bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11831: Late Outcome of Percutaneous Mitral Commissurotomy: Randomized Comparison of Inoue versus Double-Balloon Technique
Authors: Lee Sahmin , Kang Duk-Hyun , Kim Dae-Hee , Song Jong-Min , Choi Kee-Joon , Zo Joo-Hee , Song Jae-Kwan , Park Seong-Wook , Park Seung-Jung
Published: July 2021

Introduction:
Percutaneous mitral commissurotomy (PMC) using either the Inoue or the double balloon technique showed similar, excellent 7-year outcomes, but very late results after successful PMC have been unknown.

Hypothesis:
We assessed late results of PMC up to 20 years in a randomized trial comparing Inoue versus double-balloon technique.

Methods:
Between 1989 and 1995, a total of 302 patients (77 men, 41±11 years) with severe mitral stenosis were randomly assigned to undergo PMC using Inoue (n=152; group I) or double-balloon technique (n=150; group D). The end points were the composite clinical events of death, mitral surgery, repeat PMC, or deterioration of NYHA class ≥3 that occurred after enrollment.

Results:
The successful immediate results [post-PMC mitral valve area (MVA) ≥1.5 cm
2
and mitral regurgitation (MR) grade ≤2] were achieved in 127 (84%) patients of group I and 122 (81%) patients of group D (p= NS). During median follow-up of 20.7 years (IQR, 18.9 to 22.9), clinical events occurred in 82 (53.9%) patients of group I (37 deaths, 44 mitral surgeries, 9 repeat PMCs and 3 NYHA class ≥3) and 79 (52.7%) patients of group I (34 deaths, 51 mitral surgeries, 5 repeat PMCs and 4 NYHA class ≥3). The event-free survival rates were not significantly different between group I and group D (49.3% and 55.3% at 20 years, respectively; HR, 1.22; 95% CI, 0.88-1.70; p=0.23) (Figure). On multivariate Cox analysis, absence of commissural MR (HR, 1.75; 95% CI, 1.22-2.51; p=0.002), immediate post-PMC MVA <1.8cm
2
(HR, 1.54; 95% CI, 1.04-2.27; p=0.03), and atrial fibrillation (HR, 1.53; 95% CI, 1.04-2.23; p=0.03) were independently related with clinical events after successful PMC.

Conclusions:
In this randomized trial, the Inoue and double-balloon methods showed similar, good outcomes up to 20 years, and the achievement of effective commissurotomy with development of commissural MR or immediate post-PMC MVA ≥1.8cm
2
is important in optimizing the late results of PMC.
Abstract 11917: Midlife Cardiovascular Risk Factors and Late-Life Unrecognized and Recognized Myocardial Infarction Detected by Cardiac Magnetic Resonance (ICELAND-MI, the AGES-Reykjavik Study)
Authors: McAreavey Dorothea , Vidal Jean-Sébastien , Aspelund Thor , Eiriksdottir Gudny , Schelbert Erik B , Kjartansson Olafur , Cao Jie J , Thorgeirsson Gudmundur , Sigurdsson Sigurdur , Garcia Melissa , Harris Tamara B , Launer Lenore J , Gudnason Vilmundur , Arai Andrew E
Published: July 2021

Introduction:
The association of midlife atherosclerosis risk factors (RF) with later unrecognized myocardial infarction (UMI) is unclear. We investigated associations of midlife RF with UMI and recognized MI (RMI) detected 31 years later by cardiac magnetic resonance (CMR).

Methods:
The Reykjavik Study (1967-91) collected serial measures of RF in subjects born 1907-35, mean (SD) age 48 ± 7 years. In ICELAND-MI (2004-07), 936 randomly selected survivors (76 ± 5 years) were evaluated by CMR. Analysis included logistic regression and random effects modeling adjusted for age, sex, and covariates. All comparisons are relative to the no MI group.

Results:
At baseline midlife evaluation, atherosclerotic risk assessed by a modified Framingham risk score was significantly higher in RMI and UMI than in no MI (7.4 ± 6.3%; 7.1 ± 6.2% vs 5.4 ± 5.8% respectively, p<0.001). RMI and UMI were more common in men (65%, 64% vs 43%; p<0.0001). Compared with no MI, baseline systolic BP was significantly higher in UMI (138 ± 17 mm Hg vs 133 ± 17 mm Hg; p=0.006), and trended higher in RMI (p=0.06). Likewise, baseline diastolic BP was significantly elevated in both RMI and UMI (88 ± 10 mm Hg and 87 ± 10 mm Hg vs 84 ± 10 mm Hg; p<0.02). Serum cholesterol was significantly higher in RMI (6.7 ± 1.1 mmol/L vs 6.2 ± 1.1 mmol/L; p=0.005), as were serum triglycerides (1.4 ± 0.7 mmol/L vs 1.3 ± 0.7 mmol/L; p<0.03). Serum cholesterol trended higher in UMI (p=0.08).

Compared to no MI, serial midlife systolic and diastolic BP were significantly higher in RMI [beta=4.03 ± 1.64 (SE) mm Hg, p=0.014 and 2.05 ± 0.94 mm Hg, p=0.025, respectively] as were cholesterol and triglycerides [0.43 ± 0.11 mmol/L, p=0.001 and 0.31 ± 0.07 mmol/L, p<0.0001, respectively]. Systolic BP was significantly higher in UMI [beta=2.76 ±1.31 mm Hg, p=0.036, figure].

Conclusions:
Midlife vascular risk factors are associated with UMI and RMI detected by CMR 31 years later. Systolic BP was the most important individual risk factor associated with later UMI.
Abstract 11921: Altered Cardiomyocyte Functional Response to Vasopressin in Heart Failure
Authors: Li Tiankai , Zhang Xiaowei , Cheng Heng-Jie , Li Wei-Min , Cheng Che Ping
Published: July 2021

Background
. In heart failure (HF), circulating levels of arginine vasopressin (AVP) are elevated and there is direct relationship between a rise in AVP levels and increased morbidity and mortality. Recent observations further demonstrated the increased AVP 1A receptor (V1AR) expression in failing human hearts and suggested that these alterations may alter cardiac contractile behavior in HF. However, the direct cardiac effects of V1AR in normal and HF remain undetermined. The cellular basis for AVP-associated adverse clinical consequences in HF is unclear. We assessed the hypothesis that in HF, AVP may produce negative modulation on [Ca
2+
]
i
regulation and cause direct depression in cardiomyocyte contractile performance.

