bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15833: Circulating MicroRNAs Provide Insight Into Potential Molecular Links Between Hypertensive Disorders of Pregnancy and Cardiovascular Disease
Authors: Dayan Natalie , Schlosser Kenny , Stewart Duncan J , Okano Marisa , Grand’Maison Sophie , Pilote Louise
Published: April 2024

Introduction:
Hypertensive disorders of pregnancy, such as preeclampsia and gestational hypertension, are strong sex-specific risk factors for cardiovascular disease (CVD). The molecular determinants underlying this risk have not been clearly defined, but potentially involve sustained vascular damage and/or dysfunction. This may be reflected by alterations in the levels of specific circulating microRNA (miRNA).

Study Objective:
To identify miRNAs that circulate at different levels in women diagnosed with acute coronary syndrome (ACS), with and without a prior history of preeclampsia or gestational hypertension.

Methods:
The present study is a derivation cohort of women with a diagnosis of premature (age < 55 yrs) ACS, divided into three groups based on a prior history of gestational hypertension, preeclampsia, or normotensive pregnancy (n=11-13/group). The three groups were closely matched on potential confounding variables including age, chronic hypertension, diabetes, smoking status and type of ACS. Total RNA was extracted from citrate plasma of each participant, and the relative levels of 372 miRNAs were measured by high-density PCR array. Measurements and analyses were performed blinded to exposure status.

Results:
The circulating levels of 16 miRNAs were significantly (p<0.05) altered in the preeclampsia versus normotensive pregnancy groups (from -2.8 fold down to +2.0 fold change), and 32 miRNAs were significantly altered between the gestational hypertension and normotensive pregnancy groups (from -2.8 to +2.7 fold change). These miRNAs showed little to no overlap with previously published reports of circulating miRNAs that were altered acutely at the time of preeclamptic pregnancy or ACS event. Several priority candidates have previously been functionally annotated, including miRNAs linked to angiogenesis (miR-126-3p), inflammation (miR-146a-5p), and cholesterol metabolism (miR-122-5p).

Conclusions:
Circulating levels of multiple miRNAs were altered between female ACS patients with and without prior hypertensive disorders of pregnancy. These miRNAs provide novel insight into the potential molecular pathways that may contribute to vascular dysfunction and risk of CVD.
Abstract 15849: Exercise Training in Patients With Implantable Cardioverter Defibrillator: A Meta-analysis of Efficacy and Safety Outcomes
Authors: Parashar Akhil , Salahuddin Usman , Pandey Ambarish , Piccini Jonathan , Krishnaswamy Amar , Bhargava Mandeep , Kapadia Samir , Berry Jarett
Published: April 2024

Introduction:
Implantable cardioverter defibrillators have been shown to improve survival, however, many patients with ICDs experience fear of shocks and avoid physical activity. Little data exist on efficacy and safety of exercise training in heart failure patients with ICDs. We performed a meta-analysis of currently available randomized clinical trials to assess the efficacy and safety of exercise training in this patient population.

Methods:
Randomized clinical trials that evaluated the efficacy of exercise training in patients with ICDs were included in the pooled meta-analysis. Primary efficacy outcome was change in cardiorespiratory fitness measured as peak oxygen uptake during a maximal treadmill test (CRF, mL/kg/ per minute). Primary safety outcome was difference in proportion of patients experiencing ICD shocks between exercise and control groups.

Results:
We included study level data from 1,532 patients (812 in exercise group and 720 in control group) derived from 5 studies which met the inclusion criteria. In the pooled analysis (figure panel 1), patients with ICD undergoing exercise training had significantly improved CRF [Weighted mean difference (95% CI): 1.86 ml/kg/min (0.71 to 3.01)]. There was also a significant reduction in the likelihood of ICD shocks (figure panel 2) in the exercise group compared to control group [Pooled odds ratio (95% CI): 0.71 (0.55 to 0.92)].

Conclusion:
Exercise training is associated with significant improvements in CRF levels and reduction in the likelihood of ICD shocks among patients with ICDs.
Abstract 15854: Prognostic Value of Coronary CT Angiography and Coronary Artery Calcium Score Performed Before Revascularization
Authors: Takamura Kazuhisa , Fujimoto Shinichiro , Kondo Takeshi , Kumamaru Kanako , Kawaguchi Yuko , Suda Shoko , matsumori Rie , Kato Etsuro , Hiki Makoto , Takase Shinichi , Rybicki Frank J , Daida Hiroyuki
Published: April 2024

Introduction:
Cardiac events after revascularization are equally attributable to recurrence at site of culprit lesions and development of non-culprit lesions. Because coronary CT angiography (CCTA) performed before revascularization can evaluate all plaque, including non-culprit lesions, and in theory can serve as a predictor of cardiac events after treatment. We evaluated the hypothesis that CCTA and coronary artery calcium score (CACS) performed before revascularization predicts cardiac events after treatment.

Methods:
Among 2238 consecutive patients without known coronary artery disease who underwent coronary CCTA and CACS, 359 patients underwent revascularization within 30 days after CT; in 337 of 359 (93.9%) follow-up clinical information was available. In addition to known cardiac risk factors, CT findings were evaluated as predictors of cardiac events after revascularization: CACS and the presence of CT-verified high risk plaque (CT-HRP). Improvement of predictive accuracy by including CT findings was evaluated from discrimination (Harrell’s C-statistics) and reclassification (net reclassification indices (NRI)) standpoints.

Results:
During the follow-up period (median: 673, interquartile range: 47-1529 days), a total of 98 cardiac events occurred. Cox proportional hazard model revealed that age, diabetes, triglyceride, CACS and non-culprit CT-HRP were significant predictors of overall cardiac events. Although not statistically significant, discriminatory power was greater for the model with CACS (C-stat: 63.2%) and the model with both CACS and CT-HRP (65.8%) compared to the model including neither CACS nor CT-HRP (60.7%). Reclassification improved by including CACS into the model when compared to the model without it (NRI=12.7%; category-free NRI=40.7%) and CT-HRP added to CACS further improved the classification (NRI=6.9%; category-free NRI=14.3%).

