bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16855: Left Ventricular Volumes, Stress, and Strain in Normal Children and Young Adults Measured by 3-Dimensional Echocardiography
Authors: Kuebler Joseph D , Nathan Meena , Marx Gerald , Colan Steven , Harrild David M
Published: March 2022

Background:
3D echocardiography (3DE) is increasingly being used clinically to calculate ventricular volumes and function. Normal pediatric values of 3D LV volumes and strain are not well established; moreover, there are no reports of the stress-strain relationship (an index of contractility) based upon 3D technology in this cohort.

Methods:
3D LV datasets were obtained as part of routine echocardiographic examinations in eligible pediatric patients (≤ 21 years of age) between January 2014 and March 2015. Included patients had structurally normal hearts. Exclusion criteria included non-cardiac disorders with a potential impact on ventricular function and family history of cardiomyopathy. Image acquisition was performed using the Philips IE33 with X3/5/7 probes. Strain (3D; circumferential, GCS; and longitudinal, GLS) was analyzed according to a commercial 3D speckle-tracking analysis package (4D LV Analysis 3.1; Tomtec). LV mid-wall global average stress was calculated from the 3D LV volumes and 2D cross-sectional area/long-axis dimensions.

Results:
237 patients were included (age= 0.2 mo-21 y). The correlation between 3D and 2D LV mass and volumes was excellent (mass, R=0.94; end-diastolic volume, R=0.94; end-systolic volume, R=0.90; p<0.001 for all). Mean+-SD strain values (%) were: 3D=-33.9±2.8; GCS=-28.0 ± 3.1; GLS=-20.7 ± 3.0; only GLS varied significantly with age (R=0.26; p<0.001). Overall, 3D strain was inversely linearly related to wall stress (R=0.26; p<0.001); the strongest relationship was present in patients from age 0-5 years (R=0.48; p<0.01). When normalized to stress, absolute LV strain decreased with age (Figure 1: R=0.33; p<0.001).

Conclusions:
3DE may be used to calculate LV stress, strain, and volume parameters. Among strain parameters, age-related changes were seen only in GLS. Examination of the stress-strain relationship using these techniques may yield new insights into maturational changes in myocardial contractility.
Abstract 16863: Alirocumab Effect on Glycemic Measures in Patients Without Diabetes at Baseline
Authors: Colhoun Helen M , Ginsberg Henry N , Robinson Jennifer G , Leiter Lawrence A , Müller-Wieland Dirk , Henry Robert R , Cariou Bertrand , Baccara-Dinet Marie T , Pordy Robert , Merlet Laurence , Eckel Robert H
Published: March 2022

Background:
Statin use has been reported to have modest adverse effects on glycemia and incidence of diabetes mellitus (DM). We assessed effects of alirocumab (ALI), a PCSK9 inhibitor with substantial effect on LDL-C, on development of incident DM or impaired glucose control (IGC) in patients without diabetes at baseline in 10 trials in the ODYSSEY Phase 3 program.

Methods:
Five trials were controlled with placebo (N=2318 ALI vs 1174 placebo), and 5 with ezetimibe (N=864 ALI vs 618 ezetimibe), ranging in length from 24 to 104 wks. Most patients were receiving background statin. Different ways of assessing ALI effect on glycemic measures were used, including occurrence of treatment-emergent adverse events (TEAEs) related to DM, and fasting plasma glucose (FPG) and HbA1c measured at baseline and every 12-24 wks thereafter. Additional analysis using all 3 parameters was conducted (see Table footnote).

Results:
Duration of exposure is shown in the Table. At baseline, 32.8% of patients had DM, 93% based on medical history. Another 37.4% had IGC at baseline, based on laboratory data (93.6%) or medical history (6.4%). In patients without DM at baseline, there was no difference between ALI and control groups in occurrence of TEAEs related to DM with HR (95% CI) = 0.79 (0.44-1.43) in the placebo-controlled pool and 0.55 (0.22-1.41) in the ezetimibe-controlled pool. Mean change in FPG and HbA1c over time showed no meaningful differences between treatment groups by baseline glycemic status. In the additional analysis shown in the Table, there was no notable difference between ALI and control groups in % of patients with baseline normoglycemia developing DM or IGC, or those with baseline IGC developing DM.

Conclusions:
In 10 studies involving 4974 patients comparing ALI to either placebo or ezetimibe (median exposure 66 or 27 wks, respectively), data show no significant effect of ALI on transition to IGC or DM. Longer follow up with larger numbers is needed to conclusively rule out an effect.
Abstract 16890: Improved Rates of Bystander Cardiopulmonary Resuscitation, First Responder Defibrillation and Outcome in Black and White Patients but More Improvement for White Patients: Results From the North Carolina Heartrescue Project
Authors: Malta Hansen Carolina , Kragholm Kristian , Pearson David A , Tyson Clark , Dupre Matthew E , Jollis James G , Strauss Benjamin , Anderson Monique L , McNally Bryan , Becker Lance B , Granger Christopher B
Published: March 2022

Introduction:
Known differences in bystander cardiopulmonary resuscitation (CPR) and survival for out of hospital cardiac arrest (OHCA) exist for blacks compared with whites. Following the HeartRescue project, bystander and first responder interventions and survival increased in North Carolina (NC). Our objective was to study how these improvements were distributed by racial groups.

Methods:
Using the CARES registry, we identified OHCA cases of cardiac etiology from counties in NC (population 3 million) with 100% case capture from 2010-14. Unadjusted incidence rates per 100,000 were calculated based on US Census data (2010-13). Temporal changes in rates of bystander CPR, first responder defibrillation, and outcomes were assessed according to black or white race.

