bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 5604: Door-to-Balloon Time - Are We Evaluating the Wrong Metric?
Authors: Peterman J. Mark , George Anil , Giugliano Gregory R , Schweiger Marc J
Published: July 2021

Primary Percutaneous Coronary Intervention (PPCI) for STEMI is a time-sensitive process, commonly assessed by door-to-balloon time (D2B). Indeed, agencies responsible for tracking the success of an institution’s program and those setting reimbursement have established D2B among its core measures of quality. However, reperfusion of the infarct-related artery (IRA) can occur at times other than that of the initial balloon or device deployment. Therefore, we hypothesized that door-to-reperfusion time (D2R) differs significantly from D2B. We studied 68 consecutive patients who presented to our ER with STEMI and underwent PPCI between December 17, 2007 and June 1, 2008.
D2B
(time from ER arrival to the first use of an intracoronary balloon or thrombectomy device in the IRA) and
D2R
(time from ER arrival to the first documentation of TIMI 2 or 3 flow in the IRA) were recorded for each patient. All patients received aspirin, unfractionated heparin, and eptifibatide pre-procedure. In our series of 68 consecutive cases, D2R was equal to (11pts) or shorter than (44 pts) D2B in 55 (81%) patients. D2R occurred in a median of 59 min (IQR 49 – 70.5 min) and D2B in a median of 65 min (IQR 53–75.5 min). The difference between D2B and D2R was highly statistically significant (median +3 min, IQR 0 to 8 min, Wilcoxon p < 0.0001). Additional device and/or drug therapy beyond the initial balloon inflation was required to establish TIMI 2–3 flow in 9% (6/68) of cases. D2B was longer than 90 minutes when D2R was less than 90 minutes in 3 of 68 (4%) cases. Our findings indicate that in PPCI, D2B commonly overestimates, and occasionally underestimates, D2R. D2R < D2B was attributable to pre-procedural anticoagulants or guidewire crossing of the occlusion. Considering that coronary reperfusion, which correlates with myocardial salvage, is the goal of PPCI, D2R appears to be the better metric by which to judge quality of care. Use of this more accurate metric may allay an unnecessary and inappropriate force to rush to device therapy.
Abstract 5609: In-Stent Restenosis - Benign or Dangerous? Clinical Presentation of Coronary Restenosis in Sweden
Authors: Omerovic Elmir , Ramunddal Truls , Grip Lars , Boren Jan , Matejka Goran , Albertsson Per
Published: July 2021

Background
Restenosis after percutaneous coronary intervention (PCI) was earlier thought to be a benign event clinically manifested as stable exertional angina. The aim of this prospective multicenter registry study was to investigate the incidence of acute coronary syndrome in patients with restenosis in Sweden.

Methods
Using data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), we analyzed all registered cases of PCI for restenosis (in-stent, after balloon angioplasty) from 1995 to 2005 in Sweden. Both multivessel and single vessel interventions were included. Restenosis presentations were classified as:

stable angina;

unstable angina/non-STEMI;

STEMI; and

other reasons.

As routine angiographic screening was not performed, restenosis episodes were defined clinically based on symptoms.

Results
We identified 6642 cases of restenosis in 2978 patients (4790 in men, 1852 in women). Restenosis presented in 39.7% of cases as stable angina, in 46.0% as unstable angina/non-STEMI, in 11.5% as STEMI and in 2.8% as other reasons. Cardiogenic shock was reported in 48 patients. Women had a higher incidence of unstable angina/non-STEMI compared with men (52.3% v. 43.6%) but a lower incidence of STEMI (9.6% v. 12.2%). The frequency of STEMI was lower with restenosis after balloon angioplasty v. in-stent restenosis (6.9% v. 13.8%), and after drug-eluting stents v. bare metal stents (7.9% v. 18.5%). Mortality rate was 1.7% at 30 days, 3.2% at 6 months and 4.6% at one year in patients with restenosis. These covariates were independent predictors of acute coronary syndrome: gender, age, vessel diameter, smoking, stent type, number of stents, treated vessel, previous stroke and previous infarction.

Conclusion
The majority of patients with coronary restenosis present either with acute MI or unstable angina requiring hospitalization and new interventions. Women may have a higher risk of developing acute coronary syndrome due to restenosis. Prevention of restenosis may be an important target for improvement of “hard” clinical outcomes in patients undergoing coronary revascularization.
Abstract 5639: Persistent Depression Predicts Mortality among African Americans with Myocardial Infarction
Authors: Parashar Susmita , Dawood Nazeera , Khizer Saadia , Kelley Mary E , Spertus John , Vaccarino Viola
Published: July 2021

Depression predicts adverse outcomes after myocardial infarction (MI), but the relative prognostic importance of new, past or current versus persistent depression among African Americans with MI is unknown. In a prospective MI registry in an inner-city hospital, we measured depressive symptoms in 397 African Americans hospitalized with MI using the Patient Health Questionnaire (PHQ). Patients were categorized as past (received depression treatment prior to MI), new (PHQ>=10 at hospitalization and no past depression), persistent (new plus past depression) or never-depressed. We examined the association between depression categories and 3-yr mortality using multivariable models after adjusting for demographic, clinical, and quality of care variables. There were no differences in sociodemographics, comorbidities and clinical factors among the past (7%), new (23%), persistent (6%) or never-depressed (64%) groups except a younger age in persistent depression group. Patients with persistent depression but not new or past depression had a higher mortality compared with the never-depressed (52% vs. 31%; P=0.02; 36% vs. 31%, P=0.90 and 28% vs. 31%, P=0.7 respectively). Patients with persistent depression were almost three times as likely to die at 3 yrs post-MI (adjusted HR 2.9; 95% CI 1.5, 5.5) as those who were never-depressed (Figure

). Previously treated depression that persists at MI hospitalization, but not new or past depression, strongly predicts post-MI mortality in African Americans. These findings suggest the need to screen MI patients for persistent depression.

