bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16756: Quantitative Coronary CT Angiography Demonstrates Increased Total Burden and Non-Calcified Plaque in Psoriasis
Authors: Mehta Nehal N , Rodriguez Karen , Jahanshad Amir , Natarajan Balaji , Krishnamoorthy Parasuram , Playford Martin P , Doveikis Julia , Ahlman Mark A , Bluemke David A
Published: July 2021

Introduction:
Coronary computed tomography angiography (CCTA) directly characterizes composition of plaque in coronary heart disease (CHD). Although the use of CCTA has been established in clinical CHD, no study to date has ever examined how psoriasis (PSO), a chronic inflammatory skin disease associated with increased risk for myocardial infarction (MI), affects CHD by CCTA. Therefore, our goal was to understand whether psoriasis increases CHD detected by CCTA and establishes CHD plaque characteristics compared to subjects with clinical coronary disease and healthy volunteers.

Methods:
Subjects with PSO (N=54), CHD (N=75) and healthy controls (N=5) underwent quantitative coronary CCTA imaging (Toshiba MDCT). Total coronary plaque was assessed using QAngioCT (Medis, Netherlands) as the total coronary artery wall volume. Furthermore, to better understand the determinants of CHD [total burden (TB) and non-calcified plaque burden (NCB)], we performed deep phenotyping for lipid markers including lipid particle size and numbers, HDL efflux, and metabolic parameters of insulin resistance such as Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) in psoriasis.

Results:
Our study showed that PSO was associated with higher TB and NCB of CHD when compared to both CHD and control groups (See Table 1). These findings were robust to adjustment for CHD risk factors (Framingham risk score) and luminal density (TB β=7.6, p<0.001 & NCB β=5.1, p=0.001). NCB was strongly associated with BMI (β=0.38, p<0.01), HDL efflux capacity (β=-10.9, p<0.05) and insulin resistance estimated by HOMA-IR (β=0.53, p<0.05) in psoriasis.

Conclusions:
This is the first study to show that psoriasis increases total burden of CHD which is non-calcified providing compelling evidence for the association between psoriasis and MI. Determinants of this NCB suggest focusing therapies on lipid and metabolic derangement in psoriasis may reduce this risk of future events.
Abstract 16801: Improved Transplant-Free Survival of Children With Dilated Cardiomyopathy: Analysis of Two Decades From the Pediatric Cardiomyopathy Registry
Authors: Singh Rakesh K , Canter Charles , Shi Ling , Colan Steven D , Dodd Debra A , Everitt Melanie D , Jefferies John L , Kantor Paul F , Lu Minmin , Pahl Elfriede , Rossano Joseph , Towbin Jeffrey A , Wilkinson James D , Lipshultz Steven E ,   for the PCMR Investigators
Published: July 2021

Background:
Previous studies of pediatric patients with dilated cardiomyopathy (DCM) have suggested improvement in survival has been due to utilization of heart transplantation. We sought to characterize the changing clinical characteristics and outcomes of pediatric patients with DCM phenotype over the past two decades.

Methods:
Longitudinal data from 1953 children diagnosed with DCM in the NHLBI Pediatric Cardiomyopathy Registry (PCMR) from 1990-2009 were divided into two cohorts based upon year of diagnosis: “Era 1” (1990-1999, n=1199) and “Era 2” (2000-2009, n=754). Clinical information at diagnosis and incidence of transplant and death without transplant were analyzed by DCM etiology and era. Competing risks methodology was used to estimate the cumulative incidence of death or transplant by era.

Results:
The majority of patients in both groups had idiopathic DCM (71 vs. 71%, p=0.96). Median age (1.6 vs. 1.7 yrs, p=0.45), left ventricular end diastolic Z scores (+4.2 vs. +4.2, p=0.84) and fractional shortening (16 vs. 17%, p=0.28) at diagnosis were similar. Era 2 patients were more likely to be treated with ACE inhibitors (71 vs. 62%, p=0.004), beta-blockers (24 vs. 6%, p<0.001), and diuretics (89 vs. 84%, p=0.002). A total of 291 patients (15%) died without transplantation, with a median time from diagnosis to death of 0.4 years. Cox regression modeling demonstrated Era 1 was associated with a higher rate of death (HR=1.5, 95% CI=1.2-2.0, p=0.002) but not transplant (0.9, 95% CI=0.7-1.1, p=0.25) when controlling for etiology group. Competing risks estimate (Figure) showed that Era 1 was associated with a higher death rate (p<0.001), while heart transplant rate was not significantly different by era (p=0.068).

Conclusions:
Children with DCM phenotype have improved survival in the more recent era. This appears to be associated with factors other than the availability of transplantation, which was equally prevalent in both eras.
Abstract 16854: End-Stage Renal Disease Associated With Metabolic Syndrome: A Study of Biomarkers Relevant to Cardiovascular Risk
Authors: Fareed Jawed , Bansal Vinod , Hoppensteadt Debra , Syed Daneyal , Ahmad Syed
Published: July 2021

Introduction:
Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors which contribute to myocardial infarction and stroke in end stage renal disease (ESRD) patients. Several metabolic biomarkers have been identified and their circulating levels provide a better understanding of the pathogenesis of MS/ESRD. The purpose of this investigation is to profile biomarkers of MS in ESRD patients.

Materials and Methods:
Plasma samples from 87 patients with ESRD undergoing maintenance hemodialysis and 50 normals were collected prior to a routine session. These samples were profiled for metabolic biomarkers using protein chip bioarray technology. The protein chip array was comprised of several biomarkers of MS. All results were compiled in terms of group means +/- 1 SD (SEM) and statistically analyzed.

