bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15821: Safety and Efficacy of Non-invasive Ventilation During Exercise Training in Patients With Acute Heart Failure. A Randomized Prospective Controlled Study
Authors: Oliveira Mayron F , Santos Rita L , Mendez Vanessa M , Sperandio Priscila A , Umeda Iracema I , Correa Edileide B , Ferraz Almir S
Published: July 2021

Background:
Exercise training (ET) is well established to improve functional capacity and quality of life in patients (pts) with chronic heart failure. However, the ET benefits in acute heart failure (AHF) are unknown. Purpose: We aimed to study the safety and efficacy of ET alone or combined with non-invasive ventilation (NIV) compared to standard medical treatment in hospitalized pts with AHF.

Methods:
Twenty-nine pts with AHF (68% ischemic), 56±7 years, left ventricle ejection fraction of 25±5%, NTproBNP of 2456±730, 6-minute walk test distance (6MWD = 225±39meters) were randomized into 3 groups: ET + NIV with sub therapeutic positive airway pressure (PAP) (ET,n=9), ET + NIV set to 14 of inspiratory and 8 cmH2O of expiratory PAP, respectively (EV,n=11) and standard treatment (CO,n=9). The ET and EV groups performed a daily session of unloaded exercise on cycle ergometer for 20 min or tolerance limit, for 8 consecutives days. In EV and ET, oxygen pulse saturation (SpO2), heart rate (HR), respiratory rate (RR), blood pressure (BP), blood lactate were measured at baseline (D1), during exercise, and at day 10 (D10). Serious adverse events (death or worsening heart failure) were also assessed on D10.

Results:
Length of hospital stay was shorter in EV group (17±10 days) compared to ET (23±8 days) and CO (39±15 days) (p<0,05). There were more serious adverse events in CO (66,6%) compared to both EV and ET (15%). Dobutamine use at D10 was less frequent in EV (18,2%) and ET (22,2%) groups than in CO (33,3%) (p<0.05). There was a marked improvement in Δ6MWD between D1 and D10 in EV (Δ127±72 meters), though increase in Δ6MWD was also seen in ET (Δ72±26 meters) and CO (Δ41±19meters), p<0,05. The EV group also showed higher endurance and lower peak HR at end-exercise than ET at D10 (128±10 vs. 92±8 min and 73±12 vs. 104±25 bpm, respectively; p<0,05). There was a similar reduction in NTproBNP levels but no differences were found in BP, SpO2, RR and blood lactate.

Conclusion:
Aerobic exercise in AHF was safe, reduced length of hospital stay and need for inotropics at D10. NIV + ET increased exercise endurance with lower cardiovascular stress.
Abstract 15907: Does Fractional Flow Reserve Truly Identify Coronary Stenoses Causing Myocardial Ischemia?
Authors: Arena Giulia , Morello Alberto , D’Andrea Antonello , Calabrò Paolo , Tuccillo Bernardino , Punzo Francesco , Scotto di Uccio Fortunato , Acampa Wanda , Assante Roberta , Zampella Emilia , Cuocolo Alberto , Golino Paolo
Published: July 2021

Background:
Despite the clinical importance of coronary physiological assessment, the relationship between coronary flow reserve (CFR) and fractional flow reserve (FFR) remains poorly defined.

Hypothesis:
We aimed at studying the relationship between absolute CFR and FFR in patients with stable coronary artery disease (CAD).

Methods:
Twenty-six patients with moderate (30%-70%) pretest likelihood of CAD underwent 82Rb PET/CT cardiac imaging at rest and after pharmacological stress (dipyridamole 0.142 mg/kg/min for 4 min). CFR was considered abnormal if ≤1.74. Patients then underwent coronary angiography and FFR was measured during intracoronary administration of adenosine (200 μg). FFR was considered abnormal if ≤0.8. A total of 30 stenoses were studied.

Results:
A significant, albeit modest, correlation exists between CFR and FFR (r=0.44, p=0.02). In particular, of the 16 stenoses with a pathological FFR value ≤0.8, only 6 showed a reduced CFR (black dots), while the other 10 had a normal CFR (red dots); in contrast, of the 14 lesions with an FFR value above 0.8, only one showed a reduced CFR (red dot), while the other 13 had a normal CFR (black dots).

Conclusions:
In this preliminary series, FFR values >0.8, indicating a non-significant stenosis, show an excellent correlation with absolute CFR, while pathological FFR values (<0.8) poorly correlate with a reduced CFR. This discordance should be probably taken into account when facing the choice of recommending revascularization solely on the basis of FFR values.
Abstract 15938: Disaggregating Cardiovascular Disease Mortality Among Hispanic Subgroups
Authors: Rodriguez Fatima , Hastings Katherine G , Wang Elsie , Boothroyd Derek , Cullen Mark R , Echeverria Sandra E , Palaniappan Latha
Published: July 2021

Background:
Hispanics are currently the largest minority group in the US and face a disproportionate burden of cardiovascular disease (CVD) risk factors. Hispanics paradoxically experience lower mortality rates as compared to their non-Hispanic white (NHW) counterparts. This phenomenon has been largely observed in Mexicans and it is unknown whether this holds true for other Hispanic subgroups, and if these favorable trends persist over time.

Methods:
We examined data from the National Center for Health Statistics U.S. Mortality Multiple Cause-of-Death data from 2003-2011 to identify CVD deaths for the three largest Hispanic subgroups in the U.S. (Mexicans, Puerto Ricans, and Cubans). CVD deaths were extracted from mortality records using the underlying cause of death based on ICD-10 coding (I00-I09, I11, I13, I20-I51.9, I60-I69). Race/ethnicity was recorded on death certificates by the funeral director using state guidelines. Population estimates were calculated using linear interpolation from 2000 and 2010 U.S. Census.