This research has received full or partial funding support from the American Heart Association, AHA Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).

Figure 1.

Differences in the influence of symptom cluster on event-free survival in HF patients with depressive symptoms
Abstract 5663: Intracardiac Echocardiography From Within the Left Atrium Improves the Accuracy of Image Integration During Catheter Ablation of Atrial Fibrillation
Authors: Singh Sheldon M , Heist E. Kevin , Donaldson David M , Mela Theofanie , Ruskin Jeremy N , Mansour Moussa C
Published: July 2021

Background:
Intracardiac echocardiography (ICE) can be integrated with pre-procedural CT or MR imaging to direct catheter ablation of atrial fibrillation (AF). Prior work has described ICE imaging of the left atrium (LA) with the ICE probe in the RA, but it is feasible to image the LA from an ICE probe placed directly into the LA via a trans-septal puncture performed for the mapping/ablation procedure. The purpose of this study was to determine whether direct LA imaging with ICE results in improved image integration during AF ablation compared with LA imaging indirectly from the RA.

Methods:
Twenty-five consecutive patients undergoing an AF ablation procedure with the CARTO-Sound system were studied. A 10 French phased array catheter with an embedded CARTO navigation sensor was employed to provide 2D echocardiogram images of the LA - 13 patients underwent imaging from the RA alone and 12 patients from the LA. The accuracy of the image integration was assessed by

the average integration error after surface registration and

the requirement to take supplementary electroanatomic mapping points to obtain acceptable image integration.

Results:
Twenty-five patients (56% paroxysmal AF, average LA size = 42±8 mm, average EF = 63±10 %) were examined. There was no difference in the time or number of ultrasound contours required to create a LA anatomic map with ICE imaging from the RA versus the LA (24±17min vs. 24±25min, P=1.0, 24±16 contours vs. 29±18 contours, P=0.5). The average integration error for all patients was 2.19±0.59mm. Direct LA imaging was associated with improved integration error compared to indirect LA imaging from the RA (1.85±0.33mm versus 2.51±0.62mm, P=0.004). Image integration using RA acquired LA images had a tendency to be less accurate resulting in the primary operator acquiring additional registration points to supplement the registration process (patients requiring additional registration points for registration: 3/12 for LA imaging versus 9/13 for RA imaging of the LA, P=0.05).

Conclusion:
Direct ICE imaging from within the LA is feasible and associated with improved accuracy of image integration during AF ablation.
Abstract 5665: Assessment of Noninducibility after Catheter Ablation for Atrial Fibrillation: High Dose Isoproterenol vs Rapid Atrial Pacing
Authors: Crawford Thomas , Sarrazin Jean F , Kuhne Michael , Chalfoun Nagib , Wells Darryl , Dey Sujoya , Good Eric , Jongnarangsin Krit , Pelosi Frank , Chugh Aman , Bogun Frank , Morady Fred , Oral Hakan
Published: July 2021

Background:
Noninducibility of atrial fibrillation (AF) after catheter ablation of paroxysmal AF (PAF) identifies patients who are more likely to remain in sinus rhythm (SR). However, it is not clear whether assessment of noninducibility by rapid atrial pacing (RAP) is incremental to high dose isoproterenol (ISO) infusion.

Methods and Results:
There were 65 patients (age=56±13 years) with PAF who presented in sinus rhythm for catheter ablation. ISO was administered in escalating doses of 5/10/15/20 μg/min every 2 minutes prior to ablation. AF (or frequent PACs in 4) was inducible in 61/65 patients (94%) at a mean dose of 15±6 μg/min. Antral pulmonary vein (PV) isolation (APVI) was performed in all patients with complete isolation of all PVs. If AF did not terminate during APVI, complex fractionated atrial electrograms (CFAEs) were targeted in the left atrium (16) or coronary sinus (2) until AF terminated or all target sites were ablated. AF terminated during ablation in 41/65 (63%). Following conversion to sinus rhythm, 54 of the 61 patients (89%) who were initially inducible with ISO became noninducible during ISO re-challenge. Among these 54 patients who were noninducible by ISO, rapid atrial pacing (RAP) down to a cycle length of 180 ms (≥5 times) induced sustained AF (>60 seconds) in 17 patients (31%). At a mean follow-up of 9±4 months after a single ablation procedure, 35/54 patients (65%) who were noninducible by ISO and 2/7 patients (29%) who were inducible were in sinus rhythm without antiarrhythmic drugs. However, 11/17 patients (65%) who were inducible by RAP and 26/37 (70%) who were noninducible by RAP were in sinus rhythm without antiarrhyhtmic drug therapy (P=0.8).

Conclusions:
Noninducibility of AF in response to high dose isoproterenol infusion identifies patients who are more likely to remain in sinus rhythm after catheter ablation. Rapid atrial pacing may still result in induction of AF in 30% of patients who are noninducible by isoproterenol. However, inducibility of AF by rapid atrial pacing in patients who are noninducible by isoproterenol appears to be a nonspecific observation.
Abstract 5669: Brugada Syndrome: The Absence of Symptoms is a Poor Predictor of Identifying Individuals at Risk of Sudden Death
Authors: Papadakis Michael , Edwards Carey , Rawlins John C , Sharma Sanjay
Published: July 2021