Results:
In comparison to the normal samples, the ESRD group showed marked increase in circulating levels of all biomarkers. TNFa (47.4 +/- 18.3
vs
4.1 +/- 1.1 ng/mL) and IL-6 (7.8 +/- 9.1
vs
0.8 +/- 0.4 ng/mL) showed the most pronounced increase. C-peptide (14.5 +/- 4.1
vs
2.8 +/- 1.6 ng/mL), leptin (29.7 +/- 29.2
vs
5.2 +/- 7.9 ng/mL), resistan (16.1 +/- 6.0
vs
2.3 +/- 0.7 ng/mL) and ferritin (274 +/- 57
vs
57 +/- 63 ng/mL) showed a 5-fold increase in the ESRD group compared to normal. PAI-1 (5.4 +/- 5.2
vs
2.9 +/- 2.5 ng/mL), IL-1a (1.3 +/- 1.7
vs
0.35 +/- 0.07 ng/mL) and insulin (32.1 +/- 17.3
vs
17.1 +/- 1.7 ng/mL) showed modest increase in the ESRD patients. The increase in all of the MS biomarkers in the ESRD patients were highly significantly elevated,
p
<0.05.

Conclusion:
The specific biochip array for MS allows the selective determination of various biomarkers associated with this syndrome in the ESRD patients and normals. Parallel increase in resistan, insulin, C-peptide, and leptin points to the derangement of glucose metabolism in these patients. Increase IL-1a, TNFa, and ferritin suggests the upregulation of an inflammatory process. PAI-1 increase suggests a fibrinolytic deficit. The parallel derangement of the inflammatory process and metabolic syndrome contributes to the cardiovascular and cerebrovascular complications in these patients.
Abstract 16856: S-Glutathionylation of Endothelial Cell Proteins Facilitates Ischemic Limb Revascularization
Authors: Watanabe Yosuke , Murdoch Colin , Han Jingyan , Cohen Richard , Mastui Reiko
Published: July 2021

Reactive oxygen species (ROS) are increased during ischemia, but decreasing ROS in endothelial cells impairs revascularization. Low levels of ROS regulate protein function by inducing S-glutathionylation, a reversible post-translational protein modification that may change protein(s) function directly. Protein S-glutathionylation is increased in oxidative conditions and eliminated by glutaredoxin-1 (Glrx). We demonstrated that hind limb revascularization was impaired in global Glrx transgenic mice. In this study, we further examined the role of S-glutathionylation in revascularization by gain and loss of cell-specific Glrx expression.

Methods:
Hind limb ischemia (HLI) was created by femoral artery ligation. HLI surgery was performed in 1) “Tet-Off” endothelial specific Glrx transgenic mice (EC-Glrx TG), 2) global Glrx knockout (KO) mice, 3) myeloid cell-specific Glrx deleted mice. EC-Glrx TG was generated by breeding VEcadherin-tTA and tet-operated Glrx mice, treated with doxycycline in utero and until 8 weeks of age to avoid overexpression during development. 3) Myeloid cell-specific Glrx deleted mice were generated by bone marrow transplant using Glrx KO and wild type bone marrow, respectively. Blood flow recovery was analyzed by LASER Döppler.

Result:
S-glutathionylation of ischemic limb was increased more than two-fold compared with non-ischemic limb. S-glutathionylation was decreased in endothelial cells from EC-Glrx TG and increased in Glrx KO cells. 1) Blood flow recovery was significantly impaired in EC-Glrx TG mice compared with wild type littermate 1 week after HLI surgery (12% vs 39%, p<0.01), and 40% of ischemia limbs became necrotic and were lost in 2 weeks in EC-Glrx TG mice, while all limbs survived in WT mice. In contrast, 2) Blood flow recovery was improved in Glrx KO mice (57% in KO mice vs 42% in WT mice, p<0.01), 3). Myeloid-specific deletion of Glrx did not alter the blood flow recovery.

Conclusions:
Glrx in endothelial cells, not in myeloid cells, plays an important role in ischemic revascularization. Our data suggest that ROS-induced S-glutathionylation in EC positively regulates revascularization after limb ischemia.
Abstract 16858: Factors Associated With Length of Stay and Cost of the Fontan Surgery: A Multi-Institutional Study
Authors: Menon Shaji C , Hinkle Kevin , McFadden Molly , Wilkes Jacob , Minich L. LuAnn
Published: July 2021

Introduction:
We sought to determine factors associated with length of stay (LOS) and cost of the Fontan surgery in a contemporary large multi-institutional cohort.

Hypothesis:
Independent and modifiable risk factors associated with longer LOS and higher cost will be identified.

Methods:
We performed a retrospective cohort study of Fontan surgey (1/2004 - 7/2013) using the Pediatric Health Information Systems (PHIS) database (40 US children’s hospitals). Outcome parameters were LOS and costs at Fontan surgery. Predictor variables were demographics (race, insurance, region, rural vs city, commute time, surgical volume), cardiac and other diagnoses, Glenn events, readmission between Glenn and Fontan, and age at Glenn and Fontan. Following a stepwise selection procedure, significant predictors of LOS and cost were included in a generalized linear model with the appropriate inverse Gaussian distribution and the log link function with LOS and cost (adjusted to 2012 $ and region) as the dependent variable.

Results:
For the 2187 patients (62% male) who had Fontan surgery, the median age at surgery was 1146 days (IQR: 943-1369) and at Glenn was 165 days (IQR: 133-208). Following Fontan, the median ICU LOS was 3 days (IQR: 2-6) and total LOS was 9 days (IQR: 7-14). The median total hospital cost was $93, 900 (IQR: 67,800-136,100). Post-operative mortality was 1% (N=21). Region, insurance, race, surgical volume were the predominant factors associated with both cost and LOS (Table 1).

