bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10275: Aortic Dilatation is Common in Hypertrophic Cardiomyopathy
Authors: Geske Jeffrey B , Orme Nicholas M , Tajik A J , Ommen Steve R
Published: July 2021

Introduction:
Aortic dilatation has been associated with various cardiac conditions, although its prevalence and clinical correlates in hypertrophic cardiomyopathy (HCM) remains unclear.

Hypothesis:
We hypothesized that tubular ascending aorta dilatation would be common in a large referral population of patients with HCM. Furthermore, we hypothesized that aortic size would correlate with age and presence of left ventricular outflow tract obstruction.

Methods:
1704 patients with HCM underwent echocardiographic measurement of the tubular ascending aorta during index evaluation at a tertiary HCM referral center. End-diastolic ascending aorta dimension was indexed to body surface area, with dilatation defined as two standard deviations above normal (>19 mm/m2). Aortic size and presence of aortic enlargement were correlated with clinical and echocardiographic parameters.

Results:
Aortic dilatation was present in 304 patients with HCM (18%). Indexed ascending thoracic aorta dimension was 16.5 (IQR 17.8-18.2) mm/m2 (Figure 1). Indexed dimension increased linearly with age (R=0.53, p<0.0001). Women and patients with a history of systemic hypertension were more likely to have aortic enlargement (29.8% vs 9.9% and 24.1% vs 10.6%, p<0.0001 for both). There was a correlation between resting left ventricular outflow tract gradient and indexed aortic dimension (R=0.12, p<0.0001) and patients with either resting (≥30 mmHg) or provocable obstruction (≥50 mmHg) were more likely to have aortic enlargement (19.6% vs 14.3%, p=0.006).

Conclusions:
In this large cohort of patients with HCM, aortic dilatation was common. Key correlates of aortic enlargement included age, female sex, history of hypertension and left ventricular outflow tract obstruction. Given an increased prevalence of aortic dilatation in HCM, further study is needed on the clinical impact of aortic dilatation.
Abstract 10286: Myocardial Nitroso Redox Balance and Postoperative Atrial Electrical Remodelling Following Elective Cardiac Surgery on Cardiopulmonary Bypass: Molecular Mechanisms and Translational Implications of Perioperative Statin Therapy
Authors: Jayaram Raja , Goodfellow Nicky , Zhang Mei Hua , Reilly Svetlana , Jones Michael , Pal Nikhil , Sayeed Rana , DeSilva Ravi , Casadei Barbara
Published: July 2021

Background:
Systemic inflammation and increased myocardial production of reactive oxygen species (ROS) are associated with the development of postoperative atrial fibrillation (AF) and low cardiac output syndrome in patients undergoing cardiac surgery. Statins have been shown to exert rapid anti-inflammatory and antioxidant effects by inhibiting myocardial NOX2 oxidases and by increasing the bioavailability of nitric oxide (NO).

Methods and Results:
We first assessed the impact of cardiac surgery and cardiopulmonary bypass (CPB) on the atrial nitroso-redox balance in 116 patients and then investigated the effect of perioperative treatment with atorvastatin (80 mg once daily, for up to 6 days before surgery and 5 days thereafter) on nitric oxide synthase (NOS) activity, biopterin content, and the sources of ROS production (all by HPLC) in samples of the right atrial appendage obtained before and after CPB and reperfusion and on the postoperative atrial effective refractory period (AERP; by programmed electrical stimulation delivered using right atrial epicardial leads) in a placebo-controlled double-blind trial (ClinicalTrials.gov Identifier: NCT01780740) in 80 patients undergoing first-time elective cardiac surgery.

Our findings show that increased ROS production by NOX2 and mitochondrial oxidases and uncoupling of the endothelial NOS isoform (eNOS), secondary to enzyme’s S-glutathionylation, are the main mechanism underlying the atrial nitroso-redox imbalance after CPB and reperfusion. Compared with placebo, atorvastatin prevented the rise in atrial NOX2 activity and maintained the functionally coupled status of eNOS. The AERP lengthened progressively over first four postoperative days and did not differ between the treatment groups (n= 29).

Conclusions:
Short-term statin therapy, at the dose conventionally used to lower LDL-cholesterol, prevents NOS uncoupling and nitroso-redox imbalance in the atrial myocardium of patients undergoing on-pump cardiac surgery. However, these changes have no significant impact on atrial refractoriness.
Abstract 10300: The Effects of the Bone Morphogenetic Protein Receptor Type 2 Mutation on the Right Ventricle in Pulmonary Arterial Hypertension
Authors: van der Bruggen Cathelijne E , Happé Chris , Trip Pia , Spruijt Onno A , Rol Nina , Houweling Arjan C , Girerd Barbara , Dorfmüller Peter , Mercier Olaf , Humbert Marc , Handoko Louis M , van der Velden Jolanda , Vonk Noordegraaf Anton , Bogaard Harm Jan , Goumans Marie José , de Man Frances S
Published: July 2021

Introduction:
The effects of a mutation in the bone morphogenetic protein receptor 2 gene (BMPR2) gene on right ventricular (RV)adaptation are currently unknown. Therefore, we investigated RV function in PAH patients with and without BMPR2 mutation by combining in vivo measurements with molecular and histological analysis of human RV and left ventricular (LV) tissue.

Methods:
97 idiopathic or familial PH patients were genetically screened for the presence of a BMPR2 mutation. 28 patients carried a BMPR2 muation, 69 did not. In vivo measurements were assessed using right heart catheterization (RHC)and cardiac magnetic resonance imaging.To investigate the role of TGF-β and BMPRII signaling, human RV and LV tissue were studied in controls (n=6), mutation carriers (n=5) and non-carriers (n=11).

