bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16743: A Kinase Interacting Protein 1 Does Not Protect From Adverse Cardiac Remodelling but Attenuates Myocardial Ischemia - Reperfusion Injury
Authors: Booij Harmen G , Yu Hongjuan , de Boer Rudolf A , van Gilst Wiek H , Silljé Herman H , Westenbrink B D
Published: July 2021

Introduction:
A kinase interacting protein 1 (AKIP1) attenuates myocardial ischemia / reperfusion (I/R) injury and stimulates beneficial cardiac remodeling in cultured cardiomyocytes. Whether these findings translate into functional benefits
in vivo
remains to be established.

Hypothesis:
We assessed the hypothesis that cardiac overexpression of AKIP1 attenuates myocardial heart failure development or I/R-injury in mice.

Methods:
We created transgenic mice with cardiac-specific overexpression of AKIP1 (AKIP1-TG). First, AKIP1-TG mice or their wild type littermates were subjected to transverse aortic constriction (TAC) and myocardial infarction (MI) with permanent ligation of the left coronary artery. Second, infarct size after 45 minutes ischemia followed by 24h reperfusion was assessed with Evans Bleu and triphenyltetrazolium chloride staining.

Results:
AKIP1-TG mice and wild type littermates displayed similar left ventricular remodeling and function after TAC or MI as measured with magnetic resonance imaging. Histological indices of heart failure severity, including cardiomyocyte cross-sectional area, capillary density and fibrosis were also similar. However, infarct size relative to the area at risk was reduced 2-fold in AKIP1-TG mice after I/R (15% ± 3 vs. 29± 4 %, p<0,05) and accompanied with a marked reduction in apoptosis (5,4 ± 0,5% vs. 8,1 ± 1,1%, p<0,05). AKIP1 overexpression did not influence cardiac transcription or signaling. Subcellular fraction studies showed enrichment of AKIP1 in mitochondria. In addition, AKIP1 attenuated calcium induced swelling of mitochondria (0.77 ± 0.01 vs. 0.71 ± 0.01, p<0.05), suggesting a direct role for AKIP1 in the mitochondrial permeability transition pore.

Conclusions:
In conclusion, AKIP1 does not influence cardiac remodeling in models of chronic heart failure. However, AKIP1 does attenuate myocardial I/R injury through stabilization of the mitochondrial permeability transition pore.
Abstract 16776: Drug-eluting Stents in Large Coronary Vessels Improve Both Safety and Efficacy in Women Compared to Bare-metal Stents
Authors: Bjerking Louise H , Hansen Kim W , Sørensen Rikke , Jeger Raban , Kaiser Christoph , Pfisterer Matthias , Galatius Søren
Published: July 2021

Objectives:
Drug-eluting stents (DES) are associated with lower rates of target vessel revascularization (TVR) compared with bare-metal stents (BMS), possibly with a particular benefit in women. Inferences on efficacy and safety of DES compared to BMS have been difficult to study in female subgroups as clinical trials often enroll a low proportion of women. Therefore we investigated the safety and efficacy of DES vs. BMS in women and men in a pooled analysis of two randomized stent trials.

Methods:
BASKET PROVE and BASKET PROVE II were all-comers trials including patients with coronary artery disease requiring at least one stent ≥ 3.0 mm. 4605 patients were randomized to DES vs. BMS and followed for 2 years with a primary endpoint of major adverse cardiac events (MACE: cardiac death, non-fatal myocardial infarction, TVR). The safety (cardiac death and myocardial infarction) and efficacy (non-myocardial infarction TVR) of DES vs. BMS in men and women with large coronary vessels were examined with adjusted Cox proportional hazard models.

Results:
At baseline, women presented with higher age and more hypertension and heart failure than did men. Risk factors such as smoking, prior myocardial infarction or revascularization were more frequent in men. DES reduced MACE rates at 2 years compared to BMS in both women (6.8 vs. 14.9 %, hazard ratio (HR) 0.40 (0.27-0.60)) and men (7.8 vs. 12.3 %, HR 0.61 (0.49-0.76)), although the reduction in MACE rates was more pronounced in women (p-value for interaction, 0.05). DES significantly reduced the overall rates of non-fatal myocardial infarction and cardiac death compared to BMS in women (HR 0.52 (0.28-0.99)) but not in men (HR 0.75 (0.53-1.05)). The stent-dependent difference in MACE was mainly driven by a difference in non-myocardial infarction TVR in women (2.7 vs. 8.9 %, HR 0.25 (0.14-0.44)) and men (3.8 vs. 7.6 %, HR 0.48 (0.36-0.65)).

Conclusions:
In patients requiring stenting of large coronary arteries we found that DES, as compared to BMS, were associated with improved safety in women, but not in men. Although, DES demonstrated superior efficacy over BMS in both genders, women benefited more than men. Our findings suggest that DES should always be the stent of choice in women - even in patients at low risk of restenosis.
Abstract 16789: Activation Sequence within the Pulmonary Vein as the Driving Sources of Atrial Fibrillation: Three-dimensional Analysis Using a Non-contact Mapping System
Authors: Yamabe Hiroshige , Kanazawa Hisanori , Hoshiyama Tadashi , Ito Miwa , Kaneko Shozo , Ogawa Hisao
Published: July 2021

Background:
The mechanisms how the activation within the pulmonary vein (PV) drives the atrial fibrillation (AF) has not been elucidated.

Objectives:
To define the AF maintenance mechanism by PV, we analyzed the activation sequence within the PV during AF.

Methods:
Selective endocardial mapping of the left superior PV (LSPV) was performed during AF in 11 patients with paroxysmal AF using a three-dimensional non-contact mapping system (EnSite 3000). In addition, we analyzed how the circumferential radiofrequency energy applications around the LSPV alter the activation of the LSPV and terminate AF.

