bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13316: Statin Therapy Prevents the Development of Contrast-induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes
Authors: Zografos Theodoros , Siasos Gerasimos , Oikonomou Evangelos , Mourouzis Konstantinos , Dimitropoulos Stathis , Anastasiou Miriam , Antonopoulos Alexis , Vavuranakis Manolis , Tsalamandris Sotiris , Zaromitidou Marina , Tsigkou Vicky , Tousoulis Dimitris
Published: July 2021

Introduction:
Contrast-induced nephropathy (CIN) is often encountered following percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) and is associated with high in- hospital morbidity and mortality. Statins may prevent the development of CIN, however their efficacy in patients with ACS has not been evaluated.

Hypothesis:
We conducted a meta-analysis of randomized controlled trials (RCTs) to assess statin efficacy in the prevention of CIN in patients undergoing PCI for ACS.

Methods:
PubMed, EMBASE, MEDLINE and the Cochrane Central Register were searched for RCTs from inception to September 2014 to compare high-dose statins (rosuvastatin 40mg/day, atorvastatin 80mg/day or simvastatin 80mg/day) with low-dose (atorvastatin 10mg/day, simvastatin 10mg/day) o placebo treatment in patients with ACS, undergoing PCI. Study-specific odds ratios (ORs) were calculated, and between-study heterogeneity was assessed using the I2 statistic. We used a random effects model meta-analysis to pool the OR.

Results:
Seven RCTs, including 5174 patients were included in the analysis. CIN occurred in 126 (4.9 patients in the high dose statin group and in 232 (8.9%) patients in the low dose or placebo group (OR: 0.50, 95% confidence interval: 0.38- 0.66, p<0.001). The observed heterogeneity between the included studies was low (I2=19%, p=0.28).

Conclusions:
High-dose statin therapy is effective at preventing the development of CIN in the high-risk population of patients undergoing PCI for ACS.
Abstract 13327: Prediction of Upcoming Therapeutic Episodes of ICD Through Routine Data in Routine Device Clinic of ICD Patients
Authors: Fujiishi Tamami , Niwano Shinichi , Murakami Masami , Nakamura Hironori , Igarashi Tazuru , Ishizue Naruya , Oikawa Jun , Kishihara Jun , Fukaya Hidehira , Niwano Hiroe , Ako Junya
Published: July 2021

Background:
Although implantable cardioverter-defibrillator (ICD) prevents sudden death of patients with life-threatening arrhythmia, prediction of upcoming ICD therapy, if possible, would be an important issue in device management. In the present study, the relationship between ICD therapeutic episodes and preceding routine device data was evaluated to clarify the predictors for ICD actuation in near future.

Methods:
The study population consisted of 100 consecutive ICD patients. All patients were followed up in the device clinic in every 4-month period, and their total follow-up periods of 22.8±4.1 months were divided into 734 4-month observation windows. The common data in device clinic including 12-lead ECG, chest X-ray, and interrogated device data were compared between patients with and without ICD therapeutic episodes during upcoming 4-month windows. To avoid inappropriate weighting on data of specific cases, such as unusual data in cases with frequent shock therapy, sampling number was limited 4-8 times in one case, and all data were evaluated as change during preceding 4 months, e.g., QTc calculated by subtracting 4 month preceding QTc from the recent QTc.

Results:
During 3.2±1.3 month follow-up, among 734 observation windows, appropriate and inappropriate ICD therapies appeared in 54 (ATP: 29, shock: 25) and 20 (ATP: 11, shock: 9) windows. When the patients were divided into spontaneous rhythm and paced-rhythm groups (n=558 and 170), spontaneous rhythm group did not show any significant difference in parameters between the windows with and without therapeutic episodes. In contrast in paced-rhythm group, RV lead impedance was significantly lower in the windows with therapeutic episodes in comparison with those without (-19.8±43.5Ω vs. 7.4±44.7Ω, p=0.047).

Conclusions:
Upcoming ICD therapy in near future might be able to be predicted by change in RV lead impedance at least in cases with paced-rhythm in ICD patients. It might reflect the electrical instability in cases with ICD therapeutic episodes.
Abstract 13357: Cystatin C Based Estimated Glomerular Filtration Rate (eGFR) Predicts Adverse Clinical Outcomes More Effectively Than Creatinine Based eGFR in Patients With Peripheral Artery Disease
Authors: Yoichiro Otaki , Watanabe Tetsu , Takahashi Hiroki , Yamaura Gensai , Arimoto Takanori , Shishido Tetsuro , Miyamoto Takuya , Kubota Isao
Published: July 2021

Introduction:
Kidney dysfunction is reported to be associated with adverse outcome in patients with peripheral artery disease (PAD). Estimated glomerular filtration rate (eGFR), which is recently-popularized index for assessing kidney function, is calculated using serum creatinine or cystatin C level. Cystatin C based eGFR (eGFRcys) is less affected by age, gender, and muscle mass compared to creatinine based eGFR (eGFRcr).

Hypothesis:
We hypothesized that eGFRcys is a feasible prognostic parameter despite muscle sarcopenia in patients with PAD.

Methods:
We calculated both eGFRcr and eGFRcys according to kidney disease improving global outcomes (KDIGO) guideline in 235 PAD patients who underwent endovascular therapy. Patients were prospectively followed during a median follow up period of 618 days, with the end points of major adverse cardiovascular and cerebrovascular events (MACCE).

Results:
A multivariate Cox proportional hazard analysis revealed that eGFRcys, but not eGFRcr, was an independent predictor of MACCE. The C index was larger for eGFRcys than eGFRcr (0.70 versus 0.61; P=0.0071). Kaplan-Meier analysis demonstrated that incidence of MACCE was increased with advancing chronic kidney disease stage based on eGFRcys, but not eGFRcr, in patients with PAD. Net reclassification index was improved by addition of eGFRcys to basic predictors.

