optimal TG level were only achieved in about two-thirds of the population.
Abstract 20038: Maternal Pre-Pregnancy Overweight is Associated with Increased Cardiovascular Disease Mortality in the Framingham Heart Study
Authors: Mendelson Michael , Lyass Asya , de Ferranti Sarah D , Andersson Charlotte , Fox Caroline , O’Donnell Chris , Gillman Matthew , D’Agostino Ralph B , Levy Dan
Published: July 2021

Introduction:
In the U.S., obesity among women of childbearing age is highly prevalent. Maternal obesity is associated with offspring obesity and cardiovascular disease (CVD) risk factors, potentially through epigenetic and early developmental mechanisms. There is limited evidence on the association of maternal overweight with offspring CVD events and mortality.

Methods:
We analyzed prospectively collected data from 1971 to 2012 on 879 Framingham Heart Study Offspring cohort participants with either directly measured pre-pregnancy maternal body mass index (BMI) (n=361) or offspring-reported maternal pre-pregnancy overweight status (n=518). Our outcomes included a composite measure of any CVD event or mortality, CVD mortality and all-cause mortality. Cox proportional hazard models were conducted, initially age and sex adjusted, and then additionally adjusted for potential mediators including traditional CVD risk factors. Pharmacologic treatments for diabetes, hypertension, and/or dyslipidemia were included as time-varying covariates.

Results:
Maternal pre-pregnancy overweight (BMI >= 85th percentile or self-report) was available for 879 Framingham Offspring Study participants (mean age [SD] at baseline 30 [5] years; 49% female; mean follow-up [SD] 32 [8] years). There were 193 CVD events, 28 CVD deaths, and 138 total deaths among the offspring. Maternal overweight was associated with an increased hazard ratio (HR) with CVD mortality (HR 10.5 [2.6-43]; p=0.001), all-cause mortality (HR 3.1 [1.5-6.4]; p=0.002), and marginally associated with the composite endpoint of CVD events and mortality (HR 1.7 [95% CI 0.99-2.8]; p=0.05). Adjustment for offspring BMI, diabetes, hypertension, and dyslipidemia attenuated the associations. In sensitivity analyses restricted to only those with directly measured maternal pre-pregnancy BMI, effect estimates remained robust (similar hazard ratios but larger confidence intervals).

Conclusions:
Maternal pre-pregnancy overweight is associated with offspring CVD mortality. The association is likely mediated in part through classical CVD risk factors such as offspring obesity, hypertension, diabetes, and dyslipidemia.
Abstract 20119: Incidence and Predictors of Left Ventricular Thrombus in ST Elevation Myocardial Infarction
Authors: Driesman Adam , Hyder Omar , Lang Chris , Abbott Jinnette
Published: July 2021

Introduction:
Anticoagulation with coumadin is often employed after anterior ST-segment elevation myocardial infarction (STEMI) complicated by left ventricular (LV) dysfunction to prevent LV thrombus and cardioembolic events. However, the combination of dual antiplatelet therapy used for coronary stents and coumadin has been repeatedly shown to have a high incidence of bleeding. The current guidelines give coumadin a class II recommendation and support an individualized approach to treatment.

Hypothesis:
Determining the incidence and predictors of LV thrombus in a contemporary STEMI population at high risk for LV thrombus may assist in clinical decision making.

Methods:
Anterior STEMI patients at our institution between 2006 and 2013 treated with primary percutaneous intervention (PCI) that had an echocardiogram performed within 1 week and an ejection fraction of less than 40% or less than 50% with anterior apical akinesis were retrospectively identified. 687 patients with anterior STEMI were screened and 310 met inclusion. Demographic, clinical, and angiographic data was extracted from the medical record. Patients were categorized in 2 groups according to echocardiographic findings (no LV thrombus or probable/definite LV thrombus). The groups were compared by chi squared or T-test where appropriate. Logistic regression analysis was performed.

