bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10422: Sesn2 Mediates Metformin Rescued Age-Related Cardiac Dysfunctions of Cardiorenal Syndrome
Authors: Iglesias Migdalia , Ren Di , Slotabec Lily , Wang Hao , Zoungrana Linda Ines , Krause-Hauch Meredith , Li Ji
Published: June 2023

Introduction:
Cardiorenal syndrome (CRS) consists of disorders of the kidneys and heart, whereby dysfunction of one organ may induce dysfunction of the other. Acute kidney injury (AKI) leads to a reduction in blood flow and energy supply to the heart. AMP-activated protein kinase (AMPK) as an energy sensor regulates energy metabolism
via
interacting with a scaffold protein Sesn2. The anti-diabetes drug metformin is an AMPK agonist, and it has been reported to regulate substrate metabolism under physiological and pathological conditions. But the beneficial role of metformin in CRS remains unknown.

Hypothesis:
Age-related impaired AMPK signaling contributes to cardiac intolerance to AKI-induced insults in the elderly. Metformin treatment ameliorates CRS through triggering Sens2/AMPK activation.

Methods:
Young (3-5 months) and aged (21-23 months) C57BL/6J wild type (WT), cardiomyocyte specific knock out (cSesn2

-/-

) and littermates (Sesn2

f/f

) C57BL/6J mice were subjected to AKI with a laparotomy and the renal artery and vein were clamped for 15 min followed by 72 hr of reperfusion (IRI). Seahorse XF Analyzer for mitochondrial respirational functions.

Results:
The higher levels of serum creatinine were observed after IRI-induced AKI in the aged versus young WT and cSens2

-/-

versus Sesn2

f/f

mice. Interestingly, administration of metformin can significantly reduce serum creatinine levels by IRI-induced AKI in young/aged WT and Sesn2

f/f

but not cSesn2

-/-

mice. Renal histological analysis showed higher incidence of tubular necrosis in the aged versus young AKI mice, the tubular necrosis was significantly reduced in the metformin treated young and aged AKI mice. Echocardiography data showed that AKI caused cardiac systolic dysfunctions in all experimental groups, while metformin treatment improved cardiac functions of young/aged WT and Sesn2

f/f

but not cSesn2

-/-

mice. Moreover, metformin treatment triggered AMPK activation and improved mitochondrial respiration rate and ATP production of cardiomyocytes from young/aged WT and Sesn2

f/f

but not cSesn2

-/-

hearts.

Conclusions:
Aging augments cardiac vulnerability to IRI-induced AKI. Metformin can rescue cardiac dysfunctions and renal injury caused by AKI through Sesn2/AMPK signaling pathway.
Abstract 10425: Needle Fragment Embolization Leading to Cardiac Tamponade
Authors: Azizi Abdul H , Mehta Samir , Fender Erin , Marshall Erik
Published: June 2023

Background:
Intravenous drug use (IVDU) may rarely result in needle embolism (1). We present a patient with history of active IVDU who was found to have pericardial effusion causing tamponade from needle fragment embolization.

Case:
41-year-old female with history of active fentanyl use presented with pleuritic chest pain and dyspnea. EKG was consistent with acute pericarditis and she was started on colchicine and ibuprofen with symptomatic improvement. CT scan of the chest revealed a linear radiopaque structure along the inferior margin of pericardium (Figure 1). She had asymptomatic hypotension and echocardiogram showed moderate sized pericardial effusion with early signs of cardiac tamponade. She underwent median sternotomy and surgical evacuation of~400 ccs of hemopericardium and retrieval of intrapericardial needle fragment with anterior right atrial exit site. She did well post-operatively.

She had previously presented 10-months prior with neck pain and lateral radiograph of the neck showed a needle fragment over the distal cervical trachea (Figure 2). Patient left against medical advice prior to treatment.

Decision Making:
Pericardiocentesis was deferred and surgical alternative was chosen after multidisciplinary discussion as she was asymptomatic and there was concern for ongoing bleeding from the needle exit site. Treatment options include conservative clinical monitoring in asymptomatic patients, pericardiocentesis/pericardial window, and surgical exploration of the mediastinal cavity (1).

Conclusion:
We describe a case of needle fragment embolization leading to cardiac tamponade requiring surgical evacuation and retrieval of foreign body.
Abstract 10432: Variables Associated With Mortality in Patients With ST Elevation Myocardial Infarction and Heart Failure at Admission. Registry ARGEN-IAM-ST
Authors: Zoni Cesar R , D'Imperio Heraldo , Zapata Gerardo , Charask Adrian , Macin Stella M , Castillo Costa Yanina , Gagliardi Juan , Perna Eduardo R
Published: June 2023

Introduction:
Hemodynamic complications associated with ST elevation myocardial infarction (STEMI) continue to be an unfavorable prognostic marker in patients (pts) who develop it. Objectives: Know the demographic, clinical, laboratory, electrocardiographic, and reperfusion variables associated with the change in mortality of STEMI patients with heart failure (HF) at admission. Material and Method: Data from the National Registry of STEMI of Argentina (ARGEN-IAM-ST) from 1/1/2016 to 9/30/2020 were analyzed. Pts with Killip and Kimball equal to or greater than 2 at admission were included. They were divided into alive vs dead according to this condition during hospitalization. Demographic, clinical, electrocardiographic, laboratory variables, and reperfusion characteristics at admission were compared. Univariate and multivariate analyzes were performed.