Conclusions:
High CACS and the presence of non-culprit CT-HRP performed before revascularization are significant predictors of cardiac events after revascularization.
Abstract 11181: Late Outcomes Following Bridge-use of Stent-Graft for Blunt Traumatic Aortic Injury in the Younger Patients
Authors: Tsukube Takuro , Haraguchi Tomonori , Okada Yasushi , Nakai Chikashi , Nakayama Shinichi , Mori Takeki
Published: April 2024

Introduction:
Thoracic endovascular aortic repair (TEVAR) for the younger patients remains controversial because of anatomical characteristics of the aortic arch in youth. We have performed TEVAR as an initial treatment for traumatic aortic injury (TAI) complicated with multiple organ injuries. This study evaluated the early and late outcomes of the younger patients with this approach.

Methods:
Between 9/03 and 5/16, 56 patients with TAI were treated surgically, including 37 patients underwent TEVAR, 9 underwent open aortic repair (OAR), and 10 required emergent room thoracotomy (ERT), as an initial treatment. The mean age of the patients was 53.6 (SD 19.7) y/o, including 17 patients of younger patients (age under 40 y/o). The mean injury severity score (ISS) was 51.8 (SD 19.8), site of aortic injury was isthmus in 51 patients, and mode of injuries included motor vehicle crashes in 43 and falls in 13. Open aortic repair was selected if multiple organ injuries were not involved or if TEVAR was not suitable due to difficult anatomy of arch branch vessels, and ERT was performed as salvage surgery.

Results:
Mortality of TEVAR, OAR, ERT group was 13%, 25%, 100%, respectively. In TEVAR group, removal of the stent-graft and secondary OAR were undertaken in 22% (8/37) due to graft malfunctions. Mean time interval from TEVAR to secondary OAR was 39.5 days, and none of the patient died postoperatively. Incidence of secondary OAR was significantly higher in the younger patients (44%, 7/16) when as compared with patients over 40 y/o (2.5%, 1/40). Overall, in the younger patients, OAR was eventually undertaken in 75% (12/16), including 5 as an initial treatment and 7 as the secondary treatment. The mean follow-up periods were 61.5 (SD 25.1) months. Of 45 patients in TEVAR and OAR groups, cumulative survival rate was 78.8% in 5 years, and freedom from aortic event was achieved in 70.8% in 5 years.

Conclusions:
TEVAR is a safe and effective procedure as an initial treatment of TAI with multiple organ injuries. In the younger patients, TEVAR is recommended as a bridge-use to the secondary open aortic repair.
Abstract 11195: Differences in ST-T Changes Between Takotsubo Cardiomyopathy and Reperfused Non-Q-Wave Anterior Acute Myocardial Infarction
Authors: Kosuge Masami , Ebina Toshiaki , Hibi Kiyoshi , Iwahashi Noriaki , Maejima Nobuhiko , Matsuzawa Yasushi , Kimura Kazuo
Published: April 2024

Introduction:
In both takotsubo cardiomyopathy (TC) and reperfused non-Q-wave anterior acute myocardial infarction (AMI), giant negative T waves (Neg T) commonly appear after the resolution of ST-segment elevation (ST elevation) in precordial leads, reflecting viable but sympathetically denervated myocardium.

Hypothesis:
ST-T changes may differ between between TC and reperfused non-Q-wave anterior AMI, reflecting the differences in underlying electrophysiologic mechanisms between these 2 diseases.

Methods:
We studied 38 patients with TC and 253 with a first non-Q-wave anterior AMI who were admitted within 6 hours after symptom onset. All patients with anterior AMI underwent emergency coronary angiography, and the occlusion of the left anterior descending coronary artery was documanted and successful reperfusion (TIMI grade 3) was obtained. ECGs on admission and those with the greatest amplitude of subsequent Neg T (mean 2 days later) were studied.

Results:
As compared with patients with anterior AMI, those with TC were older (70 ± 11 vs 62 ± 11 years, p < 0.01), more likely to be women (84% vs 20%, p<0.01) and had a lower peak creatine kinase (461 ± 493 vs 1506 ± 934 mU/ml, p<0.01) despite lower left ventricular ejection fraction on admission (40 ± 9 vs 51 ± 10%, p < 0.01), respectively. TC was associated with a smaller maximal ST elevation on admission (4.6 ± 4.7 vs 5.9 ± 3.1 mm, p<0.01), a greater maximal amplitude of Neg T (10.0 ± 4.1 vs 8.0 ± 4.8 mm, p < 0.01), a greater number of leads with Neg T (9 ± 1 vs 6 ± 2, p < 0.01) and a longer maximal QTc interval (643 ± 99 vs 586 ± 79 ms, p < 0.01) in subacute phase, respectively. The prevalences of initial ST elevation and subsequent Neg T differed between TC and anterior AMI (Figure).

Conclusions:
ST-T changes in the acute and subacute phases clearly differed between TC and reperfused non-Q-wave anterior AMI. In TC, deeper NegT were more broadly distributed, suggesting that TC might be associated with more extensive viable but denervated myocardium.
Abstract 11239: Fat and Lean Mass Distributions and Cardiovascular and All-cause Mortality in Older Adults: the Cardiovascular Health Study
Authors: Spahillari Aferdita , Mukamal Kenneth , Kizer Jorge R , Gottdiener John S , Djoussé Luc , Lyles Mary F , Bartz Traci M , Murthy Venkatesh L , Shah Ravi V
Published: April 2024

Introduction:
Understanding contributions of fat and lean tissue to cardiovascular and all-cause cardiovascular mortality may help clarify areas of prevention in older adults

Hypothesis:
We hypothesized that greater fat and lower lean mass would be associated with a higher risk of mortality.

