bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract O.68: Corticosteroid Pulse Therapy for Acute Kawasaki Disease: Consideration for the Long-Term Prognosis of Coronary Artery Lesions
Authors: Kitagawa Atsushi , Ishii Masahiro , Ogihara Yoshihito , Ogata Shouhei , Iemura Motofumi , Suda Kenji
Published: July 2021

Background:
The use of corticosteroids as treatment for Kawasaki disease (KD) patients is still controversial. And the effects of corticosteroids on coronary artery lesions (CALs) development and later vascular remodeling are also unclear. The purpose of this study was to compare the long term prognosis of KD with CALs between corticosteroid administration patients and no corticosteroid using patients.

Methods:
Five hundred sixty nine patients with KD were studied at Kurume University Hospital from 1996 to 2004. Clinical records of 66 patients (46 males, 20 females) with CALs were reviewed. The median age at diagnosis was 1.5 (range 0.2 - 13.2) years and median follow-up period was 8.9 (range 0.1 - 16.4) years. Coronary artery sizes were measured by body surface area (BSA) adjusted z-score to using echocardiography. CALs were defined as coronary artery z-score > 2.5, and CAL regressions were defined as z-score < 2.5.

Results:
Sixty four patients were treated with intravenous immunoglobulin (IVIG), and 51 (79.7%) patients were unresponsive to the initial IVIG treatment. Twenty seven (40.9%) patients were received corticosteroid pulse therapy in the acute phase. The maximum CAL z-score in the acute phase, there were not significant differences between corticosteroid administration patients and no corticosteroid using patients (5.1 ± 2.2 vs. 4.9 ± 2.3, p = 0.277). The CAL z-score at the end of this study period, there were not significant differences between two groups (2.1 ± 2.0 vs. 2.3 ± 2.3, p = 0.432). The ratio of CAL regression in the study period (33.3% vs. 46.2%), the mean interval between the onset of KD and CAA regression (0.6 ± 0.5 vs. 0.8 ± 0.5 years, p = 0.209), and the ratio of coronary artery stenosis or occlusion (14.8% vs. 15.4%), there were not significant differences between two groups.

Conclusion:
Corticosteroid pulse therapy for KD patients may not be worsened CALs in the acute phase and long-term after the onset.
Abstract O.73: Long-term Results Of Percutaneous Transluminal Coronary Rotational Atherectomy For Localized Stenosis Caused By Kawasaki Disease
Authors: Tsuda Etsuko , Hoshino Shinsuke , Asaumi Yasuhide , Hayama Yosuke , Yamada Osamu
Published: July 2021

We report the results of percutaneous transluminal coronary rotational atherectomy (PTCRA) for localized stenosis caused by Kawasaki disease (KD). Thirteen male and a female, aged 5 to 29 years (median 13 years), underwent PTCRA and the interval from the PTARA to the latest angiogram ranged from 3 months to 16 years (median 6 years). The target vessels were the left anterior descending artery (3 patients), the left circumflex (2), left main trunk (2) and the right coronary artery (7). The immediate results of PTCRA were successful in all patients, and the mean stenosis degree improved from 86 ± 11% to 36 ± 13%. Five cardiac events occurred within one year (acute myocardial infarction 2, transient complete atrioventricular block 1 and re-PTCRA 2). The survival rate and cardiac event free rate at 15 years after PTCRA were 93% and 71%, respectively. For the graft patency, 4 pts who underwent PTCRA within 10 yeas old, had asymptomatic occlusion within 1 year. The patency rate at 15 years after PTCRA was 69%, in 10 pts who underwent it more than 10 years old. Cardiac events and restenosis occurred within a year after PTCRA. The results in patients less than 10 years old was poor. If a graft is patent in one year after procedure, long-term patency may be expected in patients more than 10 years old.
Abstract 10009: Aortic Hemodynamic and Mechanical Properties are Concomitantly Reduced in Pulmonary Arterial Hypertension
Authors: Schafer Michal , Jazaeri Omid , Kheyfets Vitaly O , Hunter Kendall S , Shandas Robin , Buckner Kern , Fenster Brett E
Published: July 2021

Introduction:
Although pulmonary arterial hypertension (PAH) has significant impact on flow and tissue remodeling in the pulmonary vasculature, previous studies indicate that PAH is also associated with increased stiffness and endothelial dysfunction in the systemic circulation. Alterations in vascular properties of the systemic circulation may have hemodynamic relevance for left ventricular adaptation to PAH. Reduced wall shear stress (WSS) and vascular elastic markers are known manifestations of vascular disease and may provide insight into the vascular behavior of the systemic circulation in PAH.

Hypothesis:
We hypothesized that WSS and mechanical elasticity are altered in the thoracic aorta in PAH, and that these measures correlate with pulmonary hemodynamics.

Methods:
As part of a prospective study, 18 patients with PAH and 5 age-matched controls underwent the same day right heart catheterization (RHC) and 4 dimensional flow cardiac magnetic resonance (4D CMR) for computation of WSS in four aortic regions (endovascular landing zones 1 to 4). The aortic capacitance was calculated as the ratio of stroke volume (SV) and pulse pressure (PP). The elastic modulus was defined as the inverse aortic strain divided by PP. The difference in median values was assessed via Wilcoxon ranked sum method and Spearman rho was used for linear regression analysis.

Results:
The WSS (N/m2) was significantly reduced in all four aortic zones (zone 1: 0.540 vs. 0.800, p = 0.0325; zone 2: 0.424 vs. 0.615, p = 0.0402; zone 3: 0.419 vs. 0.625, p = 0.0250; zone 4: 0.513 vs. 0.794, p = 0.0046). While aortic capacitance (mL/mmHg) was significantly reduced in the PAH subjects (1.82 vs. 5.97, p = 0.008), the elastic modulus (mmHg) was higher (3.52 vs. 8.25, p = < 0.001). The most significant correlation was between the WSS in zone 4 and pulmonary vascular resistance (rho = -0.70, p = 0.006) and mean pulmonary artery pressure (rho = -0.62, p = 0.002).