Results:
Despite a similar mean pulmonary artery pressure (noncarriers 54±15 vs. mutation carriers 55±9 mmHg)and pulmonary vascular resistance (755 (483-1043) vs. 931 (624-1311) dynes*s/cm
5
), mutation carriers presented with a more severely compromised RV function (RV ejection fraction: 37.6±12.8 vs. 29.0±9 %: p<0.05, cardiac index 2.7±0.9 vs. 2.2±0.4 l/min/m
2
). Differences continued to exist after treatment. TGF-β and BMPRII signaling, as well as hypertrophy, fibrosis, capillary density and inflammation were similar between mutation carriers and non-carriers.

Conclusions:
Despite a similar afterload, RV function is severely more affected in BMPR2 mutation carriers compared to non-carriers. However, these differences cannot be explained by a different TGF-B, BMPR2 signaling or cardiac adaptation.
Abstract 10323: Tadalafil Therapy Improves Endothelial Thrombomodulin in Hypoxemic Patients With Pulmonary Arterial Hypertension Associated With the Eisenmenger Syndrome
Authors: Clavé Mariana M , Maeda Nair Y , Thomaz Ana M , Mesquita Sonia M , Bydlowski Sérgio P , Lopes Antonio A
Published: July 2021

Introduction:
Thrombomodulin (TM) is a plasma membrane chondroitin sulfate proteoglycan acting as a natural endothelial anticoagulant and anti-thrombotic factor. Binding of TM to thrombin leads to protein C activation with subsequent cleavage of activated coagulation factors V and VIII. In pulmonary arterial hypertension (PAH), particularly in hypoxemic patients with Eisenmenger syndrome, endothelial dysfunction is associated with heightened circulating levels of von Willebrand factor antigen (VWF:Ag) and tissue plasminogen activator (t-PA), but decreased TM reflecting diminished endothelial production.

Hypothesis:
Plasma TM, t-PA, VWF:Ag and functional parameters may be improved in patients with Eisenmenger syndrome subjected to chronic treatment with tadalafil.

Methods:
Fifteen patients aged 12 to 51 years (median 30 years) were evaluated at baseline, and 90 and 180 days of treatment with oral tadalafil (single daily dose of 40 mg). The functional capacity was accessed using the six-minute walk test and endothelial markers were analyzed by enzyme-linked immunoassays.

Results:
At baseline, levels of all three endothelial markers were altered in patients compared to controls (respectively, 8.62±3.50 ng/mL
vs
. 5.13±1.69 ng/mL for t-PA, 121±21 U/dL
vs
. 94±23 U/dL for VWF:Ag and 1.92±0.49 ng/mL
vs
. 3.41±0.50 ng/mL for TM. Tadalafil treatment resulted in improvement of exercise capacity (six-minute walked distance, 6MWD) and peripheral oxygen saturation (O
2
Sat), with decreased hematocrit (Htc). Plasma TM increased mildly but significantly, while t-PA level decreased (Table).

Conclusion:
In the Eisenmenger syndrome, PAH therapy with tadalafil improves not only the physical capacity, O
2
Sat and Htc, but also endothelial markers. The modest increase in circulating TM may reflect improved endothelial TM production and protection against
in situ
thrombosis, a largely known complication of this syndrome.
Abstract 10335: Systolic Motion of the Basal Right Ventricular Freewall is the Strongest Predictor of Global Function: A High Resolution 3D Cardiac Magnetic Resonance Study
Authors: Dawes Timothy , de Marvao Antonio , Shi Wenzhe , Rueckert Daniel , Cook Stuart , O'Regan Declan P
Published: July 2021

Background:
Right ventricular (RV) function has prognostic value in disease cohorts and the general population although its complex geometry and motion make rapid assessment difficult. Several two-dimensional regional measures are used to estimate global RV function, however the optimal measure is not known.

Methods:
High-resolution 3-dimensional cardiac magnetic resonance (3D-CMR) cine imaging of the whole heart was acquired in 300 healthy volunteers and a computational model of RV motion created. From this model, points where regional function was significantly associated with global function were identified, and a two-dimensional, Optimized Single-Point Marker (SPM-O) of global function developed. This marker was prospectively compared with tricuspid annular plane systolic excursion (TAPSE), septum-freewall displacement (SFD) and their fractional derivatives (TAPSE-F, SFD-F) in a test cohort (n=300). Performance in predicting RVEF was compared by correlation, bootstrapped linear regression and mean absolute error.

Results:
Three-dimensional imaging suggested that RVEF was significantly associated with systolic function in a contiguous 7.3cm
2
patch of the basal RV freewall which combined components of transverse (38%), longitudinal (35%) and circumferential (27%) contraction. SPM-O was identified where this patch coincided with the four-chamber view and combined longitudinal and transverse contraction. In the test cohort, all single-point surrogates correlated with RVEF (p<0.01), but correlation was significantly higher for SPM-O (R = 0.44) than TAPSE (R = 0.24, p<0.002) and SFD (R = 0.22, p<0.001), and non-significantly higher than TAPSE-F (R = 0.40, p=0.50) and SFD-F (R = 0.43, p=0.86). SPM-O explained more of the observed variance in RVEF (19%) and predicted RVEF more accurately than any other 2D marker (median error 2.8 vs 3.6%, p<0.001).

