bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14891: Six-minute Walk Distance Predicts the Readmission due to Decompensated Heart Failure in Early Elderly and Late Elderly Patients With Chronic Heart Failure
Authors: Tabata Minoru , Kato Michitaka , Shimizu Ryosuke , Akiyama Ayako , Kamada Yumi , Tanaka Shinya , Hamazaki Nobuaki , Aoyama Akihiro , Kamiya Kentaro , Masuda Takashi
Published: July 2021

Background:
Patients with chronic heart failure (CHF) are frequently readmitted to the hospital. Six-minute walk distance (6MWD) is a clinical measure to assess their exercise capacity and prognosis. However, few reports documented whether the 6MWD reflects the exercise capacity and prognosis in elderly CHF patients.

Purpose:
This study aimed to investigate whether the 6MWD measured at the hospital discharge predicted the readmission due to decompensated CHF in early elderly and late elderly CHF patients.

Methods:
Patients who were admitted to the hospital were prospectively followed up for 3 years after the discharge, if they had the first hospitalization due to CHF with NYHA III or IV. Consequently, we studied 177 patients (74±6 years, 112 males) and investigated their 6MWD at the discharge and readmission over 3 years. Patients were divided into 2 groups: early elderly group (65-74 years; n=108) and late elderly group (≥75 years; n=62). We determined significant factors affecting the readmission due to CHF and their cut-off values in the two groups using multivariate logistic regression analysis and the area under the receiver operating characteristics (ROC) curve.

Results:
50 % of early elderly patients and 42 % of late elderly patients were readmitted within 3 year after the discharge. The multivariate logistic regression analysis detected the 6MWD at the discharge as a significant limiting factor for readmission in the two groups (P<0.001, respectively). The odds ratio of readmission with each 10-meter decrease of 6MWD and its cut-off value were 1.34 (P<0.001) and 405 meters for the early elderly group, and 1.37 (P<0.001) and 345 meters for late elderly group, respectively (Figure).

Conclusion:
This study demonstrated that the 6MWD was shown as a strong predictor for readmission due to decompensated heart failure in elderly patients with CHF. The predictive cut-off values of 6MWD were 405 and 345 meters in the early elderly and late elderly patients, respectively.
Abstract 14933: Long (>12 Months) and Short (<6 Months) versus Standard Duration of Dual Antiplatelet Therapy After Coronary Stenting: A Systematic Review and Meta-Analysis
Authors: Sharma Shikha , Briasoulis Alexandros , Mallikethi-Reddy Sagar , Palla Mohan , Sudhakar Rajeev , Siddiqui Fayez , Afonso Luis
Published: July 2021

Background:
Dual antiplatelet therapy (DAPT) is recommended for 6-12 month after drug-eluting stent (DES) implantation to prevent ischemic events and late stent thrombosis. The optimal duration of DAPT has not been established.

Methods:
We performed a meta-analysis of the comparative effects of short- and long- vs standard DAPT duration on adverse cardiovascular and major bleeding. We conducted an EMBASE and MEDLINE search for studies in which patients were randomized to treatment with a different duration of DAPT.

Results:
We identified 5 prospective randomized studies comparing short- vs standard DAPT and 3 comparing long vs. standard DAPT duration with a total of 28,343 patients. Short term DAPT has similar incidence of stent thrombosis, MI and death compared to standard DAPT whereas major bleeding was significantly lower in short DAPT therapy. Long term DAPT was associated with lower rates of stent thrombosis and MI but significantly increased major bleeding and all-cause mortality compared to standard therapy

Conclusion:
We found that short DAPT is safer and as effective as standard DAPT in patients with second generation DES. Extended DAPT is associated with less ischemic events at the expense of high bleeding and mortality rates.
Abstract 15015: Prognostic Value of Serial Changes of High-Sensitivity Cardiac Troponin I and T Using Reference Change Values Among Hemodialysis Patients
Authors: Sandoval Yader , Herzog Charles A , Love Sara A , Wu Alan H , Hu Yan , Gilbertson David T , Brunelli Steven M , Young Amy , Ler Ranka , Apple Fred S
Published: July 2021

Introduction:
Measurement of the biological variation of cardiac troponin (cTn) allows determination of reference change values (RCVs) to use for interpreting serial testing. Using plasma collected serially over 12-months from a stable outpatient hemodialysis (HD) population, our goals were two-fold. First, we calculated RCVs for hs-cTnI and hs-cTnT assays. Second, we determined outcomes based on hs-cTnI and hs-cTnT RCVs.

Methods:
hs-cTnI (Abbott) and hs-cTnT (Roche) were measured in 677 stable outpatient HD patients (enrolled May 2011-November 2012). Hazard ratios (HR), based on RCVs calculated for each hs-cTn assay, for ‘all-cause’, ‘sudden cardiac death (SCD)’ and ‘infectious’ mortality were determined with serial measurements obtained 3 months apart.

Results:
Patient demographics were: mean age 59±14y; mean dialysis duration 5.2±4.2y; 53% male; 59% African American and 50% diabetic ESRD. 18.6% of patients died during a 3-year follow-up. RCVs were: hs-cTnI, +37% and -30%; hs-cTnT, +25% and -20%. Patients with serial hs-cTnI and hs-cTnT changes >RCV had all-cause mortality of 25.2% and 23.8% respectively, compared to 15.0% and 16.5% with ≤RCV (both p<0.05). Outcomes and adjusted HRs are shown in Table. Patients with serial hs-cTnI and hs-cTnT changes >RCV showed a greater risk of all-cause mortality compared to ≤RCV (HR: 1.9 (95% CI: 1.4, 2.8), p=0.0003; and HR: 1.7 (95% CI: 1.2, 2.4), p=0.0066; respectively). However, only hs-cTnI changes >RCV were predictive of SCD (HR: 2.6 (95% CI: 1.3, 5.1), p=0.005).