Methods:
A total of 1335 participants of the Cardiovascular Health Study who underwent dual-energy x-ray absorptiometry (DEXA) scans were included. We used principal components analysis (PCA) to define two independent sources of variation in DEXA-derived body composition, corresponding to principal components composed of fat (“fat PC”) and lean (“lean PC”) tissue. We used Cox proportional hazards regression using these PCs to investigate the relationship between body composition and mortality.

Results:
Mean age was 76.2±4.8 years (56% women) with mean body mass index 27.1±4.4 kg/m
2
. In spline models, fat PC had a non-linear association with mortality in unadjusted but not adjusted models; lean PC was associated with mortality risk linearly. The lowest quartile of the fat PC (least adiposity) was associated with a greater hazard of all-cause mortality (HR = 1.24, 95% CI 1.04-1.48, P=0.02) relative to fat PCs between the 25
th
-75
th
percentile, but the highest quartile did not have a significantly greater hazard (P=0.70). A greater lean PC was associated with lower all-cause (HR=0.91, 95% CI 0.84-0.98, P=0.01) and cardiovascular mortality (HR=0.84, 95% CI 0.74-0.95, P=0.005).

Conclusions:
Greater lean tissue mass is associated with improved cardiovascular and overall mortality in the elderly. The lowest levels of fat tissue mass are linked with adverse prognosis, but the highest levels show no significant mortality protection. Prevention efforts in the elderly frail may be best targeted toward improvements in lean muscle mass.
Abstract 11287: The Relationship of All-Cause Mortality to Average On-Treatment Systolic Blood Pressure is Significantly Related to Baseline Systolic Blood Pressure: Implications for Interpretation of the SPRINT Study
Authors: Okin Peter M , Kjeldsen Sverre E , Devereux Richard B
Published: April 2024

Background:
The SPRINT study demonstrated that targeting systolic blood pressure (SBP) <120 mm Hg was associated with lower cardiovascular event and mortality rates. However, in the LIFE study, a lower achieved SBP (<130 mm Hg) was associated with increased mortality. Mean baseline SBP in SPRINT was 140 and a third of the population had a baseline SBP ≤132, raising the question of whether the lower baseline SBP in SPRINT could in part account for these differences.

Methods:
All-cause mortality in relation to tertiles of on-treatment average SBP achieved was examined in patients with baseline SBP ≤ or > 25
th
percentile value of 164 mm Hg during 4.8±0.9 years follow-up in 7998 non-diabetic hypertensive patients with ECG left ventricular hypertrophy randomly assigned to losartan- or atenolol-based treatment. Average on-treatment SBP <142 (lowest tertile) and average SBP 142 to <152 (middle tertile) were compared with average SBP ≥152 (highest tertile and reference group).

Results:
In the overall population, there was a highly significant interaction between baseline SBP ≤164 and average on-treatment SBP <142 in Cox analysis (χ
2
=15.48, p<0.001). Among patients with baseline SBP >164, in multivariate Cox analyses adjusting for other potential predictors of mortality and a propensity score for having baseline SBP ≤164, compared with average on-treatment SBP ≥152 an average on-treatment SBP <142 was associated with 32% increased risk of mortality (HR 1.32, 95% CI 1.01-1.65), whereas average SBP of 142 to <152 was associated with 24% lower mortality risk (HR 0.76, 95% CI 0.59-0.98). In contrast, in parallel Cox analyses among patients with baseline SBP ≤164, both an average on-treatment SBP <142 (HR 0.60, 95% CI 0.36-0.99) and average SBP of 142 to <152 (HR 0.51, 95% CI 0.30-0.89) were associated with statistically significant lower risks of mortality compared with average SBP ≥152.

Conclusions:
All-cause mortality risk associated with achievement of an average SBP <142 is strongly related to baseline SBP level in LIFE. These findings suggest that the lower mortality associated with a lower targeted SBP in SPRINT may not be applicable to patients with considerably higher baseline SBP than SPRINT patients. Further study is necessary to better understand these findings.
Abstract 11328: Impact of Periodontitis on Long-term Clinical Outcomes in Patients With Atrial Fibrillation
Authors: Im Sung Il
Published: April 2024

Introduction:
Relationship between atrial fibrillation (AF) and inflammation was shown in previous studies.

Hypothesis:
However, there was limited data about the association between the periodontitis and atrial fibrillation in the long-term follow up. The aim of this study was to evaluate the impact of periodontitis on long-term clinical outcomes in patients with AF.

Methods:
The Kosin University echocardiography, electrocardiogram (ECG) and periodontitis database were reviewed from 2010 to 2015 to identify patients with AF and periodontitis. Patients were followed for a median of 2.1 years and were divided into two groups according to the absence or presence of periodontitis in patients with AF.

Results:
Among 227 patients with AF, 47 (20.7%) patients had periodontitis. Total any event rates were significantly higher in patients with periodontitis compared to those without periodontitis (
P
<0.001). Arrhythmias including AF, atrial tachycardia, atrial premature beat, ventricular tachycardia, and ventricular premature beat also occurred in 36 patients, with a significantly higher incidence in patients with periodontitis than in those without periodontitis (
P
<0.001). In univariate analysis, age, CHA
2
DS
2
VASc, Left atrial volume index (LAVI) and periodontitis were significantly associated with arrhythmic events and total any events including bleeding events, thromboembolic events, arrhythmic events, re-hospitalizations and mortality. In multivariate analysis, LAVI (
P
=0.005) and periodontitis (
P
<0.001) were independent risk factors for arrhythmic events and periodontitis (
P
<0.001) for total any events at the long-term follow-up.

