bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10418: Complex Action Potential Regulation in Cardiomyocytes from Induced Pluripotent Stem Cells (iPSC-CMs) Reveals a Novel Arrhythmia Susceptibility Mechanism
Authors: Wada Yuko , Yang Tao , Hall Lynn , Solus Joseph , Oneill Matthew , Muhammad Ayesha , Glazer Andrew , Roden Dan M
Published: March 2022

Background:
While the cardiac sodium channel (
SCN5A
) variants S1103Y and R1193Q have been associated with LQT3 and drug-induced arrhythmia, they are too common to be highly arrhythmogenic: S1103Y allele frequency is 8.1% in Africans and R1193Q 6.1% in East Asians. We have previously reported that S1103Y had no effect on QT in a large biobank or on action potential duration (APD) in iPSC-CMs. Here, we identify a mechanism underlying control of normal baseline repolarization with these variants and study whether the mechanism is generalizable.

Methods:
Late sodium current (I
Na-L
), I
Kr
, and sensitivity to the blockers dofetilide (I
Kr
) and GS967 (I
Na-L
) were measured in natural or genome-edited iPSC-CMs carrying S1103Y, R1193Q, or R518X, a common
KCNQ1
nonsense variant in the Jervell Lange-Nielsen (JLN) syndrome and unaffected family members.

Results:
Although APD was unaffected by S1103Y, I
Na-L
was increased 2~16-fold in SY/YY compared to SS cells (p<0.01) and GS967 shortened APDs only in SY/YY but not in SS cells (p<0.001). Further, I
Kr
was increased in SY/YY ([SY] 1.2 pA/pF, n=17, p<0.001, [YY] 1.2 pA/pF, n=11, p<0.01) compared to SS cells (0.67 pA/pF, n=20) and challenge with dofetilide prolonged APD by 100 msec at much lower concentrations in SY/YY (median 4.1 nM [SY], 4.2 [YY], n=5-11) compared to SS cells (249 nM, n=14, p<0.001); afterdepolarizations were seen more often in SY/YY (8/16) than in SS cells (1/14). R1193Q also displayed no difference in baseline APD but increased I
Kr
and I
Na-L
and increased dofetilide sensitivity. In R518X JLN iPSC-CMs, I
Ks
was absent as expected but I
Kr
was increased (1.9 pA/pF, n=5), and editing R518X to wild-type increased I
Ks
(1.3 pA/pF, n=10) and dramatically decreased I
Kr
(0.2 pA/pF, n=4).

Conclusions:
S1103Y and R1193Q increase I
Na-L
but unexpectedly do not affect baseline repolarization. We hypothesize that increased I
Kr
through as yet undetermined mechanisms maintains normal repolarization but at the cost of increased sensitivity to I
Kr
block. The findings with R518X suggest this may be a general mechanism. Our data show that preposition to genetically- or drug-mediated arrhythmias is determined by a complex interaction among multiple repolarizing currents that is not fully captured by heterologous expression systems.
Abstract 10420: Protective Role of Bariatric Surgery in Prevalence and Risk of Atrial Fibrillation in Obese Patients on Long-Term, with Gradually Waning Effect Over a Decade: A Meta-Analysis
Authors: Desai Rupak , Jain Akhil , Wiltshire Dwayne , Went Terry R , Chhina Arashpreet , Pulakurthi Yashwitha Sai , Garg Vibhor , Keesari Praneeth Reddy , Allagoa Theresa , Maqsood Muhammad Haisum , Singh Sandeep , Deshmukh Abhishek , Kumar Gautam , Sachdeva Rajesh
Published: March 2022

Background:
Bariatric surgery (BS) has been shown to be beneficial in improving co-morbid conditions in morbidly obese patients. Long-term cardiovascular complications remain undefined and warrant further investigation. We examined the prevalence and risk of atrial fibrillation (AF) in obese patients who underwent BS.

Methods:
PUBMED/Medline, SCOPUS, EMBASE databases were systematically reviewed using relevant keywords to search prospective and retrospective studies reporting AF with long-term (at least >1-year follow-up) follow-up in patients who had undergone BS. Random effects models were used for meta-analysis and subgroup analysis. I
2
statistics was used to identify substantial (>75%) heterogeneity.

Results:
Nine studies (3 USA, 2 UK, 4 Sweden) including 24,164 patients who had undergone BS (mean BMI cut off: 35, mean age 42 years) with 29,330 controls were included in the analysis with a median follow-up of 8 years. Pooled prevalence of AF was lower in BS arm (3.0%, 95%CI: 1.4%-5%) as compared to non-BS arm (3.8%, 95% CI: 1.8%-5.0%). The Forest Plot
(Fig. 1)
depicts significantly reduced odds of having AF in patients who have undergone BS vs controls (OR: 0.74, 95%CI: 0.60-0.91, I
2
=70.2%, p<0.01). Sensitivity analysis using the leave-one-out method did confirm equivalent results. On subgroup analysis, AF prevalence in the BS group was slightly higher in studies with a mean age of ≥50 years (4.8%, 0-12%) as compared to cohorts with mean age <50 (2.0%, 1.4-5.0%). The pooled rate of AF was low on short-term follow-up compared to long-term follow-up after BS: 1.5% (0.9-2.5%) in 1-5 years, 1.9% (0.2-4.5%) in 6-10 years, 5.4% (0-13.9%) ≥10 years of BS.

Conclusions:
Obese patients undergoing BS had nearly 25% lower risk and lower pooled rate of AF when compared to controls over 8 years of follow-up. The protective effect of BS on reduced risk of AF was seen to gradually wane over longer follow-up which warrants continued efforts to effectively control CVD risk factors.
Abstract 10426: Worse Clinical Outcomes in Patients with Acute Coronary Syndrome and Prior or New Onset Heart Failure: Insights from 47,474 Patients in a Pooled Analysis of Randomized Clinical Trials
Authors: Goodwin Nathan , Clare Robert M , Wojdyla Daniel , Harrington Josephine , Badjatiya Anish , Udell Jacob A , Butler Javed , Januzzi James L , Parikh Puja , James Stefan K , Alexander John H , Lopes Renato D , Wallentin Lars C , Ohman E Magnus M , Hernandez Adrian F , Jones William S
Published: March 2022

Introduction:
Heart failure (HF) frequently complicates acute coronary syndrome (ACS). Despite known associated high rates of mortality, there are only limited data regarding recurrent ischemic events and re-hospitalization for HF (HHF) in those with HF and ACS.