Results:
Complex fractionated electrograms (CFE) were observed at the second half of the proximal LSPV at the roof (n=5), ridge (n=11) and carina (n=7). Mean CFE area was 9.1±3.4 cm2, which occupied the 19.8% of the LSPV area. Frequent episodes of pivoting activation associated with wave break and fusion was observed at this CFE area. The frequency of pivoting activation around the functional conduction block, wave break and fusion at the CFE region were significantly higher than those at the non-CFE region (32.5±12.2 vs. 4.6±5.8 times/sec; p<0.0001, 9.2±5.1 vs. 1.4±3.1 times/sec; p=0.0007, and 12.9±4.8 vs. 6.4±4.4 times/sec, p=0.0044). After isolation of ipsilateral right PV, subsequent circumferential radiofrequency energy applications around the left PV terminate the AF with a mean number of 13.5±7.8 applications, including LSPV roof (n=3.0±2.2) and LSPV ridge (n=5.6±1.9) lesions. AF was terminated before left PV isolation in all patients. The frequency of pivoting activation, wave break and fusion at all PV area just before the AF termination were significantly lower than those before ablation (8.1±11.7 vs. 37.0±14.7 times/sec; p<0.0001, 2.3±5.8 vs. 10.6±6.6 times/sec; p=0.005, 6.9±6.8 vs. 19.3±7.1 times/sec, p=0.0004), suggesting that linear lesion eliminate the random wave propagation over the CFE area.

Conclusions:
AF was driven by the high frequent episodes of pivoting activation associated with wave break and wave fusion observed over the CFE area at the proximal PV. Linear lesions along the left PV including CFE area of the LSPV eliminate the meandering activation over the CFE area, resulting in the termination of AF.
Abstract 16793: Association of Impairment of Myocardial Metabolism and Ventricular Arrhythmic Events in Patients With Hypertrophic Cardiomyopathy by Single Photon Emission Computed Tomography With A Solid-state Dedicated Cardiac Camera
Authors: Utanohara Yuko , Iguchi Nobuo , Tamura Harutoshi , Takayama Morimasa , Umemura Jun , Sumiyoshi Tetsuya , Tomoike Hitonobu
Published: July 2021

Background:
Ventricular arrhythmic events have adverse implications for patients with hypertrophic cardiomyopathy (HCM). However, little has been reported on the relationship between myocardial metabolic abnormalities and ventricular arrhythmia. Iodine-123-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) is used to assess myocardial metabolic abnormalities. A solid-state dedicated cardiac camera (D-SPECT) provides precise assessment of abnormal uptake and reduction of radiation dose in HCM by high sensitivity and high spatial resolution.

Objective:
The aim of this study was to evaluate the utility of BMIPP using D-SPECT for prediction of ventricular arrhythmic events in patients with HCM.

Methods:
We studied 125 consecutive HCM patients who underwent dual SPECT with D-SPECT using BMIPP and technetium-99m sestamibi (MIBI) or thallium-201 (TL). Reduced uptake on the BMIPP image compared with the MIBI / TL perfusion image was defined as perfusion-metabolic mismatch. In quantitative analysis, a polar map was divided into 17 segments and the score of each segment was derived from the average percent uptake. Mismatch scores (MS) were calculated from the differences between the BMIPP and MIBI / TL scores. Ventricular arrhythmic events were defined as ventricular tachycardia, appropriate ICD therapy and sudden cardiac death.

Results:
Patients with the obstructive type of HCM had a significantly higher MS than those with the non-obstructive type. Significant correlation between the MS and left ventricular mass (r = 0.28, p < 0.01) and maximal wall thickness (r = 0.27, p < 0.01) were observed. MS was significantly higher in patients with ventricular arrhythmic events than in those without events (p < 0.05). In ROC analysis, patients with a higher MS had significantly more arrhythmic events than those with a lower MS (cutoff value: 74.5, AUC: 0.644, p < 0.01). In multivariate analysis, the MS was identified as an independent factor associated with ventricular arrhythmic events (p < 0.01).

Conclusions:
Abnormal uptake of BMIPP in patients with HCM is associated with ventricular arrhythmic events. Dual SPECT with D-SPECT using BMIPP and MIBI / TL is a useful modality for risk stratification and may reveal the existence of substrate for ventricular arrhythmia.
Abstract 16794: Variation in Achievable Chest Compression Depth Assessed by Cardiac MRI
Authors: Nestaas Sverre , Rosseland Vigdis , Steensaeth Knut Haakon , Kramer-Johansen Jo
Published: July 2021

Introduction:
Recommended chest compression depth during cardiopulmonary resuscitation (CPR) for adults was increased to 5-6 cm in 2010. According to the cardiac pump theory each compression squeezes blood from the heart and the amount of blood per compression would be expected to be limited by the blood filled structures directly underneath the compression point.

Methods:
Cardiovascular MR (CMR) survey axial scans acquired from consenting patients referred for CMR were analyzed. We measured the external anterior-posterior (AP) diameter (AP) and the cumulative height of blood-filled structures in the perpendicular line in an axial plane from the compression point in the center of the inter-nipple line (INL) (Compression line). Results are means with standard deviation (SD) and mean differences with 95 % confidence intervals (CI), P-values from unpaired, two-sided t-test.

Results:
We included 144 patients, age 52 (17), 110 (76 %) males, 74 (60 %) having one or more pathological finding from the exam. The most prominent structure identified in the studied midline was (decreasing order): Left Atrium (41 %), Right Ventricle (31 %), Right Atrium (12 %), Left Ventricular Outflow Tract (LVOT)/Root of Aorta (8 %), Pulmonary Outflow Tract (2 %), other (6 %). Altogether, LVOT was present in 35 % and Left Ventricle in only 2 % of compression lines. Mean (SD) AP diameter for males and females was 25 (2) cm and 22 (2) cm (mean difference 2 cm (95 % CI 1, 3; P<0.001)), and the blood filled length of the compression line (APblood) were 6.5 cm (2) and 4.7 cm (2) (mean difference 1.8 cm (95 % CI 1.1, 2.5, P<0.001)), respectively. This comprised 22 % (10) and 26 % (7) of the AP diameter, for men and women, respectively. In a linear regression gender, body mass index (BMI), but not pathological findings were significant predictors of external AP diameter. Only gender was found to predict APblood.