Conclusion:
This is the largest multicenter contemporary study describing the factors (particularly healthcare delivery factors) associated with resource utilization during the Fontan hospitalization. Health care delivery variables dominated the factors predicting increased resource utilization. Changes in health care policy should target health care delivery risk factors (race, region, insurance, driving distance, surgical volume) to reduce cost in this resource intensive population.
Abstract 16863: Does Maintenance Anticoagulation Variability Influence Adverse Outcomes in Patients with Continuous Flow Left Ventricular Assist Devices?
Authors: Haglund Nicholas A , Lai Christine , Miller Patricia B , Davis Mary E , Stulak John , Keebler Mary E , Boord Jeffrey , Maltais Simon
Published: July 2021

Introduction:
Anticoagulation (AC) with vitamin K antagonists (VKA) are used to reduce the risk of thrombus in patients with continuous flow left ventricular assist devices (CF-LVAD).

Hypothesis:
We sought to determine if AC variability was associated with adverse bleeding or thrombus outcomes in CF-LVAD patients.

Methods:
We analyzed VKA AC variability during the maintenance AC phase from 30 to 90 days in 91 CF-LVAD (HeartMate-II 49, HeartWare 42) patients between 2011 and 2014. Patients were divided into AE and NO AE groups based on bleeding and thrombus outcomes. VKA AC data (measured and interpolated INR values, INR frequency, VKA dose), medications that affect VKA metabolism, markers of hepatic function and anti-platelet agents were compared between groups.

Results:
Baseline (mean age 52±12, male 79%, INTERMACS 3/4 80%) and perioperative (bypass time 82±48, length of stay 15.4±7.3) characteristics were comparable between AE and NO AE groups (all p>0.05). Adverse outcomes occurred in 12 (13%) patients (bleeding= 4, pump thrombus=6, stroke=2). In the overall cohort, patients spent a median time of 63% (47, 78) in therapeutic INR (2-3) range during maintenance phase VKA AC. Interestingly, variation in maintenance phase AC was comparable between AE and NO AE groups (all p>0.05; Table). Medications that affect VKA metabolism, hepatic function and anti-platelet medications were similar between groups (all p>0.05) (Table). Time in therapeutic range was comparable between devices (HM-II 56% vs HW 65%; p=0.09).

Conclusions:
During maintenance VKA anticoagulation, CF-LVAD patients spent 37% of time outside the therapeutic INR range. VKA anticoagulation variability, antiplatelet therapy and medications that affect VKA metabolism were not associated with bleeding or thrombus outcomes. Investigation into other variables that may account for recently reported increased adverse events are urgently needed.
Abstract 16921: Atrial Fibrillation is Associated with Significant Physical Function Decline in Older Adults
Authors: Magnani Jared W , Wang Na , Garcia Melissa E , Phillips Caroline L , Sullivan Lisa M , Butler Javed , Newman Anne , Benjamin Emelia J , Harris Tamara
Published: July 2021

Introduction:
Atrial fibrillation (AF) is associated with significant morbidity in older adults. The effect of AF on physical function has had limited investigation. We related incident AF to prospective change in physical function across serial assessments in the Dynamics of Health, Aging, and Body Composition Study (HABC).

Methods:
HABC is a prospective study of older adults age 70-79 initiated in 1997-98. Physical function has been assessed in the cohort with the HABC performance battery (HABCPPB), scored 0-4, consisting of gait speed, chair stands, and balance assessments, administered at years 1, 4, 6, 8 and 10. Incident AF was ascertained from linkage with Center for Medicare and Medicaid Services, and dated by the first in-patient or second of 2 out-patient encounters. We used mixed effects regression analysis to relate incident AF to 4-year decline in the HABCPPB. Analyses incorporated age and AF as time-varying covariates and relevant multivariable adjustment (demographics; smoking, alcohol; cardiovascular disease [CVD] risk factors; prevalent CVD; and time varying hypertension, diabetes, CVD, and cancer).

Results:
Following exclusions, 2753 (age 73.6±2.9 years, 52% women, 41% black race) HABC participants were eligible for the analysis. We determined that older adults who developed AF at ages 74, 78, and 82 had significantly greater (
P
<0.001) 4-year decline in physical function than those without AF. The
Figure
compares the trajectories of 4-year HABCPPB decline in those with and without AF at ages 70, 74, 78, and 82. For age centered at 74, the difference in 4-year decline in HABCPPB in those with and without AF was -0.10 (95% CI -0.21, 0.00); -0.21 (-0.31, -0.11) at age 78; and -0.32 (-0.48, -0.15) at age 82. These differences in physical function decline remained significant (P<0.001) following multivariable adjustment.

Conclusions:
In a community-dwelling cohort of older adults, AF was associated with significant 4-year decline in physical function.
Abstract 16984: Role of Inositol 1,4,5-Triphosphate Receptor 2 in Post-Ischemic Heart Failure
Authors: Santulli Gaetano , Chen BiXing , Forrester Frances , Wu Henry , Reiken Steve , Marks Andrew R
Published: July 2021

Introduction:
The type 2 inositol 1,4,5-triphosphate receptor (IP3R2) is the predominant isoform expressed in ventricular cardiomyocytes. IP3R2-mediated Ca
2+
release has been proposed to participate in atrial arrhythmogenesis. However, its involvement in post-ischemic heart failure (HF) has not been elucidated.

Methods:
To investigate whether myocardial IP3R2 plays a functional role in HF, we generated myocardial specific IP3R2 knock-out (KO) mice by crossing IP3R2
flox/flox
mice (obtained by opportunely placing loxP sequences flanking exon 3 of
IP3R2
gene) with α-MHC
Cre
mice.