Methods:
We used a pooled dataset of four randomized clinical ACS trials (Platelet Inhibition and Patient Outcomes [PLATO], Apixaban for Prevention of Acute Ischemic Events 2 [APPRAISE-2], Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome [TRA-CER], and Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndrome [TRILOGY ACS]). We assessed the association between HF status (history of HF,
de novo
HF, no HF) at presentation for ACS on death, future ischemic events, and HHF at one year following hospital discharge using Cox proportional hazards analysis and estimated cumulative event rates using cumulative incidence function.

Results:
Of 47,474 patients presenting with ACS, 11.1% showed evidence of acute HF, 55.0% of whom had no previous history of HF. Patients with prior/chronic HF were more likely to present with acute HF than those with no previous HF (40.3% vs 6.9%). Compared to those without HF, patients with prior and
de novo
HF were at a significantly increased risk at one year of all-cause mortality (adjusted HR (aHR) 2.10, 95% Confidence Interval [CI] 1.80-2.45, and aHR 1.51, CI 1.18-1.93, respectively), MACE (aHR 1.50, CI 1.34-1.69, and aHR 1.40, CI 1.14-1.72), recurrent MI (aHR 1.58, CI 1.41-1.78, and aHR 1.40, CI 1.15-1.70), stroke (aHR 1.93, CI 1.67-2.32, and aHR 1.38, CI 1.09-1.75), and HHF (aHR 2.38, CI 2.09-2.71, and aHR 1.53, CI 1.24-1.88).

Conclusion:
Following an ACS event, both prior and
de novo
HF were found to be major predictors of death, recurrent ischemic events, and HHF by one year. These findings highlight the need for improved strategies to prevent and manage adverse outcomes in this high-risk population.
Abstract 10432: Simultaneous Recording of Skin Sympathetic Nerve Activity and Blood Pressure in Ambulatory Outpatients with Postural Orthostatic Tachycardia Syndrome
Authors: Liu Xiao , Rosenberg Carine , Lee Andrew , Leier Mary E , Dinh Harrison , Rader Florian , Chen Peng-Sheng
Published: March 2022

Introduction:
neuECG is a method to simultaneously record ECG and skin sympathetic nerve activity (SKNA). Postural orthostatic tachycardia syndrome (POTS) is known to be associated with increased cardiac sympathetic norepinephrine release.

Hypothesis:
Average SKNA correlates positively with heart rate (HR) and blood pressure (BP) in POTS patients.

Methods:
We used Bittium Faros 180 Holter Monitor (sampling rate 1,000 Hz) to record neuECG and SpaceLab OnTrak arterial BP monitor (ABPM) to record BP simultaneously over 24-hr in 20 POTS patients (19 women, 38±12 years old). The Faros signals were high pass filtered at 300 Hz to display the SKNA. The same original signals were bandpass filtered 0.05-150 Hz to display ECG. BP was measured every 30-min when awake (7AM to 9 PM) and hourly at night (9 PM to 7 AM).

Results:
Fig 1 shows an example of typical recording from a 38-year-old woman. Panel A shows average SKNA (aSKNA) 1-min prior to HR and BP measurement. The overall successful ABPM measurement was 90% with average BP of 126/75 mmHg. B shows bursts of SKNA in daytime (red dot in A), but no bursts at night (blue dot in A). C shows a positive correlation between HR, systolic BP (SBP) diastolic BP (DBP) and mean BP (MBP) with aSKNA. For all patients studied, 16 of 20 showed positive correlation between MBP and aSKNA (r=0.559±0.152, p<0.05 for all) and 15 of 20 showed positive correlation between HR and aSKNA (r=0.511±0.175, p<0.05 for all). The nocturnal aSKNA averaged 0.919±0.059 μV (N=17) and 1.060±0.215 (N=3) (p<0.001) in patients with and without nocturnal dip, respectively. However, the overall 24-hr aSKNA (1.036±0.120 vs 1.044±0.095, μV) was not different between these two groups.

Conclusions:
aSKNA positively correlated with BP and HR in ambulatory outpatients with POTS. High aSKNA at night was associated with nocturnal non-dipping of BP.
Abstract 10439: Deacetylation of Histone H2AX by Sirt1 Regulates DNA Damage Response and Protects Cardiomyocytes Against Doxorubicin-Induced Injury
Authors: Kuno Atsushi , Hosoda Ryusuke
Published: March 2022

Introduction:
Accumulated DNA damage has been implicated in doxorubicin (DOX)-induced cardiotoxicity. We recently found that deletion of SIRT1, a histone deacetylase, in the cardiomyocyte worsens DOX-induced cardiac injury in mice. However, its molecular mechanism remains unclear. Ser139 phosphorylation of histone H2AX catalyzed by ATM (mutated in ataxia-telangiectasia) at the sites of DNA damage mediates DNA repair.

Hypothesis:
Deacetylation of H2AX by SIRT1 mediates DNA damage response and protects cardiomyocytes from DOX-induced injury.