Methods
. We assessed LV myocyte functional and calcium transient ([Ca
2+
]
iT
) responses to AVP (10
-7
M) in 8 control and 12 SD rats with isoproterenol (ISO) induced HF (2 months after 170 mg/kg sq for 2 days) in the absence and presence of selective V1AR blockade ([Pmp1, Tyr (OMe) 2, Arg
8
] AVP, 10
-6
M), or pretreatment of myocytes with G
i
inhibitor (PTX, 2 μg/ml, 6 hrs).

Results
. Compared with controls, ISO-treated rats had established HF after ISO at 2 months with significant LV dilatation and decreased ejection fraction (EF, 31% vs 61%). In normal myocytes, versus baselines, AVP superfusion caused no significant changes in myocyte contraction (dL/dt
max
)

(130.6 vs 136.8 μm/s), relaxation (dR/dt
max
) (99.5 vs 103.5 μm/s) and [Ca
2+
]
iT
(0.24 vs 0.24). In contrast, in HF, myocyte function was impaired and further depressed by AVP. Versus HF baselines, AVP resulted significantly decreases in dL/dt
max
(24%, 57.2 vs 75.4 μm/s) and dR/dt
max
(20%, 39.3 vs 49.0 μm/s) accompanied by reduced [Ca
2+
]
iT
(17%, 0.14 vs 0.17). In HF myocytes, these AVP mediated effects were abolished by prior exposure of myocytes to V1AR blockade or PTX.

Conclusions
. HF alters AVP cardiac effects. In HF, AVP exacerbates the dysfunctional [Ca
2+
]
i
homeostasis, producing decreased the peak systolic [Ca
2+
]
iT
. AVP causes direct inhibitions of LV myocyte contraction and relaxation, These effects are coupled with the activation of V1AR and are likely to be mediated through the PTX-sensitive G protein pathway and may thus play an important role in promoting functional impairment in HF.
Abstract 11965: Cardiovascular Risk Factor Reduction Through a Paleolithic Diet
Authors: McKechnie Connor , McKechnie Madeline , McKechnie Julia , McKechnie Ronald , Talreja Deepak
Published: July 2021

Introduction:
The paleolithic diet consists of grass-fed pasture-raised meats, seafood, vegetables, and also includes fruits, seeds, nuts and eggs. This diet has been shown to contribute to weight loss and mimics the diet our hunter-gatherer ancestors may have consumed. Weight loss is achieved through avoiding refined sugars, starches, dairy and legumes while consumption of protein, carbohydrates, and fat is relatively balanced.

Objective:
To study the effect of the paleolithic diet on the cardiovascular risk factor profiles of adults in the Hampton Roads area of Virginia.

Methods:
35-85 year old non-diabetic adults, with one or more cardiovascular risk factor, were invited to participate. A comprehensive nutritional education program was provided to each participant prior to the 60-day intervention. Baseline weight, blood pressure, fasting glucose, hemoglobin A1c, high-sensitive C-reactive protein, fasting lipid panel and NMR Lipoprofile were assessed through an initial health screen. Each participant maintained daily food logs and met weekly with the multi-disciplinary study team to review their logs. The health screen was repeated after the 60-day intervention and intake logs were evaluated.

Results:
Weight loss averaged 12 lbs (6.7%, p=0.092). VLDL-particle number (VLDL-P, p=0.045), triglycerides (p=0.003), and HDL-particle number (p=0.011) levels significantly decreased. LDL-particle number (LDL-P) and LDL-cholesterol (LDL-C) did not significantly change, nor did fasting glucose or HbA1c. Blood pressure significantly improved (systolic, p<0.0001; diastolic, p=0.0003). Participants in the lowest tertile for weight loss had higher baseline risk factors including BMI, LDL-P, LDL-C, fasting glucose and HbA1c levels, yet lower baseline VLDL-P, triglycerides and blood pressure. Greater weight loss was associated with greater reductions in VLDL-P, triglycerides and lipoprotein insulin resistance index.

Conclusions:
The paleolithic diet promoted cardiovascular risk factor modification through weight loss, improved blood pressure, reduced triglyceride, and reduced lipoprotein markers associated with insulin resistance.
Abstract 12041: Therapeutic Effects of Induced Pluripotent Stem Cells Secretome In Monocrotaline-induced Pulmonary Arterial Hypertension Rats
Authors: Huang Wei-Chun , Ke Meng-Wei , Cheng Chin-Chang , Chiou Shih-Hwa , Wann Shue-Ren , Shu Chih-Wen , Chiou Kuan-Rau , Tseng Ching-Jiunn , Shen Min-Ci , Huang Wan-Tin , Li Tzu Jung , Kang Pei-leun , Mar Guang-Yuan , Liu Chun-Peng
Published: July 2021

Introduction:
Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by the increased vascular resistance and the remodeling of pulmonary arteries. Evidences of accumulated inflammatory cells in the lung suggested that chronic inflammation might play a role in PAH. Regenerative cell therapy emerged as a potential treatment for PAH through regulating the host’s immune response.

Hypothesis:
The secretome of induced pluripotent stem cells (iPSCs) was investigated for their preventive and therapeutic effects in the pathogenesis of monocrotaline (MCT)-induced PAH rat.

Methods:
PAH was developed by the subcutaneous injection of MCT in rats. The conditioned medium of cultured iPSCs (iPSC CM) was applied daily in prevention (an hour after MCT injection) or reversal (14 days after MCT injection) by IP injection throughout the full 28 days of experiment. The effects of iPSC CM were interpreted by the analyses of systolic pressure (RVSP) and the hypertrophy index of right ventricle, also the regulation of inflammation in lung and the underlying mechanism.

