bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17597: Quantitative T Wave Analysis Can Identify Patients With Symptomatic Long QT Syndrome
Authors: Sugrue Alan , Bos J. Martijn , Kremen Vaclav , Qiang Bo , Friedman Paul A , Ackerman Michael J , Noseworthy Peter A
Published: July 2021

Introduction:
Long QT syndrome (LQTS) is a genetic disorder associated with abnormal ventricular repolarization and a predisposition for torsade de pointes and sudden cardiac death. Identification of markers to elucidate high risk patients is of major practical importance. Our aim was to use a novel, automated quantitative T wave analysis program to distinguish symptomatic from asymptomatic LQTS patients.

Methods:
We analyzed a genotyped cohort of 420 patients (22 ± 15.7years, 43% male) with either LQT1 (61%) or LQT2 (39%). ECG analysis was conducted using novel software that we created to automatically detect subtle changes in T wave morphology. Symptomatic patients were defined as those with a history of syncope or resuscitated cardiac arrest that was suspected of being LQTS triggered. Classification was performed using the top three T wave features in a linear discriminant classifier by 10x10 cross-validation.

Results:
Symptomatic LQT1 patients have a greater QTc duration in lead aVF (437 msec vs 416 msec, p <0.0001), a greater T wave center of gravity on the x axis (COGx) in lead V2 (0.304 vs 0.280, p <0.0001) and longer Tpeak-Tend/QT in lead II (0.208 vs 0.188, p < 0.0001) than asymptomatic patients with LQT1. Use of these 3 features enabled classification of symptomatic status in 72% of LQT1 cases, compared to 68% when QTc was used to classify alone. Symptomatic LQT2 patients had a longer QTc in Lead 1 (460 vs 418 msec, p < 0.0001), COGx in 4th segment of T wave was greater in lead V5 (0.399 vs 0.350, p<0.0001), and the Tpeak-Tend interval in V2 was longer (126 vs 99 msec, P =0.0004). Use of these 3 features enabled correct classification in 73% of LQT2 cases, compared to 67% when QTc was used alone.

Conclusions:
Application of an automated T wave analysis program was able to identify T wave features that distinguished the patients who presented as symptomatic LQTS, associated with syncope or resuscitated cardiac arrest. Use of these features could help assess arrhythmic risk and guide management strategies for patients with LQTS.
Abstract 17600: Improved Iterative Reconstruction Reduces Artifacts and Results in Larger Measurements of Ileofemoral Artery Size on Computed Tomography in Patients Referred for Transcatheter Aortic Valve Replacement
Authors: Minhas Anum , Patel Smita , Kazerooni Ella , Conte Antonio , Labounty Troy
Published: July 2021

Background:
Computed tomography (CT) is typically used to measure ileofemoral artery size in patients considered for transcatheter aortic valve replacement (TAVR). However, these patients often have significant arterial calcification, which can introduce artifacts and limit measurement accuracy. We hypothesized that improved iterative reconstruction would improve image quality and reduce artifacts, resulting in larger measured size.

Methods:
We examined 56 patients undergoing CT for possible TAVR, and compared image quality and ileofemoral arterial size between separate reconstructions of the same studies, comparing standard (STD) advanced statistical iterative reconstruction and improved model-based iterative reconstruction (MBIR). A blinded reader identified the sites with the smallest luminal diameter, and provided identical short-axis reformats for both reconstructions. A separate blinded reader graded image quality and made measurements in a random sequence. We compared mean and minimal diameters, image quality (1 poor, 4 excellent), and signal and noise.

Results:
Mean age was 77 ± 10 years and 54% were male. Table 1 compares measured diameters and image quality between STD and MBIR reconstructions. Between STD and MBIR images, ≥moderate beam-hardening artifacts were observed in 30% (17/56) and 9% (5/56) of patients, respectively (p=0.008); severe artifacts were seen in 23% (13/56) and 5% (3/56) of patients, respectively (p=0.01). Overall image quality of STD and MBIR images was graded as good or excellent in 70% (39/56) and 91% (51/56) of cases, respectively (p=0.008).

Conclusion:
In patients referred for TAVR, improved iterative reconstruction resulted in higher image quality, fewer beam-hardening artifacts, and larger measurements of ileofemoral artery size.
Abstract 17609: Comparison of All-cause and Bleeding-related Hospitalizations Among Non-valvular Atrial Fibrillation Patients Receiving Oral Anticoagulants
Authors: Deitelzweig Steve , Bruno Amanda , Gupta Kiran , Trocio Jeffrey , Tate Natalie
Published: July 2021

To compare the risk of hospitalization among non-valvular atrial fibrillation (NVAF) patients newly initiated with an oral anticoagulant (OAC): apixaban, dabigatran, rivaroxaban, or warfarin.

Retrospective cohort study using Humana Medicare Advantage data from 7/1/2009 - 9/30/2014. NVAF patients ≥18 years receiving one OAC on the index date with 6 months continuous enrollment prior to index prescription date and 3 months post-index were eligible. Hospitalizations were identified by standard codes for inpatient admission. Bleeding-related hospitalizations required an additional code for major/clinically relevant non-major (CRNM) bleeding. A cox proportional hazards model was used to estimate the hazard ratios (HR) of hospitalizations adjusted for age, sex, region, comorbidities and comedications. Adherence for each OAC was also calculated using a proportion of days covered approach to understand medication taking behaviors.

Among the 53,168 patients initiated on an OAC, 2,028 (3.8%) apixaban, 5,644 (10.6%) dabigatran, 7,667 (14.4%) rivaroxaban and 37,829 (71.1%) warfarin. Patients in apixaban cohort were older (mean 75.5 years, P <0.05) with higher mean CHA
2
DS
2-
VASc score (P <0.05). Abixaban patients had a higher mean HAS-BLED score vs. dabigatran (P <0.0001), lower mean score vs. warfarin (P <0.0001) and did not differ significantly vs. rivaroxaban (P =0.46). Patients receiving apixaban had a significantly lower risk for all-cause hospitalization across cohorts, and a sig. lower risk for bleeding-related hospitalization vs. patients receiving rivaroxaban or warfarin (Table). Adherence ranged from 87.8% to 90.4% across cohorts.