Methods and Results:
Wild-type (WT) and tamoxifen-inducible cardiomyocyte-specific SIRT1 knockout (SIRT1 cKO) mice received DOX (4 IP injections of 5 mg/kg/week) or a vehicle. Immunoblotting showed that myocardial phospho-Ser139 H2AX level was increased by 1.6-fold in WT at 1 week after final DOX, but such a response was absent in SIRT1 cKO. Ser1981 phosphorylation of ATM by DOX were comparable in WT and SIRT1 cKO. The increase in TUNEL-positive nuclei by DOX was greater in SIRT1 cKO (0.13 to 0.38%) than WT (0.07 to 0.19%), suggesting higher DNA damage in SIRT1 cKO. In H9c2 cardiomyocytes, SIRT1 knockdown (KD) also abolished Ser139 phosphorylation of H2AX by DOX without changing phospho-ATM levels. Increases in DNA damage evaluated by the comet assay and cleavage of caspase-3 by DOX were also enhanced by SIRT1 KD. Immunostaining for acetyl-Lys5 H2AX in the heart sections revealed that acetyl-Lys5 H2AX levels were increased in SIRT1 cKO by 58% compared with WT. In H9c2 cells, acetyl-Lys5 H2AX level was also increased by SIRT1 KD and reduced by expression of wild-type SIRT1. In COS7 cells, a mutant in which Lys5 was substituted to glutamine (K5Q H2AX), a mimic of acetylated Lys5, showed attenuated Ser139 phosphorylation of H2AX by DOX. DOX-induced cleavage of caspase-3 was enhanced in H9c2 cells expressing K5Q H2AX as well as S139A H2AX, that cannot be phosphorylated at Ser139, compared with cells expressing WT H2AX.

Conclusions:
Aberrant Lys5 acetylation of H2AX via SIRT1 suppression interferes Ser139 phosphorylation, leading to accumulation of damaged DNA and promotion of the apoptotic response. Such regulation of the DNA damage response underlies protection by SIRT1 against DOX-induced cardiotoxicity.
Abstract 10440: Independent Prognostic Utility of
11
C-Pittsburgh Compound B Positron Emission Tomography in Light Chain Cardiac Amyloidosis Patients
Authors: Choi You-Jung , Koh Youngil , Lee Hyun-Jung , Hwang In-chang , Park Jun-bean , Yoon Yeonyee E , Kim Hyung-kwan , Kim Yong-Jin , Cho Goo-yeong , Sohn Dae-won , Paeng Jin Chul , Lee Seung-pyo
Published: March 2022

Introduction:
Recent advances in nuclear molecular imaging have allowed a more specific, non-invasive approach to the diagnosis and prognostication of cardiac amyloidosis (CA).
11
C-Pittsburgh compound B positron emission tomography/computed tomography (PiB PET/CT) is one of the widely studied nuclear molecular imaging. However, it remains to be verified whether it has any independent additional prognostic value.

Hypothesis:
11
C-PiB PET/CT would have independent prognostic value in patients with light chain CA (ALCA).

Methods:
A prospective cohort study of 58 consecutive patients with ALCA who underwent
11
C-PiB PET/CT, were stratified into 2 groups based on a myocardial
11
C-PiB uptake or not on PET/CT. The primary and secondary outcomes were all-cause death and cardiovascular death, respectively.

Results:
During a median 13.6 month follow-up, 29 patients died, of which 12 died from cardiovascular events. Patients with positive
11
C-PiB PET uptake had worse event-free survival from all-cause deaths (60.5% vs. 28.7%,
P
=0.001) and cardiovascular deaths (84.9% vs. 58.5%,
P
=0.001). A positive myocardial
11
C-PiB PET/CT was an independent predictor for all-cause death (adjusted hazard ratio [aHR] 4.143, 95% confidence interval [95%CI] 1.243-13.816,
P
=0.021) and cardiovascular death (aHR 5.598, 95%CI 1.060-29.560,
P
=0.043). When
11
C-PiB PET/CT was combined with troponin I and N-terminal probrain Natriuretic Peptide, the performance of prediction significantly improved by net reclassification index of 0.872 and by integrated discrimination improvement statistics of 0.177.

Conclusions:
11
C-PiB PET/CT is a strong independent predictor for all-cause and cardiovascular mortality, and provides incremental prognostic benefits in patients with ALCA. Further investigations are warranted on whether PET/CT should be included in the risk stratification for the ALCA patients
Abstract 10441: Sex-Specific Decline in Coronary Flow Reserve with Aging
Authors: Toya Takumi , Ahmad Ali , Corban Michel T , Sara Jaskanwal D , Ozcan Ilke , Lerman Lilach O , Lerman Amir
Published: March 2022

Introduction:
Coronary vasomotor response is different between males and females. Overall, females have lower coronary flow reserve (CFR) than males due to higher baseline coronary flow than males.

Hypothesis:
Sex has an essential role in the interaction between age and CFR.

Methods:
We included 668 patients with nonobstructive coronary artery disease who underwent invasive coronary vasoreactivity testing using intracoronary incremental doses of adenosine (18-72 μg). Changes in CFR (hyperemic flow velocity/baseline flow velocity) with aging were separately analyzed between males (N=207, mean age 53±13 years) and females (N=461, mean age 54±12 years). We further divided patients by age of 53 which is average age of menopause.

Results:
In males, CFR decreased with aging in younger patients <53 years and tended to decrease in older male patients (all ages [N=207]: r=-0.33,
P
<0.0001; <53 years [N=99]: r=-0.27,
P
=0.01; ≥53 years [N=108]: r=-0.17,
P
=0.07) (
Figure A
). In contrast, CFR did not decrease with aging in younger females <53 years, whereas there was a significant negative correlation between CFR and age in older females ≥53 years (all ages [N=461]: r=-0.15,
P
=0.001; <53 years [N=211]: r=-0.006,
P
=0.39; ≥53 years [N=250]: r=-0.25,
P
<0.0001) (
Figure B
). Baseline microvascular resistance (BMR) was similar between younger and older males (
P
=0.30), whereas older females had higher baseline BMR than younger females (
P
<0.0001) (
Figure C
).