Conclusions:
In the average male 5-6 cm chest compression depth at the level of the INL seems feasible, but for over half of the women compressions deeper than 5 cm would probably compress connective and muscle tissue rather than just squeeze blood from the heart, even though the blood-filled proportion of the AP diameter was larger in women than in men.
Abstract 16795: Comparison of Success Rate, Procedural Factors, and Radiation Exposure for Coronary Angiography Between Right and Left Radial Approach: Korea Transradial Coronary Intervention Prospective Registry (KOTRI)
Authors: Lee Jun-Won , Youn Young-Jin , Hong Soonchang , Ahn Sung Gyun , Ahn Min-Soo , Kim Jang-Young , Yoo Byung-Su , Lee Seung-Hwan , Yoon Junghan , Her Sung Ho , Han KyooRok , Cheong Sang Sig , Cho Byung Ryul , Bae Jang-Ho , Rha Seung-Woon , Cho Yun-Hyeon , Lee Jin-Bae , Cha Kwang Soo , Kim Hee-Yeol , Hyon Min Su , Seo John , Choi Jae Woong , Park Keum-Soo , Jeong Myung Ho , Kim Sang Wook , Lee Jae-Hwan , Kim Kyung-Soo , Kim Doo-Il
Published: July 2021

Introduction:
The use of radial artery is gradually increasing because transradial approach have shown less mortality and bleeding complications compared to transfermoral approach. But, there is little known about the differences according to radial access site except for fluoroscopic time and learning curve.

Hypothesis:
We aimed to compare the success rate, procedural factors and radiation exposure according to radial access site in patients who performed coronary angiography (CAG).

Methods:
The study population was derived from TRI prospective registry from 20 institutes in Korea from Feb 2013 to Sep 2013. Exclusion criteria were patients with data missing≥30%, invalid data, less than 19-year old patients, patient received interventional treatment, and patient who performed CAG via femoral approach. A total of 3496 among 5779 patients was assessed for data analysis. Success rate for CAG, crossover rate, procedural factors, fluoroscopic time and fluoroscopic dose were compared between right radial (RR) and left radial (LR) approach.

Results:
Mean age was 62.9±11.6 years and male was 1974 patients (56.5%). The use or EMLA cream was higher in LR group (29.2% vs. 14.0%, p<0.001). CAG with single catheter was similar between RR and LR group (14.5% vs. 15.1%, p=0.652). Success rate for CAG was higher in RR group (99.4% vs. 98.1%, p=0.001). Crossover rate was higher in LR group (1.9% vs. 0.6%, p<0.001). Most common cause for crossover was puncture failure 0.3% vs. 1.2%, p=0.002). Puncture time and CAG time were faster in LR group (2.1±2.7 mins vs. 2.5±3.0 mins, p<0.001; 104±7.4 mins vs. 11.3±8.7 mins, p=0.003). LR group showed lower fluoroscopic time, dose (3.5±3.6 mins vs. 4.9±6.6 mins, p<0.001 ; 37.5±47.8 Gycm2 vs. 41.1±42.2 Gycm2, p<0.001) and higher total contrast volume (84.8±41.1 mL vs. 77.4±33.9 mL, p<0.001).

Conclusions:
In KOTRI analysis, success rate for CAG was higher in RR group, but radiation time and dose were lower in LR group. Most common cause of crossover was puncture failure.
Abstract 16820: Albuminuria and Outcomes in Patients With Non-ST-segment Elevation Acute Coronary Syndromes: Results From the TRACER Trial
Authors: Akerblom Axel , Clare Robert , Lokhnygina Yuliya , Wallentin Lars , Held Claes , Van de Werf Frans , Moliterno David , Patel Uptal , Leonardi Sergio , Armstrong Paul , Harrington Robert , White Harvey , Aylward Philip , Mahaffey Kenneth , Tricoci Pierluigi
Published: July 2021

Introduction:
Patients with acute coronary syndromes (ACS) and kidney dysfunction are at increased risk of recurrent cardiovascular (CV) adverse events. Urinary albumin excretion (albuminuria) has been independently associated with CV outcomes. However, in a high-risk population of patients with ACS, the additional prognostic information of albuminuria to estimated glomerular filtration rate (eGFR) is less clear.

Hypothesis:
We studied the relationship between albuminuria and CV death and myocardial infarction (MI) in 12,944 patients with non-ST-segment elevation (NSTE)-ACS.

Methods:
Albuminuria was collected routinely at baseline by dipsticks and stratified into no/trace albuminuria, microalbuminuria (≥30mg/dL), and macroalbuminuria (≥300mg/dL). Baseline serum creatinine was obtained. Kaplan-Meier event rates for CV death, and the combination of CV death or MI were calculated. Multivariable adjusted Cox regression models, with baseline characteristics and biomarkers, and the addition of eGFR (Chronic Kidney Disease - Epidemiology (CKD-EPI) equation), were assessed.

Results:
Levels of albuminuria were available in 9736 patients (75.2%), and both serum creatinine and albuminuria measurements in 9473 (73.2%) patients. More patients with macroalbuminuria, compared with patients with no albuminuria, had diabetes (66% vs. 27%) or hypertension (86% vs. 68%) There was a significant increased risk in CV events with macroalbuminuria, which was significant in the adjusted model but did not remain significant when eGFR was added to the model (Table).

Conclusions:
High-risk patients with NSTE-ACS and albuminuria at presentation have an increased risk of adverse CV outcomes. However, in the present cohort, albuminuria did not provide additional independent prognostic value to eGFR.
Abstract 16831: Identifying Barriers to Hypertension Care: Development and Validation of a Behavioral Assessment Tool for Optimizing Linkage and Retention to Hypertension Care in Kenya (LARK Hypertension Study)
Authors: Douglas Alexandra , Rotich Jackson , Kiptoo Peninah , Lagat Kennedy K , Mutai Kennedy , Tarus Emmanuel , Kofler Claire , Naanyu Violet , Menya Diana , Kamano Jemima H , Inui Thomas S , DeLong Allison , Horowitz Carol R , Fuster Valentin , Vedanthan Rajesh
Published: July 2021

Introduction:
Hypertension is the leading risk factor for global mortality. Hypertension treatment rates are low, partly due to inadequate linkage and retention to care. The LARK Study evaluates the use of community health workers (CHWs), equipped with a behavioral assessment and a tailored behavioral change strategy, to improve linkage and retention to hypertension care in Kenya. Here we describe the development and validation of the assessment tool used by CHWs to identify patients’ barriers to care, facilitating behavioral change communication.