Conclusions:
eGFRcys could be a reliable marker for MACCE and risk stratify patients at high risk more effectively than eGFRcr in patients with PAD.
Abstract 13376: Oral Treatment With a Zinc Complex of Acetylsalicylic Acid Prevents Diabetic Cardiomyopathy in a Rat Model of Type 2 Diabetes
Authors: Korkmaz-Icöz Sevil , Alsaid Samer , Radovits Tamás , Li Shiliang , Ruppert Mihály , Brlecic Paige , Karck Matthias , Szabó Gábor
Published: July 2021

Introduction:
Type 2 diabetic patients are at an increased risk of cardiomyopathy and heart failure is a major cause of death amongst these patients. Growing evidence indicates that proinflammatory cytokines can cause sustained development of insulin resistance and anti-inflammatory medications may reverse this process.

Hypothesis:
We investigated the effects of an oral administration of zinc and acetylsalicylic acid in the form of bis(aspirinato)zinc(II) complex Zn(ASA)2 on different aspects of cardiac damage in the Zucker diabetic rat (ZDF), an experimental model of type 2 diabetic cardiomyopathy.

Methods:
The nondiabetic control and the diabetic ZDF rats were pretreated orally with vehicle or Zn(ASA)2 for 24 days. At the age of 30-32 weeks, both the electrical activity and the left ventricular (LV) structural/functional parameters were assessed via electrocardiogram and pressure volume (PV) conductance catheter system.

Results:
The Zn(ASA)2 treatment significantly decreased the blood glucose concentration (39.6±3.1 vs 50.4±2.6 mM), normalized the impaired LV contractility index (Emax 3.7±0.4 vs 1.9±0.6 mmHg/μl), the passive LV stiffness (end diastolic PV relationship: 0.064±0.008 vs 0.084±0.014 mmHg/μl), and the diastolic dysfunction (LV end diastolic pressure: 6.5±0.6 vs 7.9±0.7 mmHg). Furthermore, the ECG revealed a restoration of the prolonged corrected QT intervals (63±3 vs 83±4 ms, p<0.05) by Zn(ASA)2. A histological examination revealed an increase in the cardiomyocytes transverse cross section area in diabetic rats compared to the controls, which was significantly decreased after Zn(ASA)2. Furthermore, a significant increase in fibrotic formation was observed in the diabetic rats compared to controls, and Zn(ASA)2 administration showed similar collagen content in the ZDF+Zn(ASA)2 rats and in the nondiabetics. A significant increase in the density of TUNEL positive cell nuclei in the diabetic hearts, indicating DNA fragmentation, was significantly decreased by Zn(ASA)2. Additionally, in the diabetic heart, Zn(ASA)2 significantly decreased nitrotyrosine formation.

Conclusions:
The oral administration of Zn(ASA)2 may have therapeutic potential with the aim of preventing cardiac complications in type 2 diabetic patients.
Abstract 13386: Persistence of Transplanted Explant-derived Human Cardiac Stem Cells Contributes to Therapeutic Regeneration of Injured Mycardium
Authors: Richardson Elizabeth , Mount Seth , Mayfield Audrey E , Rafatian Ghazaleh , Latham Nicholas , Stewart Duncan J , Davis Darryl R
Published: July 2021

Introduction:
Cardiac stem cells (CSCs) mediated improvements in cardiac function have been attributed to the rescue of reversibly damaged tissue, proliferation of endogenous cells and differentiation of transplanted CSCs into new myocardium. Despite evidence that CSC therapy improves post-ischemic function, controversy surrounds the extent to which physical incorporation and persistence of transplanted cells contributes to the benefits of CSC therapy. In this study, we use “on demand” ablation of transplanted CSCs to dissect the contribution of engrafted cells to myocardial repair.

Methods/Results:
Diphtheria toxin (DT) was used to induce transplanted human cell death. Human CSCs were cultured from atrial appendage biopsies obtained during clinically-indicated surgery. Exposure of human CSCs to DT prompted expression of annexin V ± propidium iodide in 37±10% of treated cells within 12 hours (p≤0.05 vs. human CSCs not exposed to DT) and resulted in a progressive decline in viable human cell counts (Figure A); suggesting that DT may provide the ideal means of ablating transplanted human sourced cells within a DT resistant host. The influence of short term persistence of transplanted CSCs was investigated in a series of SCID mice by applying DT or vehicle 1 week after intra-myocardial injection of human CSCs (Figure B). A decline in the ejection fraction in CSC-treated mice underscores the importance of transplanted cell persistence on CSC-mediated cardiac repair. This decrease was paralleled by increases in scar size (1.4±1.0 fold greater % scar, p=0.05), reduced contractility (1.2±0.1 fold lower dP/dT max, p=0.04) and impaired relaxation (1.6±0.2 fold lower dP/dT min, p=0.05) as compared to mice that received CSCs alone.

Conclusions:
Elimination of CSCs 1 week after transplantation reduces CSC-mediated cardiac repair- suggesting that persistent paracrine secretion and/or cell replacement contribute to the maintenance of therapeutic regeneration.
Abstract 13434: Cardioprotection of Rosuvastatin Against Cardiac Dysfunction After Coronary Microembolization via Alleviating Inflammatory Induced Microinfarctions
Authors: Chen Zhangwei , Cao Yuanyuan , Qian Juying , Ma Jianying , Zou Yunzeng , Ge Junbo
Published: July 2021

Backgrounds:
It has been demonstrated that statins plays a critical role on prevention the risk of myocardial infarction. However, it is unclear about the effect of statins on coronary microembolization (CME), which is one of common complication after coronary intervention.

Objectives:
This experimental study was designed to evaluate the protective role of rosuvastatin on cardiac dysfunction caused by CME.