Conclusions:
CFR decreased with aging in males and older females, but not in younger females, potentially highlighting the role of protective hormonal differences in maintaining low baseline coronary tone in younger females.
Abstract 10446: Sex-Specific Genetic Loci Shared Between Sex Hormone Biomarkers and Coronary Heart Disease Are Associated with Sex- and Tissue-Specific Gene Expression
Authors: Hu Jie , Li Jun , Xu Xin , Rexrode Kathryn M , Liang Liming
Published: March 2022

Introduction:
Sex differences in coronary heart disease (CHD) have been well-recognized, but the underlying mechanisms are poorly understood. To examine sex differences in the shared genetics between sex hormone biomarkers and CHD, we have previously performed a sex-stratified genome-wide association study for testosterone (T), sex-hormone binding globulin (SHBG), and CHD using data from the UK Biobank (187,888 men and 221,014 women). We then performed sex-stratified genome-wide cross-traits meta-analyses and identified 13 loci coregulating T or SHBG and CHD, with the coregulation effects specific to one sex (
P
meta
<5х10
-8
in one sex and
P
meta
≥1х10
-5
in the other).

Hypothesis:
The identified sex-specific coregulatory loci are associated with gene expression in a sex-dependent manner, which could help elucidate sex-specific biological functions of shared genetics between sex hormones and CHD.

Methods:
Based on gene expression data in 49 different human tissues for >900 post-mortem donors of both sexes (the Genotype-Tissue Expression project; V8 release), we estimated genetic effects on sex- and tissue-specific expression for the 13 identified sex-specific coregulatory loci. False discovery rate (FDR) was used to account for multiple testing.

Results:
We observed 149 significant locus-gene associations in men (FDR
men
<0.05) and 72 in women (FDR
women
<0.05) in various tissues. Moreover, 19 locus-gene pairs showed sex-differed associations in various tissues (FDR for sex-locus interactions <0.05), 13 of which were in brain tissues (5 in cortex, 3 in cerebellum, 3 in hypothalamus, and 2 in basal ganglia); all of these loci were associated with expressions of genes whose transcription start sites are located at over 1 million bases away or on a different chromosome. We also observed 11 locus-gene pairs in male-specific tissues (9 in testis and 2 in prostate) and another 9 pairs in female-specific tissues (5 in vagina, 3 in ovary, and 1 in uterus).

Conclusions:
Sex-specific genetic loci shared between T or SHBG and CHD are associated with gene expressions in various tissues, predominantly in brain tissues, and such associations significantly differ by sex. Our findings may help advance the understanding of mechanisms underlying sex differences in CHD.
Abstract 10447: Prognostic Significance of Circulating Monocyte Counts in Patients with Chronic Heart Failure
Authors: Komorita Takashi , Yamamoto Eiichiro , Egashira Koichi , Takae Masafumi , Oike Fumi , Fujisue Koichiro , Sueta Daisuke , Usuku Hiroki , Takashio Seiji , Matsushita Kenichi , Tsujita Kenichi
Published: March 2022

Introduction:
We previously reported that a high monocyte count was an independent and incremental of cardiovascular events in patients with coronary artery disease. To elucidate the prognostic value of monocyte in heart failure (HF), we investigated the association of monocyte counts in patients with HF with their future cardiovascular events.

Methods:
Consecutive HF patients referred for hospitalization at Kumamoto University Hospital between 2006 and 2013 were registered. We further divided HF patients into two types according to left ventricular ejection fraction (LVEF) (HF with reduced LVEF (HFrEF) and HF with preserved LVEF (HFpEF)). We defined high monocyte group as monocyte counts≥420/mm
3
in HFrEF patients and as monocyte counts≥308/mm
3
in HFpEF patients.

Results:
In this study, HFrEF was 200 patients and HFpEF was 478 patients. Kaplan-Meier analysis revealed that HFrEF patients with high monocyte group (≥420/mm
3
) had a significant higher risk of HF-related events (P=0.001) compared with those with low monocyte groups (<420/mm
3
). By contrast, high and low monocyte groups in HFpEF patients had no significant difference in HF-related events. Multivariate Cox hazard analysis identified a high monocyte count as an independent and significant predictor of future HF-related events in HFrEF patients (hazard ratio:2.24, 95% confidence interval: 1.01-4.99, P=0.04).

Conclusions:
A high monocyte count was an independent and incremental predictor of HF-related events in HFrEF, but not in HFpEF patients.
Abstract 10448: Combined Associations of Physical Activity and Particulate Matter with Subsequent Cardiovascular Disease Risk Among 5-Year Cancer Survivors
Authors: Choi Daein , Choi Seulggie , Kim Kyae Hyung , Kim Kyuwoong , Chang Jooyoung , Kim Sung Min , Kim Seong Rae , Cho Yoosun , Lee Gyeongsil , Son Joung Sik , Park Sang Min
Published: March 2022

Introduction:
Cardiovascular disease (CVD) is considered an important cause of death among cancer survivors. While engaging in physical activity is known to reduce the risk for CVD, it exposes participants to particulate matter (PM). The combined association of physical activity and PM with subsequent CVD risk is yet unclear.

Methods:
The study population consisted of 18,846 cancer survivors who survived for at least 5 years after an initial cancer diagnosis from the Korean National Health Insurance Service database. For PM, 4-year average levels were determined in administrative district areas and moderate-to-vigorous physical activity (MVPA) information was acquired from the results of national health screening examinations. The adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the risk of CVD were calculated by multivariate Cox proportional hazards regression. Considered covariates were age, sex, household income, area of residence, smoking, alcohol intake, body mass index, systolic blood pressure, fasting serum glucose, total cholesterol, and comorbidities.

Results:
Among patients with low PM2.5 (19.8-25.6 μg/m
3
) exposure, ≥5 times/week of MVPA was associated with lower CVD risk (adjuster hazard ratio; aHR 0.77, 95% confidence interval; CI 0.60-0.99) compared to 0 times/week of MVPA. In contrast, ≥5 times/week of MVPA among patients with high PM2.5 (25.8-33.8 μg/m
3
) exposure was not associated with lower CVD risk (aHR 0.98, 95% CI 0.79-1.21). Compared to patients with low PM2.5 and MVPA ≥3 times/week, low PM2.5 and MVPA ≤2 times/week (aHR 1.26, 95% CI 1.03-1.55), high PM2.5 and MVPA ≥3 times/week (aHR 1.34, 95% CI 1.07-1.67), and high PM2.5 and MVPA ≤2 times/week (aHR 1.38, 95% CI 1.12-1.70) was associated with higher CVD risk.