Conclusions:
Our findings are unique in two ways. First we determined the biological variation of hs-cTnI and hs-cTnT in a large HD population. Second, based on the RCV for each hs-assay, serial changes in hs-cTnI and hs-cTnT >RCV identify patients at greater risk of all-cause mortality, with hs-cTnI also predictive of SCD. These findings support the use of serial changes >RCV for risk-stratification in HD patients.
Abstract 15037: Hyperreninemic Aldosteronism in Caucasian and African-American Patients With Apparent Resistant Hypertension
Authors: Kalra Rajat , Ghazi Lama , Calhoun David A , Oparil Suzanne , Dudenbostel Tanja
Published: July 2021

Introduction:
While primary aldosteronism (PA) is a recognized and relatively well-defined cause of resistant hypertension (RHTN), there is a relative paucity of data defining patients with hyperreninemic aldosteronism (HA) and RHTN.

Hypothesis:
We sought to identify characteristics of patients with HA and compare them to patients with and without PA within a large cohort of patients with RHTN.

Methods:
We analyzed 1236 RHTN patients who were referred to our Hypertension Clinic with and underwent complete biochemical work-up including plasma aldosterone concentration, plasma renin activity, and 24-hour urinary aldosterone. Demographics, antihypertensive drug regimen, comorbidities, biochemical parameters and evaluation for secondary RHTN, where indicated, were evaluated. Hyperreninemic aldosteronism was defined as plasma renin activity >1 ng/mL*hr, aldosterone-renin-ratio of ≈ 8 or more, and 24-hour urinary aldosterone >12 mcg/24h.

Results:
In 128 eligible patients with resistant hypertension and HA, the mean age was 52.9±12.1 years with 56% being males (Table). Systolic and diastolic blood pressures were 149.2±22.0 and 87.9±15.5 mm Hg, respectively. Significant numbers of HA patients had co-morbid obesity (63.3%) and obstructive sleep apnea (44.9%). Compared to patients with PA, patients with HA had statistically significant lower proportions of patients with African-American race and systolic blood pressure. Compared to all RHTN patients, HA patients had lower mean age and systolic blood pressure, but were more likely to be male and have obstructive sleep apnea.

Conclusions:
Resistant hypertension due to hyperreninemic aldosteronism appears to predominantly affect obese, middle-aged males. Patients with HA causing RHTN have distinct differences from PA patients with RHTN. More investigation is required to identify appropriate treatment protocols for this poorly defined subset of patients with RHTN.
Abstract 15107: Long-Term Treatment With Sitagliptin Provides Multiple Ultrasonic-Evaluated Antiatherosclerotic Effects Independent of Diabetic Improvement for Type-2 Diabetics
Authors: Murakami Tatsuaki , Mizuno Sumio
Published: July 2021

Introduction:
Diabetes mellitus (DM) is thought to be highly involved in complex atherothrombogenic processes, but the long-term antiatherosclerotic therapies in patients with type-2 DM have not been established.

Hypothesis:
Therefore we assessed hypothesis long-term treatment sitagliptin, a dipeptidyl peptidase-4 inhibitor recently developed antidiabetic agent, chronically inhibits atherosclerotic progression in patients with type-2 DM.

Methods:
Thirty-two type-2 diabetic patients with stable coronary artery disease were randomized to group-S where they received sitagliptin (50mg/day), or to group-C where they received enhanced antidiabetic therapy without a dipeptidyl peptidase-4 inhibitor for 2 years. We quantified flow-mediated endothelium-dependent dilation of right brachial artery after 5 minutes forearm occlusion (BFMD), and intima-media thickness of brachial artery (BIMT) using high-resolution ultrasonography. We also quantified intima-media thickness of common carotid artery (CIMT) using high-resolution ultrasonography. Changes in BFMD, BIMT, and CIMT were compared between the two study groups.

Results:
Group-S (n=16) manifested good compliance to the long-term treatment and improvements in diabetic and lipid variables represented by HbA1c and LDL after long-term medication of sitagliptin, while there were no improvements in group-C. BFMD (%) improved after medication in group-S (from 3.9±1.8 to 6.4±2.6, p<0.01) and BIMT (mm) decreased in group-SG (from 0.35±0.10 to 0.32±0.11, p=0.03), while both remained unchanged in group-C (BFMD; from 4.1±2.0 to 4.1±1.9, p=0.88, BIMT; from 0.34±0.13 to 0.35±0.12, p=0.54). CIMT (mm) did not increase in group-S (from 1.10±0.35 to 1.08±0.39, p=0.16) but increased in group-C (from 1.09±0.46mm to 1.16±0.47mm, p<0.01). Changes of BFMD or BIMT in group-S did not correlate to those of HbA1c (BFMD: r=0.17, p=0.79, BIMT: r=0.11, p=0.85).

Conclusions:
This study suggests that long-term treatment of sitagliptin safely improves arterial function and inhibits progression of wall thickness independent of reversal for diabetic status, which may have beneficial potentials for long-term management of atherosclerosis in type-2 diabetics.
Abstract 15142: Endogenous Cardiac Stem Cells’ Activation in Response to Injury Potentiates Their Regenerative Ability
Authors: Smith Andrew J , Aquila Iolanda , Henning Beverley J , Scalise Mariangela , Nadal-Ginard Bernardo , Ellison Georgina M , Torella Daniele
Published: July 2021