In a real-world setting, initiation with apixaban was associated with a significantly lower risk for all-cause hospitalization, and a significantly lower risk of bleeding-related hospitalization compared to rivaroxaban or warfarin.

Table: Adjusted Hazard Ratios of All-cause and Bleeding-related Hospitalizations
Abstract 17619: Interstage Growth Trajectory is Associated With Interstage Survival in the Absence of Post-operative Complications Following the Norwood Procedure
Authors: Evans Charles F , Abraham Danielle S , Kaushal Sunjay , Rosenthal Geoffrey L
Published: July 2021

Introduction:
Low birth and procedure weight have been identified as risk factors for mortality after the Norwood operation. There are no strong data to show that growth during the interstage period is associated with interstage survival.

Hypothesis:
We hypothesize that positive growth trajectory following the Norwood operation is associated with improved interstage transplant-free survival.

Methods:
We conducted a retrospective cohort study using the National Pediatric Cardiology Quality Improvement Database. The exposure, growth trajectory, was the slope of the least-squares regression line of body mass index-for-age Z-scores over time. The outcome was interstage transplant-free survival. We constructed a multivariable logistic regression model to examine the association between interstage growth trajectory and interstage transplant-free survival.

Results:
The study population included 1501 infants who were discharged alive from the Norwood operation between June 2008 and January 2015. The most common diagnosis was hypoplastic left heart syndrome with aortic and mitral atresia (34%). The most common operation was the Norwood procedure with a right ventricle to pulmonary artery shunt (55%). Interstage survival was 89%. Growth trajectory was positive in 945/1392 (68%) for whom sufficient data were available. The occurrence of at least one post-operative complication was identified as an effect measure modifier (p=0.02). When adjusted for sex, birth weight, presence of a secondary cardiac diagnosis, type of operation and post-operative arrhythmia, positive growth trajectory was significantly associated with interstage survival in the absence (OR=3.7, 95% CI 1.7, 8.0) but not in the presence (OR=1.1, 95% CI 0.7, 1.7) of post-operative complications.

Conclusions:
Positive interstage growth trajectory is significantly associated with transplant-free interstage survival in the absence of post-operative complications.
Abstract 17672: Myosin Binding Protein C Gene Mutation (
S593Pfs*9
) Induces Heart Failure and Reduced Ca Transient Amplitude in Zebrafish
Authors: Ogimoto Akiyoshi , Musso Gabriel , Werdich Andreas A , White David A , Beerens Manu E , Sips Patrick , Kapur Sunil , Burch Micah L , Flores Ludmila M , Higaki Jitsuo , MacRae Calum A
Published: July 2021

Introduction:
Mutations in the cardiac myosin-binding protein C (
MYBPC3
) gene have been implicated in over one third of hypertrophic cardiomyopathy (HCM) cases. These mutations have been reported to be associated with delayed expression of hypertrophy and a relatively good prognosis. However, we previously reported that a patients with a
S593Pfs*9
mutation (a single base deletion of a thymidine residue at nucleotide 11645 in exon 18) in this gene deteriorated into the“end-stage” HCM, characterized by left ventricular systolic dysfunction, cavity dilation, and heart failure. This mutation causes a truncated MYBPC3. The precise functional and pathological consequences of this mutation are not fully characterized. The aim of this study was to recapitulate the
S593Pfs*9
mutation in the zebrafish to define the pathologic mechanisms.

Methods:
We used the CRISPR/Cas9 system to generate a genocopy of the
S593Pfs*9
with a specific guide RNA injected with Cas9 into one-cell stage embryos.

Results:
Gross morphological examination of the mutants showed a smaller ventricle and pericardial edema compared with controls. There were significant reductions in heart rate (125 +/- 31 vs 148 +/- 9 /min), end-diastolic volume (EDV) (0.41 +/- 0.16 vs 0.72 +/- 0.18 nl), end-systolic volume (ESV) (0.24 +/- 0.08 vs 0.36 +/- 0.13 nl), stroke volume (SV) (0.16 +/- 0.12 vs 0.36 +/- 0.09 nl) in mutants compared with control embryos at 48 hours post fertilization (hpf). In addition, the calcium transient amplitude (0.17 +/- 0.02 vs 0.23 +/- 0.02 ratio units) was also significantly reduced in the mutant hearts compared with the control hearts at 48 hpf.

Conclusions:
Our data demonstrate that the
S593Pfs*9
mutants exhibit reduced EDV, ESV, and SV and define early abnormalities of Ca
2+
handling that may drive the development of heart failure at later stages. This model will allow the mechanistic dissection of MYBPC-associated heart failure and enable chemical screens for novel drugs.
Abstract 17673: The Effectiveness of Improved ICD Programming by Race: A MADIT-RIT Sub-study
Authors: Jackson Larry R , Thomas Kevin L , Zareba Wojciech , Lahiri Marc , Saba Samir , Aktas Mehmet , McNitt Scott , Schuger Claudio D , Daubert James P , Moss Arthur J , Kutyifa Valentina
Published: July 2021

Introduction:
There are limited data on the risk of inappropriate and appropriate ICD therapy and on the efficacy of different ICD programing strategies as a function of race.

Methods:
In MADIT-RIT, we evaluated the risk of inappropriate and appropriate ICD therapy by self identified race, and assessed the efficacy of improved ICD programming with either a high rate cut-off VT zone ≥ 200 bpm (Arm B), or long 60 sec delay in the VT zone 170-190 bpm (Arm C), as compared to conventional ICD programming with 2.5 sec delay beginning at 170 bpm (Arm A) among black and white patients.