Conclusions:
Cancer survivors who conducted ≥5 times/week of MVPA benefited from lower CVD risk upon low PM2.5 exposure. High levels of PM2.5 exposure may attenuate the risk-reducing effects of MVPA on the risk of CVD.
Abstract 10452: Exploring the Role of Mitochondrial Genetic Variants in Coronary Artery Disease
Authors: Vilne Baiba , Abbo Bryan , Donins Uldis , Rudaka Irina
Published: March 2022

Introduction:
Large-scale genome-wide association studies have identified >200 single-nucleotide variants (SNVs) significantly associated with coronary artery disease (CAD), collectively explaining <20% of the heritability.

Hypothesis:
Mitochondrial (MT) genetic variants presents an underexplored one potential source of the “missing heritability”.

Methods:
We analyzed 265 MT-SNVs in ∼500,000 UK Biobank individuals, exploring two different CAD definitions: including (SOFT=34,782) vs. excluding (HARD=20,405) angina, using the array, sex, birth year and first five principal components as covariates.

Results:
In SOFT cases, four MT-SNVs survived multiple testing correction (at FDR<5%), all conferring increased CAD risk: m.10400C>T (rs28358278, OR=1.28, MAF=0.02, T114T in MT-ND3), m.15301G>A (rs527236045, OR=1.03, MAF=0.04, L185L in MT-CYB), m.11251A>G (rs869096886, OR=1.03, MAF=0.2, L164L in MT-ND4) and m.15452C>A (rs193302994, OR=1.03, MAF=0.2, L236I in MT-CYB), the latter two previously associated with height in the UK Biobank. In HARD cases, no MT-SNVs survived multiple testing correction, the most significant nominal (P <0.05) findings being for four SNVs, whereof m.295C>T (rs41528348, OR=1.05, MAF=0.1, in the D-LOOP) and m.12612A>G (rs28359172, OR=1.05, MAF=0.04, V92V in MT-ND5) could potentially increase CAD risk, whereas m.12372G>A (rs2853499, OR=0.97, MAF=0.22, L12L in MT-ND5), m.11467A>G (rs2853493, OR=0.97, MAF=0.22, L236L in MT-ND4) and m.15301G>A (rs193302991, OR=0.97, MAF=0.04, L185L in MT-CYB) may confer protective effects. Previously, several of these variants have been associated with a number of blood cell traits in the UK Biobank, including the mean corpuscular hemoglobin levels (m.295C>T, m.12612A>G, m.12372G>A) and volume (m.295C>T and m.12612A>G). In addition, m.12372G>A was significantly association with five other blood cell traits, including the mean platelet volume and white/red blood cell count, as well as with several renal biomarkers, and m.12612A>G was associated with height.

Conclusions:
Our results indicated only spurious associations of the MT-SNV with the occurrence of CAD. More data in larger study cohorts may be needed to conclusively determine the role of MT-DNA in CAD.
Abstract 10466: Randomized Clinical Trials Assessing Patients with Acute Myocardial Infarction-Related Cardiogenic Shock - A Systematic Review of Used Cardiogenic Shock Definitions and Outcomes
Authors: Josiassen Jakob , Frydland Martin , Hassager Christian , Moller Jacob E , Perner Anders , Grand Johannes
Published: March 2022

Introduction:
Cardiogenic shock (CS) is a critical complication to acute myocardial infarction (AMI), with short-term mortality rates exceeding 40%. However, the definition of CS varies between trials, which may comprise interstudy comparability.

Aim:
The aim of the current study was to review differences and similarities of CS definitions used in randomized clinical trials (RCT) assessing patients with AMI-related CS.

Methods:
From the electronic databases MEDLINE and EMBASE we identified 19 AMI-related CS trials comprising a total of 2674 unique patients with CS.

Results:
Seven trials investigated left ventricular assist devices, eight investigated medical treatments, three percutaneous coronary interventions, and one trial investigated targeted temperature management. The inclusion criteria, baseline hemodynamics, endpoints and mortality varied markedly between trials. Hypotension was the most frequent inclusion criterion (17 (90%) trials), with a systolic blood pressure value <90mmHg combined with vasopressor use as the most frequent definition, Figure. Twelve (63%) trials had signs of impaired end-organ perfusion as an inclusion criterion and 10 (53%) signs of impaired cardiovascular function most frequently low cardiac index and reduced left ventricular ejection fraction. Ten (53%) trials included patients resuscitated from a cardiac arrest, three trials excluded cardiac arrest-patients whereas six trials did not state whether cardiac arrest was an exclusion criterion. Mortality ranged from 8 % to 73%.

Conclusions:
RCTs of AMI-related CS show marked heterogeneity in inclusion criteria and outcomes potentially hampering interstudy comparability. Consensus criteria for CS appear needed for future selection of patients.
Abstract 10467: Rising Burden of Cardiovascular Disease Risk and Major Adverse Cardiac Events in Young African American Patients: A National Analysis of Two Cohorts 10-Years Apart (2017 vs. 2007)
Authors: Desai Rupak , Went Terry R , Koshiya Hiren , Wiltshire Dwayne , Garg Vibhor , Allagoa Theresa , Chhina Arashpreet , Ali Khan Mir Zeeshan , Vyas Ankit
Published: March 2022

Background:
Previous reports have suggested disparities in healthcare access in the US. We aim to compare the burden of CVD risk factors and major adverse cardiac events (MACE) and in-hospital outcomes among young hospitalized African Americans (18-44 years) selecting two nationally representative samples a decade apart.