Results:
Of 7,558 OHCA patients, 36.3% were black (incidence: 94.7/100,000) and 63.7% were white (64.8/100,000). From 2010-14, bystander CPR increased by 34%, irrespective of race (Figure). No improvement in first responder defibrillation was seen for black patients (2010 to 2014: 40.3% to 44.4%, p=0.38), but was demonstrated for white patients (38.3% to 47.2%, p<0.01). Return of spontaneous circulation improved significantly for black patients (23.0% to 27.6%, p<0.01) and more significantly for white patients (19.2% to 34.0%, p< 0.01). No significant increase in survival over time was seen for black patients (8.6% to 9.2%, p=0.32), but was demonstrated for white patients (5.6% to 11.7%, p< 0.01). Among patients receiving bystander CPR, favorable neurologic outcome increased significantly regardless of race (relative increase 59% for blacks and 81% for whites).

Conclusion:
After the HeartRescue quality improvement program, bystander CPR increased by 34% in black and white patients. There were substantial improvements in survival with favorable neurologic outcome in both black and white patients receiving bystander CPR, however gains in interventions and outcomes were greater for whites.
Abstract 16899: Change in Cardiorespiratory Fitness is Inversely Related to Mortality Among Black and White Patients: Data From the Henry Ford Exercise Testing (FIT) Project
Authors: Ehrman Jonathan K , Brawner Clinton A , Al-Mallah Mouaz H , Qureshi Waqas T , Schairer John R , Blaha Michael J , Keteyian Steven J
Published: March 2022

Background:
Cardiorespiratory fitness (CRF) is inversely related to all-cause mortality and cardiovascular-related morbidity and mortality. However, there is limited data describing whether change in CRF is associated with improved outcomes.

Hypothesis:
Change in CRF between two clinical exercise stress tests is related to risk of all-cause mortality.

Methods:
In this retrospective, observational study, we identified 14,305 patients (age = 55 ± 11 y; 39% women; 30% non-white) who completed two clinically-indicated exercise tests that were at least 12 mo apart between 1991 and 2009 within the Henry Ford Health System. CRF was quantified in metabolic equivalents of task (METs) estimated from peak treadmill speed and grade. All-cause mortality was identified through April 2013 using the Social Security Death Index. Cox regression analysis was used to evaluate the risk of mortality associated with change in CRF between tests 1 and 2. Change in CRF was analyzed as the change in categorization between Poor Fitness (<7 METs) and Fit (≥ 7 METs) and as an absolute change in peak METs. Based on data at test 1, covariates included age; sex; race; cardiovascular risk factors; medications; and history of coronary artery disease, heart failure, and atrial fibrillation; as well as year of test 1 and years between tests 1 and 2.

Results:
The mean time between test 1 and 2 was 4.3 ± 2.8 y. During 9.4 ± 3.9 y of follow-up after test 2, there were 1,980 (14%) deaths. Adjusted Cox regression results are shown in the Table. Among all patients, each 1 MET increase in CRF at test 2 was associated with a 5% lower risk of mortality (hazard ratio 95% confidence interval 0.94, 0.97; p < 0.001).

Conclusions:
Among men and women referred for a clinical exercise test, change in CRF from Poor Fitness to Fit is associated with a 38% lower risk of all-cause mortality relative to patients who remain Unfit. These data support the importance of improving CRF and the clinical utility of serial assessments of CRF in risk assessment.
Abstract 16904: Are All Omega-3s Created Equal? Comparison of the Bioavailability and Efficacy of Four Omega-3 Preparations
Authors: Butt Rodney W , Cockerline Carla A , Rowe William J , Laidlaw Maggie
Published: March 2022

There are many omega-3 products available in the prescription and non-prescription marketplace. Neither health care professionals nor consumers may be aware of the potential influence of the manufacturing processes and source(s) of the starting material. Manufacturers of the various omega-3 preparations imply that their product is superior to others, based on its structural characteristics, whether phospholipid, triglyceride or ethyl ester.

The objective of this study was to compare the ability of four (4) different omega-3 preparations to raise whole blood fatty acid levels. This was a Prospective, Open-label, Blinded Endpoint (PROBE), four period, cross-over study. Thirty-five (35) healthy subjects were randomized to consume one of four test articles for four weeks, followed by a four-week washout, and this process was repeated until all products had been consumed by all subjects. The test article doses were based on their label specifications. The four products and daily doses were:

Triglyceride fish oil:

EPA of 650 mg, DHA of 450 mg

Ethyl Ester fish oil:

EPA of 756 mg, DHA of 228 mg

Phospholipid krill oil:

EPA of 150 mg, DHA of 90 mg

Triglyceride salmon oil:

EPA of 180 mg, DHA of 220 mg

Blood samples before and after supplementation were quantified for whole blood fatty acids by gas chromatography flame ionization. Bioavailability was assessed for each product individually, based on its change from baseline. Percentage change from baseline was then compared across all four products.

TG fish oil was statistically superior to all of its comparators in the bioavailability of EPA+DHA, and of DHA alone. Its EPA percentage increase was more than four times that of PL krill oil and TG salmon oil. Only the two TG products significantly increased whole blood

DHA levels. For investigators and clinicians, the type and dose of omega-3s may be clinically important when assessing potential clinical impact.
Abstract 16911: Behind the Looking Glass: Comparing Time to First Event versus Multiple Events Analyses in a Post-myocardial Infarction Clinical Trial
Authors: Lee Kerry L , Roberts Rhonda S , Mark Daniel B , Al-Khalidi Hussein R , Boineau Robin , Rosenberg Yves , Stylianou Mario , Lamas Gervasio A
Published: March 2022

Introduction:
Standard analysis of clinical trials with composite endpoints compare time-to-first event. Subsequent events are not counted and therefore not taken into account in treatment comparisons. We compared standard analyses to analyses that take into account all the events a patient may have experienced.