Results:
Both prevention and reversal, the hemodynamic values of RVSP and hypertrophy index were significantly improved in MCT-induced PAH rats after iPSC CM treatment. Attenuated expression of pro-inflammatory M1 macrophage markers was observed in either the lung of MCT-induced PAH rats or in co-cultured human M1 macrophages after iPSC CM treatment. To investigate the potential molecules secreted by iPSCs into iPSC CM, two major ingredients, named α1-antitrypsin and feutin-a, were identified by protein mass spectrometry and confirmed by western blotting with specific antibodies. Both components were mentioned to be involved in the anti-inflammatory effects observed in various lung diseases.

Conclusions:
In this study, iPSC CM represented therapeutic benefits on MCT-induced PAH rats though attenuating inflammation. Molecules exhibit anti-inflammatory potential existed in the iPSC CM, such as α1-antitrypsin and feutin-a, might hold the promise as new therapeutics of regenerative cell therapy via paracrine mechanism.
Abstract 12050: The CHA2DS2-VASc Score Predicts High Mortality in Hospitalized Heart Failure Patients
Authors: Watanabe Shunsuke , Yoshihisa Akiomi , Kanno Yuki , Takiguchi Mai , Miura Shunsuke , Sato Akihiko , Shimizu Takeshi , Nakamura Yuichi , Yamauchi Hiroyuki , Owada Takashi , Abe Satoshi , Suzuki Satoshi , Oikawa Masayoshi , Sakamoto Nobuo , Yamaki Takayoshi , Sugimoto Koichi , Kunii Hiroyuki , Nakazato Kazuhiko , Suzuki Hitoshi , Saitoh Shu-ichi , Takeishi Yasuchika
Published: July 2021

Background:
Atrial fibrillation (AF) is common in patients with heart failure (HF). CHA2DS2-VASc score is an originally risk assessment tool for stroke in patients with AF. Recently, it has been reported that CHA2DS2-VASc score is associated with mortality in patients with acute coronary syndrome with or without AF. We aimed to examine the value of the CHA2DS2-VASc score as a risk assessment tool in patients with HF. Methods and Results: Consecutive 1011 patients admitted for treatment of HF were divided into three groups based on CHA2DS2-VASc score: low score group (CHA2DS2-VASc score 1-3, n=316), moderate score group (CHA2DS2-VASc score 4-6, n=549) and high score group (CHA2DS2-VASc score 7-9, n=145). Of 1011 HF patients, 387 (38.3%, mean age 70.5 years, male 247) had AF. We compared patient characteristics and prospectively followed all-cause mortality among the three groups. The high score group, as compared to low and moderate score groups, had higher cardio-ankle vascular index (9.0 vs. 8.5, 7.9, P=0.001), lower levels of hemoglobin (11.2 vs. 12.1, 13.4 g/dl, P<0.001), sodium (138.5 vs. 138.4, 139.4 mEq/l, P=0.002) and estimated GFR (40.0 vs. 52.7, 64.3 ml/min/1.73m
2
, p<0.001). In contrast, left ventricular ejection fraction was similar among the three groups. Importantly, all-cause mortality was higher in high score group than in low and moderate score groups (P<0.001). In the multivariable Cox proportional hazard analyses, CHA2DS2-VASc score was an independent predictor of all-cause mortality (all patients: HR 1.203, P<0.001; AF patients: HR 1.152, P=0.009; non-AF patients: HR 1.228, P<0.001). Conclusions: The CHA2DS2-VASc score was an independent predictor of all-cause mortality in HF patients with or without AF. CHA2DS2-VASc score may help to identify patients at high risk for mortality and need for optimization of risk-reducing treatment in HF patients.
Abstract 12063: High-risk Plaque Co-localizes With Low Endothelial Shear Stress and Expansive Remodeling in Human Coronary Arteries:
A 3D Optical Coherence Tomography Study
Authors: Chatzizisis Yiannis S , Toutouzas Konstantinos , Giannopoulos Andreas A , Riga Maria , Antoniadis Antonios P , Mitsouras Dimitrios , Fujinom Yusuke , Koutkias Vassilis G , Cheimariotis Grigorios , Doulaverakis Charalampos , Tsampoulatidis Ioannis , Chouvarda Ioanna , Kompatsiaris Ioannis , Nakamura Sunao , Rybicki Frank J , Maglaveras Nicos , Tousoulis Dimitris , Karvounis Charalambos , Giannoglou George D
Published: July 2021

Background:
High risk plaque accounts for the majority of acute coronary events. Low endothelial shear stress (ESS) is a key factor of the natural history of atherosclerosis. The role of ESS in high risk plaque formation is not well studied in man.

Hypothesis:
To explore the association of low ESS with high risk plaque and to identify the ESS milieu and vascular remodeling response in high risk vs. non high risk plaque.

Methods:
35 coronary arteries from 30 patients were 3D reconstructed with fusion of coronary angiography and optical coherence tomography
(Fig A-D)
. ESS was calculated in the 3D reconstructed arteries using computational fluid dynamics
(Fig E)
and classified into low, moderate and high in 3 mm long segments. In each segment: i) fibroatheromas were classified into high risk and non high risk based on fibrous cap thickness and lipid pool size ii) vascular remodeling was classified into constrictive, compensatory and expansive.

Results:
Fibroatheromas in low ESS segments had significantly thinner fibrous cap compared to high ESS segments (89±84 vs.138±83 μm, p<0.05). Lipid pool size was comparable across all ESS categories. The majority of low ESS segments co-localized with high risk plaques (29 vs. 9%, p<0.05), whereas the majority of high ESS co-localized with non high risk plaques (24 vs. 9%, p<0.05,
Fig F
). Compensatory and expansive remodeling was the predominant remodeling response in low ESS segments containing high risk plaques. In non-stenotic fibroatheromas (expansive or compensatory remodeling) low ESS was predominantly associated with high risk plaques (29 vs. 3%, p<0.05) whereas high ESS was associated with non high risk plaques
(Fig F)
.