Conclusions:
The patients with periodontitis were associated with higher total any events and arrhythmic events, suggesting more intensive medical therapy with close clinical follow-up will be required.
Abstract 11370: Coronary Artery Calcium Incidence Varies by ASCVD Risk: Insights From the Dallas Heart Study
Authors: Mehta Anurag , Joshi Parag , Ayers Colby , Nasir Khurram , Berry Jarett , Rohatgi Anand , Khera Amit
Published: April 2024

Introduction:
Absence of coronary artery calcium (CAC=0) is associated with favorable cardiovascular outcomes and can be useful for down-classifying risk in middle-aged asymptomatic individuals. Identifying predictors of incident CAC can inform preventive measures.

Hypothesis:
We hypothesized that in a young, multi-ethnic, population-based cohort, increasing atherosclerotic cardiovascular disease (ASCVD) risk would be associated with incident CAC on repeat scanning.

Methods:
Participants of the Dallas Heart Study (DHS) underwent CAC scanning at baseline (EBCT) and at follow up (MDCT), after a mean interval of 6.9 years. Participants with baseline CAC=0 were included, and those with clinical ASCVD or on statin therapy were excluded. Incident CAC was analyzed as CAC >0 as well as CAC >10 at follow up. ASCVD risk was calculated using the 2013 AHA/ACC risk estimator.

Results:
Among 2,272 participants with baseline and follow up CAC measurements, 756 participants meeting exclusion criteria had absent CAC (CAC=0) at baseline, with a mean age of 42 years, 65.6% women, and 42.2% blacks. Of these individuals, incident CAC occurred in 23.8% using CAC >0 and in 8.3% using CAC >10. Risk markers associated with incident CAC >0 included baseline 10-year ASCVD risk, family history of coronary heart disease, low density lipoprotein particle concentration, diabetes and statin use at follow up. In fully adjusted analyses, only baseline 10-year ASCVD risk was associated with incident CAC >0. The prevalence of CAC >0 at follow up by baseline 10-year ASCVD risk categories of <5%, ≥5 to <7.5%, and >7.5% was 21.2%, 41.5%, and 51.4%, respectively (p-trend<0.01). The prevalence of CAC >10 was 7%, 12.2%, and 27.1% respectively.

Conclusions:
In this young cohort, one in four individuals with absent CAC developed incident CAC after approximately 7 years. Reassessing risk, including consideration of repeat CAC measurement in those with higher baseline 10-year ASCVD risk, may be warranted.
Abstract 11378: Dynamic Secretion Analysis by Novel Microfluidic Platform mFLISA Reveal Contextual and Precise Paracrine Signatures Preventing Cardiac Injury
Authors: Kshitiz Kshitiz , Ellison David D , Suhail Yasir , Afzal Junaid , Woo Laura , Levchenko Andre
Published: April 2024

It is now increasingly recognized that a variety of stem cells offer therapeutic benefit to injured tissues via paracrine signaling. Paracrine signaling via secreted ligands is an important mediator of cell function. It has been a challenge to precisely measure cellular secretions in relevant physiological contexts. Here we introduce a high throughput platform combining protein microprinting and microfluidics, μFLISA, to directly measure cellular secretion and estimate the kinetics for the detected secretome (Fig. 1A). μFLISA design allows for precise evaluation of the diffusion of secreted molecules, as well as retroactive determination of the dynamics of secretion without time course measurements (Fig. 1B). Furthermore, its unique architecture facilitates precise control over measurement timings in response to arbitrary biological stimuli. Using μFLISA we estimated the secretion dynamics for different constituents of the secretome for bone marrow derived stem cells (BMSCs), reported to provide benefit in response to myocardial injury. We found that secretory kinetics are highly contextual and are regulated in response to individual factors present in myocardial infarction, e.g. hypoxia (Fig. 1B). Using an in vitro model of ischemia reperfusion with human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs), we estimated the absolute concentration of BMSC secretome in response to reperfusion insult (Fig. 1C). We provide strong evidence for the hypothesis that secretion by stem cells is contextual, is regulated by injury signals from myocardium, and that both the absolute concentration and dynamics of paracrine signaling determines cardioprotection. Precise estimation of concentration and kinetics of BMSC secretome will facilitate our understanding of the molecular mechanisms involved in stem cell mediated cardioprotection, as well as pave the way towards a cell-less therapy by mimicking the paracrine signaling by stem cells.
Abstract 11414: Comparison of the Cardiovascular and Bleeding Risks in Patients With Acute Myocardial Infarction Newly Treated With Ticagrelor versus Clopidogrel in East Asia: A Nationwide Propensity-matched Cohort Study in Taiwan
Authors: Lee Cheng-Han , Li Yi-Heng , Cheng Ching-Lan , Kao Yang Yea-Huei , Chao Ting-Hsing
Published: April 2024

Background:
The Platelet Inhibition and Patient Outcomes (PLATO) trial showed that ticagrelor improved clinical outcomes in patients (pts) with acute coronary syndrome compared with clopidogrel. There were few real world data on the efficacy and safety of ticagrelor in East Asians in whom bleeding is a major concern with potent antithrombotic drugs.

Methods:
We conducted a nationwide population-based cohort study by using 2012 to 2014 Taiwan National Health Insurance Research Database. The 18-month clinical outcomes in pts with acute myocardial infarction (MI) treated with ticagrelor vs. clopidogrel were compared. Overall, we identified 27,339 acute MI pts (mean age 62.2 years, 71% male) who survived 30 days after the acute MI attack and took dual antiplatelet agents. Cohorts of ticagrelor and clopidogrel were 1:8 matched based on propensity score. The primary efficacy endpoints were all-cause death, recurrent MI or ischemic stroke. The safety endpoints consisted of major gastrointestinal (GI) bleeding and intracerebral hemorrhage (ICH).