Conclusions:
Systolic motion of the basal RV freewall in the four-chamber plane is a more accurate surrogate of global function than other two-dimensional estimators. However, the performance of two-dimensional estimators is fundamentally limited by a failure to adequately summarize three-dimensional contractile patterns, such as those found in the right ventricle.
Abstract 10336: Left Ventricular Deformation at 2-year Follow-up in Treatment-naive Rheumatoid Arthritis Patients is Associated With High Inflammation Parameters: A Open Cohort Study
Authors: Løgstrup Brian B , Masic Dzenan , Laurbjerg Trine B , Deibjerg Lone K , Urbonavience Grazina , Hedemann-Nielsen Agnete , Ellingsen Torkell
Published: July 2021

Introduction:
Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease (CVD). The role of autoimmunity and especially citrullination in the pathogenesis of the increased risk of CVD and the time-course of left ventricular (LV) dysfunction are unknown.

Hypothesis:
To assess LV function by speckle-tracking echocardiography and the amount of coronary calcium by coronary computer tomography (CCT) in relation to anti-cyclic citrullinated peptide antibody (anti-CCP) status during a 2-year follow-up period in a open cohort of treatment-naive RA patients.

Methods:
Thirty-nine treatment-naive early RA patients (21 women) were included at time of diagnosis and followed for 2 years. Disease activity, IgM rheumatoid factor (IgM-RF) and anti-CCP was assessed at time of diagnosis and at 2-year follow-up. We assessed both the LV deformation by speckle-tracking echocardiography whereby we measured global longitudinal systolic strain (GLS) and coronary calcium score (Agatston′s score) by coronary computer tomography (CCT) at time of diagnosis and at 2-year follow-up.

Results:
We found GLS similar at baseline and after 2-year follow-up (GLSBASELINE: -16.56±3.1% vs. GLS2-YEAR: -16.27±2.8%; p=0.66). However, in patients with anti-CCP ≥340 at baseline and patients who persistently had an anti-CCP ≥340 at 2-year follow-up (n=10), we observed a significant decrease in deformation compared to patients who did not (n=29); (2.9±3.2% vs. -0.6±2.7%; p=0.002). Furthermore, we observed a significant association between the changes in GLS over 2 years (GLSDELTA: 0.27±3.21%) and anti-CCP (r=0.63; p<0.0001), which remained significantly associated (p<0.0001) after correction for relevant confounders.

No significant progression in coronary calcium score was observed in the observation period.

Conclusions:
LV deformation is reduced in treatment-naive RA patients with persistently elevated anti-CCP and deformation abnormalities is associated with the degree of anti-CCP positivity in a 2-year follow-up period. Our observations make deformation analysis by speckle-tracking echocardiography a strong tool to detect early development of myocardial dysfunction in treatment naive RA.
Abstract 10357: The Usefulness of Home Blood Pressure Measurement in the Diagnosis of Hypertension: A Prospective Multicenter Study
Authors: Nah Deuk-Young , Chung Jin-Wook , Bae Jun-Ho , Lee Dong-Seok , Rhee Moo-Yong
Published: July 2021

Introduction:
The major hypertension guidelines suggest methods for diagnosing hypertension by measuring the 24-hour ambulatory blood pressure (ABP) or home blood pressure (HBP) if hypertension is suspected.

Hypothesis:
there is no consensus of cut off values for HBP as the criterion for hypertension and also optimal duration of home blood pressure measurement (HBPM).

Methods:
319 suspected hypertension patients (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, average value of three times measurements of blood pressure in the office) were included in four university hospital. The blood pressure (BP) measurement taken by patients in his/her home with HBPM device (Watch BP Home, Microlife, Swiss) and measured three times with one minute interval at morning and evening for 7 days. The 24-hour ambulatory blood pressure measurement (ABPM) was performed by Mobil-O-Graph (IEM. GmbH, Germany). The device was set to obtain BP readings at 30-minute intervals during the day and night. The definition of hypertension was as follows, SBP ≥135 mmHg or DBP ≥85 mmHg for HBPM and SBP ≥130 mmHg or DBP ≥85 mmHg for ABPM. For the analysis for diagnostic accuracy of HBPM, we used ABPM as a reference standard for the diagnosis of hypertension.

Results:
We decided to exclude 53 patients due to dropout or lack of valid BP measurement (valid leadings <70% of tried measurements of ABPM and less than 5-days HBPM). Finally we analyzed BP measurement data of 266 patients. Dropout or invalid BP measurement was more common in ABPM than HBPM. HBP was measured at least 6 days in more than 90% patients and white coat hypertension was diagnosed more frequently in the HBPM. HBPM had a more than 98.6% positive predictive value and 46.8% negative predictive value for the diagnosis of hypertension when put the criteria on ABPM. There are no difference of diagnostic accuracy for the diagnosis of hypertension according to the 5-day, 6-day and 7-day HBPM.

Conclusions:
A 5-day HBPM is enough for the diagnosis of hypertension considering ABPM as a reference. The cut off value of hypertension in HBPM is same to the current guideline values (135/85 mmHg) in this study. HBPM is an effective and available method for the diagnosis of hypertension in suspected hypertensive patients.
Abstract 10397: Higher Waist Circumference is the Start of Cardiovascular Structural and Functional Changes in Childhood Obesity
Authors: Harada Kenji , Harada Yukiko , Toyono Manatomo
Published: July 2021

Background:
Higher waist circumference (WC) is associated with cardiovascular disease, however, little is known about the association between WC and cardiovascular functional change in children. The purpose of this study is to examine the relationships between numbers of cardiovascular risk factors and left ventricular (LV) geometry and function in children.