Conclusions:
PAH is associated with reduced WSS in the thoracic aorta, suggesting reduced systemic flow conduction in PAH. WSS and mechanical vascular markers may aid in the understanding of the impact of PAH on systemic hemodynamics and tissue mechanics.
Abstract 10246: Hydroxychloroquine Pretreatment Reduces Myocardial Ischemia-Reperfusion Injury: Role of Cardiac Extracellular-Signal-Regulated Kinase 5 and Autophagy
Authors: Yang Feiyan , Yin Chang , Xi Lei , Kukreja Rakesh C
Published: July 2021

Background:
Hydroxychloroquine (HCQ) is an antimalarial drug, which is also widely used to treat chronic rheumatologic diseases. Since HCQ was reported to inhibit cell autophagy and to activate extracellular-signal-regulated kinase 5 (ERK5) in vascular endothelial cells, we designed the current study to determine the effects of HCQ on cardiac ischemia-reperfusion (I-R) injury and post-I-R expression of ERK5 and autophagy marker proteins.

Methods:
Adult C57BL/6J mice of both genders were pretreated with HCQ (50 mg/kg, i.p.) 1 hour prior to isolation of the hearts, which were subjected to 30 min of no-flow global ischemia followed by 60 min of reperfusion in Langendorff mode. Ventricular function was continuously assessed and myocardial infarct size was determined at the end of I-R. Heart samples were collected following normoxic perfusion (no-ischemic controls), I-R, or I-R with HCQ for assessing ERK5 and autophagy-related proteins with Western blots.

Results:
HCQ pretreatment reduced infarct size significantly in the female hearts (P<0.05) as compared with the male hearts (Fig. A). Post-I-R cardiac function was better in HCQ-treated males (Fig. B). I-R resulted in a robust increase in total ERK5 (Fig. C) and phosphorylated ERK5 (Thr218/Tyr220) in both genders, which was abolished in HCQ-treated groups. Conversely, either I-R or HCQ did not affect the post-I-R cardiac expression of autophagy-related proteins (e.g., Atg5, Beclin-1, LC3II/LC3I ratio), except Beclin-1 phosphorylation was inhibited in HCQ-treated male hearts, but not females (Fig. D).

Conclusions:
Acute HCQ pretreatment affords cardioprotection against I-R injury in both genders. Interestingly, cardioprotective effects of HCQ are associated with a strong inhibitory effect on the induction of ERK5 following I-R in the heart, indicating a novel molecular mechanism underlying the HCQ-induced cardioprotection. However, the cardioprotective dose of HCQ has no major impact on cardiac autophagy.
Abstract 10264: Additional Value of a Combined Genetic Score to Framingham Risk Score
Authors: Pereira Andreia , Mendonca Isabel , Rodrigues Ricardo , Gomes Susana , Neto Micaela , Sousa Ana C , Henriques Eva , Guerra Graca , Borges Sofia , Pereira Decio , Palma dos Reis Roberto
Published: July 2021

Introduction:
Previous studies consistently reported statistically significant relative risk for coronary artery disease (CAD) with multiple genes. The utility of genetic risk scores (GRS) as additive risk predictors to standard stratification like Framingham risk score (FS) remains inconclusive.

Objectives:
To evaluate the ability of a
multiloci
GRS to provide additive value to 10 year risk FS subgroups (low risk <5%, intermediate risk 5-20%, high risk >20%) in a south European sample.

Methods:
Case-control study of 2555 individuals, 1321 (51.7%) coronary patients and 1234 (48.3%) of controls without coronary disease with a mean age of 52±8.3 years divided in three groups according to FS (FS<5, n=403, 53.3% male, FS 5-20, n=1657, 78% male and FS>20, n= 495, 89.7% male). The
multiloci
GRS was determined with specific
primers
of 29 different genetic variants associated to atherosclerotic/CAD disease. A multiplicative model was used based on risk multiplication (odds ratio - OR) of each genotype. Multivariate analysis and respective ROC curves and area under curve (AUC) were performed for each Framingham risk subgroup. The analysis was repeated adding GRS and pairwise comparison of the two ROC Curve was done by the DeLong test.

Results:
By multivariate analysis GRS was an independent predictor for CAD (OR=2.05; 1.66-2.54, p<0.0001). Diabetes, arterial hypertension, dyslipidemia and smoking (OR= 3.07 (2.47-3.80); OR=2.07 (1.73-2.49); OR=3.1 (2.37-4.07); OR=3.11 (2.58-3.74); all p<0.0001) were also independent CAD predictors. GRS added significant predictive value to Framingham score across the intermediate (0.70 to 0.73 (p<0.0001) and high risk group from 0.68 to 0.72 (p=0.005).

Conclusion:
GRS proved to add significant incremental value only in intermediate and high risk subgroups. In these subgroups, the inclusion of genotyping may be considered to better clarify cardiovascular risk.
Abstract 10383: Comparative Assessment of Medical Therapy, PCI, or CABG on Clinical Outcomes in Diabetic Patients With Stable CAD According to Coronary Angiography and Left Ventricular Function: Patient-level Meta-analysis of the BARI-2D, COURAGE, and FREEDOM Trials
Authors: Mancini G. B. John , Farkouh Michael E , Chaitman Bernard R , Boden William E , Frye Robert L , Hartigan Pamela M , Vlachos Helen , Siami Flora S , Sidhu Mandeep S , Bittner Vera A , Fuster Valentin , Brooks Maria M
Published: July 2021

Introduction:
The benefits of optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery have been evaluated in patients with Type 2 Diabetes Mellitus (T2DM) and stable coronary artery disease (CAD) but analyses have not been stratified by detailed angiographic CAD burden or left ventricular ejection fraction (LVEF).