Methods:
The Trial to Assess Chelation Therapy (TACT) enrolled 1708 post-MI pts in a factorial trial comparing edetate disodium infusions versus placebo infusions and oral vitamins and minerals versus oral placebo. TACT had a composite primary endpoint: death, MI, stroke, coronary revascularization, and hospitalization for angina. Pre-specified primary analysis for TACT was based on the standard approach of considering time until the occurrence of the first event. Two different approaches for multiple events analyses were compared to the standard approach: 1] a generalization of the Cox model to handle recurrent events, developed by Andersen & Gill (AG), and 2] a marginal modeling approach developed by Wie, Lin, and Weissfeld (WLW). Each considers the correlation among multiple events occurring within a pt.

Results:
There were 743 events in TACT. 483/1708 (28%) of the patients had at least 1 event. Time-to-first-event analysis did not use information on 260 (35%) events. The standard analysis for edetate disodium vs placebo produced a hazard ratio (HR) 0.82, 95% confidence intervals 0.69,0.99, p=0.035. Both multiple events analyses demonstrated narrower confidence intervals and lower P values. AG: HR 0.80 (0.66,0.96), p=0.017; and WLW: HR 0.79 (0.66, 0.95), p=0.010. In the comparison of the active edetate + active MVM vs placebo edetate + placebo MVM, there were 247/858 (29%) pts with at least 1 event, but there were 371 events. Therefore, 124 (33%) were not used. Results of the standard analysis for edetate + MVM showed HR 0.74 (0.57,0.95), p=0.016; for AG HR 0.66 (0.51,0.85),p=0.002, and for WLW HR 0.38 (0.30,0.49), p<0.001.

Conclusion:
In this post-MI trial, a standard time to first event analysis did not make use of over 1/3 of events. Multiple events analysis can improve the precision of the estimate of benefit by producing narrower confidence intervals. These methods could be considered to reduce sample size and budgets in future clinical trials.
Abstract 16914: On-treatment Outcomes in Patients With Worsening Renal Function With Rivaroxaban Compared With Warfarin: Insights From ROCKET AF
Authors: Fordyce Christopher B , Hellkamp Anne S , Lokhnygina Yuliya , Lindner Samuel M , Piccini Jonathan P , Becker Richard C , Berkowitz Scott D , Breithardt Guenter , Fox Keith A , Halperin Jonathan L , Hankey Graeme J , Mahaffey Kenneth W , Nessel Christopher C , Singer Daniel E , Patel Manesh R
Published: March 2022

Introduction:
ROCKET AF demonstrated the noninferiority of rivaroxaban vs. warfarin in preventing stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (AF). It is unknown whether outcomes differ among patients with worsening renal function (WRF) on rivaroxaban compared with warfarin.

Methods:
After excluding patients with insufficient data to calculate creatinine clearance (CrCl, Cockcroft-Gault; n=1624), we included all remaining patients (n=12,612) randomly assigned to either rivaroxaban or dose-adjusted warfarin. The primary efficacy endpoint was the composite of stroke or SE; the primary safety endpoint was the composite of major bleeding and clinically relevant non-major bleeding. On-treatment WRF, as defined in recent cardiovascular studies as a decrease of ≥20% from screening CrCl, was evaluated as a time-dependent covariate in Cox proportional hazards models.

Results:
Baseline characteristics were generally similar between patients who maintained stable renal function (SRF) (n=9292) and patients with WRF (n=3320). Overall rates of stroke or SE, myocardial infarction, and bleeding were also similar, but WRF patients had an increase in vascular death (1.41 events/100 pt-years for SRF to 2.21 for WRF p=0.026). WRF patients on rivaroxaban had a reduction in stroke or SE compared with WRF patients on warfarin (1.54 events/100 pt-years for rivaroxaban to 3.25 for warfarin) that was not seen in SRF patients (p=0.050 for interaction; Figure). WRF patients on rivaroxaban had a greater incidence of hemoglobin fall ≥2 g/dL (3.56 events/100 pt-years for rivaroxaban to 1.85 for warfarin), that was not seen in SRF patients (p=0.047 for interaction). However, there was no difference in major or clinically relevant non-major bleeding.

Conclusions:
Among patients with on-treatment WRF, rivaroxaban was associated with lower rates of stroke and SE compared with warfarin without an increase in the composite bleeding endpoint.
Abstract 16917: Hemodynamic Effects of Synchronized Chest Compression in a Porcine Post Countershock PEA Model
Authors: Quan Weilun , Herken Ulrich , Paradis Norman
Published: March 2022

Purpose:
Post countershock Pulseless Electrical Activity (PCC-PEA) is encountered frequently during resuscitation from cardiac arrest. External chest compression (CC) remains the principal treatment for PCC-PEA, but unsynchronized CC may interfere with myocardial recovery. We investigated the efficacy of CC synchronized to PEA’s R waves as compared to standard CC in an animal model.

Methods:
Seven domestic pigs weighing 35-42 kg were anesthetized, endotracheally intubated and mechanically ventilated. Aortic and right atrial pressures were invasively monitored and coronary perfusion pressure (CPP) calculated. Carotid blood flow (CBF) was continuously monitored by a flow probe. VF was electrically induced and left untreated for 3 minutes before delivering the 1st shock. If the post countershock rhythm remained in VF a 2nd shock was delivered after an additional period of VF from 1 to 2 minutes. Countershocks were continued until PEA was obtained. If shock resulted in a perfusing rhythm, VF was re-induced. After PEA was induced, 15 seconds of chest compression or medium energy pacing were delivered to the animal per another concurrent protocol. The rate of standard CC was 100. Animals were then randomized to receive synchronized or standard CC for 15 seconds, with continuous alternation of therapy for the maximum 120 seconds before the 1
st
administration of epinephrine. A standard CPR rescue protocol continued for maximum of 20 minutes. If ROSC was achieved, the animal received at least 4 minutes for recovery before the study sequence was repeated.