Methods:
Mice CME models were developed by injecting a total of 500,000 polyethylene micro-particles (average 9-12 diameters) into the left ventricle when transiently obstructed the ascending aorta for 15 seconds. There were three groups: sham-operation group (n=6), CME group (n=8) and rosuvastatin therapy group (n=7, oral received 20mg/kg per day one week before CME). Cardiac function was evaluated by echocardiography at baseline, 3 days and 10 days after procedure. HE staining was performed to detect the area of microinfarctions, while serum and myocardial expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by ELISA and immunohistochemistry.

Results:
Compared with sham-operation group, left ventricular ejection fraction (LVEF) was significantly decreased in CME group (3 days later: 53.2±6.0% vs. 62.8±6.8%, P=0.002; 10 days later: 54.4±8.1% vs. 64.3±5.7%, P=0.014). Pre-treatment with oral rosuvastatin one week before CME improved cardiac dysfunction (3 days later: 59.8±5.4% vs. 53.2±6.0%, P=0.013; 10 days later: 61.2±5.2% vs. 54.4±8.1%, P=0.037). We also found that rosuvastatin therapy not only decreased the average area of microinfarctions (7.4±3.7% vs. 3.2±3.2%, P=0.012), but also inhibited myocardial expression of inflammatory factors, including TNF-α and IL-6.

Conclusions:
Inflammation mediated microinfarctions could be involved in cardiac dysfunction after coronary microembolization. Rosuvastatin could improve heart function by alleviating local myocardial inflammatory responses.
Abstract 13456: Screening for Transthyretin Cardiac Amyloidosis Using 99mTc-Pyrophosphate Scintigraphy in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Narotsky David L , Kodali Susheel K , Mauer Mathew S , Bokhari Sabahat , Hamid Nadira , Pozniakoff Ted , Weinberg Richard , Nazif Tamim M , George Isaac , Vahl Torsten , Hahn Rebecca T , Castano Adam
Published: July 2021

Background:
Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure with preserved ejection fraction (EF). Bone scintigraphy has emerged as a non-invasive imaging approach that is highly sensitive and specific for identifying ATTR-CA. We conducted a prospective cohort study using
99m
Tc-pyrophosphate scintigraphy (
99m
Tc-PYP) to determine the prevalence of ATTR-CA and other clinical associations with
99m
Tc-PYP positivity in older patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR).

Methods:
A total of 40 patients (53% men) with severe AS underwent
99m
Tc-PYP planar cardiac imaging within 30 days of TAVR. Myocardial uptake was assessed with both a semi-quantitative visual score (range 0: no uptake to 3: uptake greater than bone) and by quantitative analysis by drawing a region of interest over the heart, mirroring it to the contralateral chest, and calculating a heart-to-contralateral ratio (HCL). Semi-quantitative score ≥ 2 and HCL ≥ 1.5 were considered positive for ATTR-CA. Demographics and pre-TAVR clinical history, laboratory values, EKG, and echocardiographic data were also analyzed for association with
99m
Tc-PYP positivity.

Results:
Among 40 patients (mean age 85.2
+
5.3 years),
99m
Tc-PYP uptake was found in 10% (n=4), all men. Mean semi-quantitative score was 2.8±0.5 and HCL was 1.6±0.1. Elevated BNP (1379±689 vs 438±483 pg/ml, p=0.02), decreased serum albumin (3.2±0.5 vs 3.8±0.5 g/dL, p=0.02), and both larger interventricular septal wall (1.3±0.4 vs 1.0±0.2 cm, p=0.01) and left posterior wall thickness (1.3±0.6 vs 0.9±0.2 cm, p=0.04) at diastole were associated with
99m
Tc-PYP positivity. There was no difference in EF, but myocardial contraction fraction, the ratio of stroke volume to myocardial volume, was significantly lower, 24±12% vs 45±18%, in
99m
Tc-PYP positive patients (p=0.03).

Conclusions:
99m
Tc-PYP has potential as a screening tool for ATTR-CA in high-risk populations. Our data suggest that ATTR-CA may be prevalent in patients undergoing TAVR, particularly men, 20% of whom had a positive
99m
Tc-PYP scan. Identifying specific etiologies of heart failure in TAVR patients may be important for prognostication and response to therapy.
Abstract 13458: Caspase Recruitment Domain-Containing Protein 9 Deficiency Mitigates Obesity-Induced Cardiac Dysfunction
Authors: Cao Li , Qin Xing , Zheng Tiantian , Nair Sreejayan , Ren Jun , He Guanglong
Published: July 2021

Obesity has become an epidemic and is associated with cardiovascular anomalies. Obesity-induced low-grade chronic inflammation and macrophage infiltration into the heart plays a critical role in the development of cardiac dysfunction. Because the adaptor protein caspase recruitment domain-containing protein 9 (CARD9) regulates the innate immunity in macrophages via activation of pro-inflammatory cytokines, we hypothesized that CARD9 mediates chronic inflammation and plays a detrimental role in obesity-associated cardiac dysfunction.

Male C57BL/6 wild-type (WT) and CARD9 knockout (CARD9-/-) mice were fed normal chow (ND, 12% fat) or a Western diet (WD, 45% fat) for 5 months starting at 4 weeks of age. At the end of 5-month WD feeding, cardiac geometry and function were evaluated using echocardiography. Immunofluorescence assay was performed to detect macrophage infiltration in the heart. Heart tissue homogenates, plasma, and supernatants from cultured macrophages were collected to measure the activities of pro-inflammatory cytokines by ELISA kits. Western immunoblotting analyses were performed on isolated peritoneal macrophages and heart tissue to dissect the pro-inflammatory signaling pathways. WD feeding induced insulin resistance and glucose intolerance in the WT mice and the effects were attenuated in the CARD9-/- mice. Myocardial fractional shortening and ejection fraction were significantly compromised in the WD-fed WT mice and CARD9 knockout preserved cardiac function. CARD9 knockout also significantly decreased the number of infiltrated macrophages in the heart. In addition, myocardium-, plasma- and macrophage-derived cytokines IL-6, IL-1β and TNFα were attenuated in the CARD9-/- mice compared to the WT mice. WD feeding resulted in increased protein phosphorylation levels of p38 MAPK in the heart and macrophages which were suppressed in the CARD9-/- mice.