Results:
708 pts were included. Mortality was 28.39% (N=201) (Figure 1). When comparing the alive vs dead groups, the mean age was 62.96 (SD±12.02) vs 66.70 (SD±12.05) years, p=0.0002; women 21.10% (N=107) vs 32.30% (N=65), p=0.002 respectively. The baseline characteristics are observed in Table 1. Reperfusion was performed in 88.56% of alive vs. 85.07% of dead [OR 0.74 (95%CI 0.46-1.18), p=0.2]. Successful reperfusion by primary percutaneous coronary intervention (PPCI) was more frequent in the alive, 96.59% vs 76.15% [OR 0.11 (95%CI 0.05-0.23), p<0.001], table 2. In multivariate analysis, successful reperfusion with thrombolytics was associated with a decrease in mortality, OR 0.19 (95 %CI 0.04-0.81), p=0.025; as well as successful reperfusion with PPCI, OR 0.11 (95%CI 0.05-0.28), p<0.001. The rest of the variables that modified survival are shown in Table 3.

Conclusions:
Patients with STEMI who are admitted with HF and die during hospitalization have different baseline characteristics than those who survive. Successful reperfusion therapy is associated with decreased mortality.
Abstract 10435: Blood Flow Patterns Regulate Efferocytosis in Endothelia Cells
Authors: Liu Shijie , Ding Zufeng
Published: June 2023

Introduction:
Flowing blood generates a frictional force called shear stress that plays an important role in endothelial dysfunction and atherosclerosis. The disturbed flow (d-flow) pattern causes the preferential localization of atherosclerotic lesions, while regions with steady laminar flow (s-flow) are protected against atherosclerosis. Efferocytosis is a process by which apoptotic tissue is recognized for engulfment by phagocytic cells. Defective efferocytosis promotes advanced atherosclerosis.

Hypothesis:
We hypothesized that blood flow patterns regulate EC efferocytosis and subsequent endothelial dysfunction and contribute to the development of atherosclerosis.

Methods:
Primary human aortic ECs (HAECs) were exposed to s-flow and d-flow in a step-flow channel, and the changes of efferocytosis receptors in ECs and endothelial dysfunction were investigated. To investigate whether defective efferocytosis plays a role in endothelial dysfunction, HAECs were transfected with a control plasmid or MerTK CRISPR/Cas9 knockout plasmid.

Results and Conclusions:
Our results showed that efferocytosis regulators, such as Gas6, Pros1, and MerTK, were upregulated under s-flow conditions while inhibited under d-flow conditions compared to static conditions. Our data also showed that MerTK knockout decreased expression of VE-cadherin and CD31, while increased expression of Snail, Slug, and Twist1 as well as α-SMA, N-cadherin, calponin, and FSP1. Of note, VE-cadherin is a strictly endothelial-specific adhesion molecule located at junctions between ECs. As expected, our data showed that MerTK knockout markedly inhibited VE-cadherin expression, indicating that defective efferocytosis increases endothelial barrier dysfunction. This indicates that MerTK-mediated defective efferocytosis in ECs may play an important role in arterial areas exposed to d-flow where prone to atherosclerosis.
Abstract 10454: Heart Failure With Recovered Ejection Fraction is Good Therapeuticmerkmal for Adaptive-Servo Ventilation Therapy in Patients With Heart Failure
Authors: FUJII TAKAAKI , Takama Noriaki , Iwai Ryutarou , KODAMA CHIKA , TAKIZAWA DAIKI , Yuasa Naoki , Amanai Shiro , Kuno Takahiro , Harada Tomonari , Hasegawa Hiroshi , Kobari Takashi , Ishibashi Yohei , Aihara Kazufumi , Sorimachi Hidemi , Tamura Shuntaro , Kato Toshimitsu , Obokata Masaru , Ohyama Yoshiaki , Koitabashi Norimichi , Kaneko Yoshiaki , Ishii Hideki
Published: June 2023

Introduction:
Heart failure with recovered ejection fraction (HFrecEF) is a complex clinical entity in which biology and clinical management. Previous clinical trial showed adaptive-servo ventilation (ASV) therapy is harmful for patient with heart failure with reduced ejection fraction (HFrEF), whereas we can initiate ASV for patients with HFrEF by adhering rigidly to Japanese statement about the proper use of ASV for HF.

Hypothesis:
It is still unclear whether ASV therapy is really harmful in patients with HFrecEF. Our aim is to estimate that ASV therapy is really harmful in patients with HFrecEF by estimating biomarkers and fatal cardiovascular events.