Results:
The mean age of the study population was 61.8% and 71.5% were male. The incidence of LV thrombus was 15% (n=263 no thrombus; n=47 probable/definite thrombus). Patients with LV thrombus were less likely to have hyperlipidemia, and more likely to have post procedure TIMI 0-1 flow and no stent use compared to patient with no LV thrombus. After adjustment, variables associated with LV thrombus risk were cardiac arrest (OR 4.06, 1.3-12.7), unfractionated heparin post PCI (2.43, 1.16-5.1), and stent use (DES 0.22, .06-.77, BMS 0.23 .07-.75, compared to balloon angioplasty).

Conclusions:
The incidence of LV thrombus in at risk STEMI patients remains high in contemporary practice. Development of a clinical risk score is limited by the lack of a sufficient number of predictive variables. Further investigation is needed to determine the optimal anticoagulation strategy in these patients.
Abstract 20143: Direct in vivo Quantification of Intraplaque Hemorrhage and Fat in Atherosclerosis by Magnetic Resonance Imaging
Authors: Koppal Sandeep , Warntjes Marcel , Swann Jeremy , Dyverfeldt Petter , Kihlberg Johan , Moreno Rodrigo , Magee Derek , Roberts Nicholas , Treanor Darren , de Muinck Ebo D
Published: July 2021

Introduction:
Intraplaque hemorrhage (IPH) and lipid core (LC) are hallmarks of rupture-prone atherosclerotic plaque.

HYPOTHESIS:
We hypothesized that IPH and LC can be quantified using R2* and fat measurements derived from four-point Dixon magnetic resonance imaging (MRI).

Methods:
Four patients scheduled for carotid endarterectomy underwent MRI in a 3T scanner applying: (a) T1weighted: TE=9ms, TR=1053ms (b) 4-point Dixon 3D gradient echo: TE=3.6ms, R=18ms, flip angle=10°, 2 REST slabs (c) 4-D flow MRI: TE=3.1ms, TR=5.4ms, flip angle=10°. IPH and fat were quantified from Dixon using custom software (Figure: visualization of IPH, red and LC, yellow as measured from Dixon MRI). After surgery, plaques were paraffin embedded and
enface
images were taken every 50μm. Every 200μm sections were taken for histology. A 3D histology volume was generated from this data and registered to MRI with the vessel lumen as a landmark. Area of IPH and LC upon histology was correlated to MRI values within these areas and MRI signal within IPH and LC was compared to MRI signal outside these areas.

Results:
Registration of 3D histology was through combining features from T1weighted MRI, first echo from Dixon and 4D flow MRI. Throughout all plaques the correlation between R2* and area of IPH as well as fat from Dixon and area of LC upon histology was high (IPH: Pearson r 0.451, 95% CI: 0.364 t- 0.530, P<0.0001; LC: Pearson r 0.148, 95% CI: 0.0635 - 0.231, P<0.001). Throughout each plaque R2* within IPH was significantly higher than outside (mean difference±SEM/patient: (i) 11.96 ± 2.091 (ii) 7.616 ± 2.154 (iii) 12.66 ± 1.412 (iv) 14.13 ± 2.144; P<0.001). Fat from Dixon was significantly higher inside LC than outside (mean difference±SEM/patient: (i) 1.796 ± 0.386 (ii) 3.078 ± 0.328 (iii) 6.610 ± 0.651 (iv) 0.481 ± 0.242 N=167; P<0.0001).