Conclusions:
Novel combined anatomic and functional imaging with 3D OCT showed that low ESS and non-constrictive remodeling are associated with high risk plaque in man. Further studies are needed to assess the role of ESS and vascular remodeling in high risk plaque rupture and precipitation of clinical outcomes.
Abstract 12065: CPR Prompting Devices: Unintended Consequences Impacting High Performers
Authors: Mulvey Christie L , Rudy Sally J , Rodgers David L , Bortner Tammi J , Sinz Elizabeth H , Kass Lawrence E
Published: July 2021

Introduction:
Prompting devices for chest compressions have been advocated as a means of improving CPR quality in previous AHA guidelines. Studies have shown overall CPR quality improves with the use of these devices.

Hypothesis:
This study compared the impact of prompting devices on providers with varying levels of experience and proficiency.

Methods:
A convenience sample of 53 subjects with varying degrees of CPR experience, ranging from zero to frequent opportunities to perform CPR, were enrolled. Using a skills recording CPR manikin, data on each subject’s chest compression performance was obtained. All subjects performed an initial one-minute cycle of continuous chest compressions with no prompting device. After a brief rest, subjects were randomized to use one of two CPR prompting devices (Philips MRX with Q-CPR or Laerdal Medical CPRmeter). An additional one minute of CPR was conducted with the first device. Subjects were then crossed over to use the other prompting device after another brief rest.

Results:
Across the entire group, nearly all parameters significantly improved with the prompting devices, confirming previous studies on the efficacy of CPR prompting devices. However, when subjects’ results were examined by breaking the group into three performance levels (high, medium and low) based on the
Overall CPR Score
generated by the manikin software, there were differences in performance. Paired
t
-tests were conducted on the low and high performance groups. The low-level group significantly improved across 7 of 8 variables with both devices. The high-level group had only minor changes from baseline (both positive and negative) in most variables, but had significant or near significant decrease in proficiency in one variable - percent correctly released compressions (
p
= 0.011 for Philips device;
p
= 0.052 for the Laerdal device).

Conclusions:
CPR prompting devices improve the overall quality of chest compressions. Individuals with existing high performance CPR skills could be distracted by the device, reducing the quality of compressions compared to using no device. When a CPR prompting device is introduced into a health care system, all providers, especially high performers, require practice with the device in order to acclimate to its use.
Abstract 12070: Long-term Prognostic Value of Cardiac Power Index in Patients Admitted With Acute Decompensated Heart Failure
Authors: Yamada Takahisa , Morita Takashi , Furukawa Yoshio , Tamaki Shunsuke , Iwasaki Yusuke , Kawasaki Masato , Kikuchi Atsushi , Kondo Takumi , Ishimi Masashi , Hakui Hideyuki , Ozaki Tatsuhisa , Satoh Yoshihiro , Seo Masahiro , Ikeda Iyo , Fukuhara Eiji , Fukunami Masatake
Published: July 2021

Backgrounds:
Cardiac power is the rate of hydraulic work done by the heart. It has recently been shown that cardiac power index (CPI) provided prognostic independent and incremental prediction in adverse outcomes beyond traditional hemodynamic parameters in ambulatory patients with advanced heart failure. However, there is little information available on the long-term prognostic value of CPI in patients with acute decompensated heart failure (ADHF).

Methods and Results:
We studied 209 patients admitted for ADHF, who underwent right heart catheterization at the admission and were discharged with survival. CPI was calculated by: CPI W/m
2
= ([mean arterial pressure(mmHg) - [right arterial pressure(mm Hg)] x cardiac output [L/min] x K)/ (BSA m
2
) where K = 0.0022. During a mean follow-up period of 4.4±3.3 yrs, 50 patients had cardiovascular death (CVD). CPI was significantly lower in patients with than without CVD (0.407±0.138 vs 0.550±0.258 W/m
2
, p=0.0002). Multivariate Cox regression analysis revealed that CPI (hazard ratio 0.092 [95%CI 0.017-0.497], p=0.005) was significantly associated with CVD, independently of body mass index, BUN and serum sodium levels, after adjustment for age, systolic blood pressure, pulmonary vascular resistance, and serum creatinine, albumin, and hemoglobin levels. Patients with low CPI (lowest tertile<0.395 W/m
2
) had a significantly higher CVD risk than those with middle CPI(0.395-0.565 W/m
2
) and high CPI (highest tertile: >0.565 W/m
2
) (41%(28/69) vs 22%(15/70) vs 10%(10/70), p<0.0001, respectively). The adjusted hazard ratio in patients with low CPI was 3.40 (95%CI 1.46-7.92).

Conclusions:
CPI could provide the long-term prognostic information in patients admitted with ADHF.
Abstract 12071: Serum Immunoglobulin G4 Level is an Independent Predictor of Major Adverse Cardiovascular Events After Percutaneous Coronary Intervention over Long-Term Follow-Up
Authors: Sakamoto Aiko , Ishizaka Nobukazu , Ando Jiro , Nagai Ryozo , Komuro Issei
Published: July 2021

Background:
Inflammatory processes contribute to the development of atherosclerosis. However, it remains unclear whether immunoglobulin G4 (IgG4)-related immuno-inflammation may affect the progression of cardiovascular disease. We therefore analyzed the relationship between serum IgG4 level and future major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI).

Methods:
We measured serum levels of IgG4 in 562 patients (mean age, 66.9 ± 10.3 years) who underwent coronary angiography from October 2005 to September 2008. Furthermore, a total of 108 patients who subsequently received first PCI were followed-up for a median period of 2721 days (interquartile range [IR] 1591-3183). MACE was defined as cardiac death, acute coronary syndrome, cerebral stroke, and target vessel revascularization.

Results:
Serum levels of IgG4 were significantly higher in patients with coronary artery disease (34.1 mg/dL, IR 18.7-58.9) than in those without (30.5 mg/dL, IR 15.8-50.3, P=0.045). Among patients who received PCI, 40 (37.0%) patients developed MACE during the follow-up period. Patients with serum IgG4 levels of median or greater (≥37.2 mg/dL) had a significantly higher risk of MACE than those with serum IgG4 levels below median (log-rank test, P=0.017). In Cox regression analysis using age, gender, estimated glomerular filtration rate (eGFR), hypertension, dyslipidemia, diabetes, smoking, and serum levels of high-sensitivity C-reactive protein (hsCRP) as covariates, serum IgG4 level was an independent predictor of MACE (hazard ratio 2.39 per 100 mg/dL increase, 95% confidence interval 1.41-4.07, P=0.001).