Taken together, these results suggest that CARD9 knockout ameliorates obesity-induced cardiac dysfunction, potentially through reduction of macrophage infiltration and suppression of p38 MAPK phosphorylation in the heart.
Abstract 13468: The Interaction Between the Prognostic Value of Chronotropic Incompetence and Cardiorespiratory Fitness: The Henry Ford Exercise Testing (FIT) Project
Authors: Qureshi Waqas T , O'Neal Wesley T , Brawner Clinton A , Ehrman Jonathan K , Keteyian Steven J , Blaha Michael J , Al-Mallah Mouaz H
Published: July 2021

Background:
Cardiorespiratory fitness (CRF) and chronotropic incompetence (CI) have both been associated with increased all - cause mortality. We tested the hypothesis that the association of CI with all - cause mortality is modified by a CRF level above and below 10 metabolic equivalents of task (METs).

Methods:
We included 43,402 patients who completed a clinical exercise stress test between 1991 and 2009. Patients on AV nodal blocking agents, antiarrhythmics and with known coronary artery disease/heart failure were excluded. Patients were followed-up for a mean duration of 11.5±5.2 years for all-cause mortality ascertained by a search of the social security death index in April 2013. CRF was estimated in metabolic equivalents of task (METs). Cox proportional hazards regression models were used to assess the risk of all - cause mortality associated with CI with adjustments for confounders.

Results:
Compared to no CI, patients with CI were older (51±12 vs. 54±13 years), less often white (68% vs. 58%), dyslipidemic (41% vs. 37%) and more likely to be hypertensive (46% vs. 60%), diabetic (15% vs. 22%), and smoke (40% vs. 51%). On average, patients with CI had lower CRF (9.8±2.8 vs. 7.4±3.0, p <.001). In adjusted Cox regression model, CI was associated with higher risk of mortality [Hazard ratio (HR), 2.12; 95% confidence interval (2.00 -2.27); p<.001)]. The association of CI and mortality was attenuated when METs was included as a covariate in the regression model [HR, 1.49; 95% confidence interval (1.39-1.61); p<.001]. There was a significant interaction of CRF ≥ 10 METs with the association of CI and mortality (p interaction 0.004) which is shown in Figure 1. This was a subaditive and multiplicative interaction of CRF with CI.

Conclusions:
This study demonstrates that CRF attenuates the mortality risk associated with CI. In addition, patients with CI in the presence of CRF ≥ 10 METs have a much lower risk than patients with CI and lower CRF.
Abstract 13479: New Heart, Old Arrhythmia: Atrial Arrhythmias After Orthotopic Heart Transplantation
Authors: Costello Briana T , Mohamedali Burhan , Campos Enrique P , Sturgess Jessica E , Deka Anjan
Published: July 2021

Introduction:
Arrhythmias after orthotopic heart transplantation (OHT) are common. However the influence of pre-transplant atrial arrhythmia on post-OHT atrial arrhythmia has not been established. In this study we analyzed the occurrence of post-OHT atrial arrhythmias in patients with prior atrial fibrillation or flutter (afib/flutter).

Methods:
In this retrospective single center study, 56 patients who underwent OHT from 2003-14 were enrolled. Patients were stratified based on history of pre-OHT afib/flutter. Baseline demographics, and post-transplant outcomes including atrial arrythmias were recorded. Post-OHT atrial arrhythmias were defined as afib/flutter, atrial tachycardia, multifocal atrial tachycardia, and wandering atrial pacemaker Data was analyzed using student’s t-test and X2 analysis.

Results:
The cohort comprised of 20 patients with pre-transplant history of afib/flutter and 36 patients without such diagnosis. There was no statistical difference in age, gender or BMI in patients between the two groups. Our analysis revealed that patients with afib/flutter prior to OHT had significantly more atrial arrhythmias at one year compared to those without afib/flutter (31.6% vs 8.8%, p=0.034), and this difference was maintained at five years follow-up (50% vs 11.1%, p=0.001). Additionally, there was a strong trend toward increased overall mortality in in this group (35% vs 13.9%, p=0.065).

Discussion:
Our results suggest a novel finding of a link between pre and post-OHT atrial arrhythmias, particularly in the first year after transplantation. This surprising finding may be related to residual recipient pulmonary vein activity, recipient atrial anastomotic tissue, or patient related factors. Further prospective research is indicated to confirm our findings.
Abstract 13501: Measures of Three-dimensional Left Ventricular Mechanics Deteriorate Acutely After Cardiotoxic Cancer Therapy
Authors: Zhang Kathleen W , French Benjamin , Gulati Gaurav , Narayan Hari K , Bajulaiye Akinyemi , Zhang Carina , Hyman David , Ky Bonnie
Published: July 2021

Background:
Doxorubicin and trastuzumab are commonly used breast cancer therapies with established cardiotoxic effects. However, the changes in myocardial mechanics with cancer therapy cardiotoxicity remain poorly defined, and noninvasive measures are needed to identify patients at increased risk. Our objective was to define the acute changes in three-dimensional (3D) echocardiography-derived indices of cardiac mechanics in patients receiving these therapies.