Results:
MADIT-RIT enrolled 272 (20%) black and 1119 (80%) white patients. Black patients were younger, more often females, they more often had non-ischemic etiology of cardiomyopathy, a narrower QRS and they were less often implanted with CRT-D. The risk of inappropriate ICD therapy was similar among black and white patients (HR 1.25, 95% CI 0.82-1.93, P=0.30) after adjustment for relevant covariates. High rate cut-off or delayed VT therapy was associated with significant reductions in inappropriate ICD therapy among white patients (Arm B vs. Arm A, HR 0.15, P<0 .0001, Arm C vs. Arm A, HR 0.19, P 0.10). However, delayed VT therapy (Arm C) when compared to Arm A, was associated with greater reduction in appropriate ICD therapy in black patients (HR 0.08, P<0.0001), as compared to white patients (HR 0.27, P<0.0001, P interaction=0.07). There were no appropriate ICD therapies in the 170-200 bpm range in Arm C with delayed VT therapy programming in black patients, and a further reduction in appropriate ICD therapy ≥ 200 bpm (Arm C vs. Arm A, HR=0.16, p<0.001).

Conclusion:
In MADIT-RIT, there were similar reductions in inappropriate ICD therapy among black and white patients with improved ICD programming. However, black patients derived more benefit from delayed VT zone programming with greater reduction in appropriate ICD therapy compared to whites, due to a higher rate of self-terminating VT events.
Abstract 17678: Earlier Stage I Operation in Neonates With Hypoplastic Left Heart Syndrome is Not Associated With Worse Short-term Outcomes
Authors: McCarthy Ann L , Winters Madeline E , Bixler Elizabeth , Lynch Jennifer M , Newland John J , Busch David R , Ko Tiffany , Xiao Rui , Nicolson Susan C , Montenegro Lisa M , Mascio Christopher E , Fuller Stephanie , Gaynor William J , Spray Thomas L , Licht Daniel J , Naim Maryam Y
Published: July 2021

Introduction:
We have previously reported that earlier stage I palliation (S1P) is protective against White Matter Injury (WMI) for term infants with hypoplastic left heart syndrome (HLHS). The present study compares clinical outcomes from the acute hospitalization between neonates who had early (≤ 4 days) versus late surgery (> 4 days).

Hypothesis:
Earlier S1P intervention is associated with greater post-operative complications rates.

Methods:
A retrospective chart review was performed on all neonates with HLHS or variants who underwent S1P at a single institution between 10/2008 - 03/2013. Excluded were a preterm (<37 weeks gestation), left-ventricle physiology, prior operations and international referral. Anthropometric data, pre- post- and intra-operative factors, post-operative complications, and both intensive care unit (ICU) and hospital length of stay were evaluated for differences between early vs. late surgery. Analysis was performed excluding patients who had either early, or late surgery for non-elective diagnoses.

Results:
A total of 145 infants, 114 (73 with early surgery, 41 late) met inclusion criteria. The mean day of surgery was 4.2 days (early 2.7±0.1 days, late 6.9±3.7 days). There were no significant differences between the groups’ post-operative complications or operative factors (see Table 1). In addition exclusion of patients with non-elective change to their surgical date did not change results significantly. Neonates who had earlier surgery had significantly longer post-operative ICU stay (median 9 days vs. median 13 days, p = 0.02).

Conclusion:
Early surgery for neonates with HLHS was not associated with either protection against or greater risk for post-operative complications. Neonates who have earlier surgery have a longer initial post-operative ICU stay, but total ICU and hospital stay was not different than that for infants with surgery after day four.
Abstract 17680: Effectiveness of a New Smartphone Application “AED-SOS” to Call Co-rescuers Carrying an AED for Cardiac Arrests: A Randomized Controlled Trial
Authors: Hatakeyama Toshihiro , Nishiyama Chika , Shimamoto Tomonari , Kiyohara Kosuke , Kitamura Tetsuhisa , Kawamura Takashi , Iwami Taku
Published: July 2021

[Introduction]
Although earlier shock with an automated external defibrillator (AED) is the key to increase survival after out-of-hospital cardiac arrests (OHCA), it is not easy to find out an AED in emergency settings. We recently developed a new smartphone application “AED-SOS.” This application sends a special signal to the smartphone of potential co-rescuers existing in the neighborhood and indicates the OHCA scene and AED locations on the display. According to these notifications, co-rescuers find out and deliver an AED to the OHCA scene.

[Objective]
To elucidate how this new application can shorten the process to find out an AED and bring it to the OHCA scene.

[Methods]
Design: Randomized controlled trial (UMIN000016506). Participants: Lay persons aged 18 years or older. Randomization: Participants were randomly assigned to either the AED-SOS group or the control group using permuted blocks after stratification by sex. Intervention: We provided an OHCA scenario to the study participants of both groups. Participants assigned to the AED-SOS group were encouraged to use the AED-SOS application. Data collection: We observed the process until the participants or their co-rescuers brought an AED to the scene. Outcomes: The primary outcome was the time from the recognition of OHCA to AED delivery by either the participant or the co-rescuers. The secondary outcome was their travel distance.

[Results]
Among 61 participants enrolled, 52 were analyzed. The time from recognition of OHCA to AED delivery was significantly shorter in the AED-SOS group than in the control group (133.6±44.4 versus 202.2±122.2, p=0.01). The travel distance was similar between the groups (Table).

[Conclusion]
The smartphone application to prompt potential co-rescuers in the neighborhood to deliver an AED, would shorten the time from recognition of OHCA to AED delivery. It will help increase the survivors after OHCA.
Abstract 17701: Nrf2 Inhibits NF-κB Activation During Ischemia Reperfusion Injury and Suppresses Subsequent Development of Cardiac Allograft Vasculopathy in Murine Heart Transplantation
Authors: Kawajiri Hiroyuki , Ghashghai Arash , Tumiati Laura , Lazarte Julieta , Grosman-Rimon Liza , Luengas Vanessa R , Badiwala Mitesh , Butany Jagdish , Li Renke , Billia Filio , Rao Vivek
Published: July 2021

Introduction:
Recent studies suggest that ischemia reperfusion injury (IRI) activates the NF-κB pathway leading to the subsequent development of cardiac allograft vasculopathy (CAV). Nrf2 has been suggested to inhibit NF-κB activation during IRI in other organs; however, the role in myocardial IRI and CAV remains unclear. Therefore, we examined the effects of Nrf2 induction and knockout (KO) on IRI-mediated NF-κB activation as well as CAV using a murine transplant (Tx) model.