Results:
A total of 32 matched synchronization pairs were obtained from 7 animals. The PEA pulse pressure was 2.47
+
2.34 mmHg and the PEA rate was 74
+
16.5. CC with R wave synchronization maintained CBF (53.6 vs. 46.7, p=0.11) and CPP (15.6 vs. 16.6 mmHg, p=0.34), and increased CBF stroke volume (=CBF/PEA rate) (0.76 vs. 0.47 ml, p=0.0004) as compared to standard CC.

Conclusions:
During near complete electromechanical dissociation (true PEA), synchronization of external chest compression with R waves maintained CBF and CPP despite lower compression rates as compared to standard chest compression without synchronization. This may represent a first observation that synchronization may be beneficial even in true PEA.
Abstract 16940: Serum Amine-based Metabolites and Their Association With Outcomes in Primary Prevention Implantable Cardioverter Defibrillator Patients
Authors: Zhang Yiyi , Blasco-Colmenares Elena , Harms Amy , London Barry , Halder Indrani , Singh Madhurmeet , Dudley Samuel , Gutmann Rebecca , Guallar Eliseo , Hankemeier Thomas , Tomaselli Gordon , Cheng Alan
Published: March 2022

Background:
Heart failure patients are at increased risk of ventricular arrhythmias and all-cause mortality. However, existing clinical and serum markers only modestly predict these adverse events.

Objective:
We sought to use metabolic profiling to identify novel biomarkers in two independent prospective cohorts of patients with implantable cardioverter defibrillators (ICDs) for primary prevention of sudden cardiac death (SCD).

Methods and Results:
Baseline serum was quantitatively profiled for 42 known biologically-relevant amine-based metabolites among 402 patients from the PROSE-ICD Study (derivation group) and 240 patients from the GRADE Study (validation group) for ventricular arrhythmia-induced ICD shocks and all-cause mortality. In multivariate Cox models adjusted for traditional cardiovascular risk factors, 3 amines (N-methyl-L-histidine, symmetric dimethylarginine [SDMA], and L-kynurenine) were associated with all-cause mortality in both derivation and validation cohorts (Figure 1). Additionally, L-histidine, SDMA, L-kynurenine, L-4-hydroxyproline, and L-glutamine were associated with ventricular arrhythmia-induced ICD shocks in one of the cohorts, suggesting their potential to be novel markers of ventricular arrhythmia (Figure 2).

Conclusions:
Utilizing metabolic profiling, we identified several novel amine markers that were associated with appropriate shock and mortality in primary prevention ICD patients. These findings shed insight into the potential biologic pathways leading to adverse events in these patients, which will in turn aid the development of newer therapeutics for reducing SCD and mortality.
Abstract 16941: Device Therapies Among Patients Receiving Primary Prevention Implantable Cardioverter Defibrillators (ICDs): Insights From the Cardiovascular Research Network Longitudinal Study of ICDs
Authors: Greenlee Robert T , Go Alan S , Magid David J , Peterson Pamela N , Cassidy-Bushrow Andrea E , Gaber Charles , Garcia-Montilla Romel , Glenn Karen A , Gupta Nigel , Gurwitz Jerry H , Hammill Stephen C , Hayes John J , Kadish Alan , McManus David D , Multerer Deborah , Powers J. David , Reifler Liza M , Reynolds Kristi , Schuger Claudio , Sharma Param P , Smith David H , Suits Mary , Sung Sue Hee , Varosy Paul D , Vidaillet Humberto J , Masoudi Frederick A
Published: March 2022

Introduction:
Primary prevention implantable cardioverter defibrillators (ICDs) reduce mortality in select patients with left ventricular systolic dysfunction (LVSD). The occurrence of device therapies after ICD implantation in contemporary clinical practice is not well described, especially in patient subgroups designated in the Centers for Medicare and Medicaid Services (CMS) 2005 Coverage with Evidence Development (CED).

Methods:
The Longitudinal Study of ICDs assessed rates and correlates of device therapies (overall and those requiring shock) up to 3 years post-implant among 2540 patients with LVSD receiving first-time primary prevention ICDs in 7 US health care systems from 2006-2009. Implant data from the National Cardiovascular Data Registry ICD Registry were linked to electronic longitudinal health care system data and a novel centrally adjudicated repository of device therapies abstracted from medical records. Proportional hazard models evaluated associations with device therapies by appropriateness, adjusted for demographic and clinical factors.

Results:
Subjects were 26% women, 35% <65 years old, and 59% non-Hispanic white. Over a mean 26 months, 738 (29.1%) received at least 1 therapy (median 2). Estimated 3-year risk of any device therapy was 36% (24% appropriate, 12% inappropriate); for therapy requiring shock, corresponding values were 24%, 14%, 9%. The rate of appropriate therapy was higher in men than women (adjusted hazard ratio 1.84, 95% confidence interval 1.43-2.35). The rate of inappropriate therapy was higher for subjects <65 than for those >=65 years (1.40, 1.04-1.88), and lower among 2009 implants compared to 2006 (0.66, 0.46-0.95). Regarding the 3 CMS CED patient subgroups, neither ejection fraction nor heart failure symptom severity was associated with device therapy; for LVSD etiology, the rate of inappropriate therapy was nominally but not significantly higher among subjects with non-ischemic cardiomyopathy of < 9 months duration (1.38, 0.88-2.18).