Methods:
In a prospective, longitudinal cohort of women with breast cancer receiving doxorubicin and/or trastuzumab, we obtained 3D echocardiography images before therapy (baseline) and during therapy at 3 months and 1 year of follow-up. Images were acquired at a minimum of 22 frames per second and analyzed by two readers using a vendor-independent analysis platform (TomTec Cardiac Performance Analyses, Unterschleissheim, Germany). Left ventricular twist, torsion, and principal strain were quantitated semi-automatically using 3D speckle tracking imaging. Standard descriptive statistics were used to summarize these measures over time.

Results:
Eighty-seven patients (mean age at baseline 49 years, 65% Caucasian) contributed at least 1 observation to the analysis. At baseline, median twist was 10.96° (interquartile range [IQR] 6.64, 13.59), torsion was 1.41°/cm (IQR 0.86, 1.70), and principal strain was -30.40% (-33.64, -28.55). At 3 months and 1 year, there were consistent declines in twist, torsion, and principal strain as displayed in Table I.

Conclusions:
In a prospective cohort of women with breast cancer receiving doxorubicin and/or trastuzumab, left ventricular twist, torsion, and principal strain declined over the first year of therapy. Ongoing research is focused on determining the clinical significance of these changes over time.

Table 1. Longitudinal changes in 3D twist, torsion, and principal strain; summaries presented as median (interquartile range).
Abstract 13509: A Prospective Randomized Study on the Prevalence, Characteristics, and Predictors of Pulmonary Vein Reconnections and the Clinical Outcomes Between Contact Force-Guided and Conventional Circumferential Pulmonary Vein Isolation of Atrial Fibrillation
Authors: Nakamura Kohki , Naito Shigeto , Sasaki Takehito , Minami Kentaro , Goto Eri , Nakano Masahiro , Kumagai Koji , Funabashi Nobusada , Kobayashi Yoshio , Oshima Shigeru
Published: July 2021

Purpose:
To prospectively investigate the differences in pulmonary vein reconnections (PVRs) and clinical outcomes between contact force (CF)-guided and conventional circumferential PV isolation (CPVI) of atrial fibrillation (AF).

Methods:
A total of 120 consecutive AF patients (63±10 years; 88 males) undergoing an initial CPVI were randomized to ablation with a target CF of 20g (CF-group; n=60) or that with operators blinded to the CF information (Blind-group; n=60). The right and left CPVI lines were each divided into 12 segments, and the occurrence of PVRs and CF-related parameters were evaluated in each segment. Time-dependent and adenosine-dependent PVRs were assessed twice during the procedure, just after completing the CPVI and at the end of the procedure.

Results:
The CF-group had significantly fewer PVRs (0.67±0.91/patient vs. 1.16±1.16/patient; P=0.007), a higher percentage of adenosine-dependent transient PVRs (60.5% vs. 28.8%; P=0.001), and lower percentage of persistent PVRs than the Blind-group. The mean CF was higher in the CF-group than in the Blind-group (Median, 18.0g vs. 16.1g; P<0.001), with the most significant difference observed along the posterior right-sided PVs (P-RPVs) and anterior left-sided PVs (A-LPVs). In multiple logistic regression models, the mean CF was a negative predictor of PVRs along the P-RPVs and A-LPVs in the Blind-group (odds ratios, 0.728 and 0.786; P<0.001 and 0.007), while no significant predictor was identified in the CF-group or along the anterior RPVs and posterior LPVs in the Blind-group. In the Kaplan-Meier analysis, the arrhythmia-free survival rate at 12 months was 91.2% in the CF-group (29.8% with antiarrhythmic drugs [AADs]) and 89.4% in the Blind-group (21.1% with AADs), respectively (P=0.596).

Conclusions:
CF-guided CPVI can reduce PVRs and result in a higher percentage of adenosine-dependent transient PVRs, and may be particularly beneficial along regions where a relatively low CF tends to be applied: the P-RPVs and A-LPVs. The comparable clinical outcomes may be due to (1) the learning curve effect obtained by the CF-guided technique, which improved the ablation electrode-tissue contact in the Blind-group, and (2) repeated provocation and elimination of dormant PV conduction.
Abstract 13522: Annexin-A1 Bioactive Peptide Ameliorates Cardiac Surgery-Associated Acute Kidney Injury (CSA-AKI) in Rats by Upregulating the Sirtuin6/FoxO3 Pathway
Authors: Zhang Zhiquan , Ma Qing , Podgoreanu Mihai V
Published: July 2021

Introduction:
Acute kidney injury (AKI) is a prevalent and prognostically important complication of cardiac surgery. The complex multifactorial pathogenesis and lack of appropriate animal models to recapitulate the clinical insults leading to CSA-AKI have been implicated in the failure of multiple pharmacologic renoprotective strategies. We have reported anti-inflammatory and renoprotective effects of a novel Annexin-A1 (ANXA1) tripeptide (Ac-QAW) in a rodent model of experimental cardiac surgery. Here, we tested the hypothesis that Ac-QAW attenuates CSA-AKI by upregulating Sirtuin6 and Forkhead box protein O3 (SIRT6/FoxO3), key players in stress resistance, cell survival, and life span.

Methods:
Male Sprague-Dawley rats underwent 75 min of cardiopulmonary bypass (CPB) with 45 min of cardioplegic arrest (CA). Animals were treated (iv) with 1 mg/kg Ac-QAW (n = 6), the commercially available ANXA1 peptide Ac2-26 (as a positive control; n = 5), or vehicle (n = 6) at 1 h before CPB, during CA, and 1 h after CPB. At 24 h post-reperfusion, renal levels of activated caspase-3, ANXA1, SIRT6, and FoxO3 were determined by Western blot; renal and plasma levels of myeloperoxidase (MPO) were determined by ELISA.

Results:
At 24 hours post-reperfusion following CPB/CA, rats treated with Ac-QAW showed a) reduced renal caspase-3 activity (P < 0.05); b) decreased MPO in both blood and kidney; and c) increased renal levels of ANXA1 (P < 0.05), SIRT6, and FoxO3 (P < 0.01) (Figure).