Results:
The study sample consisted of all-cause deaths for the three largest Hispanic subgroups in the U.S.: Mexicans (n=689,162), Puerto Ricans n=154,402), and Cubans (n=117,751), compared to NHWs (n=17,699,740). Cubans and Mexicans were, on average, younger at time of incident CVD death as compared to NHWs (73 vs. 79, respectively). Overall, CVD mortality trends decreased from 2003-2011 for all groups (p<0.001), but rate differences between groups vary substantially, with Puerto Ricans exhibiting similar mortality patterns to NHWs and Mexicans experiencing the lower mortality (Figure 1).

Conclusions:
Significant differences in CVD mortality rates and trends were found between the three largest Hispanic subgroups in the US. These findings suggest that the current aggregate classification of Hispanics masks heterogeneity in CVD mortality reporting, leading to an incomplete understanding of health risks and outcomes.
Abstract 15948: Inhibition of NF-kB Signaling Attenuates Age-related Aggravation of Myocardial Ischemia/Reperfusion Injury
Authors: Cheng Guangming , Ye Sheng , Girgis Magdy , Zhao Lin , Chen Xing , Samanta Anweshan , Yang Yanjuan , Hauptman Jeryl , Vincent Robert , Dawn Buddhadeb
Published: July 2021

Introduction:
Emerging evidence indicates that myocardial ischemia/reperfusion (I/R) injury is more severe in aged hearts. Although nuclear factor-kappaB (NF-kB) activity increases with aging, whether this redox-responsive transcription factor plays any role in age-related worsening of I/R injury remains unknown.

Hypothesis:
We hypothesized that activation of myocardial NF-kB exerts deleterious effects during I/R injury in young as well as aged hearts; and that NF-kB signaling contributes to age-related worsening of myocardial I/R injury.

Methods:
We used transgenic mice overexpressing a mutant IkBa that prevents NF-kB activation only in the heart. Age-matched young (10-week-old) and aged (86-week-old) male non-transgenic littermates (NTg) and IkBa transgenic (Tg) mice underwent a 30-min coronary occlusion followed by 24 h of reperfusion. Following sacrifice, infarct size was measured and molecular assays were performed.

Results:
The infarct size was significantly smaller in young Tg mice compared with young NTg mice (Fig), indicating a deleterious role of NF-kB signaling during myocardial I/R injury even in the young. The infarct size in aged NTg hearts was greater compared with young NTg hearts, consistent with an age-related worsening of I/R injury effects. However, infarct size in aged Tg hearts was significantly smaller than aged NTg hearts, and similar to young Tg hearts, indicating that NF-kB signaling contributes toward age-related aggravation of I/R injury. Interestingly, the levels of molecular markers of senescence, such as p16, were lower in aged Tg hearts (Fig), indicating a deleterious role of NF-kB in cardiac aging and susceptibility to I/R injury.

Conclusions:
We conclude that inhibition of cardiac NF-kB signaling protects against age-related aggravation of acute myocardial I/R injury. These findings suggest that modulation of NF-kB signaling may be potentially used to achieve therapeutic cardioprotection in the elderly.
Abstract 15976: Comparison of Patients With Variant and Typical Takotsubo Cardiomyopathy
Authors: Kim Sijun , Palac Robert T , Gemignani Anthony S , O’Rourke Daniel J , Friedman Harley P , Friedman Scott E
Published: July 2021

Background:
Variant, or reverse, Takotsubo cardiomyopathy (TTC) is defined by left ventricular basal and/or mid-ventricular systolic dysfunction with preserved apical function. This condition is increasingly recognized, yet there have been few studies comparing variant and typical TTC. This study aims to contrast the demographic features and clinical outcomes of patients with variant and typical TTC.

Methods:
All patients at a single academic medical center with a discharge diagnosis of Takotsubo syndrome [ICD-9-CM 429.83] from 2010-2014 were identified. Patients who met the Mayo Clinic criteria for TTC were included and were then grouped into typical or variant TTC categories based on wall motion abnormality patterns.

Results:
The initial query identified 275 patients with a discharge diagnosis of TTC, of which 145 (52.7%) met diagnostic criteria for TTC. Typical TTC was present in 125 patients (86.2%) and variant TTC in 20 patients (13.8%). The demographic and clinical characteristics of these groups are summarized in table 1. Variant TTC patients were more likely to be male and subject to a physically stressful trigger. Typical TTC patients had lower left ventricular ejection fraction, higher left ventricular end-diastolic pressure, and were more likely to be intubated. Cardiac biomarkers were not significantly different between groups. In-hospital mortality, length of hospital stay, TTC recurrence and follow-up LVEF were similar between groups.

Conclusions:
There are important differences between patients with variant and typical TTC. Variant TTC is not as strongly associated with female sex, it is more frequently preceded by a physical stressor, and it has a more benign presentation. Long term outcomes are favorable in patients with variant and typical TTC.
Abstract 16055: Ongoing Prothrombotic State in the Early Phase of Pneumonia
Authors: Cangemi Roberto , Calvieri Camilla , Carnevale Roberto , Falcone Marco , Nocella Cristina , Ferroni Patrizia , Pignatelli Pasquale , Taliani Gloria , D'Angelo Armando , Violi Francesco ,   SIXTUS (thromboSIs-related eXTra-pulmonary oUtcomeS in pneumonia) study group
Published: July 2021

Introduction:
Respiratory tract infections are associated with an increased risk of acute cardiovascular and cerebrovascular events. Of note, pneumonia may be associated with arterial and venous thrombosis but the underlying pathophysiological mechanisms are still unclear.

Hypothesis:
Our aim was to investigate if in patients with community-acquired pneumonia (CAP) a pro-thrombotic state does exist and its relationship with plasma levels of endotoxin.