The identification of resident, endogenous cardiac stem cells (eCSCs) has re-shaped our understanding of cardiac cellular physiology, while offering a significant potential therapeutic avenue. The biology of these cells must be better understood to harness their potential benefits. We used an acute dose (s.c.; 5mgkg-1) of isoproterenol (ISO) to induce diffuse cardiac injury, with associated eCSC activation, in rats. As peak eCSC activation was at 24 hours post ISO-injury, c-kitpos eCSCs were isolated, characterised and their potential for growth and regenerative potential was assessed in vitro and in vivo, respectively. Activated eCSCs showed increased cell cycling activity (51+1% in S- or G2/M phases vs. 9+2% of quiescent), Ki67 expression (56+7% vs. 10+1%) and TERT expression (14-fold increase vs. quiescent). When directly harvested in culture, activated eCSCs showed augmented proliferation, clonogenicity and cardiosphere formation compared to quiescent eCSCs. Activated eCSCs showed increases in expression of numerous growth factors, particularly HGF, IGF-1, TGF-β, periostin, PDGF-AA and VEGF-A. Furthermore, significant alterations were found in the miRnome, notably increased miR-146b and -221, and decreased miR-192 and -351. ISO+5FU was administrated to mice to induce a model of chronic dilated cardiomyopathy, which is characterized by the ablation of eCSCs and the absence of cardiomyocyte replenishment. In these mice with chronic heart failure, freshly isolated quiescent eCSCs or activated eCSCs (2d post-ISO) were injected through the tail vein. 28 days after injection, activated but not quiescent eCSCs re-populated the resident CSC pool, promoted robust new cardiomyocyte formation and improved cardiac function when compared to saline-treated mice. Dual-labelling with BrdU and EdU at selected stages after ISO injury determined that activated eCSCs returned to a quiescent level by 10 weeks post-injury. In conclusion, CSCs rapidly switch from a quiescent to an activated state to match the myocardial needs for myocyte replacement after injury and then spontaneously go back to quiescence. Harnessing the molecules regulating this process may open up future novel approaches for effective myocardial regeneration.
Abstract 15184: Prevalence, Predictors and Clinical Outcomes of Unknown Coronary Artery Disease Among the Patients Undergoing Lower Extremity Endovascular Intervention
Authors: Hong Sung-Jin , Kim Byung Ok , Lee Hye Young , Jung In Hyun , Byun Young Sup , Rhee Kun Joo
Published: July 2021

Introduction:
The prevalence and clinical outcomes of unknown coronary artery disease (CAD) among the patients with peripheral artery disease, particularly for those undergoing lower extremity endovascular intervention, were not well evaluated.

Methods:
Between 2006 and 2014, a total of 208 consecutive patients (73±10 years, 165 men) without angina and prior coronary revascularization, were underwent lower extremity endovascular intervention. All patients evaluated coronary angiography without simutaneous coronary revascularization. CAD was defined as angiographically significant (≥50%) stenosis. All-cause mortality and major adverse cardiac and cerebrovascular event (MACCE) rate were compared between the patients with CAD and those without CAD. MACCE included cardiac death, cerebrovascular death, myocardial infarction, stroke, or heart failure.

Results:
Of the 208 patients, 103 patients (50%) had CAD; 1-VD (17%); 2-VD (17%); 3-VD (15%). Independent predictors of CAD were critical limb ischemia (OR=2.4) and below-the-knee lesions (OR=2.0). During the median follow-up of 1.2 years, all-cause mortality and MACCE rate at 3 year were 16.3% and 19.8%. At 3 year, patients with CAD had significantly higher mortality (19% vs. 14%, P=0.018) and higher MACCE rate (28% vs. 9%, P=0.001) compared to those without CAD. The severity of CAD had graded relations with the mortality and MACCE rate (Figure). Presence of CAD was an independent predictor of mortality (HR=1.5, P=0.025) and MACCE rate (HR=1.9, P<0.001).

Conclusions:
Previously unknown CAD was detected in half of the patients undergoing lower extremity endovascular intervention and associated with higher mortality and MACCE rate. Detection of CAD might be important for risk stratification for these patients, especially with below-the-knee lesions.
Abstract 15192: Leptin Effects on Osteoblast Differentiation of Human Valvular Interstitial Cells: New Insight Into Calcific Aortic Valve Disease
Authors: Rosa Mickael , Lorenzi Rodrigo , Tagzirt Madjid , Juthier Francis , Rauch Antoine , Jashari Ramadan , Corseaux Delphine , Staels Bart , Van Belle Eric , Susen Sophie , Dupont Annabelle
Published: July 2021

Introduction:
Calcific aortic valve disease (CAVD) affects 2% to 6% of the population over 65 years and results from dysregulated processes such as calcification, supported in part by the osteoblast differentiation of valvular interstitial cells (VIC), the most prevalent cell type in the human aortic valves. Leptin has recently been linked to aortic valve calcification in ApoE-/- mice.

Hypothesis:
Our hypothesis is that leptin could play a role in the calcifying processes implicated in CAVD via direct effects on human VIC.

Methods:
Patients who underwent aortic valve replacement for severe CAVD (n=43) or with coronary artery disease (CAD) but without CAVD (n=129) were included in this study. Presence of leptin was analyzed in human explanted calcified aortic valves and blood samples. Leptin receptors expression was analyzed in aortic valves and VIC isolated from aortic valves. Leptin effects on osteoblast differentiation of VIC in presence or not of Akt and ERK inhibitors were investigated by alizarin red staining, alkaline phosphatase (ALP) activity, and RT-qPCR analysis for osteopontin, ALP, bone morphogenetic protein BMP-2, and RUNX2.

Results:
Patients with CAVD have significant higher serum leptin concentration than CAD patients (p=0.002). The presence of leptin was observed by immunochemistry in human calcified aortic valves, with higher concentrations in calcified vs non-calcified zones (p=0.01). Both short and long leptin receptor isoforms were expressed in VIC. Chronic leptin stimulation of VIC enhanced ALP, BMP-2 and RUNX2 expression and decreased osteopontin expression. This treatment led to a higher, dose dependent, ALP activity and calcium deposition in VIC. Inhibiting Akt or ERK during leptin stimulation led to a reduced calcification by bringing the expression of calcification genes to the control levels.