Results:
In unmatched cohorts, ticagrelor-treated pts (n = 2,844) were younger with fewer comorbidities than clopidogrel-treated pts (n = 24,495). The 18-month primary efficacy endpoint rate was lower in ticagrelor group (10.1 vs. 18.3%,
p
< 0.001). In ticagrelor group, the risks of ICH (0.3%) and ICH + GI bleeding (2.9%) were similar to the data reported in the PLATO trial (ICH 0.3% and non-CABG related TIMI major bleeding 2.8%). After propensity matching, we obtained 2,389 ticagrelor users and 19,112 clopidogrel users in the cohort. After adjusting for clinical characteristics, the 18-month primary efficacy endpoint rate was 21% lower in ticagrelor than in clopidogrel group (10.5 vs. 16.0%, adjusted HR, 0.79; 95% CI, 0.68-0.93). The composite safety endpoint rate was not different between ticagrelor and clopidogrel group (3.2 vs. 4.1%, adjusted HR, 1.01; 95% CI, 0.74-1.37). Subgroup analyses show consistent benefits of ticagrelor in old pts (≥ 75 years) and in pts with diabetes, heart failure or previous MI.

Conclusions:
In the real world acute MI Taiwanese pts, ticagrelor offered better cardiovascular protection than clopidogrel without increasing the major bleeding risk.
Abstract 11438: Thyroid Hormones and Changes in Body Weight and Metabolic Parameters in Response to Weight-Loss Diets: The POUNDS LOST Trial
Authors: Liu Gang , Liang Liming , Bray George A , Qi Lu , Hu Frank B , Sacks Frank , Sun Qi
Published: April 2024

Context:
The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown.

Objective:
To examine the relationship between baseline thyroid hormones and subsequent changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting.

Methods:
In the 2-year POUNDS LOST randomized clinical trial that tested 4 weight-loss diets, thyroid hormones (free triiodothyronine [T3], free thyroxine [T4], total T3, total T4, and thyroid stimulating hormone [TSH]), and resting metabolic rate (RMR), as well as anthropometric and biochemical parameters, were determined at baseline, 6 months, and 2 years among 569 overweight and obese participants aged 30-70 years with normal thyroid function.

Results:
Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6-24 months. Baseline free T3 and total T3 levels were positively associated with baseline body mass index and RMR, whereas free T4, total T4, and TSH did not demonstrate a clear pattern of correlations with these parameters. After multivariate adjustment including dietary intervention groups and baseline body weight, higher baseline free T3 and free T4 levels were significantly associated with a greater decrease in body weight in the first 6 months. Comparing extreme tertiles, the weight loss was -5.39±0.9 vs -3.87±0.9 for free T3 (P trend=0.02) and -5.88±0.9 vs -4.09±0.9 for free T4 (P trend=0.004). The thyroid hormones did not predict weight regain between 6 and 24 months. The associations were attenuated after further adjusting for changes in RMR.

Conclusion:
In this diet-induced weight-loss setting, higher baseline free T3 and free T4 predict more weight loss, but not weight regain among overweight and obese adults with normal thyroid function. In addition, changes in RMR may partially mediate the observed associations. These findings reveal a novel role of thyroid hormones in body weight regulations and may help identify individuals more responsive to weight-loss diets.
Abstract 11609: Neurological Effects of Proprotein Convertase Subtilisin/kexin Type 9(PCSK9) Inhibitors: Direct and Indirect Comparisons
Authors: Patel Nirav , Kalra Rajat , Venkatraman Anand , Godara Hemant , Arora Garima , Bajaj NavKaranbir S , Arora Pankaj
Published: April 2024

Introduction:
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors dramatically reduce low-density lipoprotein (LDL) cholesterol levels which may lead to lower cerebrovascular (CVA) events. However, randomized control trials (RCTs) have reported increased neurocognitive (NC) deficits in patients using PCSK9 inhibitors.

Hypothesis:
CVA and NC event rates are similar in patients treated with or without PCSK9 inhibitors.

Methods:
RCTs reporting rates of stroke, transient ischemic attacks (TIAs), and NC deficits in patients using PCSK9 inhibitors were identified. Standard meta-analyses techniques were used to compare these outcomes among patients treated with and without PCSK9 inhibitors. Network meta-analyses (NMA) were also conducted to indirectly compare Evolocumab and Alirocumab on aforementioned outcomes.

Results:
Seventeen RCTs with 14,516 patients were included. Evolocumab was used in 10 RCTS in 6,403 patients whereas Alirocumab was used in 2,932 patients in 7 RCTs. Ten RCTs with 10,318 patients reported stroke. Fourteen RCTs with 12,578 patients reported NC event rates. Five RCTs with 6,710 patients reported TIAs (
Table
). None of the studies using Alirocumab reported data on TIAs. We did not observe any difference in stroke rate, NC deficits or TIAs among 2 studied groups (RR; 1.22, (95% CI: 0.50-2.96), 0.97 (0.43-2.20), and 0.37 (0.06-2.23)) respectively. We observed no difference in stroke and NC deficits among Evolocumab and Alirocumab with NMA (
Figure
).

Conclusions:
PCSK9 inhibitors did not render any protection from stroke or TIAs. Furthermore, our pooled analysis does not show any increase in NC deficits as reported in previous studies.
Abstract 11677: Associations Between Proton Pump Inhibitors and Low Cardiac Mortality in Patients With Heart Failure
Authors: Takiguchi Mai , Yoshihisa Akiomi , Sato Yu , Watanabe Shunsuke , Yokokawa Tetsuro , Miura Shunsuke , Sato Takamasa , Suzuki Satoshi , Oikawa Masayoshi , Kobayashi Atsushi , Yamaki Takayoshi , Kunii Hiroyuki , Saitoh Shu-ichi , Takeishi Yasuchika
Published: April 2024

Background:
It has been recently reported that use of histamine H
2
receptor blocker (H2RA) is associated with the blockade of right and left ventricular remodeling and reduces risk of incident heart failure (HF) in cohort of participants without cardiovascular diseases. However, the association between acid suppressive therapy such as H2RA or proton pump inhibitor (PPI) and cardiac mortality in HF patients is still unclear. Therefore, we examined impacts of the acid suppressive therapy on cardiac mortality in HF patients.