Methods:
One hundred-four consecutive patients with CAP, admitted to the University-Hospital Policlinico Umberto I of Rome, Italy, were prospectively recruited and followed up until discharge. At admission and at discharge endotoxin and systemic markers of clotting activation including protein C activity (aPC) and F1+2 were analyzed. Hospitalized patients matched for sex, age, atherosclerotic risk factors but without any type of infections were used as controls.

Results:
At admission CAP patients showed higher plasma levels of F1+2 (237 [164, 388] vs. 163 [136-313] pmol/L; p=0.023) and lower levels of aPC (36.3 [19.7, 52.4] vs.49.8 [43.7-56.0] pmol/L, p<0.001) compared to controls. Moreover, CAP patients disclosed lower aPc/F1+2 ratio (0.13 [0.07, 0.26] vs.0.28 [0.16-0.37; p<0.001), a global marker of imbalance between thrombin generation and the anticoagulation system. At discharge aPC plasma levels and aPC/F1+2 significantly increased, while F1+2 significantly decreased (p<0.001). Baseline LPS were significantly higher in patients than controls (230±34 vs 27±22 pg/ml; p<0.001); in patients a significant decrease of serum LPS was detected at discharge. Serum LPS values were correlated directly to F1+2 (Rs= 0.402, p<0.001) and inversely to aPC/F1+2 (Rs=-0.303; p<0.002). In a multivariable regression analysis CURB65 (β=-0.410 p<0.001) and LPS (β=-0.261 p<0.001) were significantly associated to aPC/F1+2.

Conclusion:
CAP patients disclose a significant increase of thrombin generation rate along with a reduced Protein C activity. Changes of clotting activation are significantly associated with LPS suggesting endotoxemia as a key factor in determining enhanced thrombin generation in CAP patients.
Abstract 16109: A Selective Cargo of Non-coding RNAs Mediate Therapeutic Potential of Human CD34+ Stem Cell-derived Exosomes
Authors: Mathiyalagan Prabhu , Liang Yaxuan , Kim David , Losordo Douglas W , Hajjar Roger J , Sahoo Susmita
Published: July 2021

Introduction:
Clinical application of human CD34+ stem cells is associated with improved exercise tolerance and therapeutic angiogenesis in patients with myocardial ischemia. We reported the first description of independent therapeutic potential of CD34+ stem cell-derived exosomes (CD34Exo) to that of parent cell by mechanisms that still remain poorly understood.

Hypothesis:
Herein, we tested the hypothesis that CD34Exo may selectively carry non-coding RNA (ncRNA) cargo targeted for pro-angiogenic signaling and ischemic tissue repair.

Methods and Results:
Murine models of myocardial ischemia employed throughout the study. Cell-free CD34Exo replicated the therapeutic activity of their parent cells by significantly improving myocardial ischemia (ejection fraction, 42±4 v 22±6%; capillary density, 113±7 v 66±6/HPF; fibrosis, 27±2 v 48±7%; p<0.05, n=7-12) compared with a PBS control. Confocal imaging and flow cytometry analyses revealed that CD34Exo was selectively internalized into endothelial cells and cardiomyocytes in the CD34Exo-injected ischemic hearts. MicroRNA (miR) profiling identified several pro-angiogenic miRs including miR-126 that are selectively enriched in CD34Exo. Mice injected with CD34Exo show elevated miR-126 and several pro-angiogenic mRNAs in ischemic myocardium, however did not affect endogenous miR-126 synthesis suggestive of direct CD34Exo-mediated miR-126 transfer. Depletion of miR-126 reduced the therapeutic efficacy of CD34Exo both in vitro and in vivo indicating a critical role for miR-126. Using fluorescent-tagged miR-126, we monitored in real-time the uptake and transfer of miR-126 by endothelial cells both in vitro and in vivo. We finally provide novel insights underlying CD34Exo function in regulating endothelial proliferation through identification of novel pathways regulated by miR-126 in endothelial cells.

Conclusion:
Our results reveal specific CD34Exo-shuttled microRNAs and pathways regulated in the ischemic myocardium. Our work presents a molecular framework for CD34Exo mechanism and function in therapeutic angiogenesis. Precise understanding of CD34Exo mechanisms could significantly amplify the therapeutic benefits of CD34Exo in ischemic tissue regeneration and repair.
Abstract 16122: Is Vitamin D Deficiency Really Associated With an Increased Incidence of Statin Intolerance?
Authors: Bair Tami L , Knight Stacey , May Heidi T , Horne Benjamin D , Anderson Jeffrey L , Lappé Donald L , Muhlestein Joseph B
Published: July 2021

Introduction:
Statin therapy is potentially the most important treatment presently available to prevent the progression of atherosclerosis. Unfortunately, a significant number of patients cannot tolerate statins due to muscle aches. Vitamin D deficiency, which is also associated with a variety of muscular symptoms, is commonly identified among patients with an indication for statin therapy. Several small studies have proposed that vitamin D deficiency may contribute to statin intolerance, but this has not been definitively demonstrated.

Hypothesis:
Vitamin D deficiency is associated with greater risk of statin intolerance.

Methods:
In the Intermountain Healthcare electronic health record, 12,066 patients had an initial 25(OH) vitamin D (VitD) level available and an indication for statin therapy with either a documented statin intolerance or evidence of active statin therapy. Patient baseline clinical characteristics were collected and multivariable logistic regression analysis was used to evaluate associations between VitD levels (stratified into four categories (ng/ml): <12 [n=660(5.5%)], 12 to <20 [2,057(17.0%)], 20 to <50 [8,183(67.8%)], ≥50 [n=1,166(9.7%)]) and statin intolerance.

Results:
Overall, 12,066 subjects (statin intolerant n=928 [7.7%]; age = 56±6 yrs; males = 37.5%, prior atherosclerotic cardiovascular disease = 1856 [15.4%]) were enrolled. Multivariable effects of VitD and other predictors on risk of statin intolerance are shown in the Table.