Methods:
A patient-level meta-analysis was undertaken among T2DM patients enrolled in COURAGE, BARI 2D and FREEDOM to assess the impact of randomization to OMT, PCI + OMT, or CABG + OMT on a composite end-point of Death/MI/Stroke and stratified by LVEF (≥ 50%, < 50%), 1, 2 or 3 vessel disease (VD) (% diameter stenosis ≥ 50%) and presence or absence of proximal left anterior descending (pLAD) disease. Hazard ratios (HR) for treatment groups were calculated from Cox regression models including all patients adjusting for trial and revascularization stratum in BARI 2D. Multivariable adjustment for risk factors was performed as a sensitivity analysis.

Results:
There were 5,034 patients included in the analysis (BARI 2D: n=2,368, COURAGE: n=766, FREEDOM: n=1,900) of whom 17% had LVEF < 50%, 29% had pLAD, and 77% had 2 or 3 VD. A total of 1,591 patients were randomized to OMT alone, 2,118 to PCI + OMT, and 1,325 to CABG + OMT. There were 1,116 events during a median 4.5 year follow-up. There was no significant effect on outcomes with OMT vs PCI + OMT irrespective of LVEF, presence/absence of pLAD and number of VD. By contrast, CABG + OMT significantly reduced the risk of Death/MI/Stroke in patients with 2 or 3 VD, irrespective of LVEF and presence/absence of pLAD (see Table). Results were similar with multivariable adjustment.

Conclusions:
In patients with T2DM and stable CAD, OMT alone appears to be as effective as PCI + OMT while CABG + OMT significantly reduces cardiovascular events in those with multivessel CAD, irrespective of LVEF or presence of pLAD.
Abstract 10384: Validation of a Simple Score to Determine Risk of Hospital Mortality After the Norwood Procedure
Authors: Chowdhury Shahryar M , Graham Eric M , Atz Andrew M , Bradley Scott M , Kavarana Minoo M , Butts Ryan J
Published: July 2021

Background:
The NIH/NHLBI Pediatric Heart Network Single Ventricle Reconstruction (SVR) trial identified risk factors for hospital mortality after the Norwood procedure. However, the ability to quantify pre-operative risk remains elusive. This study aimed to develop an accurate and clinically feasible score to assess the risk of hospital mortality in neonates undergoing the Norwood procedure.

Methods:
All patients (n = 549) in the publically available SVR database were included in the analysis. Patients were randomly divided into a derivation (75%) and validation (25%) cohort. Pre-operative patient, center, and surgeon-related covariates found to be associated with mortality upon univariate analysis (p < 0.2) were included in the initial multivariable logistic regression model. The final model was derived by including only variables independently associated with mortality (p < 0.05). A risk score was then developed using relative magnitudes of the covariates’ odds ratio. The score was then tested in the validation cohort.

Results:
A 20-point risk score using 6 variables (see Table) was developed. The derivation and validation cohorts did not differ in age, sex, mortality, and the score covariates. Mean score in derivation and validation cohort were 5.2 ± 3.2 and 5.6 ± 3.5, p = 0.35, respectively. In weighted regression analysis, model predicted risk of mortality correlated closely with actual rates of mortality in the derivation (R
2
= 0.87, p < 0.01) and validation cohorts (R
2
= 0.82, p 10). Patients were classified as low (score 0-5), medium (6-10), or high risk (>10). Mortality differed significantly between risk groups in the derivation (6% vs. 22% vs. 77%, p < 0.01) and validation (4% vs. 30% vs. 53%, p < 0.01) cohorts.

Conclusion:
This mortality score is accurate in determining risk of hospital mortality in neonates undergoing the Norwood operation. The score has the potential to be used in clinical practice to aid in risk assessment prior to surgery.
Abstract 10434: Non-Typical Angina and Mortality in Women With Obstructive Coronary Artery Disease: Results From the Women's Ischemia Syndrome Evaluation Study (WISE)
Authors: Jones Erika , Johnson B. Delia , Shaw Leslee , Bakir May , Wei Janet , Minissian Margo , Mehta Puja K , Pepine Carl , Reis Steven , Kelsey Sheryl F , George Sopko , Handberg Eileen , Bittner Vera , Bairey-Merz C. Noel
Published: July 2021

Background:
Women frequently present with non-typical angina (NTA) making ischemia diagnosis and treatment challenging. We hypothesized that mortality would be higher in women with obstructive coronary artery disease (CAD) and NTA vs typical angina (TA).

Methods:
We studied 364 Women’s Ischemia Syndrome Evaluation (WISE) participants with signs and symptoms of ischemia and obstructive CAD, defined as ≥50% stenosis by WISE angiography core laboratory. TA was defined as sub-sternal chest pain precipitated by physical exertion or emotional stress and relieved with rest or nitroglycerin, while NTA was defined as symptoms not meeting criteria for TA. Death was confirmed by National Death Index. Time to death was analyzed and plotted using Kaplan-Meier survival analyses. The analyses were adjusted by age using a Cox Proportional Hazards regression, and reported with a hazard ratio (HR) and 95% confidence interval (CI).

Results:
Overall, 249 (68%) NTA and 115 (32%) TA women had a mean age of 63 ± 12yrs and 21% were non-white. Women with NTA were more hypertensive (72% vs. 60%, p=0.03) and more often on angiotensin-converting enzyme inhibitor (37% vs 25%, p= 0.03) than women with TA. There was no difference in mean cholesterol level, CAD severity or body mass index between the two groups. Over a median of 8.8 years, 122 (34%) women died including 92 NTA and 30 TA (HR 1.5, 95% CI 1.006, 2.30) (Figure).