Methods:
Nrf2 wild-type (WT) and KO mice were used as donors, with WTs used as recipients for IRI studies and Bm12 mice for CAV studies. Donor hearts received 2hrs of cold ischemia before Tx. Twenty-five mg/kg sulforaphane (SF, a known Nrf2 agonist) was given to donors 24hrs prior to surgery and to recipients just after Tx to induce Nrf2, with saline as vehicle control (SA). Donor hearts were procured after 24hrs of reperfusion in IRI studies. In CAV studies, recipients received daily 5mg/kg SFN or saline until day 56 when donor hearts were procured (n=6/group).

Results:
In IRI, NF-κB activity measured by percentage of the cells with nuclear p65 (Figure A) was significantly higher in KO-SA compared with WT-SA (38±4 vs 24±4%, p<0.001). WT-SF displayed notably less NF-κB activity compared with WT-SA (13±5 vs 24±4%, p=0.002). The mRNA levels of NF-κB-mediated inflammatory cytokines were significantly higher in KO-SA compared with WT-SA, and WT-SF displayed lower levels of these mRNA compared with WT-SA (Figure B). In the chronic CAV studies, WT-SA displayed less coronary occlusion area compared with KO-SA (21±8 vs 42±12%, p=0.005). Furthermore, WT-SF showed significantly less coronary occlusion compared with WT-SA (21±8 vs 8±4%, p=0.005) (Figure C).

Conclusions:
Our results suggest that Nrf2 inhibits NF-κB activation during IRI and suppresses subsequent development of CAV. The Nrf2 pathway may be a promising pharmacological target to prevent development of CAV via its anti-inflammatory properties.
Abstract 17722: Recipient Treatment With Donepezil, an Acetylcholinesterase Inhibitor , Abolishes Donor Heart Ischemia/Reperfusion Injury and Chronic Graft Failure Through TNF Inhibition in an Syngenic Rat Model
Authors: Yuan Xin , Teng Xiao , Hou Jianfeng
Published: July 2021

Introduction:
Ischemia/reperfusion injury (IRI) may have deleterious consequences for donor heart. The underlying mechanisms involve inflammation that may culminate in primary or chronic graft failure.

Hypothesis:
Donepezil, an acetylcholinesterase inhibitor, can protect the post-transplanted donor heart by inhibiting systemic inflammation of the recipients.

Methods:
Here, we report in Lewis to Lewis rat syngenic heart transplantation model that ischemia/reperfusion injury resulted in primary and chronic graft failure that was prevented by recipient treatment with peroral single-dose Donepezil.

Results:
Donepezil inhibited the release of cytokines (TNF, IL-1β, IL-6 and IL18), CD11b/18 positive cell infiltration and myocardial apoptosis in the recipient rats one week postoperatively. One month after transplantation, the graft survival rate in Donepezil group was 46.7% than that in SHAM group (P<0.05); the EF value in Donepezil group was 13% higher than that in SHAM group (P<0.05). The cardiac fibrosis grade was 1 grade lower in Donepezil group than that in SHAM group (P<0.05). Methyllycaconitine blocked the actions of Donepezil, suggesting that the donor heart protection effects are α7-nAChRs-dependent.

Conclusions:
Our results reveal that recipient treatment with Donepezil protects donor hearts through TNF inhibition and TNF related downstream pathophysiological pathways. These results suggest a novel, clinically feasible strategy to protect donor hearts from IRI.
Abstract 17751: Low Appendicular Skeletal Muscle Mass is Associated With High Coronary Plaque Complexity in Patients With ST-segment Elevation Myocardial Infarction
Authors: Satou Ryosuke , Akiyama Eiichi , Suzuki Hiroyuki , Kawashima Chika , Matsuzawa Yasushi , Konishi Masaaki , Hashiba Katsutaka , Maejima Nobuhiko , Iwahashi Noriaki , Tsukahara Kengo , Hibi Kiyoshi , Kosuge Masami , Ebina Toshiaki , Sumita Shinichi , Umemura Satoshi , Kimura Kazuo
Published: July 2021

Introduction:
Loss of skeletal muscle mass is associated with diabetes, insulin resistance, inflammation, and generalized atherosclerosis. The angiographic complexity of coronary artery disease can predict outcomes in patients undergoing percutaneous coronary intervention. However, the relationship between skeletal muscle mass and ST-segment elevation myocardial infarction (STEMI) remains undetermined.

Hypothesis:
We assessed the hypothesis that low appendicular skeletal muscle mass index (ASMI) is associated with high coronary plaque complexity in patients with STEMI.

Methods:
We enrolled consecutive 112 patients with STEMI (age 64±12, male 87.5%) in this study. Appendicular skeletal muscle mass was estimated from dual-energy X-ray absorptiometry (DXA) scan before discharge and ASMI was defined as appendicular skeletal muscle mass divided by height squared (kg/m
2
). ASMI was dichotomized according to the Asia Working Group for Sarcopenia criteria, which determined low (<7.0 kg/m
2
for men and <5.4 kg/m
2
for women by DXA) and normal ASMI. And we graded the coronary plaque complexity by using the Synergy between Percutaneous Coronary Intervention with Taxus and Coronary Surgery (SYNTAX) score at the initial coronary angiography.