Risk stratification for sudden death in Brugada syndrome and hence indications for implantation of an internal cardioverter defibrillator are based on the presence of a spontaneous type 1 electrocardiogram (ECG) pattern, in association with unheralded syncope or documented polymorphic ventricular tachycardia. Increasingly, awareness of sudden death in the young and implementation of pre-participation screening programs in sport will identify young, asymptomatic patients with the Brugada phenotype. We evaluated the predictive accuracy of symptoms, particularly unheralded syncope in victims of sudden death from Brugada syndrome. Over the past 3 years we identified 22 victims of sudden cardiac death secondary to Brugada syndrome. The diagnosis was based on sudden death with normal findings at post mortem and the identification of the type 1 Brugada ECG pattern in first-degree relatives (spontaneous or following ajmaline provocation test). All relatives underwent 12-lead ECG, echocardiography, exercise testing, 24-hour Holter monitor and biochemical tests. Cardiac magnetic resonance imaging and coronary angiography were performed when appropriate. Of the victims dying from Brugada syndrome, 15 (68%) were male. The mean age of sudden death was 30 years (range 8 –56 years) and 95% died suddenly at rest or during sleep. We interviewed first-degree relatives and partners regarding prodromal symptoms or a history of epilepsy. Only 3 out of 22 victims (14%) had significant symptoms. Specifically, 2 individuals experienced unheralded syncope and 1 suffered nocturnal seizures. Only 14% had a family history of premature sudden cardiac death. Indeed we obtained 12-lead ECGs in 3 victims taken less than 6 months prior to sudden death, which failed to reveal the typical Brugada ECG phenotype. Our results indicate that the vast majority of individuals who die from Brugada syndrome in the UK are asymptomatic and raise concerns that the absence of symptoms does not necessarily mean low risk. Better understanding of the disorder and risk stratification protocols is necessary to permit genuine reassurance in asymptomatic individuals exhibiting the Brugada phenotype.
Abstract 5686: Predictors of Hypocalcemia after Wide Area Circumferential Ablation of Atrial Fibrillation
Authors: Forcina Matthew S , Luff Matthew , Amin Anish , Cuoco Frank A , Klein Matthew H , Lawhon Brent A , Knick Barbara J , Sturdivant J. Lacy , Leman Robert B , Gold Michael R , Wharton J. Marcus
Published: July 2021

Introduction:
Hypocalcemia occurs frequently after wide area circumferential ablation (WACA) of atrial fibrillation and is more common with the use of open-irrigated tip ablation catheters (ITAC) than 8-mm tip ablation catheters. The mechanism of this phenomenon is unknown, but may be related to binding of calcium to myocardial proteins, volume infusion, or other factors. The present study aims to identify variables associated with acute hypocalcemia after WACA with ITAC.

Methods:
We analyzed 106 patients undergoing WACA with ITAC. Pre- and post-procedural values of calcium, creatinine, glomerular filtration rate (GFR), hemoglobin, cardiac enzymes (CK, CK-MB and troponin-I), albumin, left atrial size, presence of post-procedure pericardial effusion, infused volume of normal saline, urine output, heparin, furosemide dosage, and procedure time were recorded. Univariate and multivariate analysis were performed to determine variables associated with post-ablation hypocalcemia.

Results:
The population had mean age of 59±9 years, mean weight of 95±22 kilograms, and 76% were male. Mean pre-procedure GFR was 101±39 mL/min, and mean volume of normal saline infused was 5.5±1.3 liters. The means for pre-procedure calcium, post-procedure calcium, and decrease in calcium were 9.2±0.4, 7.3±0.6, and 1.9±0.7 mg/dL respectively. Of the variables measured, multivariate analysis identified pre-procedure GFR (parameter estimate −0.005) and infused volume of normal saline (parameter estimate 0.11) as factors independently associated with post-ablation hypocalcemia (p value = 0.03). Factors associated with myocardial injury were not apparently related.

Conclusions:
Lower GFR and higher infused volume of normal saline correlated with acute hypocalcemia after WACA with ITAC. Rather than binding to injured myocardium, these results suggest impaired renal calcium absorption and/or dilutional effects as the principal mechanism(s).
Abstract 5693: Detection of a Founder Effect in LQT1 in Five Apparently Unrelated Families in a Regional Inherited Arrhythmia Clinic
Authors: Gray Christopher , Klein George J , Yee Raymond , Skanes Allan C , Gula Lorne J , Wong Jorge , Krahn Andrew D
Published: July 2021

The Inherited Arrhythmia Clinic follows families with inherited arrhythmia syndromes from a population of 1.5 million people. Patients referred for evaluation of Long QT Syndrome (LQTS) underwent resting and standing ECGs, and 3 forms of exercise. Patients with findings consistent with LQTS underwent genetic testing, with assessment of all 1
st
degreerelatives. A proband from each of 5 unrelated families was found to have an identical disease causing transmembrane mutation in KCNQ1, suggesting a founder effect (Exon 6, 797 T>C). Systematic screening of 1
st
degree relative of affected individuals was performed. 31 patients (age 42±24yrs (range 4 – 89 years), 18 female) were identified from the 5 families, including the 5 probands. All affected individuals were offered beta-blockers. 18 affected family members and 13 unaffected 1
st
degree relatives were identified. Several family members had malignant presentations including sudden death and unexplained drowning. One proband had torsades de pointes during an exercise test. Other family members were asymptomatic until their 8
th
and 9
th
decades when they developed cardiac ischemia and had further QT prolongation, torsades de pointes and cardiac arrest. Sudden death occurred in a deaf child; both of the child’s consanguineous parents were gene positive for the KCNQ1 mutation (Jervell and Lange-Nielsen Syndrome). There was no identifiable common relative after pedigree construction of the previous 4 –7 generations. Affected patients typically had borderline QT prolongation at rest with dramatic prolongation with exercise (Table