Conclusions:
Among WISE women with signs and symptoms of ischemia and obstructive CAD, NTA has a higher mortality compared to TA. These findings extend prior evidence that chest pain, including NTA, identifies higher risk in women with obstructive CAD. These data support intensive management and clinical follow up of women with obstructive CAD and NTA. Further evaluation regarding ischemic burden and treatment is ongoing to further understand the elevated NTA mortality.
Abstract 10770: Curcumin Mitigates the Severity of Post-Resuscitation Myocardial Dysfunction Caused by Epinephrine in a Rat Cardiac Arrest Model
Authors: Yang Zhengfei , Wang Jiangang , Yin Lu , Zhao Shen , Tang Ziren , Cahoon Jena , Tang Wanchun
Published: July 2021

Introduction:
Epinephrine significantly increases the severity of post-resuscitation myocardial dysfunction (PRMD) and reduces the duration of survival. The cardioprotective effect of curcumin against catecholamine-induced cardiotoxicity has been established. In the present study, we investigated the effects of curcumin on PRMD caused by epinephrine in a rat model of cardiac arrest.

Hypothesis:
Curcumin reduces the severity of PRMD caused by epinephrine.

Methods:
Twenty-four male Sprague-Dawley rats weighing between 450-550g were randomized into three groups: 1) Placebo group; 2) Epinephrine (20ug/kg) group; 3) Curcumin (100 mg/kg) pretreatment + epinephrine (20ug/kg) group. Ventricular fibrillation (VF) was then induced. After 8 mins of VF, CPR was initiated for 8 mins, and defibrillation was then attempted. Myocardial function was measured by echocardiography at baseline and hourly for 4 hours following successful resuscitation.

Results:
All animals except for two in the placebo group were resuscitated. Post-resuscitation myocardial function was significantly impaired in all animals. Significantly worse myocardial function was observed in the Epinephrine group in comparison with the two other groups (Figure). However, myocardial function was significantly better in the animals treated with curcumin when compared with those in the two other groups (Figure).

Conclusion:
In a rat cardiac arrest model, curcumin reduced the severity of PRMD caused by epinephrine.
Abstract 10773: Curcumin Improves the Outcomes of Cardiopulmonary Resuscitation in a Rat Model of Cardiac Arrest
Authors: Yang Zhengfei , Wang Jiangang , Yin Lu , Zhao Shen , Tang Ziren , Cahoon Jena , Tang Wanchun
Published: July 2021

Introduction:
Curcumin has been proven to provide potent protection of vital organs against regional ischemia reperfusion injury. In this study, we investigated the effects of curcumin on the outcomes of CPR in a rat model of cardiac arrest.

Hypothesis:
Curcumin reduces the severity of post-CPR myocardial dysfunction and prolong the duration of survival.

Method:
Sixteen male Sprague-Dawley rats weighing between 450-550g were randomized into two groups: 1) Placebo; 2) Curcumin (100 mg/kg) pre-treatment. Ventricular fibrillation (VF) was induced. After 8 mins of VF, CPR was initiated for 8 mins and defibrillation was then attempted. Myocardial function was measured by echocardiography at baseline and hourly for 4 hours following successful resuscitation. The duration of survival was observed for total 72 hours.

Result:
Six animals in the placebo group and seven in the curcumin group were successfully resuscitated. Post-resuscitation myocardial function was significantly impaired in all animals. However, myocardial function gradually improved 4 hours after resuscitation and was significantly better in the animals pre-treated with curcumin (Figure). Significantly shorter duration of survival of 40±29 hours was observed in the placebo group.

Conclusion:
In a rat model of cardiac arrest, curcuminim proves post-resuscitation myocardial dysfunction and prolongs the duration of survival.
Abstract 10890: Aortic Stiffness Predicts Clinical Outcome and Rate of Aortic Root Growth in Marfan Syndrome
Authors: Selamet Tierney Elif Seda , Levine Jami C , Sleeper Lynn A , Roman Mary J , Bradley Timothy J , Colan Steven D , Chen Shan , Campbell Michael Jay , Cohen Meryl S , De Backer Julie , Heydarian Haleh , Hoskoppal Arvind , Lai Wyman W , Liou Aimee , Marcus Edward , Nutting Arni , Olson Aaron K , Pearson Gail D , Parra David , Pierpont Mary E , Printz Beth F , Pyeritz Reed E , Ravekes William , Sharkey Angela M , Srivastava Shubhika , Young Luciana , Lacro Ronald V ,   for the Pediatric Heart Network Investigators
Published: July 2021

Background:
The NHLBI Pediatric Heart Network randomized trial of atenolol vs. losartan in Marfan Syndrome demonstrated no significant treatment difference in the rate of change in body surface area adjusted maximum aortic root diameter z score (AoRz).

Objectives:
To report trial results on aortic stiffness and to determine whether aortic stiffness predicts clinical outcome and change in AoRz.

Methods:
608 patients (6 mo - 25 yr) who met original Ghent criteria and had AoRz > 3 were enrolled. Echocardiograms obtained at 0, 6, 12, 24 & 36 months were centrally interpreted. Aortic dimensions were measured by 2D imaging, and stiffness indices were calculated for aortic root (AoR) and ascending aorta (AA). Where appropriate, stiffness measurements were indexed to 1/sqrt(R-R interval) to adjust for heart rate. Data were analyzed by multivariable mixed effects modeling and Cox regression.