Methods:
Echocardiography was performed in 311 children aged 7 to 13 years. Left atrial (LA) diameter, LV end-diastolic volume, ejection fraction, mass, mass-to-volume ratio, and carotid artery intima media-thickness (IMT) were measured. Transmitral peak flow velocities during early and late diastole and mitral annular myocardial velocities during early (Em) and late diastole (Am) were measured. LA systolic force and aortic stiffness were calculated. Lipids, uric acid, fasting glucose, insulin, high sensitive CRP, and homeostasis model assessment for insulin resistance (HOMA-IR) were also assessed. Subjects were divided into 4 groups: A group, WC within normal range; B group, increased WC; C group, increased WC plus any one of the following individual factors of hypertension, dyslipidemia (low high-density lipoprotein-cholesterol and/or high triglyceride), and raised fasting glucose; D group, metabolic syndrome.

Results:
Compared with the A group, LA diameter, mass/volume ratio, HOMA-IR, and uric acid were greater in the B group (p<0.05 for all). With increasing number of metabolic syndrome disorders (C and D groups), dyslipidemia, increased Hs-CRP, decreased Em/Am, enhanced LA systolic force, increased IMT, and aortic stiffening were observed (Table).

Conclusions:
Higher WC is associated with insulin resistance, hyperuricemia, and concentric LV hypertrophy. Cardiovascular structural and functional changes become apparent with increasing number of metabolic syndrome disorders. Our findings suggest that primary prevention programs should be initiated in children with increased WC.
Abstract 10402: Early Reduction of Myocardial Reactive Oxygen Species Production by Postconditioning in a Porcine Model of Cardiac Arrest and Resuscitation
Authors: Dikalova Anna E , Dikalov Sergey I , Salzman Michele M , Cheng Qunli , Matsuura Timothy R , Bartos Jason A , Yannopoulos Demetris , Riess Matthias L
Published: July 2021

Introduction:
Ischemic (IPoC) and anesthetic postconditioning (APoC) during cardiopulmonary resuscitation (CPR) are effective interventions to improve hemodynamic outcome and survival in a porcine model of prolonged cardiac arrest. We hypothesized that both strategies decrease the myocardial production of reactive oxygen species (ROS) early during reperfusion.

Methods:
After 15 min of untreated ventricular fibrillation (VF), 22 pigs were randomized to receive mechanical CPR for 4 min without (control) or with IPoC (three 20-sec CPR interruptions) or APoC with low- (2 Vol%) or high-dose (4 Vol%) sevoflurane for 3 min before euthanasia and organ harvest. Left ventricular myocardial tissue was immediately frozen in liquid nitrogen and stored at -80°C until electroparamagnetic resonance (EPR) measurements were performed to quantify ROS. Data are mean±SEM. Statistics: ANOVA with SNK-post hoc testing, alpha = 0.05.

Results:
EPR spectral changes showed that high-dose APoC (10±1 arbitrary units) and IPoC (15±4) reduced reactive oxygen species normalized to dry tissue weight compared to untreated control animals (33±2); low-dose APoC (34±4) did not.

Conclusions:
Our data show that the cardio- and neuroprotective strategies of IPoC and APoC result in decreased myocardial ROS production that can be detected as early as 4 min after reintroduction of blood flow by mechanical CPR; the effective concentration of sevoflurane, however, has to be high enough to achieve APoC. Our findings underline the importance of early organ-protective strategies and contribute to our understanding of the mechanisms of these important clinical interventions to improve outcome and survival after cardiac arrest.
Abstract 10412: The Effect of Positive Remodeling Area Index and Large Plaque Burden over Fractional Flow Reserve
Authors: Imai Shunsuke , Kondoh Takeshi , Kawase Yoshiaki , Matsuo Hitoshi
Published: July 2021

Introduction:
Coronary angiographic anatomical stenosis has not been well correlated with physiological fractional flow reserve (FFR), however, the mechanism of the discordance remains poorly understood. We focused on the patients who had no anatomical significant stenosis by coronary angiogram (CAG) but physiological significant stenosis by FFR (reverse mismatch) in the proximal or mid left anterior descending artery (LAD). We explored what coronary CT angiography (CCTA) findings of the target lesion of the LAD predict abnormal FFR.

Methods:
ECG-gated CCTA was performed using SOMATOM Definition AS+ (128 slice Siemens) and CAG underwent within 4 weeks. FFR was measured using a pressure guide wire (verrata, Volcano) during ATP infusion. Forty consecutive reverse mismatch (with no anatomical stenosis and FFR≦0.8) pts and 40 no mismatch (with no anatomical stenosis and FFR>0.8) pts were selected.

Results:
There were no significant differences in mean age (72±10y vs 74±8y), gender (M/F 21/19 vs 28/12), coronary risk factors (DM (9 vs 17), HT(32 vs 30), dyslipidemia (23 vs 18), Smoking (5 vs 4)), angle of LAD and LCX (70±21vs71±20 deg.), proximal reference lumen area (0.14±0.14 vs 0.14±0.11 mm2) and vessel area (0.15±0.04 vs 0.15±0.06mm2), distal reference lumen area (0.11±0.12 vs 0.10±0.04mm2) and vessel area (0.14±0.13 vs 0.12±0.04mm2), grade of plaque calcification, and presence of low density plaque (8 vs 7 pts) between no mismatch and reverse mismatch groups. However, vessel area (0.21±0.07mm2, P=0.0004) and positive remodeling area index (1.40±0.26, P<0.0001) at the minimum lumen area (MLA) in reverse mismatch group were higher than those (0.16±0.05mm2, 1.01±0.18) in no mismatch groups, respectively. AUC of remodeling area index was 0.924 for diagnosis of reverse mismatch on ROC analysis. Sensitivity was 82.5%, specificity was 84.6% when the remodeling area index was 1.13.