Methods:
We derived behavioral assessment items from prior research on barriers to hypertension care in Kenya. Patients, CHWs, and clinicians scored each item for clarity and representativeness, and provided qualitative feedback during focus groups. A content validity index (CVI), representing inter-rater agreement of scores, was calculated for each item. Multivariable linear mixed-effects models were used to compare CVIs and level of modification (none, minor, major, or deleted) by participant category.

Results:
We tested 70 items in 9 focus groups. Mean CVIs were greater than 0.9 in all study groups (Table). Multivariable adjustment revealed that patients and CHWs had significantly higher CVIs than clinicians. Despite this, qualitative feedback from patients and CHWsled to higher item modification rates. 37 items were retained in the linkage assessment and 57 items in the retention assessment.

Conclusions:
The mean CVI was greater than 0.9 in all study populations, indicating excellent inter-rater agreement of the overall clarity and representativeness of assessment items. However, CVI alone could not account for modifications suggested during qualitative discussions. A combination of quantitative and qualitative methods yielded the most informative evaluation of assessment items. These findings may be relevant to the validation of similar assessment tools in other low-resource settings.
Abstract 16905: Evaluation of Immediate Procedural Outcome After MitraClip Using Automated Quantitaive Real-time Volume Color Flow Doppler Transesophageal Echocardiography
Authors: Liu Shizhen , Rajagopal Vivek , Ballard William L , Mobasseri Sara , Polsani Venkateshwar , Sayegh Hassan , Milla Federico , Zhou Xiao , Qian Zhen , Martin Randolph , Mansi Tommaso , Houle Helene , Vannan Mani A
Published: July 2021

Background:
Current echocardiographic evaluation of residual MR after Mitra-Clip is based on a semi-quantitative scale (trace to 4+). We evaluated a previously validated quantitative approach using automated real-time volume color flow Doppler (3D-RTVCFD).

Methods:
30 patients (age 82 ± 5) underwent Mitra-Clip implantation guided by 3D-RTVCFD TEE (Siemens SC2000, CA). In 10 patients, data to automatically quantify 3-D regurgitant volume (RV, ml) and fraction (RF, %) and anatomic regurgitant orifice area (AROA) was available (Figure, upper panel). All patients had conventional 2-D Echo data for assessment of MR severity using the standard integrated approach.

Results:
MR was severe (4+) in 8, and moderately severe (3+) in 2 patients at baseline. MR post Mitra-Clip was mild or trace in 6 (≤1+, Group 1), and moderate in 4 (Group 2) patients. At baseline, the (mean±SD) 3-D RV/RF was 54.5±19.9 ml/60.6±10.2% and the AROA was 0.6±0.2 cm2 for the whole group. Post Mitra-Clip, the 3-D RV/RF was 23.6±10.3 ml/37.0±13.9% (p<0.01/p<0.001 vs. baseline) and the AROA was 0.3±0.1 cm2 (p<0.05). Both Group 1 and Group 2 had similar baseline RF, and both demonstrated a 39% and 38% decrease in RF post Mitra-clip, respectively (Figure, bottom graph). The decrease in AROA in both groups post Mitra-Clip was also significant (~53% in Group 1 and ~59% in Group 2). Thus, despite “moderate” residual MR using the semi-quantitative scale in Group 2, there was significant decreases in both RF and AROA. Conversely, in Group 1 some of the residual MR assessed as “mild” indeed had 3-D RF and AROA in the moderate range, post Mitra-clip.

Conclusion:
Automated quantitative 3-D real-time volume color flow Doppler TEE offers a quantitative assessment of residual MR post Mitra-clip immediately after the procedure. This may refine decision-making with regard to number of clips. Both accuracy of 3D RTVCFD TEE to quantify MR and it’s predictive value for mid- to long term procedural success need further studies.
Abstract 16929: Propensity-matched Analysis of Triple Oral Antithrombotic Therapy versus Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention
Authors: Spoon Daniel B , Lennon Ryan J , Slusser Joshua P , Holmes David R , Bailey Kent R , Mathew Verghese , McBane Robert D , Gulati Rajiv , Sandhu Guri S , Rihal Charanjit S
Published: July 2021

Introduction:
Triple oral antithrombotic therapy (TOAT) (aspirin, clopidogrel, and warfarin) is associated with an increased risk of bleeding. Despite this, the optimal management of patients with indications for warfarin following percutaneous coronary intervention (PCI) has not been established. We sought to compare long-term clinical outcomes between patients receiving TOAT with those receiving dual antiplatelet therapy (DAPT) (aspirin and clopidogrel) after PCI.

Hypothesis:
Patients with clinical indications for warfarin have higher baseline risk which is largely responsible for the observed differences in outcomes between patients receiving TOAT vs. DAPT.

Methods:
Retrospective analysis of prospectively collected data from 9,009 patients. The primary outcome was a composite of all-cause mortality, ischemic or embolic events (myocardial infarction or stroke), or bleeding. Secondary outcomes were death plus ischemic or embolic events, death plus bleeding, death, MI, stroke, and bleeding. A 2:1 propensity matched analysis was also performed.

Results:
In 9,009 patients, 812 received TOAT and 8,197 received DAPT. Median follow-up was 61 months. The primary end point occurred in 2,749 patients. At 1 year, 22% of patients treated with TOAT had the primary endpoint versus 11% of DAPT patients (p<0.001). At 1 year, secondary end points of death or ischemic or embolic events (19% vs. 10%, p<0.001), and death or bleeding events (15% vs. 5%, p<0.001) also occurred with a higher frequency with TOAT. After propensity matched analysis the above differences were no longer significant with 1 year primary endpoint rates of 19% vs. 17% respectively (HR 1.95%, CI 0.88, 1.47; p = 0.33). Following propensity matching the only significant difference between TOAT and DAPT groups was minor bleeding (5% vs. 2%; HR 2.65, 95% CI 1.39, 5.03; p=0.003).