Conclusion:
In this large cohort of patients with an indication for statin therapy, baseline VitD levels were not significantly associated with statin intolerance. Characteristics that
were
associated with statin intolerance included older age, female gender, Caucasian race, diabetes and a prior diagnosis of hyperlipidemia.
Abstract 16138: Chest and Cardiac Compression on CT/MRI and on TEE Predicts Improvement in Right Heart Chamber Size and Right Ventricular Deformation Post Pectus Excavatum Repair Surgery
Authors: Chao Chieh-Ju , Gotway Michael B , Jaroszewski Dawn E , Lester Steven , Unzek Samuel , Wilansky Susan , Chaliki Hari P , Appleton Christopher P , Mookadam Farouk , Naqvi Tasneem Z
Published: July 2021

Background:
Pectus excavatum (PE) deformity involves posterior depression of the sternum and adjacent costal cartilages. The relationship of CT/MRI chest cardiac compression indices used as indications for surgical repair of PE with echocardiographic findings and with improvement in cardiac chamber compression and function post PE repair is unknown.

Methods:
We evaluated right atrial (RA) size, tricuspid annulus (TA size, right ventricular (RV) outflow tract size as well as RV 2D strain on intra-operative trans-esophageal echocardiography (TEE) immediately pre and post surgical PE repair. Inspiratory and expiratory Haller Index (HI) and cardiac compression indices (CCI) were measured on pre op CT/MR scans (Figure). Offline measurement of chamber dimensions on TEE images was performed and Speckle tracking strain measurements were made using Syngo US Workplace software (Siemens). P<0.05 was considered significant.

Results:
60 patients, 73% male, 27% female, age 33.6±10.3 yrs underwent PE repair following CT/MRI from 2010-2014 (Figure). There was a strong correlation between expiratory CT/MRI chest AP diameter and pre-op RA size (panel A). Pre op RA and TA compression on TEE inversely correlated with pre op RV global longitudinal strain rate(RVGLSR) (panels B & C). CCI predicted improvement in RA size post PE repair (panels D & E). In addition pre op RA size on TEE correlated with improvement in RVGLSR post PE repair surgery (panel F).

Conclusion:
In patients with PE deformity, pre surgical CCI correlated with right-sided cardiac chamber compression on pre op TEE. Severity of chest and cardiac compression also predicted magnitude of improvement in right-sided chamber size and RV longitudinal deformation post PE repair. Our findings provide insight regarding the beneficial effects of PE surgery on right heart chamber compression and improvement in RV function and the important role of intraoperative TEE for patients undergoing PE repair surgery.
Abstract 16154: Head and Shoulder Elevation Improves Cerebral Perfusion Pressure During Active Compression-decompression CPR and Conventional CPR in a Porcine Cardiac Arrest Model
Authors: Moore Johanna C , Ho Ryu Hyun , Lick Michael , Tsangaris Adamantios , McKnite Scott , Metzger Anja , Rees Jennifer , Yannopoulos Demetris , Debaty Guillaume , Shin Sang Do , Kim Taeyun , Lurie Keith
Published: July 2021

Background:
Chest compressions during conventional cardiopulmonary resuscitation (C-CPR) increase arterial and venous pressures simultaneously, delivering bidirectional high pressure compression waves to the brain. It is possible that this may be detrimental neurologically and could be partially overcome by elevating the head during CPR. Previous animal study work using a tilt table has shown that a 30° head up position for the entire body during CPR significantly increases cerebral blood flow and cerebral perfusion pressure (CerPP) over a period of 5 minutes. We hypothesize that elevating the head and shoulders only will increase CerPP over a prolonged period of time with two different CPR techniques.

Methods:
Female farm pigs were sedated, intubated, anesthetized, and placed on a table designed to elevate the head and shoulders to 30°. After 8 min of untreated ventricular fibrillation and 2 min of automated C-CPR in the supine position, pigs were randomized to head up (HUP) or supine (SUP) CPR for 20 more min. In Group A, pigs were treated after 2 min of C-CPR with automated active compression decompression (ACD) CPR at 100 cycles/min plus an impedance threshold device (ITD), randomized to HUP (n=8) or SUP (n=8). In Group B, pigs were randomized after 2 min of C-CPR to treatment with HUP (n=7) or SUP (n=7) automated C-CPR. After 22 total min of CPR, defibrillation was performed. The primary outcome of the study was the comparison of CerPP at 22 min between HUP and SUP positions within each group.

Results:
After 22 min of CPR, CerPP (mmHg) was 39±7 with HUP versus 14±4 with SUP CPR (p=0.013) in Group A and 3.4±2.2 with HUP versus -6.3±2.6 with SUP CPR (p = 0.014) in Group B. There was no significant difference within groups for coronary perfusion pressure (CPP) after 22 min, but CPP trended higher with HUP in Group A (32.0 ± 4.9) versus SUP (18.8 ± 4.7)(p=0.072). The CPPs in Group B were 5.8 ± 1.1 with HUP versus 3.3±1.8 with SUP CPR, p=0.26). In Group A, 6/8 pigs were resuscitated in both positions where no pigs could be resuscitated in Group B.

Conclusions:
The HUP position using two different CPR techniques significantly improved CerPP over a prolonged period of time. This simple maneuver has the potential to improve neurological outcomes after cardiac arrest.
Abstract 16373: Improved Prognostic Performance of Novel Parameters for Grading Aortic Insufficiency Severity in Patients With Left Ventricular Assist Devices
Authors: Grinstein Jonathan , Kruse Eric , Sayer Gabriel , Fedson Savitri , Kim Gene H , Sarswat Nitasha , Adatya Sirtaz , Ota Takeyoshi , Jeevanandam Valluvan , Mor-Avi Victor , Lang Roberto , Uriel Nir
Published: July 2021

Background:
The development of aortic insufficiency (AI) following continuous flow left ventricular assist device (CF-LVAD) implantation is common, although the clinical significance remains unclear. We previously described novel echocardiographic (TTE) parameters that outperformed traditional TTE parameters in grading AI severity in these patients. The aim of this study was to evaluate the prognostic performance of these parameters compared to traditional measurements.