Conclusions:
Even if anatomical significant stenosis is not observed, FFR was depressed in patients with large vessel area and positive remodeling area index derived from CCTA at MLA. Large plaque at MLA may be one of the mechanisms of reverse mismatch.
Abstract 10426: One Year Impact of the 2013 Cholesterol Guidelines on Patterns of Lipid Lowering Treatment
Authors: Tran Josephine N , Kao Tzu Chun , Caglar Toros , Stockl Karen M , Lew Heidi C , Solow Brian K , Chan Paul S
Published: July 2021

Background:
In 2013, national organizations issued new cholesterol guidelines to emphasize evidence-based treatment with moderate- to high-dose statins for patients at high risk for atherosclerotic cardiovascular disease (ASCVD), which includes coronary heart disease, stroke, and peripheral arterial disease. Whether these new guidelines have influenced patterns of treatment one year after their dissemination is unknown.

Methods:
Using pharmacy and medical claims from a large U.S. health insurance organization, we identified 610,535 adult patients with ASCVD (n=301,440) or diabetes mellitus (n=309,095) and examined statin treatment rates before and one year after the new cholesterol guidelines. Among patients receiving statins post-guidelines, we also evaluated whether patients were treated with guideline-recommended intensity of statin therapy. A standardized difference (SD) of at least 10% was required to declare the effect size meaningful.

Results:
Overall, there was no change in statin treatment rates for patients with ASCVD (48.0% before guidelines vs. 47.3% after, SD [1.4]) or diabetes (50% vs. 51.5% after, SD [2.4]). Statin initiation rates among patients not on statins pre-guidelines were 10.1% in patients with ASCVD and 14.3% in patients with diabetes, and these gains were offset by 13.0% and 12.2% statin discontinuation rates among ASCVD and diabetes patients, respectively. Among patients taking statins one year post-guidelines, 80% of patients with ASCVD and
<
75 years of age were not on guideline-recommended high-intensity statin therapy, whereas >75% of patients with ASCVD and >75 years of age or patients with diabetes were on moderate- or high-intensity statin treatment.

Conclusion:
One year after dissemination of the new 2013 cholesterol guidelines, overall treatment rates with statins among patients with ASCVD and diabetes have not changed appreciably, and many patients remain either untreated or under-treated.

Character Count: 1683
Abstract 10476: Effect of High-dose Oral Multi-vitamins and Minerals in Patients Not Treated With Statins in the Trial to Assess Chelation Therapy
Authors: Lamas Gervasio A , Guarneri Erminia , Mark Daniel B , Boineau Robin , Bradley Ryan , Goertz Christine , Rosenberg Yves , Lewis Eldrin F , Drisko Jeanne , Lindblad Lauren , Lee Kerry L
Published: July 2021

Introduction:
Trials of conventional dose vitamin therapy have been largely negative for coronary prevention. TACT studied an ultra-high dose regimen of oral multivitamins and multiminerals (MVM) in post-MI patients. Patients off statins were a pre-specified subgroup.

Methods:
1708 patients were randomized in a double-blind factorial trial, to EDTA-based chelation or placebo, and oral MVM or oral placebo. MVM consisted of a 28-component mixture (or placebo), taken as 3 caplets twice daily throughout the 5 year study participation. To our knowledge, the oral antioxidant doses are the highest tested in a clinical trial. The primary endpoint was total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. The results of oral vitamins versus placebo were not significant [HR (95%CI) 0.89 (0.75,1.07), p=0.212]. However, the pre-specified subgroup of patients not taking statins demonstrated an interaction with MVM (p=0.012). Both unadjusted analyses and comparisons adjusted for baseline prognostic factors were performed.

Results:
There were 460 (27%) (MVM: 224, placebo: 236) TACT participants not taking statins at baseline. Common reasons were: patient refusal 32%, physician preference 28%, and other 23%. Median duration of MVM therapy was 31 months (IQR 13-59 months).76% of patients completed one full year on vitamins, while 48% completed all 5 years. MVM patients had a 38% reduction in the primary composite endpoint compared with placebo (HR = 0.62, 95% CI: 0.44-0.87, p=0.006, FIGURE). Adjusted analyses reduced the significance of the findings without materially changing the HR (HR = 0.67, 95% CI: 0.47, 0.96, p=0.03). In patients taking statins, there was no beneficial effect of MVM (p=0.774).

Conclusion:
The present analyses cannot exclude a beneficial effect of MVM treatment for post-MI patients not taking statins. This unexpected result deserves confirmatory testing since it could be quite useful in practice if correct.
Abstract 10878: Validation of Non-invasive Measures of Diastolic Function in Children: A Simultaneous Echocardiography and Conductance Catheterization Study
Authors: Chowdhury Shahryar M , Butts Ryan J , Hlavacek Anthony M , Taylor Carolyn L , Bandisode Varsha M , Chessa Karen S , Shirali Girish S , Nutting Arni , Baker George H
Published: July 2021

Introduction:
The accuracy of echocardiography in evaluating left ventricular (LV) diastolic function has not been validated in children. The objective of this study was to compare echocardiographic and gold-standard measures of LV diastolic function in children.

Methods:
Patients undergoing routine left heart catheterization were prospectively enrolled. Pressure-volume loops (PVL) were obtained via conductance catheters. The end-diastolic pressure-volume relationship was obtained via balloon occlusion of the vena cavae. PVL measures of diastolic function were divided into early active relaxation (the isovolumic relaxation time constant, tau), and ventricular stiffness (the chamber stiffness constant, β). End-diastolic pressure (EDP) was also recorded. Echocardiographic measures of diastolic function were derived from spectral Doppler, tissue Doppler, and 2D speckle-tracking. The relationships between PVL and echocardiographic measures were determined using Spearman’s correlation.