Methods:
Hospitalizations among young (18-44 years) African Americans were identified using The National Inpatient Sample databases in 2007 and 2017. Then, we compared the sociodemographic, comorbidities, and inpatient outcomes including MACE (all-cause mortality, AMI, cardiogenic shock, cardiac arrest, ventricular fibrillation/flutter, pulmonary embolism, coronary intervention) between 2017 vs. 2007 cohort. Multivariable analyses were performed controlling potential covariates.

Results:
A total of 2,922,743 (mean age 31 years, 70.3% female) admissions among young African Americans were studied (1,341,068 in 2007 & 1,581,675 in 2017). The 2017 cohort often had younger (mean 30 vs. 31 years), male (30.4% vs. 28.8%) patients with higher non-elective admissions (76.8% vs. 75%) (p<0.001) and showed a rising burden of traditional cardiometabolic comorbidities, congestive heart failure, chronic pulmonary disease, coagulopathy, depression, along with notable reductions in alcohol abuse and drug abuse compared to the 2007 cohort. The adjusted multivariable analysis showed worsening in-hospital outcomes including MACE (aOR 1.21), AMI (aOR1.34), cardiogenic shock (aOR 3.12), Afib/flutter (aOR 1.34), Vfib/flutter (aOR 1.32), cardiac arrest (aOR 2.55), pulmonary embolism (aOR 1.89) and stroke (aOR 1.53). Of note, the 2017 cohort showed a decreased rate of PCI/CABG and all-cause mortality vs. 2007 (p<0.001).

Conclusion:
Young African American patients have had an increasing burden of CVD risk factors and worsened in-hospital outcomes including MACE and stroke in the last decade, though with improved survival odds.
Abstract 10470: Comparison Between the Double-Syringe Technique and the Single-Syringe Diluted with Normal Saline Technique of Adenosine for a Termination of Supraventricular Tachycardia: A Pilot, Randomized, Single-Blind Controlled Trial (Do-Single Trial)
Authors: Kotruchin Praew , Chaiyakhan Itchaya-on , Kamonsri Phimonphorn , Chantapoh Wittawin , Serewiwattana Nattapat , Kaweenattayanon Nayawadee , Mitsungnern Thapanawong
Published: March 2022

Introduction:
Supraventricular tachycardia (SVT) is a condition commonly found in emergency settings. Adenosine is recommended as the first-line treatment for stable patients, however, it is rapidly metabolized. The ACLS guidelines recommend administration of 6-mg adenosine intravenously (IV) with an immediate 20-ml normal saline solution (NSS) IV (double syringe technique; DST). However, adenosine diluted with NSS up to 20 ml IV (single syringe technique; SST) was as well found effective for terminating the arrhythmia.

Hypothesis:
The SST is non-inferior to the DST for terminating stable SVT.

Methods:
A pilot, single-blind, randomized, controlled study was conducted from January to December 2020 at 4 hospitals in the northeastern region, Thailand. Thirty patients who presented with stable regular narrow complex tachycardia, diagnosed as stable SVT by cardiologists, were enrolled. They were randomized into the DST and SST groups, 15 patients each. We evaluated the termination of SVT (turned to normal sinus rhythm), the average successful doses, and the complication rate of each group. Analyses were based on the intention to treat principle.

Results:
The termination rate was 91.7% and 83.3% in the DST and the SST group,
P
=0.990. The success rate of 6-mg adenosine was 75% and 66.7% in the DST and the SST group,
P
=0.640. The total administration dose was 8.2±4.9 mg in the DST group, and 10.0±5.9 mg in the SST group,
P
=0.432. There was no difference in the complication rate between both groups.

Conclusions:
Adenosine diluted with NSS up to 20 ml administered IV was non-inferior to the conventional technique for terminating SVT. A further definitive study with larger sample size is required.
Abstract 10471: Prognostic Significance of Soluble Programed Cell Death Ligand-1 on Cardiovascular Outcomes in Patients with Atherosclerotic Cardiovascular Disease
Authors: Miyazaki Shuhei , Fujisue Koichiro , Yamanaga Kenshi , Yamamoto Eiichiro , Egashira Koichi , Komorita Takashi , Sueta Daisuke , Usuku Hiroki , Araki Satoshi , Takashio Seiji , Matsushita Kenichi , Tsujita Kenichi
Published: March 2022

Background:
Programmed Death-1(PD-1) and its ligand, PD-L1 regulate T cell proliferation and secretion of cytokines, leading to immunotolerance. A previous experimental study reported increased expression of PD-L1 in myocardium. Hence, PD-L1 could be associated with atherosclerotic cardiovascular disease (ASCVD). We hypothesized that serum soluble PD-L1 (sPD-L1) could be associated with cardiovascular events. We prospectively investigated the association between the serum levels of sPD-L1 and cardiovascular outcomes in patients with ASCVD.

Methods:
We prospectively measured sPD-L1 in patients with ASCVD admitted to Kumamoto University Hospital using a commercially available enzyme-linked immunosorbent assay kit and observed the occurrence of cardiovascular events between December 2017 and June 2019. The primary outcome was a composite of death from any cause, death from cardiovascular causes, nonfatal myocardial infarction, unstable angina pectoris, stroke, and heart failure hospitalization. We excluded patients complicated with cancer, hemodialysis, active collagen diseases, and inflammatory diseases.

Results:
Finally, 446 patients with ASCVD were enrolled. Median follow-up period was 322 days. A total of 153 events were recorded. Kaplan-Meier curve revealed that the higher sPD-L1 group (sPD-L1 ≧155pg/dL, median) showed significantly higher rate of cardiovascular events than the lower sPD-L1 group (19.2% vs. 28.1%, log-rank test:
P
=0.044). Univariate Cox proportional hazards analysis showed that creatinine, low density-lipoprotein cholesterol, B-type natriuretic peptide (BNP), and higher sPD-L1 (≧155pg/dL) were significantly associated with cardiovascular events. Multivariable Cox proportional hazards analysis by significant factors from univariate analysis identified that higher sPD-L1 [hazard ratio (HR): 1.699, 95% confidence interval (CI): 1.023-2.823,
P
=.041) and BNP (HR: 1.001, 95% CI: 1.000-1.001,
P
=0.036) were significantly and independently associated with cardiovascular events.