Conclusions:
R2* and fat measured from Dixon MRI reliably quantifies the extent of IPH and LC in atherosclerotic plaques as validated by 3D histology.
Abstract 20162: Comparision of Procedural and 30 Day Outcomes of Roataional vs Orbital Atherectomy in Severely Calcified Coronary Lesions
Authors: Rajamanickam Anitha , Baber Usman , Aquino Melissa , Roy Swathi , Kini Annapoorna , Sharma Samin
Published: July 2021

Introduction:
The percutaneous treatment of heavily calcified coronary lesions remains suboptimal and often requires debulking with Rotational Atherectomy (RA) which is often underutilized due to a steep learning curve. Although a novel approach using Orbital Atherectomy (OA) has been introduced, which has an easier set-up and easier learning curve, a comparative assessment of both techniques in real world cohort has not been performed

METHODS:
Retrospective analysis of our prospectively collected database between October 2013 to May 2014 for patients undergoing atherectomy in heavily calcified lesions at our center retrieved 105 OA and 196 RA procedures

RESULTS:
There were no significant differences in patient demographics.The maximal stent diameter was significantly larger in OA vs RA (3.41 mm
2
vs 3.28 mm
2
, p=0.02).There was a trend towards RA showing better Procedural success defined as successful stent deployment with TIMI 3 flow ( 95.9% vs 90.5%, p = 0.06) and Clinical Success which is procedural success without death, stroke or CABG ( 95.9% vs 90.5%, p = 0.06). Two cases of failed initial OA underwent successful RA. Procedural complications (≥ grade 3 dissection, side branch closure, perforation, slow flow/no flow or vessel closure), In-hospital MACE (a composite of death, stroke, CABG or CKMB>5X), 30 day readmission rates and 30 day MACE were not statistically significant[See Table 1 and Figure 1].

CONCLUSION:
OA demonstrated a similar safety and efficacy profile to RA with a trend towards lower procedural success but comparable complications and 30 day outcomes, suggesting OA may serve as an alternative to RA in PCI of heavily calcified lesions.
Abstract 20183: Intraprocedural C-Arm CT Imaging Identifies Incomplete Stent Frame Expansion in Self-Expanding Aortic Valve Prostheses Associated With Perivalvular Aortic Regurgitation
Authors: Lin C. Huie , Smithson Shaun , Chinnadurai Ponraj , Shen Yi-Ting , Barker Colin , Ramlawi Basel H , Reardon Michael , Little Stephen H , Kleiman Neal S
Published: July 2021

Introduction:
Transcatheter aortic valve replacement has revolutionized the treatment of severe aortic stenosis, but post implantation perivalvular aortic regurgitation may result in increased mortality.

Hypothesis:
The purpose of this study was to identify structural abnormalities in the frame of self-expanding aortic valve prostheses (CoreValve®, Medtronic, Minneapolis, MN) immediately following implantation and evaluate their relationship to subsequent perivalvular aortic regurgitation severity.

Methods/Results:
After implantation of CoreValve, 14 patients with evidence of frame deformation by fluoroscopy underwent intraprocedural C-arm CT imaging (syngo DynaCT®, Siemens Medical Solutions, USA) acquired using 5-s, 200° rotation under breath-hold and rapid right ventricular pacing (120-140bpm). CT-like multi-planar reconstructions (Figure) were performed; perimeter (P), maximum (Dmax) and minimum (Dmin) diameters of the CoreValve frame were measured at multiple levels (0mm, 8mm, 16mm) orthogonal to the longitudinal axis. Ellipticity index (EI) was measured as Dmax divided by Dmin. Color Doppler transthoracic echo was performed the day following valve implantation to assess perivalvular regurgitation. One-way ANOVA demonstrated that degree of perivalvular aortic regurgitation was significantly related to valve frame perimeter underexpansion at the inferior margin of the frame (20.8% [17.2-25.7%], p=0.011) and increased ellipticity index both at the 8mm above the edge of the frame (1.4, [1.3-1.5], p=0.012) and 16mm above the edge of the frame (1.4, [1.3-1.5], p=0.038).

Conclusions:
Intraprocedural DynaCT effective at determining aortic valve frame deformations in 3D, which was associated with increased perivalvular aortic regurgitation, and may provide a method for risk stratifying post-implantation aortic regurgitation and need for additional procedural maneuvers such as post-stent dilation or additional revalving.