Conclusions:
Together, these novel findings depict the potential role of leptin in the process of CAVD by triggering calcification processes in human VIC.
Abstract 15194: Multiple Co-morbidities Produce Left Ventricular Diastolic Dysfunction in a Large Animal Model
Authors: Sorop Oana , Heinonen Ilkka , van Kranenburg Matthijs , de Beer Vincent J , Octavia Yanti , van Geuns Robert-Jan M , van den Meiracker Anton H , van der Velden Jolanda , Danser Jan A , Merkus Daphne , Duncker Dirk J
Published: July 2021

More than 50% of patients with heart failure have preserved ejection fraction (HFpEF) characterized by diastolic dysfunction. HFpEF usually occurs in female patients with multiple comorbidities such as obesity, hypercholesterolemia, diabetes mellitus (DM) and hypertension. Here we studied the effects of DM, high fat diet (HFD), and chronic kidney disease (CKD) on diastolic dysfunction in swine.

In 11 female swine, DM type 2 (3x50mg/kg iv streptozotocin), hypercholesterolemia (HFD 1% cholesterol) and CKD by renal artery embolization (38-42μm polyethylene beads), were induced (DM+HFD+CKD). Swine were followed for 6 months. Eight female healthy swine on normal pig-chow, matched for age were used as controls (CON).

The DM+HFD+CKD showed hyperglycemia (22.7±0.9mmol/l in DM+HFD+CKD vs 6.1±0.67mmol/l in CON), hypercholesterolemia (16.9±3.4 vs 2.2±0.1mmol/l), hypertriglyceridemia (1.20±0.36 vs 0.28±0.05mmol/l) and hypertension (awake mean arterial pressure: 108±6 vs 84±3mmHg; all P≤0.05). These co-morbidities resulted in chronic systemic inflammation (TNF-α: 231±64 vs 74±24pg/ml), impaired coronary small artery endothelium-dependent vasodilation to bradykinin, capillary rarefaction (cap./fiber ratio 0.58 vs 0.99) and increased myocardial superoxide production (14.8±0.9 vs 6.4±0.3 RLU/sec/g), due to increased NOX activity (all P≤0.05). The coronary microvascular abnormalities were associated with increased myocardial collagen content (4.7±0.3 vs 2.4±0.2%) and elevated passive cardiomyocyte force, (both P≤0.05), resulting in reduced E/A ratio (0.99±0.14 vs 1.53±0.23), measured with cardiac MRI, and increased LV end-diastolic stiffness (0.79±0.19 vs 0.29±0.03 mmHg/ml/mg) derived from LV pressure-volume relations obtained with a conductance catheter (both P≤0.05). In contrast, ejection fraction was maintained, (45±4 vs 54±3%, P=NS).

In summary, multiple comorbidities, including DM, hypercholesterolemia, CKD and hypertension in female swine trigger a series of events, starting with systemic inflammation, increased oxidative stress and coronary microvascular dysfunction, resulting in myocardial stiffening, and leading to diastolic dysfunction.
Abstract 15198: Infarct Size in Patients on Chronic Statin Therapy Undergoing Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction
Authors: Cosentino Nicola , Cortinovis Sarah , Milazzo Valentina , Rubino Mara , Cabiati Angelo , De Metrio Monica , Moltrasio Marco , Lauri Gianfranco , Pontone Gianluca , Marenzi Giancarlo
Published: July 2021

Introduction:
Statin pre-treatment has been reported to have a cardio-protective effect in patients undergoing elective or urgent percutaneous coronary intervention (PCI). However, data on ST-elevation myocardial infarction (STEMI) patients undergoing primary PCI are still controversial.

Hypothesis:
We prospectively evaluated the effect of chronic statin therapy on infarct size (IS), myocardial salvage index (MSI), and micro-vascular obstruction in consecutive STEMI patients undergoing primary PCI.

Methods:
Two-hundred-thirty STEMI patients (mean age 61±11 years, 183 men) who underwent primary PCI were evaluated with cardiac magnetic resonance (CMR) imaging during hospitalization (median 4 days after primary PCI). In all patients, we measured peak troponin I level, while IS, MSI, and micro-vascular obstruction were determined by CMR.

Results:
Fifty (22%) patients were on chronic statin therapy and showed a significantly lower troponin I peak value when compared to patients without prior statins (54±47 vs. 88±106 ng/ml; P=0.02). At CMR evaluation, IS related to the index event was significantly smaller (12.5±11.5 vs. 18.5±18.5 grams,P=0.05), and MSI was higher (0.68±0.25 vs. 0.52±0.30; P=0.01) in patients with prior statin therapy. Micro-vascular obstruction was also less frequent (10% vs. 20%; P=0.14) in this group. At multivariable analysis, prior statin therapy remained significantly associated with IS and MSI (P=0.05 and P=0.02, respectively). No significant association was observed between index IS and LDL-cholesterol levels at hospital admission in the entire population (P=0.91). Moreover, no relationship between IS or MSI and statin dose (r=-0.10, P=0.56 and r=0.10, P=0.55, respectively), and length of statin treatment (r=-0.06, P=0.71 and r=0.29; P=0.10, respectively) was found.

Conclusions:
The results of the present study demonstrated that prior statin therapy is associated with significant smaller IS and higher MSI in patients presenting with STEMI and treated with primary PCI. Whether these preliminary findings will translate into a potential therapeutic strategy warrants further research.
Abstract 15214: Commuting by Public Transportation is Associated With Lower Prevalence of Excess Body Weight, Hypertension, and Diabetes
Authors: Tsuji Hisako , Shiojima Ichiro
Published: July 2021

Background:
Physical activity reduces body weight and incidence of diabetes mellitus (DM). We examined associations of commuting mode with prevalence of excess body weight, hypertension and DM.

Methods:
We studied 16,397 subjects who had the annual health checkup offered to adult citizens of Moriguchi city, Osaka, Japan in 2012. The subjects were asked about their work (Is your work physically active, sedentary or "cannot say"?) and commuting mode (walking or cycling / bus or train / car driving). Odds ratios (OR) of prevalence of excess body weight (body mass index >25.0 kg/m
2
), hypertension, and DM with 95% confidence intervals (CI) relative to the car driving group were calculated using logistic regression analyses adjusted for clinical variables.