Conclusions:
In a large single center registry with comprehensive follow up, patients treated with TOAT had higher rates of ischemic and bleeding events. However, when baseline risks are accounted for event rates are similar, other than minor bleeding, indicating patient risk characteristics are largely responsible for the observed differences in outcomes.
Abstract 16949: Failing Fontan: Genesis of a Subpulmonary Neo-ventricle From Engineered Heart Tissue
Authors: Biermann Daniel , Eder Alexandra , Seoudy Hatim , Arndt Florian , Schuler Tillmann , Peldschus Kersten , Kaul Michael G. , Reichenspurner Hermann , Mir Thomas , Riso Arlindo , Kozlik-Feldmann Rainer , Hansen Arne , Eschenhagen Thomas , Sachweh Joerg S.
Published: July 2021

Introduction:
Fontan palliation is the treatment of choice for patients with morphological or functional univentricular hearts. The unphysiologic and non-pulsatile pulmonary blood flow results in multiorgan complications and a poor long-term outcome. We evaluated graft survival and histomorphology of a pulsatile Fontan conduit generated from Engineered Heart Tissue (EHT) after implantation in a rat model.

Hypothesis:
We hypothesized that EHT matures and remains contractile in the setting of venous (Fontan-like) preload.

Methods:
EHT was generated from ventricular cardiomyocytes of neonatal Wistar rats, fibrinogen, thrombin and DMEM. After culture for 14 days constructs were implanted around the right superior vena cava of Wistar rats (n=12, 300-350 g). Immunosupression was achieved by daily subcutaneous injection of Cyclosporin A (25 mg/kg BW) and Methylprednisolone (2 mg/kg BW). MRI (Bruker) was used to assess condensation of EHTs in vivo. Animals were euthanized after 7, 14, 28 and 56 days postoperatively for histomorphological analysis. Transmission electron microscopy was used to evaluate sarcomeric integrity of cardiomyocytes within the construct.

Results:
In culture, EHTs started beating around day 8 and remained contractile in vivo throughout the experiment (d7=3/3, d14=2/3, d28=3/3, d56=2/3). All animals survived circumferential implantation of EHTs around the right SVC via a right thoracotomy. MRI (d14, n=3) revealed no constriction or stenosis of the SVC by the constructs. Hematoxylin and Eosin staining showed densely packed bundles of cardiomyocytes within the EHT conduit and intense vascularisation. Immunolabeling of actinin and connexin 43 indicated adequate maturation of cardiomyocytes after grafting around the right SVC in rats.

Conclusions:
EHTs placed around the superior caval vein of Wistar rats survive and contract for a considerable time after implantation. Histomorphology revealed a matured phenotype of grafted cardiomyocytes and an adequate vascularisation. The functional benefit of a contractile neo-ventricle to propel pulmonary blood flow in Fontan patients remains to be evaluated.
Abstract 16973: Prevalence, Determinants, and Impact of Target Lesion Calcification in Patients Undergoing Percutaneous Coronary Intervention With Newer Generation Drug Eluting Stents: Findings From a Large Multiethnic Registry
Authors: Copeland-Halperin Robert S , Baber Usman , Rajamanickam Anitha , Aquino Melissa , Roy Swathi , Kovacic Jason C , Moreno Pedro , Krishnan Prakash , Sweeny Joseph , Mehran Roxana , Dangas George , Kini Annapoorna S , Sharma Samin K
Published: July 2021

Coronary calcification increases risk for adverse events in patients undergoing PCI with bare-metal or first-generation drug-eluting stents. Newer generation devices, however, are safer and more efficacious. Whether coronary calcification relates to risk in the newer generation DES era is unclear.

We assessed the hypothesis that target lesion calcification in patients undergoing PCI with newer generation DES is associated with specific patient characteristics and clinical outcomes.

We performed a retrospective analysis of a large, multiethnic cohort of patients undergoing PCI (n=14,054) with new generation DES at a single academic center between 2009 & 2013. Coronary calcification was qualitatively assessed as none/mild, moderate or severe. Independent demographic, clinical and anatomic predictors of moderate/severe calcification were identified using logistic regression. Associations between coronary calcification and one-year MACE (death, MI or TVR) were examined using Cox modeling.

Compared to patients with none/mild (n=11,530; 82.0%) those with moderate (n=1423; 10.0%) or severe (n=1101; 8.0%) coronary calcification were older, more often Caucasian, and had more complex target lesions and greater renal dysfunction. The strongest demographic, clinical and anatomic correlates of moderate/severe calcification were Caucasian race, renal dysfunction and left main target lesion. Unadjusted MACE rates among those with none/mild, moderate and severe calcification were 9.0, 14.7, and 17.9%, respectively (p<0.001, Figure). After multivariable adjustment, hazard ratios (95% CI) for MACE associated with moderate and severe coronary calcification were 1.48 (1.27-1.72) and 1.72 (1.46-2.03), respectively.

Despite the improved safety and efficacy profile of new generation DES, moderate to severe target lesion coronary calcification is not uncommon in the contemporary DES era and remains a strong and independent predictor of MACE after PCI.
Abstract 16988: Fatty Liver Index is Reduced With Ezetimibe in an Analysis of 15,095 Patients Randomized to Ezetimibe vs Placebo in the Improve-it Trial
Authors: Simon Tracey G , Park Jeong-Gun , Corey Kathleen E , Chung Raymond T , Cannon Christopher P , Giugliano Robert
Published: July 2021

Background:
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the US, and is associated with early atherogenesis and increased risk of cardiovascular (CV) death. Although no pharmacologic therapy has proven benefit in NAFLD, recent clinical studies suggest that ezetimibe may reduce histologic evidence of liver inflammation and improve serum markers of NAFLD. In this post hoc analysis of the IMPROVE-IT trial, we assessed the impact of ezetimibe in patients with presumed NAFLD, using the Fatty Liver Index (FLI), a validated prediction score for hepatic steatosis.