Result:
ASMI correlated positively with body mass index (r=0.80, P<0.001), as well as negatively with age (r=-0.63, P<0.001), SYNTAX score (r=-0.28, P=0.003), Killip classification (r=-0.22, P=0.019), and B-type natriuretic peptide levels on admission (r=-0.27, P=0.014). The prevalence of low ASMI patients was 41% (n=46). Low ASMI patients had higher SYNTAX score (19.0±8.3 versus 13.7±7.7, P=0.001) compared with normal ASMI patients. Multivariate logistic regression analysis including age, gender and various classical risk factors demonstrated that ASMI significantly and independently correlated with moderate-severe coronary plaque complexity (SYNTAX score>22, n=22) in STEMI patients (odds ratio per 1: 0.55, 95%-confidence interval: 0.35-0.87, P=0.01).

Conclusion:
Low ASMI is significantly associated with high coronary plaque complexity in patients with STEMI, suggesting that skeletal muscle mass could play a crucial role in the pathogenesis of atherosclerosis in patients with STEMI.
Abstract 17775: Predictive Value of Endothelial Function for the Recurrence of Atrial Fibrillation After Catheter Ablation
Authors: Kanazawa Hisanori , Yamabe Hiroshige , Sugiyama Seigo , Iwashita Satomi , Hoshiyama Tadashi , Ito Miwa , Kaneko Shozo , Ogawa Hisao
Published: July 2021

Introduction:
Endothelial function has been shown to be deteriorated by the presence of atrial fibrillation (AF). Therefore, we hypothesized that serial change in the endothelial function can predict the recurrence of AF after catheter ablation (CA).

Objectives:
The purpose of this study was to examine the predictive value of endothelial function as a marker for recurrence of AF after CA.

Methods:
The consecutive 156 AF patients who underwent CA for AF were included in this study. All patients assessed their endothelial function by the reactive hyperemia-peripheral arterial tonometry (RH-PAT) and the RH-PAT index (RHI) was measured before CA, and 3 and 6 months after CA. To investigate the factors correlated with AF recurrence, clinical variables and RHI before CA, 3 and 6 months after CA were examined in patients with and without recurrence of AF. The recurrence of AF was defined as the occurrence of AF at the time of 6 months after CA.

Results:
AF recurrence was not observed in 125 patients (80%), but was observed in the remaining 31 patients (20%). Disease duration of AF (p=0.028), RHI before CA (p<0.001), RHI 3 month after CA (p=0.037), the difference in RHI before and 3 month after CA (p<0.001) were significantly correlated with AF recurrence. The multivariate Cox hazard analysis revealed that the difference in RHI before and 3 month after CA independently correlated with the recurrence of AF (p<0.001, Hazard ratio: 0.168). Furthermore, the value of RHI 3 month after CA, which decreased 0.015 or more compared with that before CA, was the independent predictor of AF recurrence (sensitivity: 0.613, specificity: 0.880, area under curve 0.722). Kaplan-Meier analysis demonstrated a significantly higher probability of AF recurrence when the RHI value 3 months after CA showed a decrease over 0.015 (log-rank test: p<0.001).

Conclusions:
The change in the endothelial function following CA sensitively reflects the recurrence of AF. The decrease in the RHI 3 months after CA compared to that before CA, with a cu-off value of 0.015, was an independent significant predictor of AF recurrence. Therefore, no recurrence of AF can be expected by the absence of decrease in RHI. We might be able to stop anti-arrhythmic drugs and anticoagulants according to the RHI improvement 3 month after CA.
Abstract 17791: Association of Enhanced Adventitial Vasa Vasorum Formation With Atherosclerotic Changes in the Human Coronary Arteries Adjacent to Myocardial Bridging -An Optical Frequency Domain Imaging Study
Authors: Wang Hongxin , Matsumoto Yasuharu , Nishimiya Kensuke , Takahashi Jun , Uzuka Hironori , Hao Kiyotaka , Tsuburaya Ryuji , Amamizu Hirokazu , Ohyama Kazuma , Komatsu Masayasu , Odaka Yuji , Ito Kenta , Shimokawa Hiroaki
Published: July 2021

Background:
Although myocardial bridge (MB) has been implicated as a cause of adverse cardiac events, its pathological significance remains to be fully elucidated. Recent advance in imaging with optical frequency domain imaging (OFDI) has enabled us to precisely evaluate the coronary arterial wall in humans, including adventitial vasa vasorum (VV). In the present study, we thus examined with OFDI whether coronary adventitial VV formation is enhanced in the MB segments in humans and if so, whether there is any correlation between adventitial VV formation and atherosclerotic changes.

Methods and Results:
We examined 15 consecutive patients (age 67±2, M/F 7/8) who were diagnosed as having MB in the left anterior descending coronary arteries without significant organic stenosis in the present OFDI study. MB was diagnosed by CAG when systolic compression was noted, as previously reported. The cross-sectional OFDI showed diffuse enhancement of VV formation at the proximal and distal segments compared with the MB site (
Figure A
). Quantitative analysis at every 1-2 mm length showed that adventitial VV area density on OFDI was significantly greater at both the proximal and the distal segments compared with the MB site (0.122±0.005 vs. 0.075±0.003 vs. 0.108±0.005 mm
2
/mm
2
, P<0.001) (
Figure B
). In addition, intimal (I) + medial (M) area was significantly greater at the proximal segments compared with the MB site and the distal segments. (2.70±0.12 vs. 1.66±0.07 vs. 1.83±0.11 mm
2
, P<0.001) (
Figure C
). Importantly, there was a significant positive correlation between the extent of VV formation and that of I+M area in the coronary artery (R=0.582, P<0.0001) (
Figure D
).