Methods:
CF-LVAD patients with varying degrees of AI (N=57) underwent Doppler TTE of the LVAD outflow cannula. All patients had AI severity graded by our novel parameters (Systolic/Diastolic ratio and the diastolic acceleration of the LVAD outflow cannula) and traditional vena contracta. The prognostic performance of novel and traditional AI parameters was determined by comparing rates of hospital readmission, need for aortic valve intervention and/or urgent transplantation and death (primary endpoints) for each parameter.

Results:
Grading AI severity using novel AI parameters led to reclassification of 21% of patients from trace/mild AI to moderate or greater AI (N=12). Using traditional AI parameters, there was no difference in the occurrence of the primary endpoint between the trace/mild group and the moderate or greater group (1.08 vs. 0.89 events/person, p=0.39) (Figure 1A). With the novel AI parameters, there were significantly more events in the patients with moderate or greater AI compared to those with trace/mild. (1.11 vs. 0.56 events/person, p=0.02) (Figure 1B). Novel parameters better predicted the need for aortic valve intervention, urgent transplantation or death than traditional methods (p=0.049) (Figure 1C-D).

Conclusions:
In patients with CF-LVADs, traditional parameters tend to underestimate AI severity and future cardiac events. Novel AI TTE parameters are better able to discriminate AI severity and predict clinically meaningful outcomes.
Abstract 16398: Comparison of Major Bleeding Risk and Associated Costs Among Newly Anticoagulated Non-valvular Atrial Fibrillation Patients
Authors: Deitelzweig Steven , Bruno Amanda , Tate Natalie , Ogbonnaya Augustina , Shah Manan , Farrelly Eileen , Lokhandwala Tasneem , Gupta Kiran , Eaddy Michael
Published: July 2021

Real-world evidence highlighting the risks and benefits of novel oral anticoagulants (NOCAs) is lacking. This study compared major and clinically relevant non-major (CRNM) bleeding risk and costs among non-valvular atrial fibrillation (NVAF) patients newly treated with apixaban, dabigatran, rivaroxaban, or warfarin. A retrospective analysis of NVAF patients newly treated with apixaban, dabigatran, rivaroxaban, or warfarin was conducted using PharMetrics Plus data from 1/ 2012 - 9/ 2014. Patients were indexed on the date of the first anticoagulant prescription, and were required to be ≥18 years old and have CHA
2
DS
2
-VASc score > 0 and ≥ 1 month of follow-up. Patients were followed until discontinuation (≥30-day gap in treatment), treatment switch, end of continuous enrollment, 1 year post-index, or end of study. Major and CRNM bleeding, and bleeding-related costs were measured. Cox proportional hazards model was used to examine the association between anticoagulants and risk of bleeding and GLM was used to evaluate bleeding-related costs. The study included 24,573 NVAF patients; distributed as apixaban 11.7%, dabigatran 12.0%, rivaroxaban 36.7%, and warfarin 39.6%. Mean age was 64.4 and 66.5% were males. HAS-BLED and CHA
2
DS
2
-VASc scores averaged 2.0 and 2.7, respectively. After adjusting for differences in baseline characteristics, when compared to apixaban patients, rivaroxaban (HR: 1.5;
P
=0.0013) and warfarin (HR: 1.7;
P
<0.0001) patients were more likely to have major bleeding, and dabigatran (HR: 1.3;
P
=0.0030), rivaroxaban (HR: 1.7;
P
<0.0001), and warfarin (HR: 1.4;
P
<0.0001) patients were more likely to have CRNM bleeding. Major bleeding risk was similar between apixaban and dabigatran patients. Major and CRNM bleeding costs, when compared to apixaban patients ($154 and $18), were significantly higher for dabigatran ($457;
P
<0.0001 and $39;
P
<0.0001), rivaroxaban ($420;
P
<0.0001 and $61;
P
<0.0001), and warfarin ($511;
P
<0.0001 and $63;
P
<0.0001) patients. Among anticoagulant-naive moderate-to-high risk NVAF patients encountered in real-world clinical setting, major bleeding was lower with apixaban compared to warfarin and rivaroxaban. Bleeding costs were lower with apixaban compared to alternative NOACs and warfarin.
Abstract 16411: Can the Types of Coronary Artery Disease Severity be Predicted Using Any Parameters of Brachial Ultrasonography and/or Carotid Ultrasonography?
Authors: Teragawa Hiroki , Fujii Yuichi , Uchimura Yuko , Ueda Tomohiro
Published: July 2021

Introduction:
It has been reported that the flow-mediated dilatation (FMD) of the brachial artery on brachial ultrasonography and carotid intima-media thickness (IMT) on carotid ultrasonography correlate with the presence of coronary artery disease (CAD).

Hypothesis:
However, it is not clear whether CAD types can be detected using these techniques. We examined whether CAD types can be detected using brachial and/or carotid ultrasonography.

Methods:
Four hundred fifteen patients (mean age 68 years, 266 men) who underwent coronary angiography (CAG) during the evaluation of CAD were enrolled. Each patient underwent brachial and carotid ultrasonography before CAG. On brachial ultrasonography, FMD) and nitroglycerine-induce dilation (NID) were measured. On carotid ultrasonography, maximum IMT, the presences of carotid plaque (>1.1 mm) and calcification were measured. On coronary angiography, if organic coronary stenosis was absent, a spasm provocation test was performed to confirm the presence of vasospastic angina (VSA). According to the CAG results, patients were divided into three subgroups: Group I, patients with organic coronary stenosis (n = 244); Group II, patients with VSA without organic coronary stenosis (n = 98); and Group III, patients without organic coronary stenosis or VSA (n = 73).