Methods and Results:
We analyzed consecutive 1191 HF patients. These patients were divided into 3 groups: no acid suppressive therapy group (None, n = 363), H2RA group (n = 164) and PPI group (n = 664). Although presence of male gender, diabetes, atrial fibrillation and reduced left ventricular ejection fraction did not differ among the three groups, prevalence of ischemic etiology, dyslipidemia, chronic kidney disease, anemia and past history of peptic ulcer was higher in PPI group than in H2RA and no acid suppressive therapy groups (ischemic etiology 32.2% vs. 27.4% and 15.7%, p<0.001; dyslipidemia 79.2% vs. 77.4% and 70.5%, p=0.007; chronic kidney disease 62.8% vs. 57.3% and 53.2%, p=0.010; anemia 64.0% vs. 54.3% and 46.0%, p<0.001; peptic ulcer 15.1% vs. 7.9% and 6.3%, p<0.001). In the follow-up period (mean 995 days), 169 cardiac deaths occurred. In the Kaplan-Meier analysis, cardiac mortality was significantly lower in PPI group than in H2RA and no acid suppressive therapy groups (11.0% vs. 21.3% and 16.8%, respectively, p<0.05). In the multivariable Cox proportional hazard analysis after adjusting for other potential confounding factors, use of PPI, but not H2RA, was an independent predictor of cardiac mortality in HF patients (PPI, HR 0.475, P<0.001 and H2RA, HR 0.968, P=0.881).

Conclusion:
Proton pump inhibitors may be associated with better outcome in patients with heart failure.
Abstract 11679: Post-resuscitation Care and Survival After In-hospital Cardiac Arrest
Authors: Girotra Saket , Nallamothu Brahmajee K , Zhou Yunshu , Vaughan-Sarrazin Mary , Chan Paul S
Published: April 2024

Background:
More than 40% of in-hospital cardiac arrest (IHCA) deaths occur in patients during the post-resuscitation period following return of spontaneous circulation (ROSC). However, the degree to which post-resuscitation survival varies across hospitals and whether this variation is explained by hospital characteristics is unknown.

Methods:
We identified 80,201 patients within Get with the Guidelines-Resuscitation who achieved ROSC following IHCA. Using a multivariable hierarchical regression model, we calculated risk adjusted rates of post-resuscitation survival for each hospital and quantified hospital variation in post-resuscitation survival using median odds ratio (OR). We also assessed the association of hospital characteristics with post-resuscitation survival.

Results:
The mean age was 65.5 years, 57% were men, and 23% were black. Nearly 1 in 4 (23.0%) patients had an initial shockable rhythm. Overall, 33.5% of patients with ROSC survived to discharge, but the rate of post-resuscitation survival varied across hospitals (median hospital rate: 33.3%; interquartile range: 29.9%-36.7%; total range: 18.9%-55.1%). The median OR was 1.35 (95% CI: 1.30, 1.39, Figure), which suggests that post-resuscitation survival for 2 patients with similar covariates at 2 randomly selected hospitals varied by 35%. Except U.S. census region (P<0.001), no hospital characteristic was associated with hospital rates of post-resuscitation survival including, academic status, total bed number, hospital ownership, use of intensivists; number and proportion of intensive care unit [ICU] beds, neurological services, and coronary angiography capability.

Conclusions:
Rates of post-resuscitation survival vary among U.S. hospitals. However, this variation is not explained by hospital structural characteristics, thus highlighting a pressing need to identify post-resuscitation best practices at top-performing hospitals in post-cardiac arrest care.
Abstract 11686: Pericellular Amyloid Infiltration in Biopsy-proven Cardiac Amyloidosis
Authors: Yokokawa Tetsuro , Sugano Yasuo , Matsuyama Taka-aki , Hideaki Kanzaki , Ohta-Ogo Keiko , Ikeda Yoshihiko , Ishibashi-Ueda Hatsue , Takeishi Yasuchika , Yasuda Satoshi , Anzai Toshihisa
Published: April 2024

Background:
Cardiac amyloidosis is a rare disease characterized by the myocardial infiltration of amyloid. There are several histopathological patterns of amyloid accumulation, of which pericellular amyloid pattern is classified when amyloid is observed around each cardiomyocyte in endomyocardial biopsy. However, the relationship between pericellular amyloid deposition pattern and clinical characteristics has not yet been investigated.

Objective:
We retrospectively investigated endomyocardial biopsy-proven cardiac amyloidosis with pericellular amyloid deposition.

Methods:
Thirty cardiac amyloidosis patients in our institution were included.

Results:
Thirteen patients (43%) were pathologically classified into pericellular amyloid deposition. In the baseline characteristics, the patients with pericellular deposition had significantly lower age (69 ± 9 vs. 75 ± 6 years, p = 0.032) and higher brain natriuretic peptide levels (681 ± 516 vs. 267 ± 393 pg/ml, p = 0.003), compared with those without pericellular deposition. Electrocardiographic findings revealed that patients with pericellular amyloid deposition had significantly higher incidence of low voltage (46 vs. 12%, p = 0.045) and pseudoinfarction pattern (46 vs. 6%, p = 0.015), compared with patients without pericellular deposition. Echocardiography revealed that patients with pericellular deposition had significantly decreased deceleration time (152 ± 49 vs. 191 ± 50 ms, p = 0.049). Hemodynamic findings did not show significant difference between groups. High-sensitivity cardiac troponin-T levels were also analyzed in 14 cardiac amyloidosis patients without ischemic heart disease. Patients with pericellular amyloid deposition had significantly higher high-sensitivity cardiac troponin-T levels, compared with patients without pericellular deposition (0.128 ± 0.07 vs. 0.046 ± 0.03 pg/ml, p = 0.016).