Conclusions:
Elevated serum IgG4 level at baseline significantly predicted MACE after PCI, as well as present coronary stenosis, over long-term follow-up even among patients without apparent IgG4-related disease. IgG4-related immuno-inflammation may play a certain role in the progression of coronary atherosclerosis.
Abstract 12119: Class I Indication for Statin Therapy in Primary Prevention by Three Cholesterol Guidelines and Prevalence of Coronary Artery Calcium in Asymptomatic Adults: Multi-ethnic Study of Atherosclerosis (MESA)
Authors: Flueckiger Peter , Qureshi Waqas , Blaha Michael , Burke Gregory , Sandfort Veit , Michos Erin D , Herrington David , Yeboah Joseph
Published: July 2021

Introduction:Statin therapy for secondary prevention of atherosclerotic cardiovascular disease (ASCVD) events provides greater relative risk reduction compared with primary prevention. Coronary artery calcium (CAC) identifies individuals with established but subclinical ASCVD disease. Identifying a population with a higher prevalence of CAC may improve the benefit and efficacy of statin therapy in the primary prevention of ASCVD. We assessed the accuracy of class I statin eligibility criterion for primary prevention by the 2013 ACC/AHA cholesterol guidelines for the presence of CAC and compared it with class I criterion for lipid lowering therapy eligibility by the 2004 NCEP/ATP III and 2011 ESC/EAS cholesterol guidelines.

Methods:4723 out of the 6814 total participants not taken statins during the baseline exam and with complete data including CAC were included in analysis. We evaluated the sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV) of class I recommendation for lipid lowering therapy (high risk designation) by the three cholesterol guidelines for three categories of prevalent CAC [CAC present/absent; CAC ≥ 100; CAC ≥300 Agatston] in participants of the Multi Ethnic Study of Atherosclerosis (MESA)

Results:Mean age 59±9 years, 47% male, 37% white, 28% black, 23% Hispanic, 12% Asian, 7.5% with diabetes, 35% current/former smokers, mean glomerular filtration rate of 83±18 ml/min and mean BMI of 28±6 kg/m2. 1978(41.9%), 816(17.3%) and 392(8.3%) had CAC present, CAC ≥100 and CAC ≥300 respectively. Table 1 shows the results.

Conclusions:The SN, SP, PPV and NPV of class I statin eligibility criteria by the 3 guidelines for subclinical ASCVD depends significantly on the definition of CAC. The 2013 ACC/AHA class I statin eligibility has a higher SN, lower SP, and higher NPV when compared with the 2004 NCEP/ATP III and 2011 ESC/EAS class I criterion for statin therapy across all three CAC categories.
Abstract 12120: Intracranial Pressure Increases Both During Mild Therapeutic Hypothermia and During Rewarming Period in Post Cardiac Arrest Patients
Authors: Naito Hiromichi , Isotani Eiji , Callaway Clifton W , Hagioka Shingo , Morimoto Naoki
Published: July 2021

Introduction:
Elevation of intracranial pressure (ICP) may induce secondary brain injury and worsen the neurological outcome. Some studies on traumatic brain injury show that rapid rewarming can result in poorer outcomes contributory due to elevation of ICP. However, little is known about ICP during therapeutic hypothermia (TH) and rewarming period in post cardiac arrest patients.

Hypothesis:
We tested if there is occurrence of increased ICP during mild TH and rewarming period and whether it is related to outcome in patients resuscitated after cardiac arrest.

Methods:
Comatose patients resuscitated from cardiac arrest, treated with TH and ICP monitored were enrolled in the study. Surface cooling device was used for TH. Patients were maintained in target core temperature of 34 °C for 24 hrs. Thereafter, the temperature was regulated to increase to normothermia (37.0 °C) at the rate of 0.25 °C/hr. ICP and cerebral perfusion pressure (CPP) were monitored during the period. Cerebral Performance Category (CPC) scale was obtained 28 days later.

Results:
Data of 9 patients were analyzed (8 [89 %] men, age: 62 ± 17 years, cardiac origin 3 [33 %]/non-cardiac origin: 6 [67 %], CPC 1: 2 patients; CPC 2: 1 patient; CPC 3: 1 patient; CPC 4: 2 patients; CPC 5: 3 patients). ICP was 7.7 ± 4.4 mmHg at the beginning of TH and significantly elevated to 17.4 ± 13.3 mmHg at the end of TH (p = 0.03). ICP was 23.6 ± 19.1 mmHg at the end of rewarming which was higher than the end of TH (p = 0.04). At the end of rewarming, ICP value ranged in variety from 10 mmHg (CPC 1) to 68 mmHg (CPC 5). CPP was 81.3 ± 15.6 mmHg at the beginning of TH and was 72.1 ± 22.7 mmHg (p = 0.22) at the end of rewarming. All the cases with CPP less than 40 mmHg within 48 hrs died.

Conclusions:
ICP is increasing both during TH of target temperature 34°C and during rewarming at speed of 0.25 °C/hr in patients after cardiac arrest. Increment of ICP seems to be greater in cases with poorer outcome. CPP decrease was not usually observed and was limited to fatal cases.
Abstract 12135: Toll-like Receptor Signalling Mediates C-kit+ Cell Migration
in vivo
Following Ischemia-reperfusion Injury via the Myd88 Pathway
Authors: Donndorf Peter , Abubaker Saifullah , Kaminski Alexander , Vollmar Brigitte , Steinhoff Gustav
Published: July 2021

Introduction:
Toll-like-receptor (TLR) mediated signalling has been shown to regulate tissue damage following cardiac ischemia-reperfusion (I-R) injury. Whether progenitor cell based cardiac regeneration might also depend on TLR-signaling has not been described conclusively. As sufficient progenitor cell migration represents a crucial step of cell-based therapy protocols, we aimed at analyzing the migratory capacity of c-kit+ bone marrow stem cells in vivo following I-R injury as well as the impact of endothelial TLR's and related signalling pathways (MyD88,TRIF)on c-kit+ cell migration.