Conclusions:
These results suggest an important role of adventitial VV formation in the pathogenesis of human coronary atherosclerosis adjacent to the MB, for which altered blood turbulence may be involved.
Abstract 17832: A New Rapid Vector Technique to Localize the PVC Origin From the 12-lead Ecg Compared to Cips
Authors: van Dam Peter M , Gordon Jeff P , Tung Roderick , Boyle Noel G , Laks Michael M
Published: July 2021

Introduction:
Prior accurate PVC localization improves the time and outcome of ablative procedures. We developed a new manual Vector Technique (VcT) to localize the PVC origin to cardiac anatomy regions. In contrast, our Cardiac Isochrone Positioning System (CIPS) is a computer based system that localizes the PVC to patient specific cardiac anatomy from the MRI and electrode positions from the 3D Camera.

Hypothesis:
We hypothesize that this new VcT can rapidly quantitate the location of PVC to anatomical regions whereas CIPS localizes the PVCs to more specific cardiac anatomical segments.

Method:
The VcT assumes the frontal plane leads are formatted on the chest as an equilateral triangle and the horizontal leads as a partial sphere. Using the concept that a lead recording perpendicular to a dipole vector is zero, the QRS axis vectors of the PVC were calculated manually within 3.8 to 7.5 degrees in the frontal and horizontal planes.

CIPS computed the electrode positions by registration of the MRI derived torso model with the 3D image of the patient. The ECG signals were used by both methods to localize the PVC origin to the cardiac anatomy.

Result:
In 12 patients (below), this manual VcT separated without overlap in the horizontal plane the PVC into Left Ventricle (LV 30-45°), Right Ventricular (RV 308-348°), and Papillary Muscle (PM 128-150°) regions, but not in the frontal plane. CIPS localized 10 PVCs to the same and 2 to adjacent anatomical segments while the vector technique cannot because of the need for a database to create a PVC anatomic segment model.

Conclusion:
This new VcT can be used by anyone to localize rapidly the PVC by a QRS vector plot to regions like the left & posterior for the RV, left & anterior for the LV, and right & anterior for the papillary muscles while CIPS can localize PVCs more specifically to anatomical segments. Using the 12 lead ECG, this VcT creates a quantitative cardiac anatomical segment model of PVC locations integrated into CIPS that can improve the accuracy of VcT.
Abstract 17847: Gasping is a Valid Predictor Of ROSC and Hospital Discharge for In-hospital Cardiac Arrest Occurring on the Ward
Authors: Marengo Luca , Ummenhofer Wolfgang , Pascal Gerster , Harm Falko , Lüthy Marc , Zürcher Mathias
Published: July 2021

Introduction:
Agonal respiration has been shown to be commonly associated with witnessed events, ventricular fibrillation, and increased survival during out-of-hospital cardiac arrest. There is little information on incidence of gasping for in-hospital cardiac arrest (IHCA). Our “Rapid Response Team” (RRT) missions were monitored between December 2010 and March 2015, and the prevalence of gasping and survival data for IHCA were investigated.

Methods:
A standardized extended in-hospital Utstein data set of all RRT-interventions occurring at the University Hospital Basel, Switzerland, from December 13, 2010 until March 31, 2015 was consecutively collected and recorded in Microsoft Excel (Microsoft Corp., USA). Data were analyzed using IBM SPSS Statistics 22.0 (IBM Corp., USA), and are presented as descriptive statistics.

Results:
The RRT was activated for 636 patients, with 459 having a life-threatening status (72%; 33 missing). 270 patients (59%) suffered IHCA. Ventricular fibrillation or pulseless ventricular tachycardia occurred in 42 patients (16% of CA) and were associated with improved return of spontaneous circulation (ROSC) (36 (97%) vs. 143 (67%; p<0.001)), hospital discharge (25 (68%) vs. 48 (23%; p<0.001)), and discharge with good neurological outcome (Cerebral Performance Categories of 1 or 2 (CPC) (21 (55%) vs. 41 (19%; p<0.001)).

Gasping was seen in 128 patients (57% of CA; 46 missing) and was associated with an overall improved ROSC (99 (78%) vs. 55 (59%; p=0.003)). In CAs occurring on the ward (154, 57% of all CAs), gasping was associated with a higher proportion of shockable rhythms (11 (16%) vs. 2 (3%; p=0.019)), improved ROSC (62 (90%) vs. 34 (55%; p<0.001)), and hospital discharge (21 (32%) vs. 7 (11%; p=0.006)).

Gasping was not associated with neurological outcome.

Conclusions:
Gasping was frequently observed accompanying IHCA. The faster in-hospital patient access is probably the reason for the higher prevalence compared to the prehospital setting. For CA on the ward without continuous monitoring, gasping correlates with increased shockable rhythms, ROSC, and hospital discharge.
Abstract 17849: Serum Vascular Endothelial Growth Factor Levels Associated With the Risk of Major Adverse Cardiac and Cerebrovascular Events After Drug-eluting Stent Implantation
Authors: Unoki Takashi , Takagi Daisuke , Takabayashi Kensuke , Ura Suichi , Yamada Akira , Yamashita Yugo , Hamatani Yasuhiro , Masunaga Nobutoyo , Ishii Mitsuru , Iguchi Moritake , Ogawa Hisashi , Satoh-Asahara Noriko , Shimatsu Akira , Abe Mitsuru , Akao Masaharu , Hasegawa Koji , Wada Hiromichi
Published: July 2021

Background:
Vascular endothelial growth factor (VEGF), a central player in angiogenesis, is not only involved in the progression of atherosclerotic plaque, but also required for preventing decompensated heart failure (HF). High circulating oxidatively modified LDL-cholesterol (oxLDL) levels are associated with vulnerability to the rupture of atherosclerotic lesions. However, the relationships of circulating VEGF and oxLDLs with major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing coronary drug-eluting stent (DES) implantation are unclear.