Conclusions:
Using a clinically relevant animal model, we provide preliminary translatable evidence that administration of Ac-QAW attenuates CSA-AKI. This may result from action by Ac-QAW to 1) reduce inflammation by increasing inflammation-resolving molecule ANXA1; 2) inhibit neutrophil transmigration; and 3) promote pro-survival mechanisms by increasing SIRT6/FoxO3 expression. More Ac-QAW studies are needed to define its exact mechanism of action and its impact on long-term functional outcomes.
Abstract 13543: Brain Injury in Adolescents With Single Ventricle Heart Disease Compared to Healthy Controls
Authors: Pike Nancy A , Tummala Sudhakar , Poulsen Marie K , Halnon Nancy J , Lewis Alan B , Kumar Rajesh
Published: July 2021

Background:
Adolescents with single ventricle heart disease (SVHD), who have undergone staged surgical palliation, have increased risk for neurocognitive deficits. However, the type and location of brain injury in SVHD adolescents remains unclear.

Purpose:
Examine brain injury, using Diffusion Tensor Imaging (DTI) based axial (gray matter injury) and radial diffusivity (white matter injury) procedures in adolescents with SVHD who have undergone surgical palliation compared to controls.

Methods:
Six SVHD (age 16.2±1 years; 4 males; BMI 20±3.5 kg/m2), and 8 controls (age 16.2±1 years; 4 males; BMI 25.4±8.1 kg/m2) were examined via brain DTI on a 3T MRI. No subject had a history of prematurity, cardiac arrest, ECMO use, genetic syndrome, head trauma or severe developmental delays. Whole-brain axial/radial diffusivity maps were calculated. Statistics consisted of ANCOVA, with age and gender as covariates (uncorrected threshold, p < 0.005).

Results:
Increased axial diffusivity in SVHD compared to controls were found in several brain sites that include frontal gyrus (p=.03), temporal gyrus (p=.01), parahippocampal gyrus (p=.008), occipital gyrus (p=.02), insular cortex (p=.04), cerebellar cortex (p=.004), pons (p=.02), and cingulate gyrus (p=.006) (Fig1). Increased radial diffusivity appeared in frontal gyrus (p=.01), cingulate gyrus (p=.001), corpus callosum (p=.04), cerebellum (p=.004), temporal gyrus (p=.004), parahippocampal gyrus (p=.004), and pons (p=.004) (Fig2).

Conclusions/Implications:
Brain injury was more extensive in gray matter than white matter and was located in autonomic and cognitive areas of the brain in adolescents with SVCHD. These findings indicate that the neurocognitive deficits commonly reported in SVCHD are likely related to brain injury. Further investigation is needed to clarify these relationships and to evaluate potential interventions to repair and/or protect these brain regions in this high risk patient population.
Abstract 13596: Magnetic Resonance - Derived Pre-contrast T1 Relaxation Time is the Accurate Marker of Diffuse Myocardial Fibrosis in Severe Aortic Valve Disease: A Comparison With Left Ventricular Myocardial Biopsy
Authors: Kockova Radka , Kacer Petr , Pirk Jan , Maly Jiri , Vsianska Martina , Sukupova Lucie , Sikula Viktor , Kotrc Martin , Praveckova Alena , Barciakova Lucia , Honsova Eva , Maly Marek , Kautzner Josef , Melenovsky Vojtech , Sedmera David , Penicka Martin
Published: July 2021

Introduction:
Diffuse myocardial fibrosis (DFM) is the major mechanism in the pathophysiology of the aortic stenosis and its complications. DMF is detectable by magnetic resonance imaging (MRI) using the T1 mapping technique.

Hypothesis:
The MRI derived native T1 relaxation time and myocardial extracellular volume fraction (ECV) will be significantly related to the extent of DMF et targeted myocardial left ventricular (LV) biopsy.

Methods:
The study population consisted of 40 consecutive patients (age 63±8y, 65% males) undergoing surgery for severe aortic stenosis (77.5%), aortic root dilatation (7.5%) or valve regurgitation (15%). All patients underwent MRI-derived T1 mapping and 2D-, 3D speckle tracking-derived strain analysis prior to surgery. The T1 relaxation time was assessed in basal interventricular septum pre and 10 min post contrast administration using the modified Look-Locker Inversion recovery sequence. A LV myocardial biopsy specimen was obtained during surgery from basal interventricular septum under the guidance of the MRI operator to assure spatial concordance with the MRI assessment. The percentage of myocardial collagen was quantified as a ratio of Picrosirius Red-positive area over total sample area using the Image J.

Results:
The average percentage of myocardial collagen was 22 ± 14.8 %. The average native T1 relaxation time and ECV was 1010 ± 48 ms and 0.288 ± 0.055, respectively. Both native T1 relaxation time with cutoff value of ≥ 1010 ms (Ss=90%, Sp=73%, AUC =0.82) and ECV with cutoff value of ≥ 0.315 (Ss=80%, Sp=90%, AUC =0.85) showed high accuracy to identify extensive (> 30%) myocardial collagen content (Figure 1A, 1B). The native T1 mapping showed significant correlation with LV mass, 2D and 3D global longitudinal strain (all p<0.05) while the ECV did not (p=NS).

Conclusions:
Native T1 relaxation time is the accurate marker of diffuse myocardial fibrosis with the significant relationship with LV morphology and myocardial function.
Abstract 13615: High-Dose Simvastatin Induce Insulin Resistance During Acute Myocardial Infarction by Inhibiting Intracellular Insulin Signaling, Without Attenuating Its Clinical Benefit
Authors: Carvalho Luiz S , Moura Filipe A , Cintra Riobaldo M , Prada Patrícia O , Saad Mario J , Coelho Otavio R , Sposito Andrei C
Published: July 2021

Background:
Hyperglycemia during the acute phase of myocardial infarction (MI) is a strong marker of mortality, but statin use in this set can potentially induce dysglycemia. We aimed to identify whether statins also induce hyperglycemia during MI and the related mechanisms as well as to evaluate its clinical relevance.