Methods:
Of the 18,144 IMPROVE-IT patients randomized to ezetimibe/simvastatin (E/S) or placebo/simvastatin (P/S), 15,095 had both baseline ALT 2x ULN and sufficient data with which to calculate FLI, a calculated score composed of triglycerides (TG), gamma-glutamyltransferase (GGT), body mass index (BMI), and waist circumference. FLI ≥ 60 has been strongly correlated with NAFLD, while values <30 indicate low probability of NAFLD. Differences in FLI between treatment arms over time were tested with non-parametric Wilcoxon rank-sum tests.

Results:
Baseline FLI was ≥ 60 in 6798 (45%) patients and <30 in 3438 (23%). E/S reduced median absolute FLI from 55.0 to 51.2 over 72 months, a reduction of 6.9%, which was significantly greater than that observed in P/S group (all p<0.001 at each time-point, Fig). Of those with initial FLI ≥ 60 treated with E/S, 26.3% had 48-month FLI score < 60 (compared to 21.6% in P/S group, p<0.001). E/S significantly reduced both TG and GGT compared to P/S (both p<0.001 at 72 months). E/S significantly reduced FLI regardless of baseline ALT (normal vs. 1-2x ULN) (
p
=0.002; interaction
p
=0.53).

Conclusion:
Ezetimibe significantly reduced surrogate markers of NAFLD, suggesting that it may offer protection against progression of non-alcoholic fatty liver disease, metabolic syndrome, and atherogenic risk.
Abstract 16993: Sex Differences in Renal Transporter Profile Indicate Lower Proximal Reabsorption in Females
Authors: Veiras Luciana C , Tran An , Ralph Donna L , Castello Costa Girardi Adriana , McDonough Alicia A
Published: July 2021

Females have lower blood pressure than males before menopause, blunted hypertensive response to AngII, and a leftward shift in pressure natriuresis. Estrogen decreases renal ACE and AT1R and increases NO and AT2R. At the renal transporter level, distal tubule Na+-Cl- cotransporter (NCC) is upregulated by estrogen and more abundant in females, while the loop of Henle (LH) Na+-K+-2Cl- cotransporter (NKCC2) is less abundant. This study aimed to compare female to male apical Na+ transporters’ abundance, distribution, phosphorylation and cleavage and to determine the functional consequences of the differences.

Sprague Dawley rats were fasted overnight then fed a 0%KCl meal before termination. The figure displays relative abundance of total and modified (P -phosphorylated, CL-cleaved, FL-full length) transporters expressed along the nephron in females versus males (defined as 1.0), determined by quantitative immunoblotting. Lower abundance of NaPi2, villin, myosin VI, together with higher NHE3-P (inactivation marker) suggest less proximal tubule (PT) reabsorption in females. Confocal immunohistochemistry confirmed that NHE3 localized to the base of the PT microvilli in females (not males) and endogenous CLi+, a marker of volume leaving the PT, was twice as high in females than males. While LH NKCC2 and its regulatory kinase SPAK were not significantly different, distal NCC, and activated NCC-P were more abundant in females, although thiazide sensitive natriuresis was not greater. ENaC α and γ subunits were more activated (-CL) in females. A saline challenge (7% of b.w. saline, i.p.) demonstrated that females excreted a saline load more rapidly than males. Taken together, these results suggest that lower proximal transporters and reabsorption provoke a volume load dependent elevation in NCC and ENaC. This profile in females likely facilitates pressure natriuresis and maintains lower blood pressures.
Abstract 16996: Controlled Pauses (“Stutter”) CPR Did Not Improve ROSC or 4-hour Survival in a Porcine Model of VF-induced Cardiac Arrest
Authors: Esibov Alexander , Taylor Tyson G , Melnick Sharon B , Chapman Fred W , Walcott Gregory P
Published: July 2021

Introduction:
Ischemic post-conditioning (IPC) has shown promise in mitigating ischemia-reperfusion injury. Controlled pauses during CPR (CP-CPR) following cardiac arrest (CA) and prolonged downtime may help invoke IPC mechanisms and have been shown to improve neurological outcome in swine. We tested whether CP-CPR would improve return of spontaneous circulation (ROSC) and/or 4-hr survival rates, compared with standard CPR from a mechanical chest compression device (M-CPR), following prolonged downtime in a porcine model of ventricular fibrillation (VF)-induced CA.

Methods:
Twenty anesthetized and instrumented pigs were block randomized to two protocols. Following 10 min of VF, mechanical CPR was initiated (100 comp/min, 50% duty cycle, 2 inch depth). Over the first 5 minutes of CPR, the M-CPR protocol group received continuous chest compressions, while the CP-CPR protocol included four 20-sec pauses in compressions starting at 40, 100, 160, and 220 sec. All other interventions were the same in the two groups. After 5 minutes, a first shock was delivered during a pause. If the shock failed to convert to a perfusing rhythm for ≥ 30 s with a systolic aortic pressure (sAoP) ≥ 50 mmHg for at least the first three contiguous sAoP values, CPR was continued in 2 min cycles, followed by a shock (if indicated) at the end of each cycle, for up to 10 cycles. As soon as these criteria were met between two CPR cycles, ROSC was documented and a post-resuscitation protocol was initiated. During the post-resuscitation protocol, inotropic agents were provided as needed to maintain sAoP ≥ 50 mmHg. Survival was declared if the sAoP was maintained above threshold for 4 hrs following ROSC.

Results:
Nineteen animals were successfully instrumented for data gathering (9 CP-CPR, 10 M-CPR). In the CP-CPR and M-CPR groups respectively, 3/9 (33%) vs. 5/10 (50%) achieved ROSC (p = 0.46); when ROSC was achieved, time to ROSC was 7.7±1.2 min vs. 5.8±1.1 min (p = 0.08). All animals that achieved ROSC survived to 4 hours.