Methods:
Murine c-kit+ stem cells were isolated from the bone marrow. In vivo migration of fluorescently labeled c-kit+ following different extents of local I-R injury was visualized by intravital fluorescence microscopy, utilizing the cremaster muscle model in male mice.C-kit+ cell migration was quantified by analyzing early (endothelial rolling) and late (firm endothelial adhesion) c-kit+ cell interaction with the local endothelium. The role of TLR-2 and TLR-4, as well as MyD88 and TRIF on c-kit+ migration following I-R-injury was analyzed by applying specific knock-out models.

Results:
A sequence of 15 min ischemia followed by 15 min reperfusion induced relevant interactions of c-kit+ cells with the microvascular endothelium(Firm endothelial adhesion:5.6±1.3 cells/mm2 in control vs. 30.2±10.1 cells/mm2 in IR, p<0.05). Prolonged I-R periods did not result in an additional gain of c-kit+ cell-endothelial cell interaction. Knock-out of TLR-2 and TLR-4 diminished I-R induced c-kit+ - endothelial cell interaction.Subsequent knock-out of downstream adaptor proteins resulted in a significantly decreased firm endothelial c-kit+ cell adhesion only for MyD88 but not for TRIF.

Conclusions:
Artificially applied c-kit+ cells are capable to interact with the target organ endothelium following I-R injury. C-kit+ cell-endothelial cell interaction following I-R injury depends on TLR associated signaling, with a special relevance being demonstrated here for the MyD88 pathway. Our findings suggest, that therapeutic blockade of TLR signaling following I-R injury for anti-inflammatory purposes might interfere with progenitor cell based therapy protocols.
Abstract 12149: Associations of Intima-Media Thickness of Different Segments of Carotid Arteries and Prevalent Cardio-Metabolic Diseases in Middle-age Adults and Elders in Taiwan
Authors: Wang Li-Yu , Chan Hsin-Lung , Chi Po-Ching , Hung Chung-Lieh , Liu Chun-Chieh , Wu Tzu-Wei , Wang Shih-Wei , Wu Yih-Jer , Wang Shwun-De , Yeh Hung-I
Published: July 2021

Background and Aim:
Carotid intima-media thickness (IMT) is a well-studied phenotype of atherosclerosis in developed countries, however, there was only a few studies in developing countries. The aim of the study was to explore the relationships between carotid IMTs and prevalent cardio-metabolic diseases in Chinese.

Methods:
1579 residents aged 40-74 years from three communities in northern Taiwan were recruited in 2010-2012. The far-wall intima-media thickness (IMTs) of the right and left common carotid arteries (CCAs), internal carotid arteries (ICA), and carotid bifurcation (BIF) were measured by B mode ultrasound. All participants were assessed for cardio-metabolic profiles and 10-year general cardiovascular risks by the Framingham Risk Score.

Results:
Correlation analyses showed that there were significant linear trends with age and estimated 10-year general cardiovascular risks for all segmental carotid IMTs. The linear trends were the strongest for CCA IMTs, followed by BIF IMTs, and the least for ICA IMTs, and stronger for the average IMTs of the right and left carotid arteries than one-sided IMTs alone. Male sex, central obesity, high BMI, high LDL-/HLD-C ratio, high blood pressure, and high blood sugar were significantly correlated with thicker carotid IMTs. Subjects affected with hypertension, diabetes mellitus (DM), metabolic syndrome, and cardiovascular diseases (CVDs) had significantly thicker carotid IMTs. After adjustment for traditional cardio-metabolic risk factors, subjects who had mean or maximum CCA or mean BIF IMTs >= the 3rd quartiles had significantly higher likelihoods of having prevalent CVDs. The adjusted ORs were 2.13 (95% CI: 1.30-3.49), 1.73 (95% CI: 1.06-2.82), and 1.59 (95% CI: 1.01-2.51), respectively. The adjusted ORs were not significant for subjects who had elevated mean or maximum ICA or maximum BIF IMTs.

Conclusions:
Carotid IMTs were significantly correlated with most traditional cardio-metabolic risk factors. Among different segmental carotid IMTs, CCA IMTs demonstrated stronger associations with prevalent CVDs and DM. Carotid IMTs may be used as an intermediate marker of advanced vascular diseases in Chinese.
Abstract 12158: Impact of Modifiable Risk Factors on Circulating Concentrations of B-type Natriuretic Peptide and Cardiac Troponin T
Authors: Srivastava Pratyaksh K , Pradhan Aruna D , Cook Nancy R , Ridker Paul M , Everett Brendan M
Published: July 2021

Introduction:
Alcohol use, physical activity, diet, and cigarette smoking are modifiable cardiovascular risk factors that have a substantial impact on the risk of myocardial infarction, stroke, and cardiovascular death.

Hypothesis:
We hypothesized that these behaviors may alter concentrations of cardiac troponin, a marker of myocyte injury, and B-type natriuretic peptide, a marker of myocyte stress. Both markers have shown strong association with adverse cardiovascular outcomes.

Methods:
In 564 women with no evidence of cardiovascular disease, we measured circulating concentrations of cardiac troponin T, measured using a high-sensitivity assay (hsTnT), and the N-terminal fragment of B-type natriuretic peptide (NT-proBNP). We used logistic regression to determine if these behaviors were associated with detectable hsTnT (>= 3ng/L) or with NT-proBNP in the highest quartile (≥117.4 ng/L).

Results:
The median (Q1-Q3) NT-proBNP of the cohort was 64.2 (37.8-117.4), and 30.3% (171/564) of the cohort had detectable circulating hsTnT. In adjusted models, women who drank 1-6 drinks per week had a lower odds of having a detectable hsTnT (OR 0.54, 95% CI: 0.33-0.89, P-trend=0.001) or an elevated NT-proBNP (OR 0.48, 95% CI 0.19-1.19, P-trend =0.03; Figure). We validated the results for B-type natriuretic peptide in a large independent cohort. No significant associations were seen for diet, exercise, or smoking.