Conclusion:
Pericellular amyloid deposition pattern was associated with electrocardiographic abnormalities, diastolic dysfunction, and ongoing myocardial damage. Our data suggest direct amyloid infiltration around the cardiomyocytes may cause myocardial damage, providing possible pathophysiological implication of the failing heart in cardiac amyloidosis.
Abstract 11814: Pulmonary Hypertension With Altered eNOS and ALK-1 Signaling in the Autoimmuno-disease Mice
Authors: Sugimoto Koichi , Sato Akihiko , Watanabe Shunsuke , Suzuki Satoshi , Machida Takeshi , Saitoh Shu-ichi , Sekine Hideharu , Takeishi Yasuchika
Published: April 2024

Background:
Pulmonary artery hypertension is often associated with connective tissue disease and major determinant of prognosis. MRL/lpr mouse, which has hypergammaglobulinemia and products various autoimmuno antibody, develops vasculitis and nephritis spontaneously and is widely used as the model of lupus nephritis or Sjogren syndrome. In this study, we examined the right ventricular pressure overload, pathological features and the signaling molecules in the lung tissues of MRL/lpr mice.

Methods:
We used the female MRL/lpr mice at the age of 12 to 18 weeks. We measured right ventricular systolic pressure (RVSP) by a micro-manometer catheter and the ratio of right ventricular weight to left ventricular weight including ventricular septum (RV/LV). Lung sections were stained with α-smooth muscle actin, and the medial smooth muscle area was expressed as a percentage of the external area of the vessel. Levels of endothelial nitric oxide synthase (eNOS), survivin, endothelin-1 (ET-1), and activin receptor-like kinase-1 (ALK-1) were analyzed by Western blotting.

Results:
RVSP in the MRL/lpr mice was significantly higher (29.8 ± 7.2 vs. 19.2 ± 1.9 mmHg, P < 0.05) than that in WT C57/Bl6 mice. RV/LV was increased in the MRL/lpr mice compared to the WT C57/Bl6 mice (0.33 ± 0.58 vs. 0.20 ± 0.67, P < 0.05). The medial smooth muscle area of MRL/lpr mice were larger than that of WT C57/bl6 (56.3 ± 4.0 vs. 39.5 ± 6.1%, P < 0.05). Western blot analysis revealed the markedly elevated levels of ET-1 and survivin as well as decreased ALK-1 expression and eNOS phosphorylation in the lung tissue of MRL/lpr mice.

Conclusion:
We demonstrated that MRL/lpr mice were complicated with pulmonary hypertension. The possible mechanisms include the vasoconstriction enhanced by increased ET-1 level and impaired vasodilatation caused by decreased eNOS phosphorylation and ALK-1 expression. In addition, upregulation of survivin promoted the medial wall thickening of pulmonary vessels. MRL/lpr mice appeared to be a useful model in considering the mechanism of pulmonary hypertension associated with connective tissue diseases.
Abstract 11886: The Impact of Poor Understanding of Heart Failure and Its Symptoms on Self-care
Authors: Lee Kyoung Suk , Moser Debra K , Dracup Kathleen
Published: April 2024

Introduction:
A comprehensive understanding of heart failure (HF) and its symptoms is one of the goals of patient education. Patients cannot be expected to adequately perform self-care and respond to symptoms appropriately with incomplete understanding of HF and its symptoms.

Purpose:
To examine whether levels of understanding of HF and its symptoms predicts self-care in HF patients who had a recent hospitalization for HF symptoms.

Methods:
Patients with HF (N=577, mean 66 years, 41% female, 35% NYHA III/IV) completed the 9-item European HF Self-care Behavior scale to assess self-care. The HF Knowledge Questionnaire was used to assess knowledge of HF and its symptoms. Three groups were formed by their different levels of understanding of HF and its symptoms: poor, moderate, and complete. Linear regression was used to determine whether levels of understanding of HF and its symptoms predicted self-care after controlling for age, gender, education, marital status, comorbidity, NYHA functional class, and depressive symptoms.

Results:
Of 577 patients, 16% and 32% of the patients had poor and moderate understanding of HF and its symptoms, respectively. Levels of understanding of HF and its symptoms independently predicted self-care. Compared with patients with complete understanding, those with poor and moderate understanding were more likely to inadequately perform self-care (standardized β=0.24 and 95% CI 3.39-6.48; standardized β=0.12 95% CI 0.53-2.93, respectively).

Conclusions:
A large minority of patients with HF had poor or moderate understanding of HF and its symptoms. Levels of understanding of HF and its symptoms predicted poor self-care behaviors in these patients. Thus, patient education must be designed to help patients achieve a thorough understanding of the disease and its symptoms to ensure successful self-care among HF patients.
Abstract 11907: Choice of Antihypertensive Combination Therapy Based on Daily Salt Intake
Authors: Toyoda Shigeru , Inami Shu , Kato Toru , Tsukada Kinji , Nakamoto Akiya , Kikegawa Yoshinobu , Suzuki Akihiro , Anraku Yukitaka , Node Koichi , Inoue Teruo
Published: April 2024

Introduction:
To achieve strict blood pressure control, combination therapy with multiple antihypertensive agents, including angiotensin receptor blockers (ARBs) are recommended. Recently, various ARB combination pills have been developed, including ARBs combined with thiazide diuretics (TZs) and calcium channel blockers (CCBs). However, it has yet to be determined which drug class, the TZs or the CCBs, is more efficacious as add-on therapy to ARBs in controlling hypertension.

Hypothesis:
This study was designed to test our hypothesis that the combination treatment with ARB/TZ would be better in hypertensive patients with high salt diet intake to lower blood pressure, compared to that with ARB/CCB.

Methods:
Hypertensive patients who failed to reach blood pressure goals despite treatment with ARBs alone were randomly assigned to receive either ARB/TZ or ARB/CCB combination therapy. Estimated daily sodium intake was calculated from spot urine values of sodium and creatinine. Blood pressure was measured at baseline, and at 4, 8 and 12 weeks after starting combination therapy.