Conclusions:
The higher levels of sPD-L1 were significantly associated with near future cardiovascular events in patients with ASCVD, suggesting sPD-L1 could be a novel prognostic predictor in patients with ASCVD.
Abstract 10477: Targeting the Methyltransferase Setd7 Prevents Myocardial Ischemic Injury: A Translational Study
Authors: Ambrosini Samuele , Montecucco Fabrizio , Kolijn Detmar , Akhmedov Alexander , Pedicino Daniela , Mohammed Shafeeq Ahmed , Kiss Attila , Beltrami Antonio Paolo P , crea Filippo , Luescher Thomas F , Hamdani Nazha , Costantino Sarah , Paneni Francesco
Published: March 2022

Introduction:
Despite appropriate revascularization strategies, a significant number of patients with myocardial infarction (MI) develop ischemic heart failure suggesting that breakthrough therapies are yet to be approved in this setting. Methylation of non-histone proteins is emerging as a central regulatory mechanism in health and disease. The methyltransferase SETD7 has shown to methylate and alter the function of a variety of proteins in vitro, however its function in the heart is poorly understood.

Hypothesis:
In the present study we sought to determine the role of SETD7 in myocardial ischemic injury.

Methods:
Experiments were performed in neonatal rat ventricular myocytes (NRVM), SETD7 knockout mice (SETD7-/-) undergoing myocardial ischemia/reperfusion (I/R) injury, rats undergoing permanent left anterior descending (LAD) artery ligation, myocardial samples from patients with and without ischemic cardiomyopathy (ICM) as well as peripheral blood mononuclear cells from patients with ST elevation MI (STEMI) and age-matched healthy controls.

Results:
We show that SETD7 is activated upon energy deprivation in cultured NRVMs and methylates the Hippo pathway effector YAP, leading to its cytosolic retention and impaired transcription of antioxidant genes. Pharmacological inhibition of SETD7 by (R)-PFI-2 restored YAP nuclear localization thus preventing mitochondrial reactive oxygen species (mtROS) and apoptosis. SETD7 deletion in mice attenuated I/R injury, mtROS and LV dysfunction by restoring YAP-dependent transcriptional programs. SETD7/YAP dysregulation was also observed in rats with permanent LAD ligation and LV specimens from ICM patients. Of note, (R)-PFI-2 treatment prevented titin oxidation and myofilament stiffness in cardiomyocytes isolated from I/R mice and patients with ICM. Finally, SETD7 was upregulated in STEMI patients and its expression negatively correlated with antioxidant genes.

Conclusions:
In the present study we show that SETD7-dependent methylation of YAP is required for its inactivation, thus leading to myocyte oxidative stress and apoptosis. Therefore, we identified SETD7 as a valid and druggable therapeutic target to protect the heart during ischemia.
Abstract 10478: Comprehensive Mechanical Modelling of Thoracic Endovascular Aortic Repair in Type A Aortic Dissection
Authors: Kan Xiaoxin , Yuan Xun , Salmasi M Yousuf , Moore James , Sasidharan Sumesh , athanasiou athanasios , Xu Xiao Y , Nienaber Christoph A
Published: March 2022

Background:
Thoracic endovascular aortic repair (TEVAR) in selected proximal (Stanford type A) aortic dissection (TAAD) cases has been reported, however, the limitation and criteria for TEVAR applied in TAAD remain controversial. Virtual stent-graft (SG) deployment simulation based on the finite element method is an emerging tool that allows TEVAR to be reproduced for detailed analysis of biomechanical interaction between native vessel wall and SG device.

Methods:
A TAAD patient underwent an unsuccessful TEVAR followed by salvage open surgical repair. Pre-TEVAR CT angiogram was used to establish the 3D geometry of the dissected aorta for later analysis. Perioperative DSA was used to measure the aortic root motion and determine SG position in the simulation model. Specimen of the harvested aortic tissue was used for histological analysis and tensile test to define isotropic hyperelastic properties of the aortic wall.

Results:
Aortic root motion was decomposed into a component normal to the sinotubular junction (STJ) and a component parallel to the STJ. The largest motion was 4.14 mm in normal direction and 3.5 mm in parallel direction. The continuous motion was used to define the displacement boundary condition at the aortic root in a finite element model.

The histology revealed preserved both elastic fibres and collagen at the proximal landing zone. A small area of inflammatory infiltration was noted at the tunica externa which may related to the dissected lamella.

Tensile testing showed that the aortic wall ruptured at the stress of 250-1250 kPa while the lamella ruptured at 80-160 kPa. Simulation precisely reproduced the SG configuration after TEVAR procedure. Maximum principal stress at 301 kPa was found on the lamella during simulation, which is significantly higher than stress tolerance of the lamella.

Conclusion:
Microstructure of the lamella and aortic wall components determine the capacity in resisting SG induced focal stress. During the deployment, the proximal end of SG landed directly onto the lamella where the maximum stress exceeded the tolerance of the lamella thus causing rupture and allowing the SG to penetrate into the false lumen.
Abstract 10480: Comparison of Left Atrial Feature Tracking Strain and Rapid Long Axis Strain for Predicting Arrhythmia Recurrence After Atrial Fibrillation Ablation
Authors: Hopman Luuk H , Mulder Mark J , van der Laan Anja M , Bhagirath Pranav , Demirkiran Ahmet , von Bartheld Bob B , Kemme Michiel J , van Rossum Albert C , Allaart Cornelis P , Gotte Marco J
Published: March 2022

Introduction:
Global left atrial (LA) strain is a predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). Recently, novel rapid LA long axis strain has been introduced. Currently, it is unknown whether this fast and simple strain approach can predict AF recurrence after PVI and hence may be a simple alternative for the cumbersome LA feature tracking (FT) strain analysis.

Hypothesis:
Rapid LA strain is a fast and simple alternative for predicting AF recurrence after PVI as compared to LA FT strain.