Results:
There were 5,908 eligible workers. Characteristics of the subjects according to commuting mode are presented in the table. Compared to the car driving group, logistic regression analyses showed that the public transportation group had a significantly lower prevalence of excess body weight (OR=0.56, 95% CI=0.45 to 0.69, p<0.0001) after adjustment for basic covariates (age, sex, smoking status, hypercholesterolemia, and physical activity of work) and hypertension, a significantly lower prevalence of hypertension (OR=0.73, 95% CI=0.59 to 0.90, p=0.0035) after adjustment for basic covariates and excess body weight, and a significantly lower prevalence of DM (OR=0.66, 95% CI=0.44 to 0.99, p=0.0427) after adjustment for basic covariates, hypertension, excess body weight, and family history of DM.

Conclusions:
The use of public transportation was associated with lower prevalence of excess body weight, hypertension, and DM.
Abstract 15259: Genetically Engineered eNOS Dimer Destabilization Impairs Blood Pressure Reducing Activity of eNOS in Mice
Authors: Suvorava Tatsiana , Pick Stephanie , Kojda Georg
Published: July 2021

Endothelial dysfunction and oxidative stress are associated with hypertension but whether endothelial superoxide plays a role in the early development of essential hypertension remains uncertain. In this study we investigated whether eNOS-derived endothelial oxidative stress is involved in the regulation of blood pressure (BP). Normal bovine eNOS (eNOS-Tg) or a novel dimer-destabilized eNOS-mutant harboring a partially disrupted zinc-finger (C101A-eNOS-Tg) was introduced in C57BL/6 mice using the endothelium-specific tie-2 promoter. Mice were monitored for aortic endothelium-dependent relaxation, systolic BP, levels of superoxide and several post-translational protein modifications indicating activity and/or increased vascular oxidative stress. Some groups of mice underwent voluntary exercise training or treatment with SOD mimetic Tempol (1mM).

C101A-eNOS-Tg (aorta, skeletal muscle, left ventricular myocardium and lung) showed significantly increased superoxide generation, protein- and eNOS-tyrosine-nitration, eNOS-S-glutathionylation, eNOS1176/79 phosphorylation and Thr172-AMP kinase (AMPKα) phosphorylation as compared to eNOS-Tg and wildtype (WT)-controls. The localization of eNOS-Tg was restricted to endothelium as evidenced by immunohistochemical staining for eNOS and an endothelial-specific marker CD31. Exercise training increased phosphorylation of eNOS and AMPKα in WT while these physiologic adaptations were absent in C101A-eNOS-Tg. Aortic endothelium-dependent relaxation was similar in all strains. In striking contrast, C101A-eNOS-Tg displayed normal BP despite higher levels of eNOS, while eNOS-Tg showed significant hypotension. Tempol completely reversed the occurring protein modifications and significantly reduced BP in C101A-eNOS-Tg but not in WT.

We observed that oxidative stress generated by endothelial-specific expression of genetically destabilized C101A- eNOS selectively prevents BP reducing activity of vascular eNOS, while having no effect on aortic endothelial dependent relaxation. Our data suggest that oxidative stress generated by eNOS dimer destabilization contributes to the regulation of blood pressure.
Abstract 15274: Post-stenting Changes in the Coronary Geometry and In-stent Restenosis in Angulated Coronary Lesions: Comparison Between Platinum Chromium and Cobalt Chromium Everolimus-eluting Stents
Authors: Kimura Toshiyuki , Watanabe Nozomi , Kuriyama Nehiro , Shibata Yoshisato
Published: July 2021

Purpose:
Geometric changes in the coronary arteries at the site of coronary stent implantation can lead wall shear stress reduction with decreased coronary flow, which affect the clinical outcome after coronary intervention. Newly developed Platinum Chromium (PtCr)-Everolimus-eluting stent (EES) is expected to improve vessel conformability and restore the natural shape of the vessel with its modified scaffold design, using the same durable polymer and antiproliferative drug as the Cobalt Chromium (CoCr)-EES. The aim of this study was to investigate the long-term effect of PtCr-EES implantation on in-stent restenosis in angulated coronary lesions, comparing with CoCr-EES.

Methods:
This retrospective study included 250 lesions with CoCr-EES implantation and 217 lesions with PtCr-EES implantation for de novo angulated lesions (>45-degree by quantitative coronary angiography). The angle of the lesions was measured in diatole and systole, and cyclic changes in the coronary angle >20 degree was defined as hinge-like motion. Long-term coronary in-stent restenosis was defined as >50% angiographic stenosis in 8 month after the procedure.

Results:
Changes in maximum coronary angle at the site of stent implantation were significantly smaller in PtCr-EES group than in CoCr-EES group compared with original angle (20.65±15.42 vs. 26.25±18.36 degree, p <0.01). There were no significant differences in the occurrence of significant in-stent restenosis between PtCr-EES and CoCr-EES (6.7% vs 10.1%, p=0.32). CoCr-EES tended to show more restenosis than PtCr-EES (12.9% vs. 0.0%, p=0.07) in extremely angulated lesions (>100-degree). Interestingly, in the lesions with hinge-like motion, PtCr-EES group showed significantly higher rate of restenosis compared with CoCr-EES group (26.3% vs 7.7%, p= 0.04).

Conclusions:
In comparison with CoCr-EES, PtCr-EES tended to restore the original curvature of the coronary vessels, and this may lead less restenosis rate in extremely angulated lesions. However, PrCr-EES might have adverse effect on long-term result after coronary stenting in the lesion with hinge-like cyclic motion.
Abstract 15303: The Impact of Heart Rate on the Incidence of Cardiovascular Events in Patients With Chronic Atrial Fibrillation: The Fushimi Af Registry
Authors: Iguchi Moritake , Ogawa Hisashi , Sugiyama Hirofumi , Masunaga Nobutoyo , Ishii Mitsuru , Esato Masahiro , Chun Yeong-Hwa , Wada Hiromichi , Hasegawa Koji , Abe Mitsuru , Akao Masaharu
Published: July 2021

Purpose:
Previous reports suggested that lenient rate control was not inferior to strict rate control among patients with chronic atrial fibrillation (AF). However, the impact of heart rate (HR) on the incidence of cardiovascular events is not clearly understood.