Conclusions:
In a representative cohort of primary prevention ICD patients in usual care, rates of device therapies were somewhat lower than in landmark trials, differed by some patient characteristics, but did not differ meaningfully for CMS CED subgroups.
Abstract 16951: Long term Incidence and 30-mortality of Myocardial Infarction in Congenital Heart Disease Survivors Compared With the General Population: A Nationwide Cohort Study
Authors: Olsen Morten , Marino Bradley S , Kaltman Jonathan R , Videbæk Jørgen , Mahle William T , Pearson Gail D , Madsen Nicolas L
Published: March 2022

The population of adults with congenital heart disease (CHD) is growing and aging. Some adult CHD survivors have an increased risk of myocardial infarction (MI) due to the specific CHD, and the presence of CHD may impair prognosis following MI depending on CHD severity. Few data exist on the incidence and prognosis of MI in the adult CHD population. We aimed to compare the incidence and mortality of MI in adult survivors of CHD with the general population with attention to the impact of CHD severity.

Methods:
In this cohort study we used two nationwide population based medical databases to identify individuals diagnosed with CHD in Denmark between 1963 and 1974 (before 15 years of age) and from 1977 to 2012 (at any age). Patients were followed from 1977 to 2012 for first time MI using data from the Danish National Registry of Patients (DNRP). The DNRP is a nationwide hospital discharge registry covering all Danish hospitals. For each CHD subject we identified 10 controls from the general population, matched by sex and birth year. A unique personal identifier assigned at birth and used in all Danish public registries enabled virtually complete follow-up for migration, death or MI. We computed cumulative incidences and hazard ratios (HR) of MI. Subsequently, we computed 30 day-mortality following MI for CHD subjects and controls, as well as the corresponding HR adjusted for age and sex.

Results:
We identified 14,038 CHD subjects. By 70 years of age, the cumulative incidence of MI was 10% among CHD subjects. The HR of MI among CHD subjects compared with controls was 3.5 (95% CI: 2.9-4.3) below 50 years of age, and 1.9 (95% CI: 1.7-2.2) > 50 years. The 30-day mortality was 16% for the 322 CHD subjects experiencing an MI during follow-up; the corresponding HR comparing 30-day post-MI mortality between CHD subjects and controls was 1.9 (95% CI: 1.4-2.6). Patients with severe CHD had a 30-day post-MI mortality HR of 4.1 (95% CI: 2.2-7.5), somewhat higher than among those with mild and moderate CHD (HR 1.5; 95% CI: 1.1-2.3).

Conclusion:
Both incidence of MI and post MI 30-day mortality were increased in individuals with CHD compared with the general population. This should be an important consideration for optimizing preventive and acute cardiovascular care for the high-risk adult CHD population.
Abstract 16962: Two-year Outcomes Following Mitral Valve Repair or Replacement for Severe Ischemic Mitral Regurgitation
Authors: Goldstein Daniel , Ailawadi Gorav , Moskowitz Alan , Perrault Louis P , Parides Michael , Gelijns Annetine , Hung Judy , Dagenais Francois , Gillinov A. Marc , Thourani Vinod , Argenziano Michael , Gammie James , Mack Michael , Demers Philippe , Atluri Pavan , Rose Eric A , O'Sullivan Karen , Williams Deborah , Bagiella Emilia , Michler Robert , Weisel Richard , Miller Marissa , Taddei-Peters Wendy C , Smith Peter K , Moquete Ellen , O'Gara Patrick , Overbey Jessica R , Kron Irving , Acker Michael A ,   CTSN Investigators
Published: March 2022

Background:
The Cardiothoracic Surgical Trials Network recently reported no difference in left ventricular end systolic volume index (LVESVI) at one year post-surgery between patients randomized to mitral repair (n=126) or replacement (n=125) for severe ischemic mitral regurgitation (MR). However, repair patients experienced significantly more recurrent MR than replacement patients. We report the 2-year follow-up of trial participants.

Methods:
We followed 251 patients randomized to repair or replacement for 2 years. LVESVI was assessed using a Wilcoxon rank sum test in which deaths were assigned the lowest rank.

Results:
Among surviving patients, mean 2-year LVESVI was 52.6 ±28mL/m2 in the repair and 60.7±39mL/m2 in the replacement arm (mean decrease from baseline 9.0mL/m2 and 6.5mL/m2, respectively). Two-year mortality was 19.1% for repair and 23.2% for replacement (HR 0.79, 95% CI 0.46-1.35; p=0.39). There was no significant between-group difference in LVESVI after adjustment for death (Z=-1.32, p=0.19). The rate of moderate or severe MR recurrence at 24 months was higher in the repair than replacement arm (36.3% vs.1.3%; p< .0001). In the repair arm, the 2-year LVESVI was 62.5 ± 25 in patients with recurrent MR vs. 47.0 ± 29 in those without MR (p=0.0042). Four repair patients and 1 replacement patient underwent MV reoperation. There was no significant difference in the composite of MACCE, functional status or quality of life at 2 years. Rates (pt-yr) of serious adverse events (1.5 vs.1.3, p=0.18) and overall readmissions (0.8 vs. 0.7, p=0.14) were not different between arms, but repair patients experienced a higher rate of serious heart failure (0.24 vs. 0.15, p=0.049) and more CV readmissions (0.48 vs. 0.33, p=0.02) than replacement patients.

Conclusions:
We observed no difference in LV reverse remodeling or survival between repair and replacement at two years. Replacement provided more durable correction of MR, as well as fewer HF events and CV readmissions.
Abstract 16987: Increased Ischemic Heart Disease And Stroke-related Hospitalizations From Cold Temperature in Ontario, Canada: Population-based Study
Authors: Chen Hong , Li Qiongsi , Wang Jun , Lavigne Eric , Burnett Richard , Goldberg Mark , Villeneuve Paul , Cakmak Sabit , Copes Ray
Published: March 2022

Introduction:
Experimental studies suggest that exposure to extreme ambient temperature, especially cold, can induce inflammatory reactions and a state of hypercoagulability which may in turn promote thrombosis and clot formation. However, epidemiological evidence relating cold temperature and cardiovascular-related morbidity is sparse. Even less is known about who is most susceptible to the effect of temperature.