Results:
The rate of change over three years in heart rate-adjusted AoR stiffness index differed by treatment (p = 0.016), with a decrease in the atenolol group and no significant change in the losartan group (-0.29 ± 0.14 vs. 0.14 ± 0.14/year). There was no significant treatment effect on the rate of change for AA stiffness index or for elastic modulus (AoR and AA). In the entire cohort, baseline AoR but not the AA stiffness index predicted the rate of change in ARz, with above-average stiffness index (≥ 10) predicting a slower annual decline of AoRz (-0.08 ± 0.02 vs. -0.15 ± 0.01 for below-average stiffness, p < 0.001), even after adjusting for baseline age. Elastic modulus was not a significant predictor of rate of change in AoRz. AoR elastic modulus >122 kPA (75th %ile) independently predicted the composite outcome of AoR surgery, dissection or death (hazard ratio 2.17, 95% CI 1.02 - 4.63, p = 0.04), controlling for baseline age and AoRz. Crude 3-year event rates were 10.4% vs. 3.2% for higher vs. lower elastic modulus groups, respectively.

Conclusions:
Atenolol reduced AoR stiffness over 3 years, while losartan did not. In this medically-treated cohort, higher baseline AoR stiffness was associated with a smaller decrease in AoRz, and a greater hazard of AoR dissection/surgery/death. These data suggest that aortic stiffness measures may identify patients at higher risk and guide management.
Abstract 11033: Association of Albuminuria With Cardiac Dysfunction in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Echocardiographic Study of Latinos (Echo-SOL) Ancillary Study
Authors: Hanna David B , Xu Shuo , Melamed Michal L , Gonzalez Franklyn , Kaplan Robert C , Rodriguez Carlos J , Kizer Jorge R
Published: July 2021

Introduction:
Higher urinary albumin has been associated with cardiac dysfunction in the general population. The generalizability of these findings to Hispanics/Latinos, a group in which ethnic CVD disparities have been documented, is unknown.

Methods:
Echo-SOL is an ancillary study of the HCHS/SOL, a population-based study of Hispanics/Latinos across 4 US sites. Echo-SOL participants underwent standard echocardiography. Urine albumin-to-creatinine ratio (UACR) was used to assess albuminuria and categorized as normal and high normal (based on the midpoint of values below microalbuminuria), microalbuminuria (≥17 mg/g for men; ≥25 for women), and macroalbuminuria (≥250; ≥355). Outcomes included left ventricular (LV) hypertrophy (using standard sex-specific cutpoints for LV mass index), LV systolic dysfunction (EF<50%), and any LV diastolic dysfunction. We assessed the association of UACR with cardiac dysfunction, adjusting for demographics (sex, age, Hispanic/Latino background) and cardiometabolic factors.

Results:
The study sample consisted of 1,525 participants (median age 54, female 65%, median BMI 29, diabetes 27%). Overall, 43% had normal UACR, 43% high normal UACR, 12% microalbuminuria, and 2% macroalbuminuria. The prevalence of LV hypertrophy was 13%, LV systolic dysfunction 3%, and diastolic dysfunction 59%. After adjustment, both micro- and macroalbuminuria were significantly associated with LV hypertrophy but not LV systolic dysfunction (Table). Increasing levels of albuminuria, even at high normal levels, were significantly associated with greater diastolic dysfunction.

Conclusions:
Higher UACR was associated with LV hypertrophy and diastolic dysfunction in the largest known population sample of US Hispanic/Latinos. These findings suggest that screening and detection of even high normal UACR could be of value to guide CVD prevention efforts among Hispanic Americans, who may represent an especially vulnerable population.
Abstract 11046: Chronic Obstructive Pulmonary Disease and Sudden Cardiac Death in Hypertensive Patients: The LIFE Study
Authors: Okin Peter M , Kjeldsen Sverre E , Devereux Richard B
Published: July 2021

Background:
Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular (CV) disease and CV mortality. A recent large, population-based study suggested that COPD is associated with an increased risk of sudden cardiac death (SCD). However, whether COPD predicts SCD in hypertensive patients during aggressive blood pressure (BP) lowering has not been examined.

Methods:
Risk of SCD was examined in relation to a history of COPD in 9193 hypertensive patients with ECG left ventricular hypertrophy (LVH) who were randomly assigned to losartan- or atenolol-based treatment. A history of COPD was present in 385 patients (4.2%). SCD, a prespecified secondary endpoint in LIFE, was defined as death that was sudden and unexpected, including observed arrhythmic deaths and those not attributable to myocardial infarction (MI), intractable heart failure (HF) or other identifiable cause, occurring within 24 hours of symptom onset or when the subject was last seen alive if unwitnessed SCD.

Results:
During mean follow-up of 4.8±0.9 years, 178 patients (2.4%) had SCD, with a higher incidence rate per 1000 person-years in those with COPD: 9.0; 95% CI, 6.1-11.9 vs 3.8; 95% CI, 3.4-4.2; p=0.001. In a univariate Cox model, COPD was associated with a > 2-fold increased risk of SCD (HR 2.36, 95% CI 1.42-3.95, p=0.001). In a multivariable Cox regression model that adjusted for other predictors of SCD in this population (randomized treatment, age, gender, race, history of atrial fibrillation, stroke or transient ischemic attack, baseline serum creatinine and glucose entered as standard covariates and incident MI, incident HF and in-treatment diastolic pressure, heart rate, QRS duration, HDL cholesterol, and use of hydrochlorothiazide or a statin entered as time-varying covariates), COPD remained associated with a nearly 2-fold increased risk of SCD (HR, 1.82; 95% CI, 1.04-3.18, p=0.035).