Results:
We confirmed cardiomyocyte-specific IP3R2 deletion in IP3R2
flox/flox
/α-MHC
Cre
mice (hereafter referred to as KO) at mRNA and protein levels. The loss of IP3R2 in the heart does not result in embryonic lethality: KO mice survived to adulthood and we did not detect any morphological or functional defects in baseline conditions. Serial cardiac ultrasound analyses performed following coronary artery ligation revealed a significant amelioration in cardiac function post myocardial infarction (MI) in KO mice compared with flox littermates (p<.05, ANOVA rep. measures, n=5-8/group). No significant differences were detected by radiotelemetry in blood pressure. Hemodynamic studies performed post-MI confirmed the improved cardiac contractility (dP/dt
max
,KO:6424±424; flox:5794±410 mmHg/s; p<.05, n=6/group). These data are further supported by increased IP3R2 levels detected in HF patients. A markedly reduced percentage of apoptotic cells after MI was revealed by TUNEL assay in cardiac sections from KO mice compared with flox controls, mirrored by an augmented caspase activity and a decreased calcineurin phosphatase activity (p<.05, n=7/group). Furthermore, we observed decreased interstitial cardiac fibrosis in failing hearts from KO mice compared with their flox littermates (p<.05, n=6/group). No obvious difference was noticed examining ultrastructural mitochondria morphology.

Conclusions:
Taken together our results indicate that myocardial IP3R2 plays a crucial role in the pathophysiology of HF, participating via a mechanism involving the calcineurin pathway in the regulation of fibrosis and apoptosis during post-ischemic cardiac remodeling.
Abstract 170: Temperature Maintenance and Oxygen Use in Newborns at Birth: A Surveillance of Clinical Practice and Compliance with Neonatal Resuscitation Guidelines
Authors: Schmölzer Georg M , Pinson Roxanne , Molesky Marion , Chinnery Heather , Foss Karen , Cheung Po-Yin
Published: July 2021

Background:
Guidelines of neonatal resuscitation are revised regularly. Gaps in knowledge transfer commonly occur when the guidelines are communicated to the clinical practitioners. Maintaining body temperature and supporting oxygenation are main goals that clinical practitioners aim to achieve in assisting newborns during the feto-neonatal transition at birth.

Objectives:
In this study, we aim to examine the compliance to guidelines in neonatal resuscitation regarding the temperature maintenance and oxygen use in newborns at birth.

Methods:
From October to November 2013, a prospective questionnaire surveillance was conducted in all attended deliveries at all four hospitals in Edmonton, Alberta, Canada. All clinical practitioners (registered nurses, physicians and respiratory therapists) were requested to complete the questionnaires immediately after the attended delivery regarding temperature maintenance and oxygenation monitoring. Descriptive statistics were used with mean±SD (range) and % presented.

Results:
During the 14-days study period, data was obtained in 518 of 712 (73%) attended deliveries of newborns with gestational age 38.6±2.0 (23-42) weeks and birth weight 3324±589 (348-6168) g. Of these deliveries, 58% were normal vaginal deliveries and 29% were cesarean sections. There were 8.8% and 8.4% newborns who required positive pressure ventilation and continuous positive pressure, respectively. Radiant warmer heat was used in 81% (419/518) with 63% (266/419) turned to full power. Room temperature was 21.6±1.6 (17-31)°C. Body temperature at 30-60 min after birth was 36.8±0.5 (32.4-38.1)°C with hypothermia (<36.5°C) in 17%. Percutaneous oxygen saturation was measured in 15% newborns and 96% had sensors placed at the right wrist. At the initiation of resuscitation, 21% oxygen was used in 76% and the oxygen concentration was adjusted according to an oxygen saturation chart in 17%. In 70% of the cases, clinical practitioners commented that this chart was not helpful.

Conclusions:
Gaps in knowledge transfer contribute to non-compliance in the guidelines of neonatal resuscitation for temperature maintenance and oxygen use. Caution is needed to avoid hypothermia and hyperoxia in at-risk populations such as prematurity.
Abstract 17014: The Impact of Risk Score (CHADS2 versus CHADS2-Vasc) on Long-term Outcomes After Atrial Fibrillation Ablation
Authors: Jacobs Victoria , May Heidi T , Bair Tami L , Crandall Brian G , Cutler Michael , Weiss J. P , Osborn Jeffrey S , Mallendar Charles , Day John D , Bunch Thomas J
Published: July 2021

Background:
Risk stratification tools are needed to better select candidates for catheter ablation of atrial fibrillation (AF). Both the CHADS2 and CHADS2-VASC scores have utility in predicting AF-related outcomes and guiding anticoagulation treatment. We sought to determine if these risk scores predict long-term outcomes after AF ablation and if one risk score provides comparative superior performance.

Methods:
CHADS2 and CHADS2-VASC scores were calculated in 2179 AF ablation patients enrolled into Intermountain Heart Collaborative Study. CHADS2 and CHADS2-VASC were categorized by recursive partitioning categories as CHADS2: 0-1, 2-4, and >4 and CHADS2-VASC: 0-2, 2-5, >5. Patient outcomes were analyzed over 5 years for AF/Aflutter recurrence and MACE (death, stroke, heart failure hospitalization and AF/Aflutter recurrence).

Results:
Average age was 65.7±10.5 years and 61.1% were male. Both scores incrementally predicted risk of AF recurrence, stroke, heart failure, and death at 5 years (Figure). Increasing CHADS2 (hazard ratio [HR] =1.19, p<0.001) and CHADS2-VASC (HR=1.15, p<0.0001) scores were both associated with AF/Aflutter recurrence. Results were similar for MACE: with increasing CHADS2 (HR=1.20, p<0.0001) and CHADS2-VASC (HR=1.15, p<0.0001) scores associated with risk. When CHADS2 and CHADS2-VASC were modeled simultaneously, only CHADS-VASC significantly predicted AF recurrence (HR=1.13, p=0.001) and MACE (HR=1.13, p=0.001).

Conclusion:
Both the CHADS2 and CHADS2-VASC scores were excellent in stratifying patients for 5-year outcomes after AF ablation. However, the CHADS2-VASC score was superior to CHADS2 when accounting for all baseline variables for predicting both AF recurrence and AF-related morbidities.
Abstract 17049: Obesity and Prognosis in Patients with Acute Cerebrovascular Accident
Authors: Hayek Sami , Zeineh Nabil , Lasorda David , Hajjali Raef
Published: July 2021

Introduction:
Limited data exist concerning the impact of obesity on prognosis in patients with acute cerebrovascular accident (CVA). Some of the published data suggest a paradoxically better outcome in obese patients with CVA while others have failed to find such an association and this relation remains unclear.