). Genetic testing in this LQTS population suggests a founder effect for the five families with the descendants clustering in our geographical region. The observations highlight the utility of genetic testing when used in conjunction with a specialized clinic setting.
Abstract 5696: Dynamic Alterations in Ventricular Repolarization in Pigs with Hibernatimg Myocardium and a Chronic LAD Stenosis
Authors: Abisse Saddam , Aguilar Myra , Ovchinnikov Vladislav , Canty John M , Fallavollita James A
Published: July 2021

Altered ventricular repolarization manifested as QT-RR hysteresis occurs in Long QT Syndrome and with acute ischemia. We hypothesized that this might identify risk of sudden cardiac death (SCD) associated with chronic coronary disease. Pigs were chronically instrumented with a left anterior descending (LAD) coronary stenosis to produce hibernating myocardium (n=11). This model develops frequent, spontaneous SCD due to ventricular tachycardia degenerating into ventricular fibrillation, in the absence of infarction. As compared to 13 Controls there was reduced LAD wall-thickening (25±2 vs 54±9%, p<0.001) and flow reserve (1.4±0.3 vs 2.7±0.5, p<0.05), with preserved ejection fraction (63±3 vs 71±4%, p=0.09), and minimal necrosis (0.4±0.2% of LV). Regional electrograms were obtained from subendocardial piezoelectric crystals. Baseline QT intervals from the LAD region were similar in both groups (Hibernating – 354±13 vs. 356±15 ms in Controls, p=0.93). The QT intervals shortened to a similar extent during atrial pacing (Hibernating – 247±8 vs. 249±10 ms, p=0.92), stellate ganglion stimulation (Hibernating – 259±16 vs. 242±11 ms, p=0.37), and intravenous epinephrine infusion (Hibernating – 255±16 vs. 237±9 ms, p=0.31), with no differences between groups. In contrast, the LAD region QT-RR relationships during epinephrine stimulation were altered in pigs with hibernating myocardium, resulting in greater hysteresis loop areas as compared to Controls (7247±2334 vs 1927±943 ms
2
, p<0.05). Interestingly, this did not reflect stress-induced ischemia since pigs with hibernating myocardium also had greater hysteresis loop areas in the remote normally-perfused regions (9295±1319 ms
2
, p=0.40 vs LAD). There were no significant regional differences in either group. Hibernating myocardium in pigs is associated with altered ventricular repolarization hysteresis. This abnormality is global, and thus dissociated from regional dysfunction, reduced flow reserve and the propensity to develop acute ischemia. Thus, dynamic alterations in ventricular repolarization may be a substrate for SCD in patients with ischemic heart disease and chronic remodeling from hibernating myocardium.
Abstract 5697: Echocardiographic Detected Hibernating Myocardium Can Predict Arrhythmic Events in Patients with Ischemic Cardiomyopathy
Authors: Matsuoka Ken , Nishino Masami , Nakamura Daisuke , Yoshimura Takahiro , Ri Yasuharu , Nakatani Shinpei , Hara Masahiko , Hashimoto Akihito , Yamagami Kiyoshi , Kato Hiroyasu , Taniike Masayuki , Egami Yasuyuki , Shutta Ryu , Yamaguchi Hitoshi , Tanaka Kenjiro , Tanouchi Jun , Yamada Yoshio
Published: July 2021

Backgrounds:
In medically treated patients with ischemic cardiomyopathy, myocardial viability is associated with a worse prognosis than scar. Hibernating myocardium (chronic regional dysfunction with reduced resting flow) assessed with nuclear imaging is a major risk factor for cardiac death when left ventricular function is depressed. End-diastolic wall thickness (EDWT) is an important and easy marker of myocardial viability in patients with suspected hibernation, as well as Tl-201 scintigraphy. Thus, in this study, we assessed whether hibernating myocardium evaluated by echocardiography could identify patients with ischemic cardiomyopathy who are at high risk for sudden cardiac death (SCD) and mortality.

Methods:
Patients with ischemic cardiomyopathy who showed low-grade cardiac function (ejection fraction (EF) < or =50%) and had no plans for coronary revascularization were enrolled. All patients underwent coronary angiography and echocardiography. Hibernating myocardium was defined as the area with major epicardial artery stenosis > or =75%, wall motion abnormality, and EDWT >6mm. The onset of SCD or mortality was determined by outpatient or telephone follow-up.

Results:
The study patients consisted of 60 consecutive patients (47 men, EF: 35 ± 8%, follow-up duration: 38 ± 16 months). Results were shown in a figure

. Hibernating myocardium significantly increased the risk of SCD and mortality.

Conclusion:
Hibernating myocardium evaluated by echocardiography can predict SCD and mortality in medically treated patients with ischemic cardiomyopathy.

Figure

Kalpan-Meler Estimates of the Time to SCD or Mortality
Abstract 5714: Influence of Body Mass Index on Early Diastolic Untwisting Velocity in Healthy Children
Authors: O’Reilly Christine , Abhayaratna Katrina , Sakuragi Satoru , Telford Richard , Abhayaratna Walter P
Published: July 2021

Background:
Childhood obesity is increasingly prevalent in the community and is predictive of adverse cardiovascular outcomes in adulthood. We hypothesised that increased body mass index (BMI) in children has an adverse influence on left ventricular (LV) untwisting, a sensitive marker of LV function that reflects a key process in the transition between LV relaxation and suction.

Methods:
Cardiac structure and function were assessed by transthoracic echocardiography. LV twist mechanics were quantitated using 2-dimensional speckle tracking imaging of the LV base and apex in short axis. Univariate associations of LV untwisting velocity (Er) were evaluated using Spearman’s correlation analysis. Significant univariate predictors (p≤0.10) were included into multivariable regression analysis to determine the independent relationship between body mass and Er (rad/s).