Conclusions:
COPD is associated with an increased risk of SCD in hypertensive patients. The higher SCD risk in COPD patients persists after adjusting for the higher prevalence of risk factors in COPD patients, in-treatment blood pressure, incident MI and HF, and the established predictive value of in-treatment ECG LVH and heart rate for SCD in this population.
Abstract 11078: Granzyme B Deficiency Protects Against Angiotensin II-induced Cardiac Fibrosis via a Perforin-independent Mechanism
Authors: Shen Yue , Cheng Fang , Sharma Mehul , Merkulova Yulia , Raithatha Sheetal A , Parkinson Leigh G , Zhao Hongyan , Westendorf Kathryn , Bohunek Lubos , Bozin Tatjana , Hsu Ivy , Ang Lisa S , Williams Sarah J , Bleackley R C , Eriksson John E , Seidman Michael A , McManus Bruce M , Granville David J
Published: July 2021

Introduction:
Granzyme B (GzmB) is a serine protease involved in immune cell-mediated apoptosis that is enabled through a mechanism involving the pore-forming protein, perforin that facilitates internalization. However, recent evidence suggests that GzmB contributes to matrix remodeling and fibrosis through an extracellular, perforin-independent process.

Hypothesis:
GzmB contributes to cardiac fibrosis through a perforin-independent pathway involving extracellular proteolysis.

Methods:
Using a murine model of Angiotensin II (Ang II)-induced cardiac fibrosis, wild-type, GzmB deficient and Perforin deficient mice were treated with Ang II for 4 weeks, and were examined for the presence of cardiac fibrosis. Echocardiography was performed in these mice to examine the cardiac function. The level of Inflammation and inflammatory cells infiltration were examined by immunohistochemistry and RT-PCR analysis. The in vitro endothelial barrier function was measured by electric cell-substrate impedance sensing.

Results:
GzmB was highly up-regulated in both murine and human cardiac fibrosis. Genetic deficiency of GzmB markedly reduced Ang II-induced cardiac dysfunction, hypertrophy and fibrosis, independently of perforin. GzmB deficiency also decreases microhemorrhage, inflammation, and fibroblast accumulation in vivo. In vitro studies identified VE-cadherin as a GzmB substrate. VE-cadherin is a key endothelial cell-cell junction protein. GzmB-mediated VE-cadherin cleavage resulted in increased endothelial permeability, and increased transcellular conductance. These results were also observed in vivo.

Conclusions:
GzmB contributes to the onset and progression of cardiac fibrosis through a perforin-independent process involving the cleavage of VE-cadherin.
Abstract 11135: Missed Opportunities! End-Of-Life Discussions and Implantable Cardioverter Defibrillator Recipients
Authors: Miller Jennifer , Thylen Ingela , Biddle Martha J , Bailey Alison L , Hammash Muna H , Moser Debra K
Published: July 2021

Introduction:
Guidelines for device based therapy of cardiac rhythm abnormalities were updated by the ACC/AHA/HRS in 2008 to include discussions beginning at the time of implantation with implantable cardioverter defibrillator (ICD) recipients regarding end-of-life (EOL) choices and withdrawal of defibrillation therapy. The level of adherence to this guideline from the patients’ perspective is unknown.

Methods:
The purpose of this study was to determine (1) ICD patients’ perspectives about discussions held with their providers focused on EOL choices regarding the withdrawal of defibrillation therapy and (2) ICD recipients’ level of knowledge regarding ICD function at EOL. ICD recipients from outpatient cardiology clinics associated with an academic health center, a community hospital, or a suburban hospital located in Central Kentucky completed the EOL-ICD questionnaire. The EOL-ICD measures three domains: experiences of EOL issues, attitudes about EOL discussions and actions, and knowledge of the ICD in relation to EOL issues. This instrument is valid and reliable in the ICD population.

Results:
Of the 115 ICD recipients (mean age = 63 yrs., 22% non-white, 24% non-partnered, with a mean educational level = 13.6 yrs., a mean duration of therapy = 5yrs., and 34% reporting one or more ICD shocks) 71% reported that they have never had discussions with their health care provider regarding what withdrawal of defibrillation therapy implies. A total of 44% believed that turning off the ICD shocks was the same as active euthanasia and that to disable defibrillation therapy required surgical intervention; 43% believed that once defibrillation was disabled it could not be enabled again; and 24% of recipients believed that the heart would stop beating due to the withdrawal of defibrillation therapy.

Conclusion:
Adherence to the guidelines regarding EOL discussions with ICD recipients was minimal from the patients' perspective. Despite national and international guideline recommendations to discuss EOL issues with ICD recipients beginning at implant, most patients report not having these discussions and many hold alarming misperceptions that could interfere with optimal EOL care.
Abstract 11427: Calcium Mobilization From Endoplasmic Reticulum Involves Calmodulin-mediated NADPH Oxidase-derived Reactive Oxygen Species Production in Porcine Aortic Endothelial Cells
Authors: Odagiri Keiichi , Hakamata Akio , Watanabe Hiroshi
Published: July 2021

Introduction:
Previous studies indicate that calcium/calmodulin (Ca
2+
/CaM) mediates the phosphorylation and activation of NADPH oxidase (NOX). In endothelial cells, elevation of intracellular Ca
2+
concentration ([Ca
2+
]
i
) level consists of two components, mobilization of Ca
2+
from intracellular stores and subsequent store-operated Ca
2+
entry (SOCE). However, little is known which component is required to regulate NOX-derived ROS production via Ca
2+
/CaM dependent pathway in endothelial cells.

Hypothesis:
We hypothesized that Ca
2+
mobilization from endoplasmic reticulum (ER), but not SOCE, is required to regulate NOX-derived ROS via Ca
2+
/CaM dependent pathway in porcine aortic endothelial cells (PAECs).

Methods:
We evaluated the association between Ca
2+
/CaM mediated NOX-derived ROS production and Ca
2+
mobilization from ER. We measured [Ca
2+
]
i
by fura-2/AM a production of ROS by C-DCDHF-DA and in primary cultured PAECs with a fluorescence imaging and analysis system.

Results:
(1) In the presence of 1mM extracellular Ca
2+
([Ca
2+
]
o
), BK induced a rapid increase [Ca
2+
]
i
and followed by a sustained increase. However, in the absence of [Ca
2+
]
o
(0mM with EGTA 1mM), BK caused only a small and transient increase [Ca
2+
]
i
which was cause by Ca
2+
mobilization from ER.