Hypothesis:
We examined the impact of obesity on in-hospital mortality in patients presenting with acute ischemic CVA in a large sample representative of the US population.

Methods:
The Nationwide Inpatient Sample, part of the Healthcare Cost and Utilization Project, is the largest publicly available inpatient database designed to provide information on characteristics and outcomes of patients discharged from United States community hospitals. Using the Nationwide Inpatient Sample, we identified 455006 adult patient discharges, with a primary discharge diagnosis of ischemic stroke or TIA. Among those, 31723 had a diagnosis of obesity.

Results:
Patients with obesity were in general younger (63 yrs. vs. 72 yrs. p<0.001), with a higher proportion of females (57% vs. 52%, p<0.001), and a higher frequency of hypertension (71% vs. 66%, p<0.001), and diabetes mellitus (55% vs. 30%, p<0.001. Obese patients were less likely to have atrial fibrillation (13% vs. 18%, p< 0.001). The in-hospital mortality rate for patients with acute CVA and obesity was 1.8%, compared to 3.2% in patients without obesity (p<0.001). After adjusting for pertinent clinical variables using logistic regression analysis, obesity remained an independent predictor of lower in-hospital mortality (p<0.001, OR 0.82[0.75-0.89]).

Conclusions:
In patients presenting with acute cerebrovascular accident, obesity is associated with lower in-hospital mortality.
Abstract 17138: Intravenous Regadenoson with Aminophylline Reversal is Safe and Equivalent to Intracoronary Adenosine Infusion for Fractional Flow Reserve Measurements
Authors: Lee John , Saberian Sepehir , White Christopher , Collins Tyrone , Reilly John P , Ramee Steven , Jenkins J S , Salvaggio Louis , Morin Dan , Patel Rajan , Benjo Alexandre , Bober Robert
Published: July 2021

Background:
Small studies have shown that Adenosine is equivalent to Regadenoson when obtaining Fractional Flow Reserve (FFR) measurements. A larger study that also evaluates time and safety of aminophylline reversal was yet to be presented.

Methods:
After IRB approved consent was obtained, 46 consecutive patients with clinically indicated FFRs were enrolled between 4/2012 and 5/2014. Each patient had FFR measured with adenosine 140 mcg/kg/min IV then allowed to return to baseline. FFR was repeated with Regadenoson 140 mcg IV bolus than reversed with aminophylline 150 mg IV and time to baseline hemodynamics were measured. Tests were compared using linear regression. Reversal time recorded in seconds.

Results:
As demonstrated in Figure1 FFR results were similar with both agents, R2 = 0.935, p<0.0001. Also, using the 0.80 cutoff, there was no divergence regarding studies significance. After aminophylline, hemodynamics returned to baseline in 112+/- 72 secs. There were no side-effects reported.

Conclusion:
The use of regadenoson for FFR measurements provides results consistent with the ones obtained with adenosine infusion. Aminophilline reversal for regadenoson was fast, well tolerated and safe. Regadenoson with aminophylline reversal may be considered as an alternative for FFR measurements.
Abstract 17145: Mitral Leaflet Growth and its Relationship with Functional Mitral Regurgitation in Non-ischemic Left Ventricular Systolic Dysfunction
Authors: Kang Yu , Chen Xiao-Jing , Zhang Qing , Sun Xiao-Ling , Chen Yu-Chen , Wang Fang , Li Ling-Li , Liang Yu-Jia
Published: July 2021

Backgrounds:
Recent studies evidenced growth of the mitral leaflet (ML) in patients with functional mitral regurgitation (FMR), casting doubt on the traditional understanding of FMR. The aim of this study was to explore whether growth of ML occurs in patients with non-ischemic left ventricular (LV) systolic dysfunction and to examine whether there was any relationship between the growth of ML and the development of FMR.

Methods:
Echocardiographic examination was performed in 3 groups of patients: patients with non-ischemic LV systolic dysfunction [LV ejection fraction (EF) <50%] and significant FMR (MR jet area ratio≥20%) (group1, n=40), patients with non-ischemic LV systolic dysfunction but no significant FMR (MR jet area ratio <20%) (group2, n=30), and normal subjects (group3, n=40). The lengths of the anterior (AML) and posterior (PML) mitral leaflets as well as the anterior-posterior mitral annular dimension (MAD) were measured to reflect the degree of ML growth and mitral annular dilation. The ratio of AML and PML to MAD (AML: MAD, PML: MAD) were calculated respectively to assess the adequacy of ML growth in the context of mitral annular dilation.

Results:
The AML, PML, and the MAD were all increased in patients with LV systolic dysfunction (group1 and group2) compared with normal subjects (group3). In patients with LV systolic dysfunction, both PML and MAD were further increased in group1 compared with group2. However, AML showed no significant difference between the 2 groups. As a result, PML:MAD showed no significant difference between group1 and group2, while AML:MAD was significantly decreased in group1 compared with group2 (Table 1).

Conclusion:
Mitral leaflet growth occurs in patients with non-ischemic LV systolic dysfunction. Insufficient growth of the anterior mitral leaflet relative to dilated mitral annulus is associated with the development of significant FMR.
Abstract 17286: Reconciling Systolic and Diastolic Measures of Left Ventricular Noncompaction Cardiomyopathy in Cardiac Magnetic Resonance
Authors: Stacey Richard B , Upadhya Bharathi , Milks Michael M , Deutsch Christian , Lin Tiffany , Hundley William G , Thohan Vinay
Published: July 2021

Background:
Previously, it was demonstrated that systolic measures identify higher levels of risk for events related to left ventricular noncompaction cardiomyopathy (LVNC) than diastolic measures. This analysis seeks to improve the ability of the diastolic measures to identify LVNC and predict associated events.