Methods:
We obtained daily data on temperature and hospital admissions for any cardiovascular cause from all 14 health regions in Ontario, Canada in 1996-2013. A distributed lag non-linear model with 21 days of lag was applied to estimate the cumulative effect of temperature on selected cardiovascular conditions, controlling for air pollutants, influenza activity, relative humidity, long-term trends and day of the week. We estimated risks for cold and heat, defined as temperatures below and above the optimal temperature, which corresponded to the point with minimum cardiovascular morbidity, for each health region, and then pooled across Ontario. To identify potentially vulnerable subpopulations, we conducted stratified analyses by selected comorbidities and demographic characteristics.

Results:
Between 1996 and 2013, we identified 1.4 million hospitalizations from ischemic heart disease, 443,447 from myocardial infarction, 355,837 from stroke, and 237,979 from ischemic stroke across Ontario. The relationship of temperature and the selected cardiovascular conditions exhibited a U shape, with the minimum risk at ~60th percentile (12oC). For cold (at the 1st percentile temperature), the adjusted rate ratio was 1.12 (95% confidence interval (CI)=1.05-1.19) for ischemic heart disease, 1.28 (95%CI=1.13-1.44) for myocardial infarction, 1.15 (95%CI=1.02-1.30) for stroke, and 1.19 (95%CI=1.03-1.36) for ischemic stroke. Heat also exhibited elevated risks, albeit not significant, for these conditions. We found that the risk of ischemic heart disease from cold was highest among those with a history of conduction disorders, whereas the risk of stroke from cold was highest in those with arrhythmias.

Conclusions:
Acute exposure to cold temperature contributed to excess hospitalizations from cardiovascular disease in Ontario.
Abstract 16992: Changes in Physical Activity and the Risk of Incident Heart Failure: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Florido Roberta , Kwak Lucia , Lazo Mariana , Nambi Vijay , Ahmed Haitham , Hegde Sheila M , Gerstenblith Gary , Blumenthal Roger S , Ballantyne Christie M , Selvin Elizabeth , Folsom Aaron , Coresh Josef , Ndumele Chiadi E
Published: March 2022

Background:
Higher physical activity is associated with a lower risk of heart failure (HF). The effects of changes in physical activity levels over time on HF risk are largely uncharacterized.

Hypothesis:
We hypothesized that persistently recommended and increasing levels of physical activity over a 6-year period are associated with reduced HF risk.

Methods:
We evaluated 11,185 ARIC participants (mean age 60; 57% female, 23% black) free of CVD at Visit 3 (1993-95) with available physical activity data at Visit 1 (1987-89) and Visit 3. Exercise physical activity was assessed using a modified Baecke questionnaire and categorized according to AHA recommendations: recommended (≥150 min/wk of moderate + vigorous activity or ≥75 min/wk of vigorous activity); intermediate (1-149 min/wk of moderate + vigorous activity or 1-74 min/wk of vigorous activity); or poor (no moderate or vigorous activity). We created cross-categories of physical activity at Visit 1 and Visit 3. The primary outcome was incident HF occurring after Visit 3 through 12/31/12. We constructed Cox regression models to estimate the hazard ratios and 95% CIs for incident HF associated with each cross-category of physical activity at Visit 1 and Visit 3, adjusting for confounders.

Results:
Over a median of 18 years, there were 1,625 HF events. Compared to those with poor activity at both visits (reference), those with persistently recommended activity had the lowest HF risk (Table; HR 0.67 95% CI: 0.58-0.78). Additionally, at each level of baseline physical activity, increasing physical activity over time was associated with decreased HF risk: an increase from poor to recommended activity was linked to a 22% lower risk of HF.

Conclusion:
While maintaining recommended activity levels is associated with the lowest HF risk, initiating and increasing physical activity over time is also linked to risk reduction. Augmenting physical activity in middle age may be an important component of strategies to prevent HF.
Abstract 17018: Prognostic Utility of Plasma galectin-3 Level as a Predictor of Clinical Outcomes in Patients Undergoing Percutaneous Coronary Intervention With Drug-eluting Stents
Authors: Seo Suk Min , Choi Ik Jun , Park Hun-Jun , Kim Pum-Joon , Koh Yoon-Seok , Chang Kiyuk , Kim Jin Jin
Published: March 2022

Background:
Galectin-3 is associated with inflammation, cell proliferation, and fibrogenesis. It is well known as a novel biomarker on predictor of cardiovascular events in patients with heart failure. However, the prognostic implications of serum galetin-3 level are unknown in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES).

Methods
A total 2,568 patients undergoing PCI with DES were consecutively enrolled from January 2004 to December 2009. We can analyzed the serum galectin-3 level of 939 patients, and compared major adverse cardiac events (MACE) including all-cause death, nonfatal myocardial infarction, nonfatal stroke and any revascularization according to galectin-3 level.

Results:
Median follow up duration was 997 days (interquartile range 766 to 1,264 days). All patients were divided into two groups according to median galectin-3 level (9.52 ng/ml, interquartile range 7.31 to 12.81); high galectin-3 group (n=470) and low galectin-3 group (n=469). High galectin-3 group had significantly higher incidence of all-cause mortality, cardiac death, and composite of MACE. High galectin-3 was a significant independent predictor of MACE (adjusted hazard ratio 1.47, 95% confidence interval 1.13 to 1.92, p=0.005).

Conclusion:
The higher galectin-3 is associated higher cardiovascular events in patients undergoing PCI with DES. The serum galectin-3 level may serve as a predictor of cardiovascular events after PCI with DES.
Abstract 17020: Visit-to-visit Variability of Systolic Blood Pressure Predicts All-cause Mortality in Patients Received Percutaneous Coronary Intervention With Drug Eluting Stents
Authors: Seo Suk Min , Choi Ik Jun , Jeon Doo Soo , Kin Jin Jin
Published: March 2022

Background:
Blood pressure (BP) and its variability are associated with atherosclerotic disease and cardiovascular events. The prognostic implications of outpatient clinic visit-to-visit blood pressure variability (BPV) are unknown in patients received percutaneous coronary intervention (PCI) with drug-eluting stents (DES).