Results:
Of the first 150 children assessed (age 10.2 ± 0.3 years; 83 boys), the mean BMI was 18.2 ± 2.8 kg/m
2
. In univariate analysis, Er was inversely related to BMI (ρ= −0.13, p=0.10), LV end-diastolic diameter (ρ= −0.13, p=0.10) and LV end-systolic diameter (ρ= −0.28, p<0.001); and positively correlated with LV torsion (ρ=0.55, p<0.001), LV twisting velocity (ρ=0.29, p<0.001), early diastolic annular velocity (e′) (ρ=0.13, p=0.10), LV ejection fraction (EF) (ρ=0.14, p=0.09) and heart rate (ρ=0.18, p=0.03). There was no correlation between Er and LV relative wall thickness or mass index (p>0.25). In multivariable analysis, body mass index was independently associated with Er, independent of LV torsion, heart rate, EF, LV chamber size and e′ (Table

).

Conclusion:
Increased body mass is independently related to lower LV untwisting velocity during early diastole in healthy children. Additional studies are required to evaluate whether lifestyle measures to reduce body mass will attenuate further deterioration in LV diastolic relaxation and suction.

Table:

Independent Predictors of Left Ventricular Untwisting Velocity in Children
Abstract 5752: Epicardial Fat Assessed by Multi-Detector Computed Tomography (mdct) is a New Risk Factor of Coronary Artery Disease in Non-Obese Patients
Authors: Iwayama Tadateru , Nitobe Joji , Ishino Mitsunori , Tamura Harutoshi , Shishido Tetsurou , Nishiyama Satoshi , Miyashita Takehiko , Miyamoto Takuya , Watanabe Tetsu , Kubota Isao
Published: July 2021

Objective: An increment of abdominal visceral fat has been reported to be a coronary risk factor associated with metabolic syndrome. However, adipose tissue surrounding heart has not been fully determined as coronary risk factors. Accurate volumetric measurement of epicardial fat can be easily obtained by MDCT. We examined the relationship between epicardial fat volume and clinical parameters in patients with coronary artery disease (CAD).

Method: We evaluated epicardial fat volume by 64 detector row CT scanner in CAD patients (obese, 13; non-obese, 11 patients) who underwent elective coronary artery bypass graft surgery and in non-CAD patients who showed normal coronary arteries on angiography (obese, 3; non-obese, 11 patients). Epicardial fat volume was obtained as the sum of fat areas on short axis images. Obese patients were defined as over 25 in body mass index (BMI).

Result: Epicardial fat volume was significantly higher in patients with CAD than in those without CAD (40.6 ± 14.7 ml vs. 20.0 ± 14.7 ml, p < 0.05). Epicardial fat volume was not correlated to following coronary risk factors such as HbA1c, fasting plasma glucose, lipid and blood pressure except for BMI. Although there was no difference epicardial fat volume between in obese patients with CAD and in those without CAD (48.3 ± 27.9 ml vs. 41.2 ± 11.0 ml, NS), it was significantly higher in non-obese patients with CAD than in those without CAD (32.1 ± 9.2 ml vs. 14.2 ± 9.2 ml, p < 0.05).

Conclusions: The quantity of epicardial fat using MDCT is related with the presence of CAD. Especially in non-obese patients, epicardial fat may affect directly progression of CAD independent of pathophysiological process of metabolic syndrome.
Abstract 5757: Magnetic Resonance Imaging with Iron-Oxide Labeling Detects Differential Cell Survival after Doxorubicin Exposure in Cardiac Myocytes, Fibroblasts, and Stem Cells
Authors: Dash Rajesh , Chan Trevor , Yamada Mayumi , Paningbatan Marietta , Swigart Phillip M , Myagmar Bat-Erdene , Yang Phillip C , Simpson Paul C
Published: July 2021

Heart failure caused by anthracycline chemotherapy, e.g. doxorubicin (DOX), is preceded by significant cell apoptosis. Early, non-invasive detection of cardiac cell death may improve patient outcomes by enabling real-time adjustment of chemotherapy. To this end, Annexin V protein (ANX) binds to membrane-bound phosphatidylserine, which is externalized in early apoptosis. We tested whether ANX conjugated to superparamagnetic iron oxide (SPIO) could detect and quantify apoptosis via T2-weighted magnetic resonance imaging (MRI). ANX was purified and conjugated to SPIO. Cultured, neonatal rat cardiac myocytes (CMs) and fibroblasts (FBs), and mouse mesenchymal stem cells (mMSCs) were exposed to DOX (1uM) for varying times, then stained with ANX-SPIO, or with fluorescent ANX (ANX-FLUOS, Roche) or TUNEL as controls. In vitro MRI (3 Tesla, GE Excite, WI) was performed on plated cells using a gradient echo (GRE) sequence (see Table

). MRI signal after ANX-SPIO incubation correlated highly with the number of ANX-FLUOS or TUNEL positive cells after exposure to varying durations of DOX (R=0.91 ANX-FLUOS vs. ANX-SPIO, n=5; R=0.80 TUNEL vs. ANX-SPIO, n=4; p<0.05). ANX-SPIO signal was detectable by MRI from as few as 15–20 apoptotic mMSCs. CMs exhibited the highest sensitivity to DOX (see Table

), with peak apoptosis after 30 minutes of DOX exposure. Conversely, cardiac FBs were resistant to DOX for 22 hours, and mMSCs showed intermediate susceptibility to DOX. Competition binding between ANX-SPIO and ANX-FLUOS confirmed the specificity of ANX-SPIO for apoptotic cells in culture. In vitro MRI of a magnetically-labeled marker of apoptosis (ANX-SPIO) can accurately detect cell death in culture with high sensitivity. MRI of ANX-SPIO can also resolve differential susceptibility to DOX in CMs, FBs, and mMSCs. This compound may hold promise for in vivo MRI detection of early anthracycline-induced cell death in the myocardium.