Results:
Of 24 patients, 18 patients were s/p heart transplant, 5 patients had a small patent ductus arteriosus or coronary fistula. Mean age was 9.1 ± 5.6 years. The median τ was 24.9 ms (IQR 22.8 - 28.4 ms), median β was 0.094 (IQR 0.035 - 0.154), and median EDP was 9 mmHg (IQR 8 - 13 mmHg). Statistically significant correlations between invasive and echocardiographic measures of diastolic function are reported in the Table. No echocardiographic measures correlated with β.

Conclusion:
Early diastolic echocardiographic measures correlate with tau and may accurately represent early active relaxation in children. Modest associations exist between echocardiographic measures and EDP. The use of these non-invasive measures in accurately assessing LV diastolic function appears promising in children. However, no echocardiographic measures correlate with chamber stiffness. The development of such measures merits further study.
Abstract 10879: Efficacy and Safety of Rivaroxaban in Patients With Venous Thromboembolism and Active Malignancy - A Single Center Registry
Authors: Saadiq Rayya , Bott-Kitslaar Dalene , Loprinzi Charles , McBane Robert , Wysokinski Waldemar
Published: July 2021

Background:
Active malignancy accounts for 20% of venous thromboembolism (VTE) in the community and is the second leading cause of death among cancer patients. Rivaroxaban offers a convenient alternative to conventional anticoagulation for VTE in cancer patients but its efficacy and safety for this group of patients is not well documented.

Patients and Methods:
All patients with cancer-associated deep vein thrombosis (DVT) or pulmonary embolism (PE), enrolled into Mayo Rochester Thrombophilia Clinic Direct Oral Anticoagulants Registry between November 1, 2012 and April 30, 2015, were followed prospectively to provide an estimate of the efficacy and safety of this form of therapy. Follow up was obtained in person or by mailed or telephone survey.

Results:
Out of the 377 patients in the registry, 118 (31%) patients (51% female, mean age 66±10 years) had active malignancy related VTE (62% DVT, 24% PE, and 14% DVT/PE) treated with rivaroxaban. The most common malignancies in this group were: gastrointestinal (20%), lung (13%) and ovary/uterine (13%). Over the follow up period, the VTE recurrence rate was 3.3% (2 DVT and 2 PE; of these, 2 occurred during periprocedural interruptions of anticoagulation); and the major bleeding rate was 3%. There were 26 deaths (22%), none related to VTE or bleeding. The main reasons for choosing rivaroxaban were lower cost compared to LMWH, no need for injections, and the lack of food/drug interactions.

Conclusions:
These data support that rivaroxaban may provide a safe, effective, and convenient alternative treatment option to standard therapy for cancer related VTE treatment.
Abstract 10895: The Association of Growth Patterns and Clinical Outcomes in Children With Dilated Cardiomyopathy: A Report From the Pediatric Cardiomyopathy Registry Study Group
Authors: Castleberry Chesney , Jefferies John L , Shi Ling , Wilkinson James D , Towbin Jeffrey A , Harrison Ryan W , Canter Charles , Rossano Joseph , Pahl Elfriede , Lee Teresa , Addonizio Linda , Rusconi Paolo , Godown Justin , Mahgerefteh Joseph , Colan Steven D , Kantor Paul F , Lipshultz Steven E , Miller Tracie
Published: July 2021

Introduction:
Although malnourishment is associated with mortality in adult dilated cardiomyopathy (DCM), a paradox exists where obesity is protective. We aim to look at the role of these risk factors in pediatric DCM.

Hypothesis:
We hypothesize malnourishment (MN) and obesity are risk factors for death or heart transplantation.

Methods:
The NHLBI- funded Pediatric Cardiomyopathy Registry (PCMR) database was used for this analysis of patients (age < 18 years) with idiopathic or familial DCM and myocarditis. Patients were categorized by anthropological measurements: MN (defined as BMI <5% for ≥2years or weight for length <5% for <2 years), obese (BMI> 95% for ages ≥2years or weight for length >95% for <2 years), and normal.

Results:
Of 904 DCM patients, 23.7% (214) were MN, 13.3% (120) were obese, and 63.1% (570) were normal (Table). Obese patients were significantly older (p<0.001) and more likely to have a family history of DCM (both p<0.05). MN were more likely to have congestive heart failure, increased cardiac dimensions, and higher ventricular mass (p<0.01). In a Kaplan Meier analysis, there was a difference in time to death or transplant by groups (Figure, p=0.0498). Adjusting for age and myocarditis, MN was associated with increased risk of death (HR: 1.857, 95%CI: 1.159-2.977, p=<0.001), but obesity was not (HR: 1.362, 95%CI: 0.722, 2.566). Competing outcome analysis showed an increased risk of death for MN (p=0.026) but no difference between groups in transplant rate (p=0.159).

Conclusion:
Malnourishment is significantly associated with poor clinical outcomes. Unlike adult DCM where obesity is protective, obesity is not associated with improved survival in pediatric DCM.
Abstract 10906: Heart Failure is Common and Under Recognized in Patients With Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: Gilotra Nisha A , Sawant Abhishek , Bhonsale Aditya , te Riele Anneline S , James Cynthia A , Murray Brittney , Tichnell Crystal , Judge Daniel P , Russell Stuart D , Calkins Hugh , Tedford Ryan J
Published: July 2021

Introduction:
The reported incidence of heart failure (HF) in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) varies depending on study cohort ranging from <10 to 20%. Though risk of fatal arrhythmias is well described, the heterogenous manifestations of HF in this population are less well known.