Methods:
A total of 58 AF patients (78% paroxysmal AF, 64% male, mean age 61±7 years) undergoing first PVI ablation were included. Prior to PVI, all patients were in sinus rhythm during cardiac magnetic resonance imaging. LA rapid strain, LA FT strain and LA volumes were derived from 2-chamber and 4-chamber cine CMR images (Figure A). All patients were routinely followed up for arrhythmia recurrence.

Results:
At one year follow-up, arrhythmia recurrence was observed in 21 patients (36%). Both, rapid LA strain and FT strain were significantly reduced in patients with AF recurrence compared to patients without AF recurrence (rapid strain: -19.96 ± 11.03% vs. -28.18 ± 9.93%, P=0.005; FT strain: -12.54 ± 4.16% vs. -15.94 ± 3.50%, P=0.002, Figure B, and C) while maximal LA volume index (LAVImax) was not different between both groups (16.98 ± 3.70ml/m2 vs. 15.04 ± 2.47ml/m2, P=0.11, Figure D). ROC analysis identified LA FT strain as having the highest area under the curve (AUC) for predicting AF recurrence after PVI (AUC: 0.75 for LA FT strain, 0.71 for LA rapid strain, 0.62 for LAVImax, figure E).

Conclusions:
Both rapid LA strain and LA FT strain are predictive of AF recurrence after index PVI in AF patients. Moreover, LA mechanical function (strain) may be a more useful marker for predicting AF recurrence than LA volume. Therefore, LA rapid strain can be a more convenient and reproducible parameter for the assessment of LA performance in clinical practice.
Abstract 10483: Dose Of Outpatient Cardiac Rehabilitation After Acute Coronary Syndrome
Authors: Kanaoka Koshiro , Iwanaga Yoshitaka , nakai michikazu , Nishioka Yuichi , Myojin Tomoya , Kubo Shinichiro , Okada Katsuki , Soeda Tsunenari , Noda Tatsuya , Sakata Yasushi , Miyamoto Yoshihiro , Imamura Tomoaki , Saito Yoshihiko
Published: March 2022

Introduction:
Cardiac rehabilitation (CR) is an effective intervention associated with a reduction in mortality and re-hospitalization for patients with acute coronary syndrome (ACS), but CR programs have not been fully implemented and doses are varied across patients.

Hypothesis:
This study aims to reveal the current practice of outpatient CR, and investigate the association between dose and long-term mortality for patients with ACS in real-world settings.

Methods:
We performed a nationwide retrospective cohort study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Patients with ACS underwent percutaneous coronary intervention between April 2014 and March 2018 and outpatient CR within 180 days after admission were included.

Results:
Of all 202,320 patients underwent percutaneous coronary intervention for ACS, a total of 20,444 (10%) patients underwent outpatient CR. The median (IQR) number of total CR sessions was 9 (3-17) times, and the median (IQR) duration per session was 3.0 (2.1-3.0) units. Patients were divided into four groups according to the total session number (≤9 or 10≤ times) and duration per session (≤40 or 60≤ minutes). Of 20,444 patients, 3,845 patients were assigned in low-number/short-duration, 6,976 patients in low-number/long-duration, 1,874 patients in high-number/short-duration, and 7,749 patients in high-number/long-duration group, respectively. After adjustment for age, sex, infarction site, comorbidities, and treatments during hospitalization, the adjusted HR for all-cause mortality was 1.01 (95% CI: 0.80-1.26, p=0.95) in low-number/long-duration group, 0.62 (95% CI: 0.45-0.86, p=0.004) in high-number/short-duration group, 0.74 (95% CI: 0.59-0.92, p=0.007) in high-number/long-duration group, compared with low-number/short-duration group.

Conclusions:
The participation rate of outpatient CR after ACS was low and the doses of sessions were varied in real-world settings. Higher number of total sessions in outpatient CR was associated with a better prognosis despite the session duration.
Abstract 10484: Cardiac Adaptation to Acute Haemodynamic Stress in Patients with Type 2 Diabetes
Authors: Chowdhary Amrit , Thirunavukarasu Sharmaine , Jex Nicholas , Coles Lauren , Xue Hui , Kellman Peter , GREENWOOD John , Plein Sven , Levelt Eylem
Published: March 2022

Background:
Due to varying cardiac workloads, efficient demand-supply matching is crucial for maintaining normal cardiac function. Cardiac metabolism is profoundly affected by changes in cardiac workload. There is scarcity of non-invasive studies evaluating how the heart adapts to hemodynamic stress in type 2 diabetes (T2D) patients.

Objectives:
Using cardiovascular magnetic resonance (CMR) and
31
Phosphorus MR spectroscopy (
31
P-MRS) we assessed changes in cardiac energetics, perfusion, strain, systolic and diastolic function in response to increases in cardiac workload with dobutamine stress in T2D patients and healthy volunteers (HV).

Methods:
24 T2D patients and 18 matched HV were recruited. Participants with ischemic heart disease were excluded.

Results:
Table-1 shows clinical and CMR/
31
P-MRS data. Compared to HV, T2D patients showed reductions in left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) at rest, and a blunted increase in LVEF and GLS during stress. Diastolic function was impaired in T2D with lower mitral in-flow E/A ratio compared to HV at rest, which was further reduced during stress in both groups. Stress myocardial blood flow was lower in T2D patients.Compared to HV, rest phosphocreatinine (PCr)/ATP ratio was 17% lower in T2D patients, with a further 8% reduction during stress. However, there was a more pronounced reduction in the PCr/ATP with stress in HV (33% relative reduction), although stress PCr/ATP remained numerically higher in HV compared to T2D patients.

Conclusions:
T2D is associated with blunted ability of the myocardium to significantly increase contractile function from rest to stress. Moreover, T2D patients show exacerbated reductions in myocardial energetics and diastolic function during stress. Although reductions in myocardial energetics and diastolic function in response to acute stress were also detected in HV, these assessments remained higher in HV at stress compared to T2D patients.