Conclusions:
In a porcine model of CA following prolonged VF, CP-CPR did not improve ROSC or 4-hr survival. The trend towards delayed time to ROSC suggests controlled pauses may impair initial resuscitation, even if they ultimately improve neurological outcome. Further studies are warranted.
Abstract 17014: Getting to Zero: Impact of Electroanatomical Mapping on Fluoroscopy Use in Pediatric Catheter Ablation
Authors: Clark Bradley C , Sumihara Kohei , McCarter Robert , Berul Charles I , Moak Jeffrey P
Published: July 2021

Introduction:
Over the past several years, alternative imaging techniques including electroanatomic mapping systems such as CARTO®3 (C3) have been developed to improve anatomic resolution and potentially limit radiation exposure in electrophysiology (EP) procedures. We retrospectively examined the effect of the introduction of C3 on patient radiation exposure during EP studies and ablation procedures at a children’s hospital.

Methods:
All patients that underwent EP and ablation procedures between January 2012 and November 2014 were included; demographic information, fluoroscopy time in minutes (FT), total radiation dose in mGy (RAD), and dose-area product in μGy/m2 (DAP) were collected. Patients were stratified by time period (before vs. after C3 introduction), structural group (normal heart, congenital heart disease (CHD), and those with normal cardiac anatomy requiring trans-septal (TS) access), and arrhythmia diagnosis (Accessory Pathway (AP), AV Nodal Reentry Tachycardia (AVNRT), atrial, or ventricular arrhythmia). Mean values were compared using a single sample t-test, as well as analysis of covariance to control for age, weight, and arrhythmia diagnosis.

Results:
Mean FT decreased after the introduction of C3 in patients with normal hearts (p<0.001), AP (p<0.001), AVNRT (p=0.002), and CHD (p=0.007). After controlling for age, weight, and arrhythmia diagnosis, there was a statistically significant decrease in FT in all three groups (normal heart, CHD and TS), in RAD in the TS group, and in DAP in both the normal heart and TS groups. In all other groups, there was a trend towards decreased RAD and DAP, but they did not reach statistical significance. After the introduction of C3, zero fluoroscopy was achieved in 18/66 (27%) and ≤ 1 minute of FT in 28/66 (42%) of ablation procedures in patients with normal hearts.

Conclusions:
We have shown a decrease in all metrics that measure radiation exposure when comparing the time periods before and after the introduction of C3, secondary to reducing fluoroscopy time, fluoroscopic pulse rate and radiation dose per pulse. Further refinements are still needed to decrease radiation exposure towards the goal of zero fluoroscopy, but this cannot be achieved without thinking beyond fluoroscopy time.
Abstract 17059: Temporal Trends in Incidence and Mortality of Acute Myocardial Infarction for 30 Years in Japan -A Report From the Miyagi AMI Registry Study
Authors: Cui Yuanji , Hao Kiyotaka , Takahashi Jun , Miyata Satoshi , Tsuburaya Ryuji , Matsumoto Yasuharu , Ito Kenta , Sakata Yasuhiko , Shimokawa Hiroaki
Published: July 2021

Background:
We have previously demonstrated the trends for increasing incidence of acute myocardial infarction (AMI) and decreasing incidence of in-hospital mortality in Japan between the late 1970s and 2000s. However, the temporal trends in incidence and mortality of AMI in the 21st century in Japan remain to be elucidated since the previous report.

Methods and Results:
Miyagi AMI Registry Study is a prospective and observational study where all AMI patients in the Miyagi prefecture (2.32 million populations) have been registered. In the present study, we divided a total of 27,220 AMI patients (male/female 19,818/7,402) into 4 age groups (≤59, 60-69, 70-79 and ≥80 years) by sex, and examined decennial trends during the last 30 years (1985-1994, 1995-2004 and 2005-2014) in terms of incidence and in-hospital mortality of AMI. Statistical analysis was performed by using the piecewise linear regression model. In patients aged ≤59 years of both sexes, increasing trend in the incidence of AMI was consistently noted throughout the last 30 years (P<0.01 in both sexes), whereas in male patients aged 60-69 years, the incidence of AMI was unaltered during the study period (P=0.11). On the other hand, in the remaining groups, including males aged 70-79 and ≥80 years and females aged 60-69, 70-79 or ≥80 years, the incidence of AMI showed a significant trend of decrease in the last decade (P<0.01 in all groups) (Figure). In-hospital cardiac mortality was also significantly decreased during 1985-1994 in all age groups in both sexes (P<0.01 in all groups), whereas in the last two decades, no such trend of in-hospital cardiac mortality was noted irrespective of sex or age.

Conclusions:
These results indicate the temporal trends in incidence of AMI in Japan, including the increases in younger ages and the decreases in elderly ages, providing a clue to further improve emergent care for AMI.
Abstract 17087: VNS Induced Early Suppression of the Excessive Inflammatory Response May Contribute to its Beneficial Effects on Chronic Heart Failure
Authors: Nishizaki Akiko , Saku Keita , Kishi Takuya , Ide Tomomi , Sunagawa Kenji
Published: July 2021

Background:
The inflammatory response plays a pivotal role in the pathogenesis of chronic heart failure (CHF). Although vagal nerve stimulation (VNS) improves CHF, the central mechanism remains unclear. Since VNS exerts powerful anti-inflammatory effects, we investigated how VNS impacts on the inflammatory regulation and the development of CHF.

Methods:
In 8 weeks old Sprague-Dawley rats, we created large myocardial infarction (MI) and started VNS 2 weeks after MI. We adjusted the intensity of VNS below the threshold of bradycardia (20 Hz, 1.5±0.9 volts, 10 sec on, 50 sec off). In the first group (EARLY) (CHF: n=8, VNS: n=13), we continued VNS for 3 days and evaluated the early impact of VNS on inflammation on the 3rd day. In the second group (LATE) (CHF: n=13, VNS: n=13), we continued VNS for 4 weeks and evaluated cardiac remodeling and function on the last day.