Methods and Results:
We enrolled 441 patients who electively underwent coronary DES implantation. Patients were followed up over 2 years. MACCE were defined as cardiac and cerebrovascular death, acute coronary syndrome, stroke, and HF hospitalization. Revascularization for asymptomatic patients were excluded. Pre-procedural serum levels of high-sensitivity CRP (hsCRP), VEGF, and two oxLDLs, serum-amyloid-A/LDL complex (SAA-LDL) and α1-antitrypsin/LDL complex (AT-LDL), were measured. During a median follow-up of 720 (IQR, 498-720) days, MACCE developed in a total of 39 patients (8.8%). Patients were divided into two groups based on the median of each biomarker. In Kaplan-Meier analyses, high-VEGF and high-SAA-LDL (
P
=0.009,
P
=0.0498 by log-rank test, respectively), but not high-hsCRP or high-AT-LDL, were significantly associated with MACCE. Multivariate Cox proportional hazard analyses revealed that natural log-transformed VEGF levels (Ln-VEGF) (HR, 1.9 per 1 SD increase; 95% CI, 1.3 to 3.0;
P
=0.001), but not Ln-SAA-LDL (HR, 1.2; 95% CI, 0.89-1.5,
P
=0.3), Ln-hsCRP, or Ln-AT-LDL, was significantly associated with MACCE after adjustment for age, sex, and established risk factors. Finally, we performed stepwise multivariate Cox proportional hazard analysis including possible confounders, such as the number of lesions and type of DES, and these biomarkers. Notably, the independent predictors of MACCE were age (HR, 1.8 per 10 years; 95% CI, 1.2-2.7;
P
=0.004), Ln-VEGF (HR, 1.9; 95% CI, 1.2-3.1;
P
=0.005) and chronic kidney disease (HR, 2.5; 95% CI, 1.2-5.0;
P
=0.01).

Conclusions:
A high VEGF value may serve as a predictor of MACCE following coronary DES implantation.
Abstract 17851: Prognostic Factors and Outcomes of Patients With Vasospastic Angina Surviving Out-of-hospital Cardiopulmonary Arrest
Authors: Kashiwa Asami , Hosaka Yukio , Takahashi Kazuyoshi , Ozaki Kazuyuki , Tsuchida Keiichi , Fujihara Yuki , Nakamura Norihito , Hiroki Jiro , Oda Hirotaka
Published: July 2021

Background:
Vasospastic angina (VSA) is reported to cause sudden cardiac death (SCD) due to lethal ventricular arrhythmias, even while a patient is undergoing drug therapy with calcium channel blockers (CCB). The prognostic factors are not fully assessed and the indication of implantable cardioverter-defibrillator (ICD) for patients with VSA is still controversial. We assessed the prognostic factors and outcomes of patients with VSA surviving out-of-hospital cardiopulmonary arrest (OHCA).

Methods:
Between November 2007 and February 2014, 129 VSA patients were diagnosed by provocative tests using ergonovine during coronary angiographies. The patients were divided into two groups: OHCA group consisted of patients with VSA surviving OHCA (n=15, median age: 58.2 ± 12.2 years) and non-OHCA group (n=114, median age: 60.3 ± 0.9 years). We analyzed the appearance of J wave in the resting ECG and T wave augmentation (more than two times compared to resting) during treadmill exercise tests in three groups (OHCA group, non-OHCA group and Control group consisting of healthy subjects (n=25, median age: 57.9 ± 1.8years)).

Results:
In resting ECG analysis, J wave was found in 9/15 (60%) of OHCA group, 42/114 (37%) of non-OHCA group and 3/25 (12%) of Control group. There was no significant difference in the appearance of J wave among the three groups. In ECG analysis of treadmill exercise tests, T wave augmentation in non-OHCA group (15/38, 39%) was significantly more frequent than that of Control group (3/25, 12%) (p=0.04). Furthermore T wave augmentation in OHCA group (10/12, 83%) was significantly more frequent than that of non-OHCA group (p=0.008). In OHCA group, all patients began treatment with CCB. Twelve of 15 patients (87%) underwent ICD therapy. During a follow up of 38.7 ± 18.4 months, three of 15 patients (20%) in OHCA group had appropriate ICD therapy or died: one patient received an appropriate ICD therapy for VF and successfully resuscitated, and two patients died suddenly among 3 patients without ICD implantations.

Conclusions:
In the risk stratification of SCD in VSA patients, T wave augmentation during treadmill exercise tests might be a new prognostic factor. ICD might result in favorable clinical outcomes for high-risk VSA patients.
Abstract 17860: Cardiac Iodine-123 Metaiodobenzylguanidine Imaging Predicts Poor Prognosis Even in Patients Admitted With Acute Decompensated Heart Failure
Authors: Tamaki Shunsuke , Yamada Takahisa , Morita Takashi , Furukawa Yoshio , Iwasaki Yusuke , Kawasaki Masato , Kikuchi Atsushi , Kondo Takumi , Ishimi Masashi , Hakui Hideyuki , Ozaki Tatsuhisa , Sato Yoshihiro , Seo Masahiro , Ikeda Iyo , Fukuhara Eiji , Fukunami Masatake
Published: July 2021

Introduction:
Cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging has been shown to provide prognostic information in patients with chronic heart failure. However, little is known about the prognostic value of cardiac MIBG imaging in patients admitted with acute decompensated heart failure (ADHF).

Hypothesis:
We assessed the hypothesis that cardiac MIBG imaging might also be useful for the prediction of poor clinical outcome in patients admitted with ADHF.

Methods:
We studied 115 consecutive patients admitted for ADHF from October 2011 to January 2013 and discharged with survival (age: 74±13 years, male: 56%, NYHA class at discharge: 2.2±0.8, left ventricular ejection fraction measured by echocardiography: 47.1±15.5%). Cardiac MIBG imaging, echocardiography and venous blood sampling were performed just before discharge. The cardiac MIBG heart-to-mediastinum ratio (H/M) and washout rate were calculated from the chest anterior view images obtained at 20 and 200min after isotope injection. The endpoints were unplanned hospitalization for worsening heart failure (WHF) and pump failure death (PFD).