Methods:
We prospectively studied 550 patients with ST-elevation MI treated without (WS) or with simvastatin (S) at 20, 40 or 80 mg/day. Of these, 27 non-diabetics were randomized to S10 or S80mg/day and performed euglycemic hyperinsulinemic clamp (EHC) associated with abdominal adipose tissue biopsy after 40 minutes of insulin infusion in the second (D2) and sixth (D6) days after MI. Measurements of plasma glucose, insulin, C-peptide on admission (D1) and fifth (D5) day were performed in all patients.

Results:
Between D2 and D6, insulin sensitivity index (ISi) measured by EHC increased (20±60%) in the S10 group and reduced (-6±28%) in S80 (p=0.025). Analysis of the biopsies by Western-blot showed a reduction in phosphorylation/activation of Akt and IRS-1 in patients treated with S80 compared to those treated with S10. Among the 550 patients, ISi was estimated by HOMA2S (plasma glucose and insulin) and varied in 40±145% (WS), 22±117% (S20), 16±61 % (S40) and -2%±88% (S80) between D1 and D5 (p=0.001). Insulin secretion at D1 estimated by HOMA2B (glucose and C-peptide) (p=0.001) and the dose of S (p=0.009) were the only independent markers of a fall in HOMA2S between D1 and D5. Among patients not treated with statins or taking 20mg/day (WS + S20), plasma glucose ≥140mg/dl at admission (stress hyperglycemia) increased by 2.25x (95% confidence interval [CI] 1.30-3.85, p=0.004) the risk of death or MI after mean 634±501 days; but not in those treated with S40 or S80 (p=0.727). Stress hyperglycemia also increased the incidence of death in 30 days after MI in the WS + S20 group (HR 3.15, 95%CI 1.41-7.01; p=0.003), but not in the S40 + S80 group (p=0.858)

Conclusion:
The use of high-dose simvastatin in MI reduces IS through the inhibition of intracellular insulin signaling pathways. IS impairment is dependent on the dose of statin and the reserve of insulin secretion. However, high-dose statins attenuate the short- and long-term clinical impact of hyperglycemia in MI.
Abstract 13650: Influence of Parathyroid Hormone on Incidence of Heart Failure Event in Patients Without History of Cardiovascular Disease
Authors: Sakuragi Satoru , Ichikawa Keishi
Published: July 2021

Introduction:
Parathyroid hormone (PTH) plays an important role in bone metabolism. High PTH level increases intracellular calcium in arterial wall, which causes hypertension and left ventricular hypertrophy. However, information on the association of PTH level with cardiovascular event in general population is still lacking. In this study, we investigated the association of PTH with biochemical and echocardiographic measurements of cardiovascular structure and function, and the influence of PTH on incidence of heart failure (HF) admission in patients without history of cardiovascular disease.

Methods:
172 subjects (84male, 68years) without history of cardiovascular disease were enrolled from September 2012 to April 2013. Subjects with LV dysfunction (LVEF <50%) and advanced chronic kidney disease (eGFR<15 ml/min/1.73m2) were excluded. Parathyroid function was assessed with intact PTH (iPTH). We examined the association of iPTH with biochemiacl markers, such as NT-proBNP, high-sensitive cardiac Troponin T (hs-cTnT), and echocardiographic markers, such as left atrial volume index (LAVI), left ventricular mass index (LVMI), LVEF, E/e.Associations of iPTH with these cardiac markers were evaluated by univariable and multivariable linear regression analysis. Association of iPTH with future cardiovascular event was also evaluated by using multiple Cox regression analysis.

Results:
In multivariable analyysis, log NT-proBNP (p=0.0121) as well as log hs-cTnT (p=0.0024) was associated with iPTH. Among echocardiographic measurements, LAVI (p=0.0161), LVMI (p=0.0343) and E/e (p=0.0001) were associated with iPTH after adjustment for age, gender, cholesterol and eGFR. In multivariate Cox regression analysis, increasing iPTH was associated with incidence of HF admission with a hazard ratio of 6.39 for iPTH over 60 pg/ml (95% CI: 1.003 to 46.111, p=0.0047) after adjustment for age, gender, prevalence of hypertension, diabetes mellitus, dyslipidemia, systolic blood pressure and heart rate.

Conclusions:
Parathyroid hormone is associated with greater cardiac markers and future heart failure. Our results suggest that treatment to reduced PTH level is helpful to prevent future cardiac event.
Abstract 13663: Cardiac Progenitor Cell Therapy Reduces Myocardial Fibrosis and Stiffness yo Improve Cardiac Function in Patients With Single Ventricle Physiology
Authors: Ishigami Shuta , Goto Takuya , Ousaka Daiki , Kasahara Shingo , Ohtsuki Shinichi , Sano Shunji , Oh Hidemasa
Published: July 2021

Backgrounds:
Patients with single ventricular physiology undergoing staged palliations may present myocardial fibrosis detected by late gadolinium enhancement (LGE) of cardiac MRI. Recent studies suggest that cardiosphere-derived cell (CDC) therapy may reduce substantial fibrosis to improve cardiac function.

Purpose:
The aim of this study is to investigate whether intracoronary CDC infusion may reverse the focal fibrotic area to functional myocardium.