Results:
FMD was lower in Groups I (3.2% ± 0.3%) and II (3.2% ± 0.4%) than in Group III (4.5% ± 0.4%, p < 0.05), and NID were lower in Group I (12.1% ± 0.4%) than in Groups II (14.6% ± 0.6%) and III (15.6% ± 0.7%, p < 0.0001). Max IMT was higher in Group I (2.38 ± 0.06 mm) than in Groups II (1.61 ± 0.09 mm) and III (1.56 ± 0.10 mm, p < 0.0001). The presence of both carotid plaque and calcification was higher in Group I (93% and 43%, respectively) than in Group II (74% and 19%, respectively) and III (60% and 19%, respectively, both p < 0.0001). Logistic regression analysis demonstrated that carotid plaque (p = 0.0162), carotid calcification (p = 0.0011) and lower NID (p = 0.0011) were predictors of the presence of Group I, whereas lower max IMT (p = 0.0002) was one of predictors for the presence of Group II.

Conclusions:
These findings suggest that brachial and/or carotid ultrasonography before CAG may provide important diagnostic information regarding CAD types.
Abstract 16554: Rapid Identification of Familial Hypercholesterolemia From Electronic Health Records
Authors: Safarova Maya S , Liu Hongfang , Kullo Iftikhar J
Published: July 2021

Background:
Familial hypercholesterolemia (FH) is an important public health burden as it is a relatively common Mendelian genetic disorder which is associated with dramatically increased lifetime risk for premature atherosclerotic cardiovascular disease (ASCVD) due to elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. Little is known about prevalence and control of FH in the US.

Objective:
To develop an electronic phenotyping algorithm for rapid identification of FH in electronic health records (EHRs) and thereby address knowledge gaps in prevalence and control of FH.

Methods:
We identified patients in the Mayo Employee and Community Health (ECH) system who met the following inclusion criteria: 1) gave research authorization, 2) any LDL-C in EHR ≥190 mg/dL; 2) triglycerides <400 mg/dL; 3) absence of secondary causes of hyperlipidemia (hypothyroidism, cholestatic liver diseases, nephrotic syndrome, renal failure, and pregnancy). Next we applied the Dutch Lipid Clinic Network (DLCN) criteria to ascertain FH cases. ASCVD-related diagnosis codes, laboratory data, and medications were obtained from structured EHR datasets. We used the Mayo natural language processing (NLP) system to ascertain presence of family and personal history of premature ASCVD, xanthomas and corneal arcus from clinical text notes.

Results:
Of a total of 131,000 patients seen in ECH clinics between July 1993 and December 2014, 6018 met the inclusion criteria. Implementing the electronic phenotyping algorithm for FH in these patients identified 178 definite and 369 probable cases (DLCN score >8 and 6-8 points, respectively) with an overall FH prevalence of 0.4% (1:240). Blinded expert review of 160 randomly chosen patients showed positive and negative predictive values for electronic phenotyping algorithm at 85% and 90%, respectively. Only 40% of these patients achieved LDL-C ≤100 mg/dL on treatment.

Conclusions:
1) An EHR-based phenotyping algorithm that included NLP had reasonable accuracy in ascertaining FH cases. 2) Implementing this algorithm revealed the prevalence of FH in the study cohort to be nearly twice the current estimate of 1:500 in the general population. 3) Less than half of the FH patients had optimal LDL-C levels on treatment.
Abstract 16584: Association of Lower Height and Higher LDL-c in a Statewide Schoolchild Cholesterol Screening Program
Authors: Pyles Lee A , Lilly Christa , Elliott Eloise , Neal William A
Published: July 2021

Introduction:
The Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) Project has screened West Virginia 5th graders since 1998 to facilitate primordial prevention of coronary heart disease (CHD) in WV. LDL-c levels above 175 mg/dl in children suggest Familial Hyperlipidemia (FH) in the child’s family and a level above 160 mg/dl with history of CHD in relatives can also establish a diagnosis.

Hypothesis:
Based on previous adult literature, the association of lower height with higher LDL level observed in adults begins in childhood and is prominent in children with LDL in FH range.

Methods:
Fifth graders are screened yearly in WV schools with parental consent for Body Mass Index and lipid panel. Lipids were analyzed with respect to either short stature < 2 SD for height or comparing 1st (shortest) and 4th quartiles of the population. Statistical analysis for age- and gender-adjusted height percentiles was performed in SAS.

Results:
59,386 children had lipid and height data. Mean LDL-c for 1st vs. 4th quartile of height was 94.08 mg/dl (95% Confidence Interval-CI 93.66-94.51) vs. 90.03 mg/dl (CI 89.65-90.42). First quartile of height students had average 4.05 mg/dl higher LDL-c (95% CI 3.48 -4.62 mg/dl). 4398 children had an LDL level above 130 g/dl, 632 above 160 mg/dl and 247 above 175 mg/dl. The Chi square analysis of short stature (height 130 g/dl was also significant (p=0.013) with increased odds of LDL-c above 130 g/dl compared to non-short stature (OR= 1.37, CL 1.07-1.75). Table 1 shows odds ratio for varying levels of elevated LDL-c for the first (shortest) vs. 4th (tallest) quartile of students.

Conclusions:
Shorter stature is associated with higher LDL-c level in WV 5th graders generally and in those children with increased risk for genetic dyslipidemia. The trend to increasing odds ratio in strata of higher LDL-c supports a recent report of association of single nucleotide polymorphisms selecting for lower genetic height and higher LDL-c.
Abstract 16595: Insulin Replacement Attenuates Autonomic Impairment but Did Not Prevent Early Diastolic Dysfunction in a Model of Type 1 Diabetes
Authors: Freitas Sarah C , Dourado Paulo M , Sanches Iris C , machi Jacqueline F , Irigoyen Maria C , De angelis Kátia
Published: July 2021

Introduction:
Insulin replacement is the most widely used therapy for treatment of patients with Type 1 Diabetes Mellitus. However, despite a restricted glycemic control, diabetic patients are prone to chronic complications, such as cardiovascular disease. The mechanisms underlying this increased risk are not well understood.