Results:
During a follow-up period of 2.0±0.8 years, 32 patients had WHF and 15 patients had PFD. At multivariate Cox analysis, out of the variables including clinical, hemodynamic, biochemical, echocardiographic and MIBG parameters, H/M on delayed image (late H/M) was independently associated with WHF (p=0.0003) and PFD (p=0.0255), although brain natriuretic peptide showed the significant association with the endpoints at univariate analysis. Kaplan-Meier analysis showed that the patients with late H/M <1.65 (mean value) had a significantly higher risk of both WHF and PFD than those with late H/M ≧1.65 (Figure).

Conclusions:
Cardiac MIBG imaging could predict poor outcome even in patients admitted with ADHF.
Abstract 17862: Benefit and Safety of Adding Ezetimibe to Statin Therapy on Cardiovascular Outcomes in 4416 Women in the IMPROVE-IT Trial
Authors: Toda Kato Eri , Giugliano Robert P , Blazing Michael A , Bohula May Erin , Guneri Sema , White Jennifer A , Park Jeong-Gun , Tershakovec Andrew , Musliner Thomas , Braunwald Eugene , Cannon Christopher P
Published: July 2021

Background:
Statin therapy is established in primary and secondary prevention guidelines both for men and women, although some people have questioned the benefits in women, where data are more limited. Adding the non-statin ezetimibe to statin therapy further reduced future CV events post ACS in IMPROVE-IT, but detailed analyses by sex have not been reported.

Methods:
In the IMPROVE-IT trial, patients hospitalized with ACS and LDL-C ≤125 mg/dL were randomized to ezetimibe/simvastatin 40mg (E/S) or placebo/simvastatin 40mg (P/S) and were followed up for a median of 6 yrs. The primary composite endpoint was CVD, MI, hospitalization for UA, coronary revascularization >30 days, and stroke. Efficacy and safety outcomes in women vs men were compared, one of 23 pre-specified subgroups.

Results:
Among 18144 patients from IMPROVE-IT, 4416 (24%) were women. Compared with men, women were more likely to be older, diabetic, and hypertensive, but less likely to have prior revascularization or multiple vessel disease. At 12 months, the median difference in LDL-C in both women and men was 16 mg/dl between E/S and P/S. Women receiving E/S had a 12% RRR of the primary endpoint (HR vs P/S, 0.88; 95% CI, 0.79 to 0.99), compared with a 5% reduction for men (HR vs P/S; 0.95, 95% CI, 0.90 to 1.01; p interaction p=0.26). There were no differences between E/S and P/S in this or safety events (E/S vs. P/S; AST and/or ALT>3ULN, 2.5% vs. 2.6%, 2.5% vs. 2.2%, cholecystectomy, 1.8% vs. 1.6%, 1.4% vs. 1.4%, myopathy, 0.2% vs. 0.2%, 0.1% vs. 0.1%, gallbladder-related AEs, 3.9% vs. 4.3%, 2.9% vs. 3.3%, in women and in men, respectively, p=all NS).

Conclusion:
IMPROVE-IT demonstrated that adding ezetimibe to statin reduces LDL-C and CV events in both women and men. A safety profile of ezetimibe supports the use of intensive, combination lipid lowering therapy to optimize CV outcomes in women as well as men.
Abstract 17868: Role of Lysosomal Acid Lipase in LDL-C Regulation in Familial Hypercholesterolemia and Metabolic Syndrome
Authors: Nohara Atsushi , Kawashiri Masa-aki , Eto Yoshikatsu , Fujisaki Miwa , Tada Hayato , Yoshida Mie , Mori Mika , Nakanishi Chiaki , Yagi Kunimasa , Inazu Akihiro , Kobayashi Takeshi , Yamagishi Masakazu , Mabuchi Hiroshi
Published: July 2021

Lysosomal acid lipase (LAL), coded by LIPA gene, is key role player of LDL receptor pathway, and LIPA is a susceptibility gene for CAD in many GWAS studies. LAL hydrolyzes cholesterol-ester in hepatocytes, and is essential for M2 activation of macrophages. Furthermore, LAL-deficiency, with increased LDL-C and premature CAD, has been focused as underdiagnosed disease similar to familial hypercholesterolemia (FH). On the other hand, little is known about the role of physiological LAL activity on atherosclerosis. We investigated LIPA gene as genetic cause of FH, and LAL activity in CAD high-risk group.

Methods:
This study consisted of two parts. First part was genetic analysis of LIPA gene. From 940 clinically diagnosed hetero-FH patients in Japan, pathogenic mutations were identified in 788 patients through screening in LDLR, PCSK9, and APOB genes. All coding regions of LIPA gene were investigated in 143 hetero-FH patients without pathogenic mutation in those genes. Identified variants were also evaluated in 200 genetically confirmed hetero-FH, 200 non-FH dyslipidemia, and 250 general population samples.

Second part was LAL acclivity measurement with very recently developed fluorometric assay method using dried blood spots. A total of 122 CAD high-risk patients (M/F: 67/55, age: 65 ± 15 yrs, established CAD: 34%, DM: 46%, hetero-FH: 25%) were investigated their LAL activity.

Results:
Analysis in LIPA gene revealed no patients with LAL-deficiency among FH without confirmed mutations. All variants identified were considered as benign. Intriguingly, common LIPA T16P carriers showed lower pre-treatment LDL-C in genetically confirmed hetero-FH (LDL-C 215±61 vs. 242±70 mg/dL,
p
<0.05).

In activity analysis, LAL activity correlated positively with BMI (R
2
: 10%,
p
<0.0005), γGTP (R
2
: 11%,
p
<0.0005), and HbA1c (R
2
: 5%,
p
<0.05), and negatively with LDL-C (R
2
: 4%,
p
<0.05). Exclusion of FH did not change these results. LAL might have a protective role in obesity, like metabolic syndrome does not necessarily reveal high LDL-C.

Conclusion:
LAL-deficiency was not common genetic cause of FH in Japan. LAL activity increased with obesity, and negatively correlated with LDL-C. Further study will clarify the role of LAL in atherosclerosis.