Conclusion:
Regular alcohol consumption is associated with lower concentrations of hsTnT and NT-proBNP, two cardiovascular biomarkers associated with increased cardiovascular risk. These results raise the hypothesis that the beneficial effects of alcohol consumption may be mediated by direct effects on the myocardium.
Abstract 12177: Important Roles of Endothelial Caveolin-1/eNOS Complex in Maintaining Microvascular Homeostasis Through Endothelium-dependent Hyperpolarization Mediated Mechanism
Authors: Saito Hiroki , Sato Saori , Ikumi Yousuke , Tanaka Shuhei , Godo Shigeo , Shimokawa Hiroaki
Published: July 2021

Background:
The endothelium plays important roles in maintaining cardiovascular homeostasis by synthesizing and releasing several vasodilators, including prostacyclin (PGI2), nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) factor. It is widely accepted that EDH plays important roles especially in microcirculation. We have previously demonstrated that endothelial NO synthase (eNOS) plays diverse roles depending on vessel size, as a NO generating system in conduit arteries and an EDH-mediated system in resistance arteries. Recently, we also have reported that caveolin-1 is involved in enhanced EDH-mediated mechanisms in resistance arteries through functional inhibition of eNOS. However, the detailed functions of caveolin-1 in the endothelium remain to be elucidated. Material and Results: We newly generated endothelium-specific caveolin-1-knockout mice (eCav-1-KO) under the control of Tie2 promoter. We confirmed that caveolae is absent in endothelial cells of those mice. Co-immunoprecipitation experiments showed the eNOS/Cav-1 complex formation in control mice, but not in eCav-1-KO mice. Western blot experiments demonstrated that the extent of eNOS phosphorylation at Ser1177 (stimulatory site) was comparable, whereas that at Thr495 (inhibitory site) was significantly reduced in mesenteric arteries from eCav-1-KO mice as compared with control mice, demonstrating hyperactivation of eNOS. Isometric tension experiments and Langendorff experiments showed that NO-mediated responses were significantly enhanced, whereas EDH-mediated responses were significantly reduced in microcirculations in eCav-1-KO mice. Importantly, eCav-1-KO mice showed altered endothelial functions and cardiac hypertrophy despite normal blood pressure level. Furthermore, the hearts from eCav-1-KO mice showed enhanced staining for nitrotyrosine, a marker of nitrosative stress in microvessels and epicardial arteries, whereas those from control mice only showed mild staining in epicardial arteries alone. Conclusions: These results indicate that endothelial Cav-1/eNOS complex plays important roles in maintaining microvascular homeostasis through EDH-mediated mechanisms in mice in vivo.
Abstract 12186: Therapeutic Effects of Blockade of IL-6/gp130 Signaling in Pulmonary Arterial Hypertension
Authors: Tamura Yuichi , Phan Carole , Tu Ly , Thuillet Raphaël , Le Hiress Morane , Huertas Alice , Fadel Elie , Simonneau Gerald , Humbert Marc , Guignabert Christophe
Published: July 2021

Background:
Interleukin (IL)-6 has been linked to the prognosis of pulmonary arterial hypertension (PAH). However, precise contributions of IL-6 and its signaling system to PAH progression is still obscure.

Objectives:
To study pathogenic roles of IL-6 cis- and trans-signaling in experimental and human PAH and to evaluate the translational potential of IL-6 signaling inhibition.

Methods:
We examined the global expression pattern of key actors of the IL-6 signaling in human lung tissues, blood samples and cultured pulmonary artery-smooth muscle cells (PA-SMCs) of 10 controls and 10 idiopathic PAH (IPAH) patients. In addition, two complementary animal models of pulmonary hypertension (PH) have been studied: the monocrotaline and SU5416 plus chronic hypoxia rat models.

Results:
In IPAH, serum levels of IL-6 and soluble IL-6 receptors (sIL-6R) proteins were higher than in control subjects. We also found stronger immunoreactivity for IL-6R, p-STAT3 and myeloid leukemia-cell protein 1 (Mcl-1, a downstream target of IL-6) in the media of remodeled pulmonary arteries and cultured PA-SMCs of IPAH patients compared with controls. These abnormalities in the IL-6/IL-6R signaling were also histologically found in the two rat models. Consistent with these findings, we also found that IL-6 with or without sIL-6R could substantially increase p-STAT3 and the anti-apoptotic Mcl-1 protein in cultured IPAH PA-SMCs compared with control cells. These effects were totally abolished in the presence of IL-6R neutralizing antibodies and an IL-6R antagonist. Finally, we found that daily treatment with IL-6R antagonist started 1 week after a subcutaneous monocrotaline injection substantially attenuates the abnormal increase in p-STAT3 and Mcl-1 and regresses established PH.

Conclusions:
We demonstrate here that anti-IL-6R strategies may represent promising novels anti-proliferative and anti-inflammatory approaches for treatment of PAH.
Abstract 12203: Clinical Characteristics of Patients With Acute Myocardial Infarction Who Did Not Receive Primary Percutaneous Coronary Intervention in Japan -Report From the Miyagi-AMI Registry Study
Authors: Hao Kiyotaka , Takahashi Jun , Ito Kenta , Cui Yuanji , Miyata Satoshi , Nishimiya Kensuke , Tsuburaya Ryuji , Matsumoto Yasuharu , Sakata Yasuhiko , Yasuda Satoshi , Shimokawa Hiroaki
Published: July 2021

Background:
In the current primary percutaneous coronary intervention (PCI) era, some patients in acute myocardial infarction (AMI) still do not undergo primary PCI in Japan. We thus aimed to elucidate the characteristics of AMI patients who did not receive primary PCI.

Methods and Results:
We analyzed the patients enrolled between 2002 and 2010 in the Miyagi-AMI Registry Study, where all AMI patients in the Miyagi prefecture have been prospectively registered for 34 years since 1979. Among a total of 8,640 patients with AMI (M/F 6205/2435, mean age 68.9±13.0 [SD] years), 1,879 (21.7%) did not receive primary PCI and their in-hospital mortality was significantly worse compared with those who received it (21.4% vs. 6.4%, P<0.01). Multivariate analysis demonstrated that female sex was significantly associated with non-performance of primary PCI [odds ratio (95% confidence intervals); 1.40(1.22-1.61), P<0.001], along with aging [1.01(1.01-1.02), P<0.001] and heart failure on admission [2.69(2.29-3.16), P<0.001]. When dividing by age, non-performance rate of primary PCI in female showed U-shaped prevalence, whereas it simply increased with aging in male
(Figure A)
. Importantly, female patients aged <80 years had a significantly higher non-performance rate of primary PCI compared with male patients, regardless of disease severity as evidenced by co-existing heart failure on admission
(Figure B)
.