Methods:
Patients who PCI from January 2009 to December 2013 were consecutively corrected. We analyzed the 1,234 patients, who measured clinic BP more than three times during follow up. The BPV is determined by standard deviation (SD) of systolic and diastolic BP, and coefficient of variation (SD*100/mean BP).

Results:
Median follow up duration was 905 days (interquartile range 529 to 1,310 days). The clinic measured BP were recorded mean 9.9 ± 4.7 times. All patients were divided into two groups according to the coefficient of variation of systolic BP (CVSBP); high CVSBP group (> 8.77, n=617) and low CVSBP group (<8.77, n=617). High CVSBP group had significantly higher all-cause mortality (7.9 versus 3.1%, p<0.001). In multivariate logistic regression analysis for prediction of all-cause mortality after PCI with DES, hazard ratio of high CVSBP group was 2.090 (95% of confidence interval 1.012-4.318, p = 0.046).

Conclusion:
The higher visit-to-visit BPV is associated higher mortality in patients performed PCI with DES. The clinic measured visit-to-visit BPV may serve as a predictor of mortality after PCI with DES.
Abstract 17034: Deletion of NAD(P)H Oxidase 2 Attenuates Angiotensin II-induced Skeletal Muscle Atrophy
Authors: Kadoguchi Tomoyasu , Kinugawa Shintaro , Takada Shingo , Fukushima Arata , Furihata Takaaki , Mizushima Wataru , Matsumoto Junichi , Tsuda Masaya , Yokota Takashi , Matsushima Shouji , Okita Koichi , Tsutsui Hiroyuki
Published: March 2022

Introduction:
Skeletal muscle atrophy is observed in aging and a variety of diseases including chronic obstructive pulmonary disease, chronic renal failure, and heart failure. It has been considered that it is associated with chronic inflammation in the skeletal muscle. We have previously reported that angiotensin II (Ang II) could directly induce skeletal muscle abnormalities including atrophy in mice.

Hypothesis:
Here, we hypothesized that the activation of NAD(P)H oxidase by Ang II induced the skeletal muscle atrophy.

Methods:
Either saline (vehicle) or Ang II (1000 ng/kg/min) was infused into male wild-type (WT) and Nox2 knock out (KO) mice via subcutaneously implanted osmotic minipumps for 4 weeks. Experiments were performed in following 4 groups; WT+vehicle (n=8), KO+vehicle (n=6), WT+Ang II (n=8), and KO+Ang II (n=6). Lower skeletal muscle limbs were removed and used for the analysis. Exercise capacity was measured by using treadmill test.

Results:
Increased activation of NAD(P)H oxidase and production of superoxide in the skeletal muscle by Ang II were completely inhibited in KO mice. Body and skeletal muscle weight, and myocyte cross sectional area were significantly decreased in WT+Ang II compared to WT+vehicle (24±1 vs. 28±1 g, 356±3 vs. 390±4 mg, and 2351±84 vs. 3221±118 μm2, respectively). These changes were significantly attenuated in KO+Ang II (27±1 g, 392±9 mg, 3012±150 μm2, respectively) Phospho-Akt and phospho-p70S6K, key molecule of protein synthesis, were decreased in WT+Ang II compared to WT+vehicle, which was attenuated in KO+Ang II. On the other hand, protein expressions of Muscle RING Finger-1 and MAFbx/Atrogin-1, key molecule of protein degradation, were significantly increased in WT+Ang II compare to WT+vehicle, which was not affected in KO+Ang II. Mitochondrial electron transfer complex and citrate synthase activities were also impaired in WT+Ang II and were not improved in KO+Ang II. In agreements with these results, exercise, Ang II-induced reduction in exercise capacity was not improved in KO mice.

Conclusions:
The deletion of Nox2 attenuated the skeletal muscle atrophy and decreased protein synthase induced by Ang II, suggesting that Nox2 plays an essential role in the development of skeletal muscle atrophy.
Abstract 17035: Dose Response Relationship Between Sedentary Time and Cardiovascular Disease Risk: A Meta-analysis
Authors: Salahuddin Usman I , Pandey Ambarish , Ayers Colby R , Kulinski Jacquelyn , Garg Sushil , Kumbhani Dharam J , de Lemos James A , Berry Jarett D
Published: March 2022

Background:
Prior studies suggest that higher sedentary time is associated with greater risk for cardiovascular disease (CVD). However, the quantitative, dose-response relationship between sedentary time and CVD risk has not been reported.

Methods:
PUBMED and EMBASE were searched for prospective cohort studies that evaluated the associations between sedentary time and CVD risk(coronary heart disease, stroke, CVD mortality). The categorical dose response association was evaluated by comparing the pooled hazard ratio (HR) for CVD associated with different levels of sedentary time (vs. lowest sedentary time) across studies. The continuous dose response was assessed among studies that allowed quantitative estimation of sedentary time using random effects generalized least squares spline models.

Results:
Nine prospective cohort studies with 561,305 participants (54.3% women) and 24,423 incident CVD events over a median follow up of 11 years were included in the meta-analysis. In categorical analysis, compared with the lowest sedentary time category median: (2 hr/day), participants in the highest sedentary time category median: (11.5 hr/day) had an increased risk for CVD [Hazard Ratio (HR) 95% CI: 1.15 (1.11 - 1.20)]. However, there was no apparent risk associated with intermediate levels of sedentary time [Second Highest Category (median 8.1 hr/day): HR (95%CI)= 0.99 (0.96 - 1.03);Third Highest Category (median 5.1 hr/day): HR (95%CI)= 1.06 (0.98 - 1.05)]. In continuous analyses, there was a non-linear relationship between sedentary time and CVD (p-value for non-linearity: 0.0001), with an increased risk for CVD observed for more than 10 hours/day of sedentary time [Pooled HR: 1.07 (1.00 to 1.14), Figure].