(2) BK (1μM) rapidly increased fluorescence intensity of C-DCDHF-DA compared with control. (150.2±51.3% and 107.2±5.6% of the baseline, respectively, p<0.05).

(3) BK-induced ROS production was inhibited by an inhibitor of NOX (VAS2870: 50μM) (125.5±9.9% of the baseline, respectively, p<0.05).

(4) When cells were exposed to BK with or without [Ca
2+
]
o
, there was no difference in BK-induced ROS production.

(5) In the absence of [Ca
2+
]
o
, BK-induced ROS production is inhibited by an inhibitor of calmodulin (W-7: 100μM) (121.3±13.1% of the baseline, p<0.05). Thapsigargin (an inhibitor of ER calcium ATPase: 1μM) and BAPTA/AM (100μM) eliminated BK-induced ROS production (110.0±5.1% and 115.7±9.5% of the baseline, respectively, p<0.05 vs 1mM [Ca
2+
]
o
).

Conclusions:
The NOX-derived ROS production by BK is mediated via Ca
2+
/CaM dependent pathway. This was strictly regulated by Ca
2+
mobilization from ER.
Abstract 11553: The CHA2DS2-VASc Score and the Risk of Ischemic Stroke by Atrial Fibrillation Status: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Alraies M Chadi , Norby Faye L , Soliman Elsayed Z , Alonso Alvaro , Chen Lin Y
Published: July 2021

Background:
CHA2DS2-VASc score has been shown to be predictive of risk of ischemic stroke (IS) in persons without atrial fibrillation (AF). These observations raise the question whether it is AF per se or the associated vascular risk factors that elevate the risk of IS.

Hypothesis:
AF elevates the risk of IS over and above vascular risk factors in the CHA2DS2-VASc score and as the CHA2DS2-VASc score increases, AF plays a more important role in determining the risk of stroke.

Methods:
Using the ARIC study_a biracial, community-based prospective cohort study we compared (a) the model discrimination of the CHA2DS2-VASc score for IS in participants with vs. without AF, and (b) the risk of IS by CHA2DS2-VASc score among participants with vs. without AF. We included 1395 participants with AF who were matched to 4060 participants without AF based on age, race, and CHA2DS2-VASc score (mean age, 62 years; 57% women; 22% blacks). Participants with prevalent IS or anticoagulant use at baseline were excluded. AF was ascertained from hospitalization discharge codes and study ECGs. IS was physician-adjudicated.

Results:
Median follow-up was 14.7 years and 288 (5.3%) participants developed IS. The C-statistic of the CHA2DS2-VASc score for IS was not significantly different in participants with vs. without AF (Table). The incidence rate difference of IS increases with increasing CHA2DS2-VASc score in participants with vs. without AF (Table, p for interaction between AF and CHA2DS2-VASc score <0.0001).

Conclusion:
Model discrimination of the CHA2DS2-VASc score for IS in individuals with AF is comparable to those without AF. However, with increasing score, the incidence rate of IS in individuals with AF increases to a greater extent than in those without AF. These findings suggest that as the CHA2DS2-VASc score increases, the disorganized rhythm of AF or other AF-related factor (e.g., left atrial dysfunction or enlargement) plays an even greater role to elevate the risk of IS.
Abstract 11621: History of Asthma Increases the Risk for Incident Cardiovascular Disease in Postmenopausal Women
Authors: Marmoush Fady Y , Roberts Mary B , Nassir Rami , Allison Matthew , Rosal Milagros , Eaton Charles B
Published: July 2021

Hypothesis and Objectives:
The state of chronic Inflammation associated with asthma may contribute to the development of cardiovascular disease (CVD) in adulthood. This study evaluated prospectively the association between history of asthma and CVD in a cohort of postmenopausal women.

Methods:
Study participants are postmenopausal women (n= 90,168) who are free of cardiovascular disease at baseline, evaluated from 1993-1998. We used self-report of physician diagnosed asthma to define the exposure. Information on treatment for asthma in addition to CVD risk factors were collected. The association between asthma and the incidence of CVD and coronary heart disease (CHD) was evaluated using cox proportional hazards models.

Results:
Among 90,168 women in the study sample, 6,921 (7.68%) reported asthma at baseline. Baseline characteristics were similar between the asthma and no asthma groups although asthmatics were more obese (36% vs 27%; p<0.0001) and had higher hypertension rates (38% vs 31%; p<0.0001). As compared to the no asthma group with CVD and CHD rates of 8,078 (9.7%) and 5,800 (6.97%), respectively, the asthma group had higher rates of CVD and CHD, 803 (11.6%) and 595 (8.6%) respectively. When adjusted to age plus all CVD risk factors, the HR for CVD events was 1.21 (95% CI 1.12-1.31) and for CHD events was 1.24 (95% CI 1.14 - 1.36). The association remained significant in different models (see table).

Conclusion:
Asthma was associated with a modestly increased risk for CVD and CHD in postmenopausal women. Further studies needed to explore this association.
Abstract 11692: First Evaluation of Corvue Algorithm Efficacy to Predict Heart Failure in Real Life: An Unnecessary Waste of Energy?
Authors: Palfy JA , Benezet-Mazuecos J , Martinez Milla J , Lopez Castillo M , Iglesias JA , de la Vieja JJ , Hernandez Gonzalez I , Rubio JM , Farre J
Published: July 2021

Introduction and hypothesis:
Repeated hospitalizations for heart failure (HF) have a negative effect on quality of life and imply an important cost for the health care system. A drop of intrathoracic impedance due to pulmonary congestion detected by cardiac devices has been hypothesized to decrease hospitalization rate. Although Optivol algorithm (Medtronic) has been widely studied, we present the first study that evaluates the efficacy of CorVue algorithm (St. Jude Medical) to predict HF in a “real-life” cohort.