Hypothesis:
With more prompt recognition of ARVD/C and subsequent prevention of SCD, HF is becoming more prevalent amongst ARVD/C patients.

Methods:
Patients from the Johns Hopkins ARVD/C Program Registry meeting the 2010 Revised Task Force Criteria with completed HF symptom survey (n=134) and/or available HF clinical assessment (n=154) were included. HF signs and symptoms were retrospectively adjudicated.

Results:
Of the 288 patients studied, 236 had evidence of structural heart disease defined as right ventricular (n=199) or biventricular dilatation/dysfunction (n=37). At least one clinical sign or symptom of HF was present in 123 (52%) of those with structural disease (42 had one and 61 had two or more signs/symptoms). The most commonly reported symptoms were dyspnea on exertion (n=87) and fatigue (n=77). Evidence of volume retention (edema or ascites) was found in 46/236 (20%), and left-sided HF symptoms were rare. Of the 105 patients with structural heart disease and known age at HF symptom onset, average time from first ARVD/C presentation to HF symptoms was 6.3 ± 8.0 years, and 40% had at least one episode of sustained ventricular tachycardia or ICD shock prior to HF symptoms. Presence of a genetic mutation for ARVD/C did not correlate with HF symptoms or structural changes. Sixteen patients underwent orthotopic heart transplant.

Conclusions:
HF symptoms are common in the ARVD/C population with structural heart disease. Though there is a small subset of patients with evident volume overload requiring therapy, there is a larger portion of patients with HF symptoms that may be under recognized.
Abstract 10956: Early and Late Vascular Responses After Stent Implantation in Human Peripheral Artery Disease
Authors: Inoue Katsumi , Kobayashi Yohei , Ishihara Takayuki , Shiraki Tatsuya , Tomoi Yusuke , Hiramori Seiichi , Soga Yoshimitsu , Iida Osamu , Ando Kenji , Uematsu Masaaki , Nobuyoshi Masakiyo
Published: July 2021

Background:
Although stent implantation is now a first-line strategy for the treatment of peripheral artery disease (PAD), little is known about the pathological findings of arterial response following lower extremity stenting.

Methods and Results:
Histopathological studies were performed on 13 iliofemoral lesions (les) obtained by autopsy or surgical resection between 2.5 months (M) and 10 years (Y) after bare metal stent (BMS) implantation. In addition, paclitaxel-coating stents (Zilver PTX) (6 les; 10 M to 2.5 Y) implanted in superficial femoral arteries were also observed. Almost all arterial specimens were characterized by fibrocalcific intimal plaques as well as underlying Mönckeberg’s medial calcinosis. There were fibrin deposits around the struts, with smooth muscle cell (SMC) infiltration in varying degrees, at 2.5 M after BMS implantation; however, endothelial cell coverage remained poor in the surface area. Furthermore, stent malapposition is a frequent phenomenon, which is related to underlying medial and intimal calcification. Arteries from more than 1 Y after stenting exhibited thickened neointima consisting of significant proliferation of SMCs and abundant extracellular matrix on the intimal side of the stent struts. However, uncovered malapposed struts with fibrin deposition were still evident, predominantly at the calcified surface. In neointima of more than 8 Y after stenting, SMCs were spindle-shaped and ordered along the luminal surface, and intercellular space contained abundant collagen fibers. However, there was advanced luminal narrowing in 2 of the les, and the luminal surface of these segments was focally disrupted and covered by mural thrombi. Zilver PTX demonstrated notable uncovered struts, even more than 2 Y after stenting, and extensive in-stent thrombi were observed in all stented segments, including 2 les with occlusive thrombosis. Conclusions: These findings suggest that a longer duration of potent antiplatelet therapy may be more appropriate after BMS implantation for PAD, compared to coronary artery stenting. Furthermore, remarkable delayed healing with significant uncovered struts caused by paclitaxel exposure can result in late stent thrombosis after Zilver PTX implantation.
Abstract 10957: Combined Assessment of High-Sensitive Troponin I and N-Terminal Pro-B-Type Natriuretic Peptide Levels Improves the Prediction of Cardiovascular Event in Outpatients With Hypertension
Authors: Matsui Shigeru , Ishii Junichi , Takahashi Hiroshi , Okuyama Ryuunosuke , Kawai Hideki , Muramatsu Takashi , Yamada Akira , Motoyama Sadako , Naruse Hiroyuki , Hayashi Mutsuharu , Izawa Hideo , Ozaki Yukio
Published: July 2021

Background:
Hypertension is one of the most prevalent risk factors in the development of cardiovascular diseases and events. We prospectively investigated the predictive value of a combination of high-sensitive troponin I (hsTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for cardiovascular event in outpatients with hypertension.

Methods:
Baseline serum levels of hsTnI and NT-proBNP were measured in 701 outpatients (mean age: 68.3 years; male 71%) with hypertension, of whom 30% had a history of cardiovascular disease; 45%, diabetes; and 56%, chronic kidney disease (estimated GFR <60 mL/min/1.73 m
2
). Left ventricular ejection fraction (LVEF) and E/e’ ratio were estimated using echocardiography with tissue Doppler imaging. Cardiovascular event was defined as cardiovascular death or admission for acute coronary syndrome, decompensated heart failure, or stroke.