Methods:
The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients in Fushimi-ku, Kyoto, Japan. At present, follow-up data were available in 3,514 patients (median follow-up period, 842 days). 1,622 patients had chronic AF, and we obtained ECG findings in 1,561 patients. We divided these patients into three groups based on their heart rate; high-HR (HR≥110) (n=179), intermediate-HR (80≤HR<110) (n=695), and low-HR (HR<80) (n=687), and explored the cardiovascular events (composite of cardiovascular death, hospitalization for heart failure, and arrhythmic events).

Results:
Mean HR was 128±13 bpm, 93±8 bpm, and 67±9 bpm, respectively. High HR group was younger than other groups, but the prevalence of heart failure was the highest (44.7%, 37.0%, 32.3%; p=0.007) and left-ventricular ejection fraction was the lowest (56.5±14.6%, 60.7±11.9%, 62.7±10.5%; p<0.0001). Prescription of beta-blocker (37.4%, 28.9%, 30.0%) and diltiazem (2.8%, 2.9%, 4.2%) was comparable, but prescription of verapamil was the highest in high-HR group (19.0%, 12.4%, 8.0%; p=0.0001), and prescription of digitalis was the highest in low-HR group (14.0%, 18.2%, 23.4%; p=0.005). Mean CHADS2 score was 2.3±1.3, 2.2±1.3, and 2.2±1.4, respectively. In Kaplan-Meier analysis, the incidence of cardiovascular events was higher in high-HR groups than intermediate- and low-HR group (9.2%/year vs 5.8%/year, p=0.02), but was similar between intermediate- and low-HR group (6.2%/year vs 5.4%/year, p=0.3). The incidence of stroke or systemic embolism was comparable between the three groups (2.6%/year, 3.6%/year, 2.4%/year). Cox proportional hazard ratios [95%CI] of high- and intermediate-HR for cardiovascular events compared to low-HR were 1.63 [1.06-2.44] and 1.10 [0.81-1.79], respectively.

Conclusions:
Among chronic AF patients, the incidence of cardiovascular events was higher in the patients with high-HR, but was similar between intermediate- and low-HR groups.
Abstract 15352: Plasma Levels of BNP are Lower in Patients With Heart failure With Preserved EF (HFpEF) as Compared With Those With Reduced EF (HFrEF)
Authors: Harada Eisaku , Mizuno Yuji , Shono Makoto , Maeda Hiroyuki , Yano Naotsugu , Tokunaga Yoshimi , Yasue Hirofumi
Published: July 2021

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is increasing in prevalence and causes substantial morbidity, mortality, and resource utilization in the aging population. The plasma level of B-type natriuretic peptide (BNP) is used as a marker of HF with reduced EF (HFrEF). However, the role of BNP in HFpEF is not well known. The purpose of the present study was to compare the levels of BNP together with the echocardiographic findings between HFpEF and HFrEF.

Methods:
The study subjects consisted of 1574 patients with HF and early diastolic flow velocity (E)/velocity of early diastolic mitral annular motion (e′) or E/e′≥15 (as a measure of elevated left atrial pressure) (574 men and 1000 women, mean age 78.8±10.7) admitted at our hospital. They were divided into 1238 patients with HFpEF (373 men and 865 women, mean age 79.7±10.2) [left ventricular (LV) EF≥50% and E/e′≥15] and 336 patients with HFrEF (201 men and 135 women, mean age 75.4±11.8) (LVEF<50%). Echocardiographic parameters, age, gender, and BNP were examined.

Results:
The levels of BNP were lower [107(47, 225) pg/ml vs. 296(121, 626) pg/ml, P<0.001] in the HFpEF group than in the HFrEF group. The frequencies of female gender, age, EF, LV posterior wall thickness were higher (all P<0.001, respectively) and LV mass, LV end-diastolic diameter (LVDd), LV end-systolic diameter (LVDs) and left atrial diameter (LAD) were lower (all P<0.001, respectively) in the HFpEF group than in the HFrEF group. A multiple regression analysis revealed EF (t=-17.0), age (t=11.2), E/e′ (t=10.5), LAD (t=9.0), LV mass (t=7.9), and LVDd (t=-5.3) were independent predictors (all P<0.001, respectively) for the BNP level (P<0.001, R2=0.40) in this order.

Conclusions:
HFpEF was associated with lower levels of BNP and smaller heart and was more prevalent in the elders and women as compared with HFrEF. Predictors for the levels of BNP were EF, age, and E/e′ in this order. These findings imply that the plasma levels of BNP reflect LVEF more than LV diastolic function (E/e′) and thus are lower in the HFpEF group than in the HFrEF group. These findings suggest that the role of BNP in HF may be different between HFpEF and HFrEF.
Abstract 15388: Persistent Pulmonary Hypertension After Transcatheter Aortic Valve Implantation: Impact on Mortality
Authors: Drakopoulou Maria , Stathogiannis Konstantinos , Toutouzas Konstantinos , Latsios George , Synetos Andreas , Aggeli Constantina , Kaitozis Odysseas , Trantalis George , Anousakis Nikos , Tousoulis Dimitrios
Published: July 2021

Objective:
Severe aortic stenosis leads to increased pulmonary arterial systolic pressure. A controversy still remains regarding the impact of persistent pulmonary hypertension (PHT) on prognosis of patients undergoing transcatheter aortic valve implantation (TAVI). We sought to investigate the impact of persistent PHT on 2-year all-cause mortality of patients with severe aortic stenosis following TAVI.