This research has received full or partial funding support from the American Heart Association, AHA Western States Affiliate (California, Nevada & Utah).

Cell-Type Specific Susceptibility to Doxorubicin Assessed by MRI
Abstract 5760: Early Detection of Arteriopathy in Metabolic Syndrome by MR Molecular Imaging with Targeted Nanobeacons
Authors: Cai Kejia , Huang Wenjing , Williams Todd A , Caruthers Shelton D , Zhang Huiying , Lanza Gregory M , Wickline Samuel A , Winter Patrick M
Published: July 2021

Metabolic syndrome elicits widespread inflammatory changes in vascular structures leading to early atherosclerosis that cannot be detected with classical imaging methods. Because pronounced early angiogenesis within the arterial wall typically accompanies activated inflammatory cells in standard models of atherosclerosis, we hypothesized that the expression of α
v
β
3
-integrins on neovascular endothelium would provide an abundant and sensitive biomarker of the metabolic vasculopathy. The mildly diabetic JCR:LA-cp rat was used as a model for MR molecular imaging of angiogenesis with α
v
β
3
-targeted gadolinium nanoparticles (NP). 5 month-old male JCR:LA-cp lean (control) and obese (affected) rats (n=5 each) were studied. The abdominal aorta was imaged with a 3.0 T clinical MRI scanner and a T1w, fat-suppressed, black-blood imaging sequence. Imaging was performed before (BSL) and 2 hours (2 HR) after NP injection (IV, 1.0 ml/kg). Fat suppressed imaging revealed large abdominal fat deposits in the obese rats but not in controls, concordant with elevated cholesterol levels (~2 times higher) in the obese rats (p<0.05). MRI contrast enhancement of angiogenesis in the aortic wall (Figure

: top, arrow) in the obese rats was significantly higher than that in the lean rats (bottom, *p<0.05) indicating the widespread presence of neovasculature despite no apparent stenosis. MR molecular imaging of angiogenesis with integrin-targeted nanoparticles may represent a sensitive high-resolution surrogate signal for detecting early metabolic vasculopathy.

This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).
Abstract 5769: Correlation of Bicuspid Valve Morphology and Pattern of Aortic Root Dilatation: A Substudy of the Aortic Stenosis Progression Observation Measuring Effects of Rosuvastatin (ASTRONOMER) Study
Authors: Bhagirath Kapil M , Jassal Davinder S , Tam James W , Sochowski Randy A , Dumesnil Jean G , Giannoccaro P J , Jue John , Pandey A S , Joyner C D , Teo K K , Chan Kwan L
Published: July 2021

Bicuspid aortic valve is the leading cause of aortic stenosis in patients younger than the age of 50. A classification scheme of bicuspid aortic valves (BAV) was recently proposed based upon leaflet orientation: Type A (fusion of right and left coronary cusps) and Type B (fusion of right and non-coronary cusps). The correlation between BAV leaflet orientation and aortic root pathology however remains ill defined. To describe a potential relationship between BAV leaflet morphology and aortic root measurements in the ASTRONOMER study, a multicentre study to assess the effect of Rosuvastatin on the progression of AS. Transthoracic echocardiography was performed with 2D and Doppler imaging following a standardized protocol. BAV morphology was classified as Type A or Type B orientation following review of the parasternal short-axis view. Echo measurements including left ventricular and aortic root dimensions were obtained according to the ASE recommendations. We identified 89 patients (56±11 years; 44 males). There were 63 patients with Type A and 26 with Type B BAV. Baseline demographic, hemodynamics, aortic root and left heart dimensions are listed in Table 1

. Patients with Type A BAV had larger aortic and ascending root dimensions than those patients with Type B BAV (p<0.05). Aortic valvular calcification and mitral annular calcification were similar between the two groups. All values are expressed as mean±SD. In patients with mild to moderate asymptomatic BAV, the presence of Type A valve orientation was associated with significantly greater aortic root parameters compared to Type B valve orientation. Whether the morphology of BAV may predict a subset of patients who will respond to statin therapy in preventing the progression of AS remains to be determined upon completion of the ASTRONOMER trial.
Abstract 004: Physical Activity, Television Watching and Genetic Predisposition in Relation to Body Mass Index in Women and Men
Authors: Qi Qibin , Li Yanping , Chomistek Andrea K , Kang Jae Hee , Curhan Gary C , Pasquale Louis R , Willett Walter C , Rimm Eric B , Hu Frank B , Qi Lu
Published: July 2021

Background
Previous studies on gene-lifestyle interaction and obesity have largely focused on a single locus, the
FTO
gene, and overall physical activity, while little attention has been given in the association for sedentary activity as indicated by television (TV) watching. We examined the interactions between leisure-time physical activity and TV watching and the genetic predisposition to increased body mass index (BMI).

Methods
Longitudinal data were obtained from 7740 women and 4564 men from 2 prospective cohorts: the Nurses’ Health Study and Health Professionals Follow-up Study. Data on physical activity and TV watching were collected 2 years prior to assessment of BMI. A genetic predisposition score was calculated on basis of 32 established BMI-predisposing variants.