Results:
For all study patients (n=87), diastolic blood pressure (DBP) reduction was greater in 49 patients receiving ARB/CCB treatment, compared to 38 patients receiving ARB/TZ treatment (11±10 vs. 6±12 mmHg, P<0.05 at 4 weeks; 12±11 vs. 5±11 mmHg, P<0.05 at 8 weeks; 13±11 vs. 7±9 mmHg, P<0.05 at 12 weeks, respectively), although the magnitude of the SBP reduction was similar in each group. In the 37 patients with a baseline estimated daily salt intake greater than 10 g and baseline systolic blood pressure (SBP) ranging from 150 to 200 mmHg, SBP was lower (130±12 vs. 141±17 mmHg
,
P<0.05) and SBP reduction was greater (35±17 vs. 24±17 mmHg
,
P<0.05) at 4 weeks in patients receiving ARB/TZ treatment, compared to patients receiving ARB/CCB treatment. In the 31 patients whose estimated daily salt intake increased at 12 weeks compared to baseline, SBP at 12 weeks was lower in patients receiving ARB/TZ treatment, compared to patients receiving ARB/CCB treatment (131±8 vs. 139±10 mmHg, P<0.05).

Conclusion:
Estimated daily salt intake is a useful tool for guiding antihypertensive therapy and should be measured repeatedly during the therapeutic course.
Abstract 11912: Glycocalyx Shedding is Markedly Increased During Acute Phase of Takotsubo Cardiomyopathy
Authors: Nguyen Thanh H , Liu Saifei , Ong Gao , Stafford Irene , Frenneaux Michael , Horowitz John D
Published: April 2024

Introduction:
Acute myocardial infarction (AMI) and other forms of myocardial acute oxidative stress are associated with variable “shedding” of vascular and other glycocalyx. This glycocalyx shedding (GCS) can be quantitated by release into plasma of glycocalyx components such as Syndecan-1 (SD1), which is the most prevalent proteoglycan. Previous in vitro studies have implicated both catecholamines and BNP release as potential accentuating factors in GCS: since these are prominent aspects of the pathogenesis of Takotsubo cardiomyopathy (TTC), we hypothesised that TTC (i) would be associated with increased GCS both acutely and during subsequent 3 months of continued myocardial inflammation and (ii) extent of GCS would be predictable on the basis of NT-proBNP and catecholamine releases.

Methods:
SD1 concentrations were measured in 49 TTC patients acutely and after 3 months in comparison with 12 normal age-matched controls and 10 myocardial infarct patients. Correlations between SD1 and (i) acute LV function, (ii) lowest BP on admission, (iii) peak catecholamine release, and (iv) extent of systemic and myocardial inflammatory activation [measured by high sensitive C-reactive protein (hsCRP), NT-proBNP concentrations, and myocardial T2 signal intensity on cardiac MRI] were sought.

Results:
Acute SD1 concentrations in TTC patients were significantly elevated compared to 3 month and control values (2-way ANOVA) (Figure). However, there was no significant difference between acute TTC and MI levels. In addition, there were no correlations between SD1 concentrations and extent of severity of acute episode.

Conclusions:
1. TTC, despite minimal associated myocardial necrosis, is associated with marked increase in GCS.

2. Extent of GCS in TTC is not closely related to either release of NT-proBNP or normetanephrine.

We postulate that GCS may contribute to some of the clinical features of TTC, such as development of pulmonary oedema without marked increases in PCWP.
Abstract 12019: Inactivation of AMP-activated Protein Kinase Sensitizes Heart to Pressure Overload-induced Hypertrophy
Authors: Wang Jinli , Quan Nanhu , Wang Lin , Chen Xu , Chu Dongyang , Rezaie Alireza , Li Ji
Published: April 2024

Introduction:
Hypertrophy triggers activation of adenosine monophosphate-activated protein kinase (AMPK), an energy sensor in the heart. We have identified activated protein C (APC) is an endogenous AMPK agonist, and the non-anticoagulant APC-2Cys mutant but not the non-signaling APC-E170A mutant stimulates cardiac AMPK activation as well.

Hypothesis:
AMPK play a critical role in preventing heart from hypertrophy induced by pressure overload. APC as a AMPK agonist inhibits pressure overload-induced hypertrophy
via
APC’s cytoprotective signaling activity.

Methods:
Wild-type (WT) and AMPK-kinase dead (KD) transgenic mice were subjected to transverse aortic constriction (TAC) surgery. Echocardiography was performed to evaluate the heart function, and histology staining revealed the morphological changes. Real-time PCR and immunoblotting were used to detect mRNA and protein levels of signaling changes.

Results:
There is no phenotype difference between wild type (WT) and AMPK-kinase dead (AMPK KD) mice under normal physiological conditions. However after 4 weeks of TAC surgery, AMPK-KD mice demonstrated significantly bigger heart as compared to WT mice (p<0.05). The cardiac functions measured by echocardiography in AMPK-KD hearts were significantly impaired as compared with WT hearts (p<0.05). The immunohistochemical staining showed that the increased macrophage infiltration and reactive oxygen species (ROS) in AMPK-KD versus WT hearts after 4 weeks of TAC surgery. The immunoblotting results demonstrated that the redox status markers such as p66
shc
, 4-hydroxynonenal and extracellular signal-regulated kinase (ERK) were up-regulated in the AMPK-KD hearts after 4 weeks of TAC surgery (all p<0.05 versus WT hearts). APC and APC-2Cys but not APC-E170A administration significantly attenuated hypertrophy and fibrosis caused by pressure overload. The macrophage infiltration and p66
shc
activation caused by pressure overload were also inhibited by APC and APC-2Cys but not by APC-E170A.

Conclusions:
Cardiac AMPK inactivation aggravates pressure overload induced hypertrophy. APC-2Cys without anticoagulant activity could be a therapeutic drug for treatment of hypertension-related hypertrophy patients without bleeding risk.