Methods:
Patients with severe and symptomatic aortic stenosis (effective orifice area [EOA]≤1 cm
2
) who were scheduled for TAVI with a self-expanding valve at our institution were prospectively enrolled. Prospectively collected echocardiographic data before and after TAVI were retrospectively analyzed in all patients. Pulmonary artery systolic pressure was estimated as the sum of the right ventricular to the right atrial gradient during systole and the right atrial pressure. PHT following TAVI was classified as absent if <35 mmHg and persistent if ≥35 mmHg. Primary clinical end-point was 2-year all-cause mortality defined according to the criteria proposed by the Valve Academic Research Consortium-2.

Results:
Hundred and forty patients (mean age: 82±9 years) were included in the study. The primary clinical end point occurred in 17 patients (12%) during a median follow-up period of 2 years. Mean pulmonary artery systolic pressure was reduced in all patients following TAVI (45±9 versus 41±6 mmHg, p<0.01). Mortality rate was higher in patients with persistent PHT compared to patients with normal pulmonary artery systolic pressure following TAVI (26% versus 14 %, p<0.01). Patients that reached the primary clinical end point had a higher post procedural mean systolic pulmonary pressure (43±9 versus 39±6 mmHg, p=0.02). In multivariate regression analysis, persistence of PHT (OR: 2.51, 95% CI: 1.109-7.224, p=0.01) was an independent predictor of long-term mortality.

Conclusions:
The persistence of pulmonary hypertension after TAVI is associated with long term mortality. Identifying the population that will clearly benefit from TAVI is still need to be validated by larger trials.
Abstract 15403: Is the Sum Greater Than the Whole? Association of Heart Risk Factors and Echocardiographic Parameters With Reduction in 6-Minute Walk Test in Stage A Heart Failure
Authors: Nolan Mark T , Wang Ying , Yang Hilda , Marwick Thomas H
Published: July 2021

Introduction:
Chemotherapy increases long-term risk of heart failure (HF), but its impact relative to other HF risk factors is unknown. 6 minute walk test (6MWT) provides prognostic information regarding hospitalization and mortality in HF patients. We sought the relative role of these factors on echocardiographic changes and 6MWT.

Hypothesis:
Prior chemotherapy is associated with greater functional impairment than other stage A HF risk factors.

Methods:
We recruited 521 asymptomatic pts from the community aged ¬>65 years with stage A heart failure (SAHF, based on at least one of: diabetes, obesity, hypertension, coronary artery disease or chemotherapy). All went echocardiographic studies and 6MWT. 45 patients had previous chemotherapy (mean interval 7±7.5 years) and underwent 6MWT. These patients were matched 2:1 using demographic and clinical characteristics with patients who did not receive chemotherapy. Fisher’s test and independent t-test were used for statistical analysis.

Results:
There were no significant difference in demographic variables. The chemotherapy group had a significantly lower 6MWT distance (mean difference -155m) and significantly higher proportion of patients with 6MWT distance < 400m (26.7% vs. 11%, p=0.043). There were no significant difference in other echocardiographic parameters assessing systolic, diastolic and geometrical parameters.

Conclusion:
Prior chemotherapy has a significant long-term effect on functional capacity in comparison with other SAHF factors. As no one echo parameter was associated with this difference, this could potentially be secondary to noncardiac (including vascular) parameters.
Abstract 15413: Comparison of Right Ventricular Functional Indices Using Two-dimensional and Three-dimensional Echocardiography to Predict Outcomes in Pediatric Pulmonary Hypertension
Authors: Jone Pei-Ni , Tong SuHong , Ivy D. Dunbar
Published: July 2021

Background:
Right ventricular (RV) function is an important determinant of outcomes in pulmonary hypertension (PH) patients. Conventional indices of fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), and RV tissue Doppler imaging myocardial performance index (RV TDI MPI) have been used as surrogates of RV function. RV ejection fraction (EF) from real time three-dimensional echocardiography (RT-3DE) has emerged as a quantitative evaluation of global RV function and has correlated well with cardiac magnetic resonance imaging. In this study, 3D RV EF was compared with conventional indices in the serial evaluation of RV function in pediatric PH patients to predict adverse events.

Methods:
Forty-eight pediatric PH patients (median age = 10 years (4 months - 27 years)) were evaluated serially (138 visits with median interval visit = 116 days (4 -368 days)) with RT-3DE to follow their ejection fraction (EF) and conventional indices from April, 2014 to May, 2015. Echocardiographic variables include measures of RV function: 3D RV EF, FAC, TAPSE, and RV TDI MPI. Adverse events included: initiation or intensification of intravenous vasodilator therapy, atrial septostomy, Pott’s shunt, or death. Receiver Operating Characteristics (ROC) analyses were performed to identify the best cut-offs in predicting adverse events in serial follow up of pediatric PH patients.

Results:
Patients were classified based on their World Health Classification (I = 16, II=16, III=11, IV=3). Two patients were not classified as they were too young. There were 13 adverse events. 3D RV EF was a good predictor of adverse events with highest area under curve (AUC) = 0.79, p<0.001(cut-off value of 38% = sensitivity 69%; specificity of 78%) compared to FAC has an AUC = 0.77, p<0.05 (cut-off value of 33% = sensitivity 63%; specificity of 78%). TAPSE and TV TDI MPI were not statistically significant (AUC = 0.54, p = 0.65; AUC 0.63, p = 0.09 respectively).

Conclusion:
3D RV EF is a good index in predicting adverse events and was better than FAC, TAPSE, and RV TDI MPI in predicting adverse events in serial follow up of pediatric PH patients. 3D RV EF can be used as a noninvasive tool in the serial evaluation of RV function in pediatric PH patients as it is easily obtained clinically.
Abstract 15447: Trends in Use of Pulmonary Artery Catheterization in Heart Failure in the United States, 2006 - 2012
Authors: Khera Rohan , Pandey Ambarish , Kumar Nilay , Girotra Saket , Fonarow Gregg C
Published: July 2021

Introduction:
Use of pulmonary artery(PA) catheterization in heart failure(HF) patients without cardiogenic shock has not been shown to improve clinical outcomes (ESCAPE trial, 2005) and is not routinely recommended in the absence of shock or respiratory failure. However, contemporary trends in PA catheter use among HF patients are not known.