Methods:
Trabeculation/possible LVNC by cMRI was retrospectively observed among 122 consecutive cases. We assessed the extent of trabeculation, end-systolic noncompacted-to-compacted ratios (ESNCCR), end-diastolic noncompacted-to-compacted ratios (EDNCCR) along with myocardial thickening (MT) and ejection fraction (EF). Deaths, CHF readmissions, ventricular arrhythmias, and embolic events were pooled to increase statistical power and used to identify potential LVNC-associated events. Using logistic regression with an ESNCCR ≥ 2 to identify LVNC as the dependent variable and EDNCCR as the independent variable, analysis were performed with receiver operating curves with and without myocardial thickening as a covariate. Next, using pooled LVNC-associated events as the dependent variable, separate models were performed for ESNCCR ≥ 2 and EDNCCR ≥ 2.3, both adjusting for age, race, gender, body surface area, left ventricular ejection fraction, number of trabeculated segments, and myocardial thickening.

Results:
The area under the curve (AUC) for EDNCCR to identify potential LVNC was 0.84, but with adjustment for myocardial thickening, the AUC was 0.98, which was significantly increased (p-value = 0.005). Without adjusting for myocardial thickening, ESNCCR ≥ 2 was associated with LVNC-associated events, but EDNCCR ≥ 2.3 was not (p-value: 0.003 vs 0.2, respectively). With adjustment for myocardial thickening, both ESNCCR ≥ 2 and EDNCCR ≥ 2.3 were associated with LVNC-associated events (p-value: 0.03 vs 0.03, respectively).

Conclusion:
In using the diastolic measure to assess for possible left ventricular noncompaction cardiomyopathy, impaired function of the underlying compacted layer is important in identifying those with a higher risk of subsequent events. Further studies are needed to determine if individuals with increased trabeculations with preserved myocardial thickening are at increased risk of future events.
Abstract 17288: Risk Prediction of 10-Year Cardiovascular Mortality Using Automated Electrocardiographic Analysis in the National Health and Nutrition Examination Survey
Authors: Shah Amit J , Janssens Cecile , Kundu Suman , Veledar Emir , Wilson Peter , Vaccarino Viola , Soliman Elsayed Z
Published: July 2021

Introduction:
Several individual ECG parameters are predictive of cardiovascular disease (CVD) mortality, and when combined in a score, may improve risk prediction.

Hypothesis:
We hypothesized that an ECG risk score (based on automated measures available on many modern ECG machines) can effectively predict CVD mortality, and augment risk classification when added to traditional risk factors (TRF).

Methods:
We examined 6786 individuals aged 40-79 years without known CVD in NHANES III (1988-1994) followed 10 years for CVD mortality. Six pre-specified ECG variables (“ECG model”), were evaluated including P, R, T axes, QT interval, QRS width, and heart rate. Three risk scores were developed for variables containing: 1) TRF only, 2) ECG factors (including age, sex, and race), and 3) TRF+ECG combined. Validation was performed using a cohort aged 40-74 years from NHANES I (n=3773), enrolled in 1971-1974. Age stratification was performed with cutoff of 65 years because of increased competing risks in older individuals.

Results:
During 10 years of follow up, 384 CVD deaths occurred. Frontal QRS-T angle, T-axis, wide QRS interval (cutoff 120 ms), heart rate-corrected QT interval, and heart rate were found to be significant predictors (p<0.05) of CVD death. As per the table, the ECG score had similar performance compared to the TRF score for the subgroup < 65 years of age in the derivation and validation cohorts. The score with combined ECG + TRF had the best performance for those aged < 65 years, and resulted in a net reclassification index of 9% in the validation cohort using cutoffs of 7.5% and 20% for low, intermediate, and high risk categories. In those aged ≥ 65 years, the combined score showed improvement vs. the TRF score in the derivation, but not validation cohort.

Conclusion:
A risk score based on routinely reported automated ECG variables and TRF predicts risk of 10-year CVD death better than TRF alone in a cohort age < 65 years without known CVD.
Abstract 17312: Amyloid-β (1-40) and the Risk of Death from Cardiovascular Causes in Patients with Coronary Heart Disease
Authors: Stamatelopoulos Kimon , Sibbing Dirk , Rallidis Loukianos S , Georgiopoulos Georgios , Stakos Dimitrios , Braun Siegmund , Gatsiou Aikaterini , Sopova Kateryna , Kotakos Christos , Varounis Christos , Tellis Costantinos C , Kastritis Efstathios , Alevizaki Maria , Tselepis Alexandros D , Alexopoulos Panagiotis , Laske Christoph , Keller Till , Kastrati Adnan , Dimmeler Stefanie , Zeiher Andreas M , Stellos Konstantinos
Published: July 2021

Introduction:
Investigation of the clinical value of biologic pathways that are involved in pathogenesis of atherosclerotic disease is essential for identification of novel therapeutic targets and improvement of cardiovascular risk stratification.

Hypothesis:
To determine the clinical value of amyloid-β 1-40 (Aβ40) measurement in predicting cardiovascular (CV) mortality in patients with coronary heart disease (CHD) and arterial stiffness progression in young healthy subjects.

Methods:
Aβ40 was retrospectively measured in blood samples collected from three independent prospective cohorts and two case-control cohorts (total n=1464). Major adverse CV events (MACE) were assessed in the two prospective cohorts (n=877) followed for a median of 4.4 years. Arterial stiffness was evaluated at baseline and after a 5-year follow-up period (n=107) in young healthy subjects. The primary endpoint was the predictive value of Aβ40 for CV mortality and outcomes in patients with CHD. Further, the associations of Aβ40 levels with arterial stiffness progression, incident subclinical atherosclerosis and incident CHD were addressed.