Hypothesis:
The insulin replacement therapy can prevent the cardiac and autonomic dysfunctions in a model of type 1 diabetes.

Methods:
18 male Wistar rats (230-260g) were divided into 3 groups (n=6/group): control (C), diabetic (D, streptozotocin 50 mg/kg) and diabetic treated daily with insulin subcutaneously (DTI). At 30 days, cardiac function was assessed by echocardiogram and after the rats were cannulated and arterial pressure (AP) was recorded.

Results:
The diabetic groups showed hyperglycemia (>350mg/dl) at the beginning of the protocol. Insulin therapy normalized the glycemia (DTI: 94±28 and C: 126±8 vs. D: 533±67 mg/dl). There was a reduction in the posterior wall thickness of the left ventricle at diastole (PWD) and in the relative wall thickness (RWT) in D group and these changes were not observed in DTI group (PWD- C: 0.122±0.008 and DTI: 0.126±0.004 vs. D: 0.086±0.006 cm and RWT- C: 0.42±0.021 and DTI: 0.4±0.013 vs. D: 0.35±0.014). Left ventricular mass was reduced in D group (D: 0.393±0.0510 vs. C: 0.581±0,054 and DTI: 0.586±0.049). The systolic function was not different (shortening fraction) between the groups. Regarding diastolic function, the isovolumetric relaxation time was not different between the groups, but there was a decrease in E/A wave ratio in the group of diabetic rats, which was not reversed by insulin treatment (D: 1.53±0.104 and DTI: 1.69±0.178 vs. C: 2.45±0.380). The baroreflex sensitivity was impaired in D group in relation to C and DTI groups (D: 1.05±0.110 vs. C: 1.39±0.100 and DTI: 1.36±0.09 bpm/mmHg). The insulin treatment normalized mean AP (DTI: 118±3.34 and C: 110±3.28 vs. D: 99±5.48 mmHg).

Conclusions:
Treatment with insulin despite normalize blood glucose, baroreflex sensitivity, hemodynamics and cardiac morphometry, was not able to attenuate diastolic dysfunction, suggesting a remaining cardiovascular risk even after insulin replacement in this model of experimental diabetes type I.
Abstract 16624: Lung Cancer Screening With CT, Coronary Artery Calcification and Cardiovascular Events
Authors: Lu Michael T , Onuma Oyere K , Massaro Joseph M , D’Agostino Ralph B , O’Donnell Christopher J , Hoffmann Udo
Published: July 2021

Background:
The Centers for Medicare & Medicaid Services (CMS) recently approved lung cancer screening with CT. It is unclear whether reporting coronary artery calcium (CAC) on lung screening CT could improve identification of adults at risk for cardiovascular events (CVD) and competing risk from lung cancer. Thus we determined the incidence of hard CVD (myocardial infarction, stroke or coronary/cerebrovascular death), lung cancer (diagnosis or death) and CAC in adults eligible and ineligible for lung cancer screening.

Methods:
This longitudinal community-based cohort study included Framingham Heart Study Offspring Cohort participant-exams age 55-77 and free of prevalent cardiovascular disease and lung cancer from exams 3 (1984 – 1987) and 7 (1998 – 2001). Participants were divided into screening eligible and ineligible groups by CMS criteria (current or recent (≤15 years) former smokers with ≥30 pack-year history). Multivariate-adjusted cox proportional hazards models assessed the effect of screening eligibility on incident hard CVD and incident lung cancer. In participants who had CAC CT at exam 7, cross-sectional association between screening eligibility, high CAC score >300 and incident CVD was assessed. Raw incidence rates are reported; p values are adjusted for age, sex and traditional risk factors aside from smoking.

Results:
Of 3085 participant-exams 20% were eligible for lung cancer screening. In mean follow up of 9.9 years, there were 281 incident CVD and 69 lung cancer events. In both groups, incident CVD was more frequent than lung cancer (eligible: 13% vs 7%, p=0.002; ineligible: 8% vs 1%, p<0.001). The screening eligible had more incident CVD (13% vs 8%, p<0.001) and lung cancer (7% vs 1%, p<0.001) than the ineligible. CAC CT was available in 107 screening eligible and 667 ineligible participants; CAC >300 was more common in the screening eligible (33% vs 23%, p=0.007).

Conclusion:
In a community-based primary prevention cohort, 20% aged 55-77 were eligible for lung cancer screening CT. CMS eligibility criteria identified disease-free persons with substantially more incident hard CVD and CAC; CVD was more common than lung cancer. The results support cardiovascular prevention and reporting of CAC as part of routine lung cancer screening CT.
Abstract 16647: Surgical Cryoablation of Ventricular Tachycardia at the Time of LVAD Implantation
Authors: Zado Erica S , Santangeli Pasquale , Supple Gregory , Betensky Brian , Riley Michael , Atluri Pavan , Dixit Sanjay , Acker Michael , Marchlinski Francis E
Published: July 2021

Introduction:
Patients (pts) with advanced heart failure (HF) undergoing implantation of a left ventricular assist device (LVAD) are at high risk of recurrent ventricular tachycardia (VT). We report the outcome of surgical VT cryoablation (VT CA) at the time of LVAD insertion in pts with advanced HF and drug-refractory VT.

Hypothesis:
Outcome will be enhanced with pre-operative mapping.

Methods:
We included consecutive patients with advanced HF and recurrent VT refractory to antiarrhythmic drug therapy and/or conventional catheter ablation, who underwent LVAD implantation and concomitant surgical VT CA.