Methods:
Thirty-three patients (age: 3.1±1.0 years) were evaluated by cMRI during enrollment and randomized to treat by Fontan palliation with or without intracoronary injection of CDCs 1 month after surgery. Eight out of 33 patients had LGE initial screening by cMRI (LGE+) and 25 patients were classified as LGE (-) group. Area of focal fibrosis was quantitated by standard deviation method. Echocardiography and cMRI were performed to evaluate ventricular strain before enrollment and during the 3 months of follow-up. Results- Baseline examination revealed that LGE (+) group showed reduced ejection fraction (P=0.01), increased cardiac volume (P=0.03), and reduced circumferential strain (base: P=0.02, mid: P=0.02, apex: P=0.0005) compared with LGE (-) group. These changes were associated with decreased ventricular elastance (P=0.02) and increased myocardial stiffness (P=0.03) approximated by catheter examination. When patients with LGE received CDC infusion, a significant reduction of scar mass (P=0.01), scar size (P=0.01), and scar volume (P=0.02) could be detected, while these parameters remained unchanged in patients received Fontan without CDC injection. In addition, CDC infusion significantly improved regional circumferential strain (P=0.0001) within the target segments with LGE.

Conclusions:
In patients with single ventricular physiology, LGE identified by cMRI before Fontan procedure may be associated with the pathogenesis of decreased cardiac elastance and increased myocardial stiffness, leading to the development of right ventricular dysfunction. Although latent heart failure could be predicted in these patients after palliations, CDC therapy may have a potential to reverse cardiac dysfunction by direct conversion of the extent and severity of myocardial fibrosis.
Abstract 13675: New Treatments for Myocardial Stunning: Creating an Optimal Drug Cocktail for CPR
Authors: Li Jing , Shao Zuo-Hui , Li Changqing , Zhu Xiangdong , Vanden Hoek Terry L
Published: July 2021

Introduction:
Myocardial stunning following sudden cardiac arrest resuscitation increases morbidity and mortality. Previous work suggests that intra-ischemic cooling protects against stunning by enhancing Akt survival signaling, with related enhancement of glucose utilization and NAD+ recovery. New or existing drugs that mimic these effects could improve cardiac arrest outcomes. Here we test agents known to activate PI3K/Akt signaling, increase pyruvate dehydrogenase activity, and enhance NAD+ content. They were tested for their ability to improve contractile recovery in a mouse cardiomyocyte stunning model.

Methods:
Primary neonatal cardiomyocytes were exposed to 30 min ischemia and 90 min reperfusion followed by 10 min isoproterenol (1μM). Therapeutic hypothermia (TH) using intra-ischemic cooling (32 ± 0.5°C), the PTEN inhibitor VO-OHpic (VO, 1μM), insulin (0.01U/ml), intralipid (ILE, 0.25%), dichloracetate (DCA, 2 mM), and the NAD+ augmentation agents NAM (10 μM), and Nampt peptide (1-200 nM) were administered at reperfusion. Akt phosphorylation was detected by Western blot. ATP content was measured by a fluorescent assay kit.

Results:
Compared to control cells, spontaneous contractions ceased within 5 min of ischemia and upon reperfusion recovered to less than 40% of baseline contractions despite isoproterenol treatment. Comparable to TH, the use of VO, DCA, NAM, insulin or ILE all induced a rapid and strong contractile recovery with the most significant sustained effect seen with VO and ILE. Both VO and TH improved recovery of ATP after reperfusion to comparable levels. NAM resulted in a rapid recovery that was not sustained with one dose, while Nampt had no effect. The most synergistic cocktail of two-drug combinations tested was VO plus NAM. VO increased Akt phosphorylation while NAM treatment did not, suggesting that the complementary protective effect of NAM was downstream of Akt activation.

Conclusions:
Treatment of contractile stunning after cardiac ischemia can be achieved by drugs that mimic critical aspects of cooling protection, including Akt activation and NAD+ supplementation. Further work is needed to test drug combinations during cardiopulmonary resuscitation (CPR) that improve myocardial recovery.
Abstract 13697: Reproductive Years and the Risk of Cardiovascular Events in Women: Insights From the National Health and Nutrition Examination Survey (NHANES)
Authors: Mansoor Hend , Elgendy Islam Y , Segal Richard , Hartzema Abraham
Published: July 2021

Background:
Prior studies show conflicting information regarding the association of reproductive year duration with cardiovascular diseases (CVD) in older women. The aim of this study is to determine whether a longer duration of reproductive years in women in the US population is associated with a lower risk of CVDs.

Methods:
Females ≥ 60 years who participated in the National Health and Nutrition Examination Survey from 2007-2012 were included. Subjects provided information about the age of both menarche and menopause as well as the presence/absence of CVD. Based on the reproductive year duration, participants were categorized into either a longer duration group (> 30 years) or shorter duration group (≤ 30 years). Subgroup analysis for each 5-year increment in the longer reproductive duration group was conducted. Generalized linear model was used in the analysis and relative risk (RR) regression was performed. Sensitivity analysis was performed excluding events after 55 years.

Results:
3,081 patients were included in the analysis. A longer duration of reproductive years was associated with a lower risk of CVD, compared to a shorter duration (RR 0.71, 95% CI (confidence interval) 0.56-0.83, p= 0.002). The reproductive durations ranging from 35-40 and 41-45 years were associated with lower risk of CVDs (RR 0.66, 95% CI 0.51-0.68, p=0.002, and RR 0.73, 95% CI 0.54-0.79, p=0.03, respectively); however; those ranging in age from 30-35 and over 45 years were not associated with lower risk of CVD (RR 0.77, 95% CI 0.57-1.40, p=0.10, and RR 0.79, 95% CI 0.37-1.69, p=0.54, respectively). Sensitivity analysis excluding the events after 55 years yielded similar estimates (RR 0.66, 95% CI 0.44-0.99, p=0.04).

Conclusion:
Longer duration of reproductive years was associated with lower risk of CVDs in older women. This effect was more evident in older women who had duration of reproductive years ranging from 35-45 years.