Conclusion:
CVD risk associated with sedentary time is non-linear with an increased risk only at very high levels (> 10 hr/day). These findings could have implications for future guideline recommendations regarding the risks related to sedentary behavior.
Abstract 17047: Pathophysiologic Progression From the Second to Third Trimester in Fetuses With Ebstein's Anomaly or Tricuspid Valve Dysplasia: Are Early Echocardiographic Features Reliable Indicators of Late Gestation Status?
Authors: Selamet Tierney Elif Seda , McElhinney Doff B , Freud Lindsay R , Tworetzky Wayne , Cueno Bettina , Escobar-Diaz Maria C , Ikemba Catherine , Kalish Brian T , Komarlu Rukmini , Levasseur Stephanie , Puchalski Michael D , Satou Gary M , Silverman Norman H , Moon-Grady Anita J
Published: March 2022

Background:
Ebstein’s anomaly and tricuspid valve dysplasia (EA/TVD) are associated with high perinatal mortality. Poor hemodynamic status in both early and late gestation is associated with worse outcome. However, it is not known whether EA/TVD fetuses with more favorable physiology earlier in gestation progress to more severe disease in 3
rd
trimester. The goal of this study was to evaluate whether initial echocardiographic indices in fetuses with EA/TVD presenting at gestational age (GA) <24 wks are reliable indicators of physiologic status later in pregnancy.

Methods:
This multi-center, retrospective study included fetuses diagnosed with EA/TVD from 2005-11 at 23 centers. Patients with initial diagnosis at <24 wks gestation and with ≥2 fetal echocardiograms ≥4 wks apart were included. A core laboratory analyzed the echocardiograms. Markers of poor outcome were defined as absence of antegrade flow across the pulmonary valve, pulmonary valve regurgitation (PR), cardiothoracic ratio >0.48, left ventricular (LV) dysfunction or TV annulus Z score >5.6.

Results:
The study included 51 fetuses. Median GA at diagnosis was 21 wks [18-24], and the median duration from 2
nd
to 3
rd
trimester echocardiograms was 12 wks [4-18]. There were 21 fetuses (41%) with >2 markers of poor outcome at <24 wks, which increased to 32 (63%) in later gestation (p=0.001). Nine of 27 fetuses (33%) with antegrade pulmonary blood flow on first echocardiogram developed anatomic or functional pulmonary atresia during follow-up, and 7 of 39 fetuses (18%) without PR initially developed it later. LV dysfunction was present in 2 patients at <24 wks but present in 14 (37%) later (p<0.01). The only variable associated with worsening physiology, from <2 markers of poor outcome in 2
nd
trimester to ≥2 markers in 3
rd
trimester, was larger TV annulus Z-score (4.1±1.0 vs. 2.4±1.9, p=0.008).

Conclusion:
These results confirm a wide spectrum of disease presentation and progression in fetuses with EA/TVD. Thus, it is imperative to assess these fetuses serially. In this cohort, there were no early markers of progression other than larger TV annulus Z-score. Great care must be taken in counseling prior to 24 wks, as the absence of factors associated with poor outcome early in pregnancy may be falsely reassuring.
Abstract 17078: A Potent Vasoconstrictor Kisspeptin-10 Induces Atherosclerotic Plaque Progression and Instability
Authors: Shirai Remina , Sato Kengo , Matsuyama Taka-aki , Koba Shinji , Hirano Tsutomu , Watanabe Takuya
Published: March 2022

Background:
Recently, there is a great deal of research interest regarding the role and effects of kisspeptin-10 (KP-10), a potent vasoconstrictor and inhibitor of angiogenesis expressed in vascular endothelial cells (ECs), in cardiovascular disease. However, it still remains unknown whether KP-10 could affect atherogenesis.

Objective and Methods:
We aimed to clarify the effects of KP-10 on atherosclerosis. We evaluated the effects of KP-10 on human umbilical vein endothelial cells (HUVECs), human monocyte-derived macrophages, human aortic smooth muscle cells (HASMCs)
in vitro
, and aortic lesions in ApoE
-/-
mice
in vivo
.

Results:
GPR54, a KP-10 receptor, was expressed at higher levels in human monocytes, macrophages, HASMCs, and HUVECs. KP-10 significantly suppressed the proliferation of EAhy.926 ECs. KP-10 significantly increased the adhesion of THP1 monocytes to HUVECs associated with increased endothelial expressions of IL-6, MCP-1, TNF-α, ICAM-1, VCAM-1, and E-selectin. KP-10 significantly enhanced oxidized low-density lipoprotein-induced foam cell formation associated with increased expressions of CD36 and acyl-CoA:cholesterol acyltransferase-1 in human monocyte-derived macrophages. KP-10 significantly suppressed the migration and proliferation of HASMCs with inducing apoptosis
via
AKT, p38, and bax upregulation, but significantly enhanced the activities of MMP-2 and MMP-9 in HASMCs. Four-week-infusion of KP-10 into ApoE
-/-
mice significantly accelerated the development of aortic atherosclerotic lesions with increased monocyte/macrophage infiltration.

Conclusions:
Our results indicate that KP-10 accelerates atherogenesis by enhancing EC inflammatory responses and macrophage foam cell formation, In addition, KP-10 suppresses EC proliferation, VSMC migration and proliferation, but enhances MMP-2 and MMP-9 activities in VSMCs, which may contribute to plaque instability, leading to plaque rupture. Thus, KP-10 may serve as a novel therapeutic target for acute coronary syndrome.