Methods:
CorVue algorithm (St Jude Medical) was activated in ICD or CRT-D patients to store information about intrathoracic impedance changes using nominal settings (with patient’s alarm emission off). Patients were followed every 3 months. Clinical events (new episodes of HF requiring ambulatory or emergency room (ER) treatment modification or hospitalization) and CorVue data were recorded. Appropriate CorVue detection for HF was considered if it occurred in the 4 prior weeks to the clinical event.

Results:
Sixty-five ICD/CRT-D patients (70 ± 1 year-old, 78% male) were included (36 ICD (55%) and 29 CRT-D patients). Device position was subcutaneous in 43 patients (69%) and submuscular in 19 cases. Time from implantation to algorithm activation was 21 ± 2 months. At inclusion, mean LVEF was 33.8 ± 1.7 % and 38 patients (59%) were in NYHA class I, 20 (31%) class II and 7 (11%) class III. After a mean follow-up of 14 ± 1 months, 51 patients (78%) remained in a clinically stable condition and 14 patients (21%) presented 20 episodes of HF: 9 hospitalizations and 11 ER/ambulatory treatment modification. On the other hand, a total of 83 CorVue algorithm alarm episodes were registered in 32 patients (49%), with a mean number of alarms per patient of 2.6 ± 0.2 (range 1 - 6). Only 5 alarm episodes (6%) resulted to be appropriate: 2 ambulatory diuretic therapy intensification and 3 hospitalizations. The sensitivity of CorVue algorithm was 25%. None of the variables analyzed to determine a better scenario for this algorithm improved significantly the diagnostic efficacy.

Conclusion:
CorVue algorithm (St Jude Medical) resulted to have a low sensitivity for the prediction of HF and its routinary activation could generate misleading information.
Abstract 11723: Incident Atrial Fibrillation is Associated With Longitudinal Increase in Subclinical Cerebral Infarcts: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Chen Lin Y , Norby Faye L , Gottesman Rebecca F , Folsom Aaron R , Mosley Thomas H , Alonso Alvaro
Published: July 2021

Background:
The mechanisms underlying atrial fibrillation (AF)-related dementia are unclear and may include (1) clinical or subclinical cerebral infarcts (SCIs) or (2) chronic subcortical ischemia which results in white matter hyperintensities (WMH). Previous studies have reported that AF is associated with a higher prevalence of SCIs. However, these studies were mostly cross-sectional and based on whites and hospitalized subjects. To overcome limitations of previous studies, we evaluated the association of incident AF with 10-year change in SCIs and WMH in ARIC, a biracial community-based prospective cohort study.

Hypothesis:
We hypothesized that incident AF is associated with an increase over time in the number of SCIs.

Methods:
We included 914 (mean age, 61.7 ± 4.4 years; 38% men; 49% black) participants without prevalent AF, prevalent or incident clinical stroke, and who had brain MRI scans in 1993-95 and 2004-06. SCIs were defined as focal, non-mass lesions ≥3 mm that were bright on T2 and proton density, and dark on T1 images. We used logistic and general linear models to assess association between incident AF and gain in number of SCIs and change in WMH volume, respectively.

Results:
The median time between the 2 MRIs was 10.5 years. During this period, 46 participants developed AF. Those who developed AF had a 2.2-fold higher odds of gain in SCIs than those without AF. Incident AF, however, was not significantly associated with longitudinal change in WMH volume (Table).

Conclusions:
Incident AF is associated with an increase over time in the number of SCIs but not with WMH progression. Further research is needed to determine whether the longitudinal increase in SCIs mediates AF-related cognitive decline and dementia.
Abstract 11752: Prognostic Value of Neutrophil to Lymphocyte Ratio in Patients Admitted With Acute Decompensated Heart Failure; A Comparison With Platelet to Lymphocyte Ratio and Glasgow Prognostic Score
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 , Fukunami Masatake
Published: July 2021

Backgrounds:
Inflammation plays a critical role in the outcomes of heart failure. As indicators of the systemic inflammatory response, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been proposed to predict the poor outcome in patients (pts) with acute coronary syndrome. Furthermore, as another systemic inflammation-based score, the Glasgow Prognostic Score (GPS) has recently been reported to provide prognostic information in pts with heart failure. However, there is no information available on the comparison of prognostic impacts of these systemic inflammatory indices in pts admitted with acute decompensated heart failure (ADHF).

Methods and Results:
We studied 305 consecutive ADHF pts discharged with survival. At the admission and discharge, NLR and PLR were measured and GPS (0,1 and 2) was also obtained by combining elevated CRP (>1mg/dl) and hypoalbuminemia(<3.5g/dl) (none=0, either=1, and both=2). During a follow up period of 4.2±3.3 yrs, 96 pts died. Neither NLR nor PLR at the admission showed an association with mortality. At multivariate Cox analysis, NLR at the discharge (p=0.01) was significantly associated with mortality, independently of age, systolic blood pressure, prior heart failure hospitalization, and serum sodium level, although PLR (p=0.01) and GPS (p=0.02) at the discharge showed a significant association with mortality at univariate analysis. By ROC analysis, AUC of NLR at the discharge was 0.705 (0.639-0.772, p<0.0001), which was greater than those of PLR (0.615[0.544-0.687], p=0.002) and GPS (0.567[0.490-0.644], p=0.09) at the discharge. Pts with highest tertile of NLR (>2.2) had a increased risk of mortality than middle tertile (NLR=2.2-1.5; HR 2.0 [1.3-3.3]) and lowest tertile (NLR<1.5: HR 4.4 [2.5-7.9]).

Conclusion:
NLR at the discharge provides more valuable prognostic value for the prediction of total mortality than PLR and GPS in ADHF pts.