Results
Overall, each additional BMI-increasing allele was associated with an increase of 0.13 (SE 0.01) kg/m
2
in BMI. The effect size for BMI in individuals in the highest physical activity quintile was attenuated compared to that in individuals in the lowest physical activity quintile (0.08 [0.02] vs 0.15 [0.02] kg/m
2
;
P
for interaction <0.001). In contrast, the genetic effect on BMI was more pronounced in individuals who spent >40 h/wk of TV watching than that in individuals who spent 0-1 h/wk of TV watching (0.34 [0.10] vs 0.08 [0.04] kg/m
2
;
P
for interaction =0.001). Each 4 Mets/d increment in physical activity (equivalents to 1h/d of brisk walking) was associated with a 0.06 (95% CI 0.03-0.08) kg/m
2
reduction in BMI (∼46% of the main effect of each additional BMI-increasing allele), while each 2 h/d increment in TV watching was associated with a 0.03 (0.01-0.06) kg/m
2
increase in BMI (∼23% of the main effect). We estimated that the difference in BMI (∼4.0 kg/m
2
, equivalents to 11.6 kg in body weight for a person 1.70 m tall) between individuals with a genetic predisposition score of 13 (minimum) and those with a score of 43(maximum) could be reduced by half (2.1 kg/m
2
, 6.1 kg in weight) by 1 h/d of brisk walking or increased by 25% (5.0 kg/m
2
, 14.5 kg in weight) by 2h/d of TV watching.

Conclusions
Greater leisure-time physical activity attenuates the genetic predisposition to increased BMI, whereas sedentary lifestyle indicated by prolonged TV watching accentuates the genetic effects on BMI. Our data suggest that both increasing exercise levels and reducing sedentary behaviors, especially TV watching, independently may mitigate the genetic predisposition to increased BMI.
Abstract 007: Treadmill Duration Predicts Cognitive Function
Authors: Zhu Na , Jacobs David R , Schreiner Pamela J , Bryan R. Nick , Launer Lenore J , Whitmer Rachel , Sidney Stephen , Demerath Ellen W , Thomas William , Bouchard Claude , He Ka
Published: July 2021

Evidence is scarce for an association between treadmill performance and cognitive function in healthy young and middle-aged adults. We assessed the hypothesis that duration on treadmill predicts cognitive function 25 years later. Participants were from the population-based Coronary Artery Risk Development in Young Adults (CARDIA) study, a multi-center study of black and white men and women aged 18-30 at recruitment in 1985-86 (year 0). The main independent variable of interest was baseline symptom-limited maximal treadmill test duration as a measure of treadmill performance potential, including its major subcomponent cardiorespiratory fitness (CRF/TPP). Cognitive functions measured were verbal memory (with the Rey auditory-verbal learning (AVLT)), psychomotor speed (Digit Symbol Substitution Test (DSST)) and executive function (modified Stroop interference test, where lower is better). We analyzed 2444 participants who had y0 treadmill testing and y25 cognitive testing. For each additional SD of treadmill duration (2.8 minutes), the DSST was 2.4 digits correctly substituted higher, the AVLT was 0.36 words recalled higher, and the Stroop test time 1.7 seconds less, after accounting for race, sex, age, highest attained education level and center of clinic visit(
Table
). Further adjustment for dietary pattern, physical activity, smoking, BMI, alcohol consumption, glomerular filtration rate, blood pressure, cholesterol and diabetes status yielded similar trends for these cognitive function tests. In conclusion, CRF/TPP predicts cognitive function 25 years later independently of other factors among apparently healthy adults.

Prospective estimation of cognitive function by treadmill duration at baseline in minimally and fully adjusted model (see text for details), N=2444.

Year 25 Digit Symbol Substitution Test: Digits correctly substituted mean±SD: 70.1±15.9
Year 25 Rey Auditory-Verbal Learning Test: Words correctly recalled mean±SD: 8.3±3.3
Year 25 Stroop Test : Seconds to correctly name colors mean±SD: 43.9±12.8

Slope
*

SE
P

Slope
*

SE
P

Slope
*

SE
P

Year 0 treadmill duration (SD) mean±SD: 10.0±2.8 minutes

Minimally adjusted
2.4
0.36
<.0001
0.36
0.08
<.0001
-1.7
0.31
<.0001

Fully adjusted
2.3
0.45
<.0001
0.39
0.08
<.0001
-1.2
0.39
0.001

*

“Slope” is the difference in the indicated cognitive function per SD (2.8 minutes) of treadmill duration.
Abstract 020: Testosterone, Sex Hormone-binding Globulin and the Metabolic Syndrome: An Individual Participant Data Meta-analysis of 20 Observational Studies Involving 12,811 Men
Authors: Brand Judith S , Rovers Maroeska M , van der Schouw Yvonne T ,   The Endogenous Hormones and Metabolic Syndrome Collaborative Group
Published: July 2021

Background:
The role of testosterone in metabolic syndrome (MetS) etiology is receiving increasing attention, given the overlap of testosterone deficiency and MetS in ageing men. We conducted an individual participant data (IPD) meta-analysis to examine this association in a uniform way and to produce more precise estimates of risk overall and in certain subgroups.

Methods:
Individual participant data of 20 observational studies including 12,811 men (mean age: 58.6 ± 15.6 years) were pooled and cross-sectional as well as prospective associations between total testosterone (TT), sex hormone-binding globulin (SHBG), free testosterone (FT) and MetS were assessed. We calculated odds ratios (ORs) and hazard ratios (HRs) by study-specific quartiles of sex hormones using mixed effects models (with random effects at the study level) and tested for effect modification by age and body mass index (BMI).

Results:
Cross-sectional analyses revealed that men with low concentrations of TT, SHBG or FT were more likely to have MetS. ORs for the lowest versus highest quartile were 4.56 (95% CI 4.02-5.16) for TT, 5.26 (95% CI 4.49-6.17) for SHBG and 2.18 (95% CI 1.88-2.53) for FT. Associations were attenuated but remained significant after adjustment for BMI and insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)). Prospective analyses yielded similar results, but of smaller magnitude (HRs for the lowest versus highest quartile were 2.00 (95% CI 1.57-2.56) for TT, 2.71 (95% CI 1.99-3.70) for SHBG and 1.41 (95% CI 1.04-1.92) for FT). Stratified analyses revealed significant interactions by age and BMI, such that associations were strongest in young and nonobese men. Sex hormone concentrations decreased gradually with increasing number of MetS components and, for single components, were most strongly associated with abdominal obesity and hypertriglyceridemia.