Conclusions:
These results indicate that in the current PCI era, various factors, including aging, heart failure on admission and sex differences, are associated with non-performance of primary PCI, which remain to be resolved in order to further improve critical care of AMI.
Abstract 12221: Impact of Serum Uric Acid on Mortality in Heart Failure With Preserved Ejection Fraction
Authors: Shimizu Takeshi , Yoshihisa Akiomi , Takiguchi Mai , Miura Shunsuke , Sato Akihiko , Nakamura Yuichi , Yamauchi Hiroyuki , Owada Takashi , Abe Satoshi , Suzuki Satoshi , Oikawa Masayoshi , Yamaki Takayoshi , Sugimoto Koichi , Kunii Hiroyuki , Nakazato Kazuhiko , Suzuki Hitoshi , Saitoh Shu-ichi , Takeishi Yasuchika
Published: July 2021

Background:
Serum uric acid is a predictor of cardiovascular mortality in heart failure with reduced ejection fraction. However, the impact of uric acid on heart failure with preserved ejection fraction (HFpEF) remains unclear. Here we investigated the association between hyperuricemia and mortality in HFpEF patients. Methods and Results: Consecutive 424 patients, who admitted to our hospital for decompensated heart failure and diagnosed as HFpEF, were divided into two groups based on presence of hyperuricemia (serum uric acid ≥ 7 mg/dl). We compared patient characteristics, cardio-ankle vascular index and cardio-pulmonary exercise test findings between the two groups. Furthermore, we prospectively followed cardiac and all-cause mortality. The hyperuricemia group (n=254), as compared with non-hyperuricemia group (n=170), had higher prevalence of male gender (55.5 vs. 41.7%, P=0.005), hypertension (79.9 vs. 69.4%, P=0.013), diabetes mellitus (38.5 vs. 26.4%, P=0.010) and use of diuretics (72.4 vs. 41.7%, P<0.001). Furthermore, the hyperuricemia group had higher levels of B-type natriuretic peptide (112.3 vs. 71.4 pg/ml, P<0.001), lower levels of estimated GFR (53.2 vs. 69.7 ml/min/1.73m
2
, P<0.001), higher cardio-ankle vascular index (8.7 vs. 7.5, P<0.001), lower peak VO
2
(14.9 vs. 17.9 ml/kg/min, P<0.001) and higher VE/VCO
2
slope (34.9 vs. 31.9, P=0.02) compared with non-hyperuricemia group. In the follow up period (mean of 897 days), cardiac and all-cause mortalities were significantly higher in those with hyperuricemia (P=0.006 and P=0.004, respectively). In the multivariable Cox proportional hazard analyses after adjusting for confounding factors including chronic kidney disease and use of diuretics, hyperuricemia was an independent predictor of all-cause mortality (hazard ratio 1.98, P=0.039).

Conclusion:
Hyperuricemia is associated with arterial stiffness, impaired exercise capacity, and high mortality in HFpEF.
Abstract 12229: MicroRNA Regulation of JAK-STAT System in the Atrial Fibrillation-Related Fibrotic Response
Authors: Chen Yu , Surinkaew Sirirat , Xiao Jiening , Wu Chia- T , Huang Hai , Sun Yiguo , Dobrev Dobromir , Nattel Stanley
Published: July 2021

Introduction:
MicroRNAs (miRNAs) are involved in cardiac remodeling, but their role in atrial fibrillation (AF) is poorly understood. JAK-STAT signalling is activated by the pro-fibrotic mediator PDGF, but its contribution to AF substrate formation is unknown. Here, we investigated miRNA regulation of the JAK-STAT system in in the heart failure (HF) induced AF fibrotic substrate.

Methods:
HF was induced in dogs by ventricular tachypacing (VTP, 240 bpm) for 2 weeks. Fibroblasts (FBs) isolated from the left atrium (LA) and left ventricle (LV) of control (CTL) dogs were treated with PDGF-AB. PDGF, JAK2, STAT3 and miRNA expression was assessed by qPCR. JAK2, STAT3 and collagen-I (COL-1) proteins were quantified by Western Blot. miRNA targets were validated by luciferase reporter assay. miRNA mimic or antisense oligonucleotides (AMOs) were used for miRNA manipulation in FBs.

Results:
HF dogs developed AF susceptibility and LA-selective fibrosis beginning at 1 wk VTP. PDGF and JAK2 mRNA, along with phosphorylated (activated) JAK2 protein, were increased in HF atria (by 1.4-2.9* fold, *p<0.05). miR-30a and miR-133a were predicted bioinformatically to target JAK2, and were downregulated by 51%-52%** and 48%-71%** (**p<0.01) in HF LA FBs at 1-2 wk VTP. PDGF-AB increased the expression of JAK2 and STAT3 mRNA (by 1.4-1.5* fold) and COL-1 protein (by 2*** fold, ***p<0.001) in canine LA FBs, while reducing the expression of miR-30a and miR-133a (by ~50%-80% ***). Smaller changes were seen in LV FBs with PDGF-stimulation. Luciferase assay confirmed miR-30a and miR-133a targeting of JAK2. Overexpression of miR-133a downregulated JAK2 mRNA (by 30%***) and protein (by 50%, p=0.05) in LA FBs. This effect was abolished by co-transfection of miR-133a and AMO-133a. The upregulation of JAK2 and COL-1 expression induced by PDGF-AB stimulation was reversed by miR-133a overexpression in LA FBs (reduced by 49%* and 53%*** versus PDGF stimulation alone).

Conclusions:
PDGF-induced disinhibition of JAK2 expression by downregulation of miR-30a and miR-133a may contribute to AF-associated fibrotic responses. MicroRNA targeting of the JAK-STAT system regulates LA FB function, appears to be involved in HF-induced LA fibrosis and is a potential therapeutic target for AF prevention.