Methods:
The National Inpatient Sample (2006-2012) was used to identify adults(>18 years) hospitalized with a primary diagnosis of HF using ICD-9 codes 402.x1, 404.x1, 404.x3 and 428.x. PA catheter use was identified using procedure codes 89.6x. Patients undergoing major surgery or receiving mechanical circulatory support were excluded. Propensity-matched analyses were performed to compare risk-adjusted in-hospital mortality in patients with and without PA catheter use.

Results:
During 2006-2012, PA catheters were used in 39,247 HF hospitalizations, at a rate of 6 per 1000 HF admissions. Patients with PA catheter placement were younger and more commonly had cardiogenic shock (11%) or respiratory failure (11%). PA catheter use increased significantly over time from 5.3/1000 HF(2006) to 7.9/1000 HF(2012)(P<0.001,Figure). In subgroup analyses, in patients with cardiogenic shock, the proportional use of PA catheter was higher and increased only modestly (118 to 121/1000 HF cases,Ptrend 0.04). In contrast, patients without shock or respiratory failure had lower proportional use of PA catheter with a substantial increase during the study period (4.2 to 6.5 per 1000 HF cases, Ptrend< 0.001). In propensity-matched analyses of patients without shock or respiratory failure, mortality in HF was higher with the use of PA catheter compared to no PA catheter use (Risk-adjusted odd ratio 1.42, 95%CI 1.30, 1.56)

Conclusions:
PA catheter use has increased significantly over time among patients hospitalized with HF after ESCAPE, even in patients without cardiogenic shock/respiratory failure and is associated with worse outcomes.
Abstract 15463: Very Early Tissue Coverage After Drug-eluting Stent Implantation
Authors: Takahara Masayuki , Nakayama Takashi , Fujimoto Yoshihide , Kobayashi Yoshio
Published: July 2021

Introduction:
Optical coherence tomography (OCT) have demonstrated neointimal coverage on drug-eluting stents (DES) struts at 6-12 month follow-up. However, there is little information about tissue coverage <30 days after DES implantation.

Methods:
OCT was performed in patients who underwent staged percutaneous coronary intervention <30 days (16.3±7.5 days) after DES implantation. Cross-sectional OCT images of DES were analyzed at 1-mm intervals.

Results:
A total of 6,054 struts of 29 stents (27 everolimus-eluting stents and 2 zotarolimus-eluting stents) in 24 lesions were analyzed. The stent length was 32.8±9.47 mm, mean stent area 7.50±2.17 mm2, mean lumen area 7.39±2.35 mm2, minimum lumen area 5.69±1.90 mm2, and minimum lumen diameter 2.41±0.39 mm. Stent coverage was observed in 73.5±20.4% of the struts, malapposition 0.85±1.53%, side branch orifice struts 1.37±2.16%, and protruding struts 1.01±4.08%. The tissue thickness was 36.9 ± 14.5 μm. The percentage of stent coverage was significantly lower in the overlapping segments than in the non-overlapping segments (Figure).

Conclusions:
Most of DES struts are covered by tissue <30 days after EES implantation. However, the percentage of stent coverage is lower in the overlapping segments.
Abstract 15511: A Novel Mitochondrial Targeted DNA Repair Enzyme Attenuates Maladaptive Myocardial Remodeling and Preserves Cardiac Function in Heart Failure
Authors: Bradley Jessica M , Otsuka Hiroyuki , Organ Chelsea L , Bhushan Shashi , Polhemus David J , Wilson Glenn L , Lefer David J
Published: July 2021

Background:
Sustained increases in mitochondrial oxidative stress results in mitochondrial DNA (mtDNA) damage further worsening oxidative damage and cellular injury. These cellular events are pivotal in development and progression of myocardial damage and heart failure. We investigated the effects of a novel mitochondrial targeted fusion protein that traffics endonuclease III (Exscien1-III) and repairs mtDNA in the setting of pressure overload heart failure.

Methods:
Male C57/BL6J mice (n=10) were subjected to transverse aortic constriction (TAC; 27 g needle) and Exscien1-III (4 mg/kg/d, i.p.) or VEH were administered daily starting at 3 wks post TAC. Left ventricular (LV) function (Vevo 2100) was assessed at baseline and biweekly for 12 weeks post TAC. At the 12 wk endpoint, mice were sacrificed and hearts were collected for biochemical and molecular assessment of cellular injury.

Results:
Exscien1-III significantly attenuated TAC-induced LV dilation at 12 wks post TAC (LVEDD: 3.9 ± 0.1 vs. 4.6 ± 0.1 mm, p < 0.05; LVESD: 3.1 ± 0.2 vs. 3.9 ± 0.1 mm, p < 0.05) compared to VEH. Exscien1-III displayed a reduced LV wall thickness (LVPWd: 1.1 ± 0.1 vs. 1.4 ± 0.1 mm, p < 0.05) at 8 wks post TAC compared to VEH. In comparison to VEH, LV ejection fraction (LVEF) was preserved in the Exscien1-III treated mice at 8-12 weeks post TAC compared to VEH (*p < 0.05; **p < 0.01). Treatment with Exscien1-III resulted in a reduction in heart weights (9.7 ± 0.4 vs. 12.15 ± 1.2 mg/mm, p < 0.05) compared to VEH. Picrosirius Red staining of LV collagen revealed that Exscien1-III significantly decreased myocardial interstitial collagen volume fraction by 55% (p < 0.05 vs. VEH).

Conclusion:
Delayed treatment with Exscien1-III attenuated interstitial myocardial collagen deposition and preserved LVEF following the onset of TAC-induced cardiac hypertrophy and heart failure. Current studies are underway to further investigate the mechanisms by which this novel mtDNA repair enzyme protects the failing heart.