Conclusion:
This meta-analysis of pooled individual data shows a robust, dose-response relationship of testosterone and SHBG concentrations with prevalent and incident MetS in men. The strong associations with abdominal obesity and hypertriglyceridemia provide insight into the underlying biological mechanisms.
Abstract 028: Web-based Delivery with Food Portion Images Improves Dietary Assessment Results
Authors: Weiss Rick
Published: July 2021

Introduction:
Dietary assessment is achieved in a variety of ways, from written records and interviews to short questionnaires based on food categories, all with mixed success. Problems faced by the clinician are limited time for conducting assessments, time and resources required to evaluate collected information and lack of resources for supporting the change process. Due to their low cost and low participant burden, Food Frequency Questionnaires (FFQs) are the most practical method of dietary assessment but improvements are needed.

Hypothesis:
VioScreen, developed from a National Cancer Institute grant using a graphical method for dietary data collection and generating reports on nutrient intake and food use patterns will reliably assess intake making it suitable for clinical counseling and research. VioScreen’s web-based self-administered dietary habits questionnaire will provide an efficient and thorough assessment of dietary intake data.

The tool:
VioScreen is the only web-based, dietary assessment tool that includes 1,200 food images and portion size options. Results are immediately available for analysis by the researcher/clinician; an optional report can be produced for the participant that includes a food pattern analysis, a list of foods and nutrients consumed, and when used by a counselor generates tailored behavioral feedback. VioScreen uses the University of Minnesota’s Nutrition Coordinating Center database to ensure up-to-date food and nutrient information.

Method:
VioScreen was evaluated through an inter-method reliability study with 74 subjects conducted at The Ohio State University by comparing a baseline and 3 month FFQ to six 24-hour recalls conducted between the two FFQ’s. Average time for completing the FFQ was 26.7 +/− 10.0 minutes.

Results:
The inter-method reliability was higher for VioScreen than for the paper FFQ VioScreen was modeled after and higher than reported for many other paper FFQs used in major epidemiological studies. Of the macronutrients, only alcohol values were similar; for all others VioScreen correlations were substantially higher, being at or above 0.80 for most macronutrients (0.90 for alcohol, 0.84 for saturated fat, 0.82 for fat, and 0.79 for carbohydrate) and 0.67 for protein. Participant evaluations of VioScreen were generally very good to excellent on ease of use and capturing foods usually consumed. All subjects rated the questionnaire as easy to use, 93% rated VioScreen as either great or excellent, 99% would complete VioScreen if asked by a doctor and 95% thought pictures helped in selecting portion sizes.

Conclusions:
Use of multiple portion size pictures, incorporation of complex skip patterns, and elimination of missing or non-interpretable responses contributed to higher inter-method reliability.
Abstract 030: Estimates of Energy Expenditure from an Accelerometer Worn on the Wrist Versus the Hip in Adults
Authors: Rosenberger Mary , Haskell William , Albinali Fahd , Mota Selene , Nawyn Jason , Intille Stephen
Published: July 2021

Epidemiological researchers have often measured physical activity by placing an accelerometer on the participants’ hip for seven days. Recently, NHANES decided to place the monitor on the wrist to increase participant wear time. This study compared established calibration methods for accelerometers on the hip versus the wrist. Healthy adults (n=37) wore custom accelerometers (Wockets) on the wrist and hip for twenty activities along with a portable metabolic unit (Oxycon Mobile) to measure energy expenditure. The activities included sedentary behaviors, treadmill walking (including uphill), cycling, work or household chores. Data included only metabolic steady state periods of the activities. Each signal from the triaxial accelerometer was filtered and integrated over 1-second intervals to obtain an area under the curve (AUC) summary, and the three axes were summed to create a single motion measure. Because traditional calibration methods do not include a specific method for assessing sedentary behavior, receiver operating characteristic (ROC) curves were used to determine a sedentary cutpoint and an exercise (moderate and vigorous activity over 3.0 METs) cutpoint for both hip and wrist. The ROC for determining sedentary behavior at the hip had greater sensitivity and specificity (71% and 96%) than the wrist (53% and 76%). The ROC for exercise also had higher sensitivity and specificity on the hip (70% and 83%) than the wrist (30% and 69%). The coefficient of variation (CV) in the signal was used to separate ambulatory activities from non-ambulatory activities. Logistic regression determined the optimal CV from the data on the hip for a two-regression model with energy expenditure, but cycling activities prevented a useful prediction model. The ROC for determining the CV associated with ambulation had a larger AUC at the hip compared to the wrist (0.83 and 0.74), and no CV separation between ambulation and non-ambulatory activities existed for the wrist. Therefore, mixed model analysis was used to predict energy expenditure on all non-sedentary activities. The prediction model on the hip resulted in an average difference of 0.17 (+/− 0.99) METs, while the wrist resulted in an average difference of 0.28 (+/− 1.47) METs. Since the CV was not useful for separating activity type at these locations, an analysis was prepared using the known activity separation of sedentary activities, ambulation, and other. On the hip, the mean difference was 0.05 (+/− .92) METs, whereas the wrist was 0.06 (+/− 1.12) METs. In conclusion, methods for estimating energy expenditure from an accelerometer on the hip do not apply to the wrist, and there is greater variation in the estimates from the wrist compared to the hip. There is improvement in energy expenditure estimates if the activity type is known, but from this study, it appears that activity type cannot be determined by CV from the wrist as as it can from the hip.