Results:
hsTnI levels significantly correlated with NT-proBNP levels (r = 0.29; p < 0.0001). During a mean follow-up period of 959 days, there were 111 (16%) cardiovascular events, including 16 cardiovascular death cases. Multivariate Cox regression analysis, including 6 clinical, biochemical, and echocardiographic variables, identified increased hsTnI (relative risk: 1.92 per 10-fold increment; p = 0.001) and NT-proBNP levels (relative risk: 2.28 per 10-fold increment; p = 0.0001) as independent predictors of cardiovascular events. Combined hsTnI and NT-proBNP tertiles was significantly associated with cardiovascular event rates (Figure). Furthermore, adding both hsTnI and NT-proBNP levels to a baseline model improved the C-index (0.769 vs. 0.736; p = 0.005), net reclassification improvement (0.387; p < 0.0001), and integrated discrimination improvement (0.044; p = 0.001) greater than a baseline model.

Conclusions:
The combined assessment of hsTnI and NT-proBNP levels may improve the prediction of cardiovascular event in outpatients with hypertension.
Abstract 10976: Diagnostic Ability of Contrast Media Induced Fractional Flow Reserve to Assess Functional Significance of Entire Coronary Artery Stenosis
Authors: Takashima Hiroaki , Kurita Akiyoshi , Saka Yuki , Waseda Katsuhisa , Ando Hirohiko , Maeda Kazuyuki , Sakurai Shinichiro , Suzuki Akihiro , Amano Tetsuya
Published: July 2021

Introduction:
Although fractional flow reserve (FFR) is helpful to evaluate functional lesion severity, the need of adenosine limits the widespread adoption of FFR.

Hypothesis:
We hypothesized that contrast media induced FFR (cFFR) with submaximal hyperemic condition could assess functional lesion severity of coronary artery stenos. The aim of this study was to evaluate the diagnostic ability of cFFR compared to FFR in entire range of coronary artery stenosis.

Methods:
A total of 96 patients with 123 lesions were prospectively enrolled in this study. At first, we measured resting Pd/Pa ratio before inducing hyperemia. Then, cFFR was obtained after intracoronary injection of 6 ml of contrast media, while FFR was measured after intravenous adenosine triphosphate administration (180 mcg/kg/min). Lesions with FFR less than or equal 0.80 were considered functional significance of coronary artery stenosis.

Results:
In 123 lesions, reference diameter, diameter stenosis, resting Pd/Pa ratio, cFFR, and FFR were 2.7±0.8 mm, 47±12%, 0.91±0.10, 0.83±0.12, and 0.81±0.12, respectively. Functional significance was observed in 41% of all lesions. Both of resting Pd/Pa and cFFR showed strong correlations with FFR (r=0.861, p<0.001, and r=0.930, p<0.001, respectively). The correlation coefficient of cFFR was significantly superior to that of resting Pd/Pa ratio (p<0.05). This strong correlation between cFFR and FFR was shown in every coronary artery (LAD; r=0.924, p<0.001, LCX; r=0.923, p<0.001, and RCA; r=0.926, p<0.001, respectively). The Bland-Altman plot demonstrated a good agreement with a mean difference of -0.02 and a standard deviation of 0.05 between cFFR and FFR across entire range of coronary artery stenosis. ROC curve analysis showed an excellent accuracy of cFFR <0.84 in predicting functional significance (AUC 0.96, sensitivity 90%, specificity 89%, and diagnostic accuracy 89%). Moreover, the cFFR >0.89 was not corresponded to functional significance of entire coronary artery stenosis.

Conclusions:
The cFFR is an accurate, rapid and easy method in predicting functional significance of entire coronary artery stenosis. This physiology-based approach may be a possible alternative method for FFR measurements in daily practice.
Abstract 11003: Hypothalamic Activated Microglia With Morphological Changes Accelerate Blood Pressure Elevation During the Hypertension Development Phase in Stroke-prone Spontaneously Hypertensive Rats
Authors: Takesue Ko , Kishi Takuya , Hirooka Yoshitaka
Published: July 2021

Introduction:
A recent paradigm shift in cardiovascular pathophysiology is the impact of inflammation on hypertension. Inflammation within the paraventricular nucleus of the hypothalamus (PVN) is an important pathology of sympathetic hyperactivity, and is mainly mediated by innate immune cells, microglia. Activated microglia with alteration of their morphology produce inflammatory cytokines. Previous reports demonstrated that microglia within the PVN have activated morphology in angiotensin II-induced hypertensive rats and spontaneously hypertensive rats compared with normotensive control Sprague-Dawley rats or Wistar-Kyoto (WKY) rats. However, the role of activated microglia in the PVN in blood pressure elevation associated with sympathetic hyperactivity remains unknown. In the present study, we determined whether inhibition of microglial activation within the PVN attenuates the blood pressure elevation in genetically hypertensive rats.

Methods and Results:
We evaluated the activation of PVN microglia, identified by microglia specific ionized calcium-binding adaptor molecule 1 immunoreactivity, by measuring the roundness and the perimeter of microglia at 6 weeks of age, early hypertension development phase in stroke-prone spontaneously hypertensive rats (SHRSP) and compared with them in age-matched normotensive WKY rats. At 6 weeks of age, increased roundness and shortening of perimeter of microglia, indicating activated microglia, were observed in SHRSP compared with those in WKY rats. Then, we performed intracerebroventricular (ICV) administration of minocycline (5 μg/h) to deactivate microglia at 6 weeks of age for 4 weeks. ICV administration of minocycline significantly attenuated systolic blood pressure elevation in SHRSP over 4 weeks (at the end of experiments; 203.2±2.2 mm Hg vs. 215.9±2.7 mm Hg, n=8-9, P<0.05), but not in WKY rats. At 10 weeks of age, morphological analysis revealed that ICV minocycline significantly decreased the roundness and increased the perimeter of microglia, indicating deactivation of microglia, within the PVN in SHRSP.

Conclusions:
Hypothalamic activated microglia with morphologic changes accelerate blood pressure elevation during the hypertension development phase in SHRSP.