Results:
The cohort included 6 pts (5 [83%] male, age 62±10 years) with ischemic (4, 67%) or nonischemic (2, 33%) cardiomyopathy. The mean LVEF prior to surgery was 19±7% (10-27%). All patients had history of recurrent VT, with 4 (67%) pts presenting in VT storm. All were on amiodarone, 1 on oral and the others on IV amiodarone along with IV lidocaine prior to surgery. Four pts (67%) had preoperative detailed electroanatomic mapping (EAM) of the VT substrate, which was used to guide surgical ablation. Cryo lesions were deployed endocardially using the LV apical core as access and/or epicardially to areas identified as scar visually complemented by preop EAM when available (figure). There were no complications related to the CA. Over a follow-up 10.3±12.7 months (range 2-35 months), 4 pts (67%) had no VT, 1 pt had 2 ATP-terminated episodes at 2 months and 1 pt had significant reduction of VT burden (from 11 shocks before surgery to 1 shock at follow-up). The 2 pts with recurrences did not have pre-operative mapping prior to surgical ablation. One patient died of non-cardiac causes at 7 months and 2 patients underwent heart transplant at 10 and 35 months.

Conclusions:
In pts with advanced HF and refractory VT, surgical ablation can be safely and effectively accomplished at the time of LVAD implantation. When ablation is guided by pre-operative EAM, the outcome may be enhanced.
Abstract 16655: Bone Marrow Cell Therapy in Patients With Ischemic Heart Disease: A Meta-analysis of Randomized Controlled Trials Using Cardiac MRI
Authors: Afzal Muhammad R , Samanta Anweshan , Ansari Briha , Jeevanantham Vinodh , Dawn Buddhadeb
Published: July 2021

Introduction:
The results from clinical trials of bone marrow cell (BMC) therapy in ischemic heart disease (IHD) have been discordant with regard to left ventricular (LV) functional improvement. This discrepancy has been attributed, in part, to the use of dissimilar cardiac imaging modalities. MRI is the gold standard for assessment of cardiac structure/function.

Hypothesis:
We hypothesized that BMC therapy will improve LV parameters in patients with IHD when assessed by cardiac MRI.

Methods:
We performed a systematic review and meta-analysis of data from randomized controlled trials (RCTs) of BMC therapy in patients with IHD that used cardiac MRI. Database searches through May 30, 2015 identified 27 eligible RCTs (enrolling 1826 patients). The MRI data on LV ejection fraction (EF), infarct size, LV end-systolic volume (LVESV), and LV end-diastolic volume (LVEDV) were analyzed with random-effects meta-analysis. Clinical outcomes were analyzed using Peto odds ratio (OR).

Results:
Compared with standard therapy, BMC therapy improved LVEF (1.62%; 95% confidence interval [CI]: 0.49 to 2.75; P=0.005) and reduced LVESV (-2.00 ml; 95% CI: -3.19 to -0.82; P=0.0009). The improvement in LVEF was similar in patients with acute myocardial infarction (MI) and chronic IHD. Perhaps more importantly, BMC therapy was associated with reduced incidence of recurrent MI (OR: 0.39; 95% CI: 0.20 to 0.78; P=0.007) along with substantial improvement in other outcome parameters, including mortality (Table). However, these changes did not reach statistical significance perhaps due to smaller patient numbers.

Conclusions:
These results from meta-analysis of RCTs using cardiac MRI indicate that BMC therapy improves LV function and outcomes in patients with IHD. These data may help resolve the controversy regarding whether the reported benefits of BMC therapy are dependent on the selection of imaging modalities.
Abstract 16703: Extended Non-anteroseptal Region Left Ventricular Hypertrophy Predicts Repeat Alcohol Septal Ablation for Refractory Hypertrophic Obstructive Cardiomyopathy: Morphological Investigation Using Cardiac Magnetic Resonance
Authors: Kitamura Mitsunobu , Amano Yasuo , Takayama Morimasa , Shibuya Junsuke , Matsuda Junya , Sangen Hideto , Nakamura Syunichi , Takano Hitoshi , Asai Kuniya , Shimizu Wataru
Published: July 2021

Introduction:
A residual gradient and repeat septal reduction therapy are more likely to occur with alcohol seplta ablation (ASA) than with surgical myectomy. We evaluated a cohort of patients treated with ASA to identify predictive factors of repeat ASA.

Methods:
Of 157 patients who underwent ASA, 19 (Group R) who underwent repeat ASA procedures remained after excluding those with planned staged ablation and isolated mid-ventricular obstruction. The median time interval between both procedures was 2.1 years. We compared Group R with patients not requiring repeat procedures (n = 105, Group S) in terms of clinical characteristics, ASA procedures, and morphological cardiac magnetic resonance (CMR), which was used to diagnose regional hypertrophy (thickness ≥ 15 mm) for each left ventricular myocardial segment.

Results:
Compared with group S, group R had a higher peak creatine phosphokinase value at the first ASA (1250 ± 522 vs. 1028 ± 520 IU/L, p = 0.046) and number of hypertrophic segments in the basal left ventricular level (segments 0-6, 2.8 ± 1.7 vs. 1.7 ± 0.8, p = 0.009). In multivariate analysis, diuretics use [adjusted odds ratio, 9.3 (95%CI: 1.6-56.2)] and the number of extended hypertrophy segments (except the anteroseptal region at the basal left ventricular level) were independent predictors of a repeat ASA procedure (adjusted odds ratio, 6.8 (95%CI: 1.5-32.1)/segment, p = 0.010). The repeat ASA rate was only 5% (1/21) among patients without non-anteroseptal hypertrophy, and 3% (1/29) among those without posteroseptal hypertrophy; however, patients with ≥2 segments of non-anteroseptal hypertrophy had an extremely high rate (50%, 7/14).

Conclusions:
CMR morphological analysis elucidated the characteristics of regional hypertrophic patterns in patients who underwent repeat ASA and found non-anteroseptal extended hypertrophy (≥ 2 segments) to be a crucial predictor of repeat ASA.