Results:
In EARLY, hemodynamic parameters or plasma BNP as an index of CHF did not change significantly. In contrast, VNS halved the invasion of CD 68 positive cells in the left ventricle (LV) (CHF: 295.1±142.1, VNS: 110.7±59.6 counts/mm2, p<0.01), and markedly reduced interleukin-1β (IL-1β) not only in plasma (CHF: 75.7±27.6, VNS: 32.9±6.8 pg/mL, p<0.01) but also in the heart (CHF: 13.2±4.6, VNS: 9.3±2.4 pg/mg, p<0.05) and spleen (CHF: 170.2±65, VNS: 115.4±58.8 pg/mg, p<0.05). TNF-α, IL-6, HMGB-1 and CRP remained unchanged. In addition, VNS significantly reduced the expression of TGF-β in LV which is a key mediator of fibroblast activation (CHF: 31±4.0, VNS: 16.6±2.0 %, p<0.01). In LATE, VNS significantly decreased cardiac fibrosis (Masson’s trichrome stain) (CHF: 4.4±0.7, VNS: 2.9±1.1 %, p<0.01), heart weight (CHF: 3.7±0.5, VNS: 3.2±0.5 g/kg, p<0.01) and LVEDP (CHF: 24.2±5.0, VNS: 17.5±7.1 mmHg, p<0.01), suggesting that VNS prevented cardiac remodeling and preserved LV function.

Conclusion:
VNS significantly decreased the invasion of macrophage, IL-1β and TGF-β production from the beginning of VNS initiation, and resulted in the decrease of cardiac fibrosis and the improvement of cardiac remodeling as well as cardiac function. VNS induced early suppression of the excessive inflammatory response may lead to its late beneficial effects on CHF.
Abstract 17097: Substantial Improvement of Primary Cardiovascular Prevention by a Systematic Score-based Multimodal and Lifestyle Approach: A Randomized Endpoint-Study - The Preford-Study
Authors: Predel Hans Georg , Gysan Detlef B , Albus Christian , Bjarnason-Wehrens Birna , Gohlke Helmut , Latsch Joachim , Millentrup Stefanie , Heming Christian , Herold Gerd
Published: July 2021

Background:
The optimization of primary preventive cardiovascular (CV) strategies is urgently needed. The objective of the present study was to evaluate the long-term effects of a standardized multimodal and lifestyle based therapeutic approach in high-risk-subjects according to the ESC-SCORE on predefined cardiovascular end-points. The ESC-SCORE allows a systematic estimation of the 10-year-risk for fatal CV events.

Methods:
The individual CV risk was assessed in a cohort of 4.196 employees of the Ford-Company, Germany, using the ESC-SCORE. Subjects were subsequently classified into three risk-groups. Subjects at high-risk, (ESC-SCORE ≥ 5%; n=447), were randomized either into a multimodal 15-week lifestyle based outpatient intervention program (INT n=224) or into a usual care group (UC n=223) and followed up for 36 months. The primary endpoint was a reduction of the ESC-SCORE in the INT as compared to the UC at the end of the trial. Secondary endpoints were a composite of fatal and non-fatal CV events (coronary artery disease, cerebrovascular or peripheral arterial disease, CV death and total mortality) and the time to the first CV event. An intention to treat analysis was performed.

Results:
After 36 months a difference of the ESC-SCORE development favoring the INT was achieved (INT: 8.70 to 10.03% vs. UC: 8.49 to 12.09%; p<0.016). Moreover, a reduction in the composite secondary endpoint was observed (INT: n=11 vs. UC: n=27; p=0.032; HR 0.45 (CI 0.22 - 0.94).

Conclusions:
Our results demonstrate an intermediate-term improvement of the ESC-SCORE as well as a reduction of predefined CV endpoints by a primary CV prevention program within 36 months in a cohort of persons determined to be at high CV risk by assessment with the ESC-SCORE.
Abstract 17107: Distribution of Anti-inflammatory Activity During Remodeling of High Density Lipoprotein: Studies With CSL112
Authors: Diditchenko Svetlana A , Navdaev Alexei V , Spycher Martin O , Wright Samuel D
Published: July 2021

Elevated levels of circulating inflammatory markers predict an unfavorable cardiovascular outcome in acute coronary syndrome patients. CSL112 is human apolipoprotein A-I (apoA-I), reconstituted with phosphatidylcholine to form HDL particles suitable for infusion. Addition of CSL112 to stimulated human whole blood ex vivo strongly reduces pro-inflammatory cytokine production. Infusion of CSL112 into human subjects or addition to human plasma ex vivo causes remodeling of endogenous HDL. Similar remodeling occurs upon incubation of CSL112 with purified HDL3 and results in accumulation of three HDL species: enlarged HDL (HDL2), a smaller, dense species (HDL3c), and lipid-poor apoA-I (pre-β1 HDL).

Study aim was to determine the anti-inflammatory activity of remodeled HDL species. CSL112 was incubated with HDL3 and the products of particle remodeling were purified by ultracentrifugation. The inhibitory effects on pro-inflammatory cytokine production were examined using human peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin-M (PHA-M) in vitro.

Lipid-poor apoA-I, HDL3c as well as parent CSL112 exerted powerful inhibitory effects on secretion of pro-inflammatory mediators (> 89.2% + 4.0% inhibition of TNF-α, IL-1β, IL-6 and Mip-1β); HDL3 and HDL2 were much less effective (< 54.1% + 3.9% inhibition). The extent of inhibition correlated positively with induction of the transcription repressor ATF3, a negative regulator of pro-inflammatory cytokine production, with lipid-poor apoA-I and HDL3c inducing higher protein levels of ATF3 in PHA-stimulated PBMC compared to control medium, HDL3 or HDL2. Anti-inflammatory activity of the remodeled species also correlated with their ability to support cellular cholesterol efflux via the ABCA1 transporter: lipid-poor apoA-I and HDL3c were potent acceptors of cholesterol; HDL2 was inactive.

The ability to generate HDL species with high cholesterol efflux and anti-inflammatory activity makes CSL112 a promising candidate for removing cholesterol and reducing inflammation in atherosclerotic plaque, thus reducing the high risk of early recurrent atherothrombotic events following acute MI (AMI). A Phase IIb trial (AEGIS-I; NCT02108262) of CSL112 in AMI patients is ongoing.