Results:
In Cox proportional-hazards models adjusted for age, gender, glomerular filtration rate, left ventricular ejection fraction, high-sensitivity C-reactive protein and high-sensitivity troponin-T, Aβ40 was an independent predictor of CV death and MACE in patients with CHD (P<0.05 for all). After multivariate adjustment, Aβ40 levels conferred a substantial enhancement of net reclassification index (continuous NRI value and 95% confidence interval: 36.7%, 12.5-60.7, P=0.001) and integrated discrimination improvement (IDI value±SE: 1.92±0.62, P<0.001) of individuals at risk in the total combined CHD cohort over the best predictive model. Further cohort-based analysis revealed that Aβ40 levels were significantly and independently associated with arterial stiffness progression, incident subclinical atherosclerosis and incident CHD.

Conclusions:
Measuring blood levels of Aβ40 identifies patients at high risk for cardiovascular death.
Abstract 17321: Race Differences in Hemodynamic Responses to Acute Mental Stress and the Role of Depressive Symptoms
Authors: Wilmot Kobina A , Al Mheid Ibhar , Ramadan Ronnie , Pimple Pratik M , Shah Amit J , Alkhoder Ayman , Obideen Malik , Kutner Michael , Long Qi , Lewis Tene` , Raggi Paolo , Bremner Douglas , Quyyumi Arshed A , Vaccarino Viola
Published: July 2021

Introduction:
Increased hemodynamic responses to psychological stress have been associated with adverse CAD events. African Americans (AA) have worse CAD outcomes than other groups. Heightened hemodynamic responses to stress may play a role. Our hypothesis was that AA would have higher hemodynamic reactivity to a standardized mental stress compared to Non-African Americans (NAA).

Methods:
We evaluated 574 patients (163 AA) with CAD, who underwent a standardized mental stress challenge. Hemodynamics were obtained at rest, during stress (speaking task), and during recovery. The rate-pressure product (RPP) was calculated as systolic blood pressure (SBP) x heart rate (HR). Hemodynamic reactivity was evaluated as the difference in RPP at rest and during stress. Depressive symptoms were measured with the Beck Depression Inventory-II (BDI).

Results:
As compared to NAA, AA patients were younger, had lower education and income, and higher prevalence of diabetes, obesity, hypertension, smoking, and depressive symptoms (BDI mean scores 9.8 vs. 7.6, p= 0.003). AA patients had higher blood pressure during all three periods (Table). However, hemodynamic reactivity with stress was significantly lower in AA than NAA (RPP reactivity 3114 vs 3620, p= 0.02). Adjusting for baseline RPP, age, gender and smoking did not substantially alter the association. However, after adjusting for depressive symptoms, the association was attenuated by 23% (p=0.16). BMI, diabetes and beta-blocker use had minimal additional explanatory role. In the final model, baseline RPP, depressive symptoms and BMI were significantly associated with a lower RPP reactivity (p<0.01).

Conclusion:
AA patients with CAD, compared with NAA, have elevated blood pressure throughout mental stress, but tend to have blunted hemodynamic reactivity to stress. Depressive symptoms, which are more elevated among AA, play a role in this different response to stress and may be implicated in the higher CAD risk of this group.
Abstract 17368: The Diagnosis of Heterozygous Familial Hypercholesterolemia: Genotype versus Phenotype
Authors: Raal Frederick , Stein Evan A , Cariou Bertrand , Gaudet Daniel , Genest Jacques , Somaratne Ransi , Bridges Ian , Wasserman Scott M , Scott Rob , Hovingh G. Kees
Published: July 2021

Background:
Heterozygous familial hypercholesterolemia (HeFH) is the most common dominantly-inherited disorder in man, affecting between 1:250 and 1:300 persons worldwide and estimates of more than 3 million with HeFH in the USA and Europe alone. Diagnosis is usually made by clinical criteria and confirmed with genetic testing. Despite next-generation gene sequencing, a causative mutation cannot be identified in up to 20% of patients even with a clinical diagnosis of definite HeFH. Given the prevalence, clinical diagnostic criteria are important tools for detection and early treatment of HeFH patients, particularly for clinicians outside of referral centers.

Methods:
The RUTHERFORD-1 and -2 studies enrolled patients with a clinical and/or genetic diagnosis of HeFH. All consenting patients in this analysis underwent FH genotyping. We compare the accuracy of clinical and genetic diagnosis of HeFH.

Results:
Of the 416 patients enrolled who consented to genetic testing, 342 (82%) were found to have genetically-confirmed HeFH. Of these patients, 288 (84%) met the Simon Broome criteria for definite and 54 (16%) for probable HeFH; 250 (75%) met the MEDPED clinical criteria for 100%, and 301 (90%) the 80% likelihood for a diagnosis of HeFH (Table).

Conclusion:
Although the optimal method to diagnose HeFH remains unclear, from these two trials there was close agreement between the two clinical classifications and genetic criteria. There were only a relatively small number of patients in whom genetic testing could not confirm the clinical diagnosis. Clinical criteria offer an inexpensive, low-technology ability for widespread screening in patients suspected of having HeFH. The advantage of genetic testing is that it allows for cascade testing of family members for the identified mutation who may not fulfill clinical criteria for the diagnosis of HeFH and application of family-oriented preventive strategies.
Abstract 17471: 3D Contrast-enhanced Ultrasound (CEUS) Imaging of Carotid Artery Plaques and Intra-plaque Angiogenesis
Authors: Gourineni Venu , Saha Sandeep , Cao Kunlin , Jin Jing , Dentinger Aaron M , Mills David M , Padfield Dirk R , Wallace Kirk D , Reddy Vijaya , Shur Boris M , Yamout Frank , McCarthy Walter , March Robert , Jacobs Chad , Liuzzo Adele , Goldin Marshall , Adam Dan , Feinstein Steven
Published: July 2021

Introduction:
Vulnerable plaque is marked by increased intra-plaque vascularity, hemorrhage and is associated with cerebrovascular (CV) events. Current use of 2D CEUS carotid imaging does not provide a true volumetric representation of the intra-plaque angiogenesis. Therefore, this is the first clinical trial using 3D CEUS to assess intra-plaque angiogenesis, in patients with clinically significant plaques prior to carotid endarterectomy (CEA).

Methods:
Data were acquired on 11 patients that were asked to participate in this pilot study prior to CEA. All patients had MR and/or CT angiogram as part of their standard care and all carotid artery plaque specimens were collected and sent for histologic evaluation. CEUS volumes were acquired using a GE LOGIQ E9, RSP6-16 4D probe and Optison. In order to assess plaque vulnerability, semi-automatic image analysis algorithms were developed to segment the lumen, plaque, and intra-plaque vascularity. Measurements derived from 3D CEUS images were validated against CT, MR, and histology.

Results:
Preliminary results from 3 patients were analyzed and lumen volumes were segmented from all available modalities (figure shows CEUS example). Lumen measurements of the CCA, ICA, and ECA from 3D CEUS were compared to MR or CT. High correlation is shown in the figure for these patients (R
2
=0.95). Further analysis of the 3D CEUS images demonstrates that we can identify intra-plaque vascularity (see segmentation from one patient). These CEUS results estimated an average cross-sectional vascular density of 7-11% in the plaque, matching histology estimates of 10% from a single slice.

Conclusion:
These results demonstrate that it is feasible to use 3D CEUS for quantitative, volumetric imaging of the carotid artery and intra-plaque angiogenesis in patients scheduled for CEA. Future work will extend this analysis to all patients and make a quantitative comparison of intra-plaque vascular density from 3D CEUS vs. multiple histology slices.
Abstract 17474: Management State of Low-Density Lipoprotein Cholesterol has a Favorable Effect on Left Ventricular Reverse Remodeling in Patients With ST-Segment Elevation Acute Myocardial Infarction
Authors: Makino Akihiro , Matsunaga Atsuhiko , Yamaoka-Tojo Minako , Kameda Ryo , Masuda Takashi , Ako Junya
Published: July 2021

Left ventricular remodeling following ST elevation acute myocardial infarction (STEMI) is still an issue in the primary percutaneous coronary intervention (PCI) era. This study aimed to examine whether control of cholesterol levels is predictive of reverse remodeling in patients with STEMI.

Subjects were 56 patients with first STEMI successfully and completely reperfused. Single photon emission computed tomography (SPECT) was used to measure LV function at 1 and 6 months after onset. Reverse remodeling was defined as a >10% reduction in LV end-systolic volume at 6-month follow-up compared with baseline SPECT. Patients were divided into reverse remodeling (n=15) and non-reverse remodeling (n=41) groups, and clinical characteristics including age, sex, body mass index, peak serum creatine kinase, number of coronary artery lesions, coronary risk factors and medications, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL-C/HDL-C ratio, and triglycerides were compared between the groups. We examined the proportions of patients with target LDL-C (<70 mg/dL), HDL-C (≥40 mg/dL), and TG (<150 mg/dL) levels, and LDL-C/HDL-C ratio of <1.5. Multivariate stepwise logistic regression analyses were performed to evaluate the relationship between occurrence of reverse remodeling and clinical characteristics.

In baseline clinical characteristics, there were significant differences between the two groups regarding to management states of LDL-C levels and the LDL/HDL ratio. The proportions of patients achieving target LDL-C levels and LDL-C/HDL-C ratio were higher in the reverse remodeling group than in the non-reverse remodeling group (80% and 17%, p<0.0001; 60% and 10%, p<0.0001, respectively). Logistic regression analysis revealed that patients with target LDL-C levels were significantly more likely to show reverse remodeling (odds ratio 19.429, 95% confidence interval 4.317-87.432, p<0.0001).

The present study showed that the good control of LDL-C independently predicts reverse remodeling in patients with first STEMI. This finding underscores the need for achieving and maintaining target LDL-C levels through secondary prevention for reverse remodeling.
Abstract 17527: Partitioning Echocardiographic Size and Function Parameters of the Right Ventricle Using CMR Normative Values from the MESA Study
Authors: Addetia Karima , El-Hangouche Nadia , Patel Amit R , Wilkinson Michael J , Lang Roberto M , Spencer Kirk T
Published: July 2021

Introduction:
Right ventricular (RV) size and function are important predictors of outcomes. There are, however, no cut-off values for degrees of RV enlargement or dysfunction. Recent guidelines on the right heart classify measurements only as abnormal or normal. In a cohort of patients with closely-spaced 2DE and cardiovascular magnetic resonance (CMR) we sought to determine magnitudes of abnormality in 2DE values by using CMR normative values as determined by the Multi-Ethnic Study of Atherosclerosis (MESA) study.

Methods:
We studied 217 patients, who had CMR (1.5T), and 2DE within 2±2.5 d. CMR RV ejection fraction (EF) and end-diastolic volume (EDV) were measured using the method of disks. The RV-focused apical 4-chamber view was used to measure the functional parameters, TAPSE (M-mode) and S’ (pulsed-wave Doppler), and fractional area change (FAC) as well as the size parameters of end-diastolic basal (RVEDDb) and mid (RVEDDm) diameters. Using CMR normal values from the MESA study for males and females separately, magnitudes of abnormality in RV enlargement and dysfunction were determined using SDs from the population mean. Patients were categorized based on CMR results. Values for corresponding 2DE size and function parameters were then calculated for each category using the regression line and cut-offs proposed.

Results:
Mean CMR and 2DE values are reported (Table 1). At least moderate correlations (r>0.50) were seen between the functional parameters and CMR RV EF and size parameters and CMR RV EDV. The best correlation was seen between RV EDA and CMR RV EDV (r=0.79). Echocardiographic parameters at 0, 2, 4 and 6 SDs from MESA-derived normal values for males and females separately are shown (Tables 2&3).

Conclusions:
Studies combining information from echocardiography and CMR performed in close proximity could enhance the ability to qualify RV size and function other than as normal or abnormal potentially providing more value to the clinician.