Methods:
The study group consisted of 78 patients with HF (age;70±12 years). Baseline LVEF was 27.8±8.5%. After optimal medical therapy, ASV was initiated as an additional HF treatment. After 6-month follow-up, we classified into 2 groups by result of LVEF after ASV therapy. Group A (n=20) was categorized as HFrecEF {low pre-LVEF (<45%) and improved post-LVEF (≧45%)}, Group B (n=58) was categorized as HFrEF {low pre-LVEF (<45%) and not improved post-LVEF (<45%)}. We estimate the changes of BNP and fatal cardiovascular events after ASV therapy.

Results:
Before ASV therapy, BNP did not show significant difference in 2 groups {Group A: 439(149-1344) pg/ml vs. Group B: 531(265-892) pg/ml, p=0.73}. After ASV therapy, the changes of BNP showed significant differences (Figure 1A), LVEF also showed significant differences in 2 groups (Group A: 52.3±7.5% vs. Group B: 30.8±3.7%, p=0.039). The fatal cardiovascular events rate after three-year follow-up showed significant good prognosis in Group A (Figure 1B).

Conclusions:
Our study showed that approximately one in four patients can change from HFrEF to HFrecEF, and ASV is acceptable and effective treatment for patients with HFrecEF by contributing to low fatal cardiovascular events and improvement of BNP level.
Abstract 10457: Improved 10-Year Cardiovascular Risk Prediction Combining Serum Metabolites With Traditional Cardiovascular Risk Factors in People With Type 2 Diabetes: Edinburgh Type 2 Diabetes Study
Authors: Huang Zhe , Klaric Lucija , Krasauskaite Justina , Khalid Wardah , Wilson James F , Price Jackie F
Published: June 2023

Introduction:
Cardiovascular disease (CVD) is the leading cause of death for people with type 2 diabetes (T2D). The predictive performance of existing CVD risk scores in T2D populations is suboptimal. Metabolomics is a promising method of identifying novel biomarkers which might improve risk prediction. We aimed to identify a group of metabolites associated with incident CVD in people with T2D and assess its predictive performance over-and-above a current CVD risk score (QRISK3).

Methods:
In 1,066 individuals with T2D (Edinburgh Type 2 Diabetes Study), a panel of 228 serum metabolites was measured at baseline and incident CVD events were identified over the subsequent 10 years. We applied 100 repeats of Cox LASSO (least absolute shrinkage and selection operator) to select metabolites with frequency >90% as candidate components for a metabolites-based risk score (MRS). The MRS was calculated using the linear predictor in an unpenalized Cox regression model where only candidate metabolites were included. The predictive performance of the MRS was assessed in relation to a reference score which refitted components of QRISK3 plus prevalent CVD and statin use at baseline. Predictive metrics were internally validated using 500-repeat bootstrapping.

Results:
In 1,021 available individuals (mean age 67.9 years, 51.7% male), 255 people developed CVD (25.0%) during a median of 10.6 years of follow-up. Twelve metabolites relating to fluid balance, ketone bodies, amino acids, fatty acids, glycolysis and lipoproteins were selected to construct the MRS. C-statistics were 0.673 (95%CI 0.642, 0.704) for the MRS alone and 0.718 (95%CI 0.689, 0.747) for the reference score, increasing slightly to 0.736 (95%CI 0.707, 0.764) for the combination of the two. The improved prediction by combining the MRS with the reference score was internally validated in bootstrapping samples, where the C-statistics for the reference score and the combination were 0.679 (95%CI 0.650, 0.708) vs. 0.699 (95%CI 0.671, 0.728) separately.

Conclusions:
Metabolomics data might improve predictive performance of current CVD risk scores based on traditional risk factors in people with T2D. External validation is warranted to assess the generalizability of improved CVD risk prediction using the MRS.
Abstract 10468: International Classification of Diseases (ICD) Codes for Congenital Heart Defects (CHD) Have Variable and Limited Accuracy for Detecting CHD Cases
Authors: Ivey Lindsey C , Rodriguez Fred H , Shi Haoming , CHONG COHEN , Chen Joy , Raskind-Hood Cheryl L , Farr Sherry , Downing Karrie F , Book Wendy M
Published: June 2023

Introduction:
Administrative data permit analysis of large cohorts but rely on ICD-9-CM and ICD-10-CM billing codes that may not accurately identify CHD cases. Variables that may improve accuracy are unknown, yet improved accuracy will improve CHD surveillance.

Methods:
We validated 1500 cases with an encounter between 1/1/2010 - 12/31/2019 identified by at least one of 90 CHD codes (41 ICD-9-CM, 49 ICD-10-CM) in 2 healthcare systems (1 adult, 1 pediatric), through medical record review and chart abstraction for presence of a CHD. Inter- and intra-observer reliability exceeded 93%.

Results:
Positive predictive value (PPV) of ICD codes for CHD (Figure 1) was 68.0% (1020/1500) overall, 95.7% (247/258) for severe codes, 52.8% (371/703) for shunt codes, 75.2% (243/323) for valve codes, 73.2% (120/164) for shunt and valve codes, and 75.0% (39/52) for a select group of 7 codes in ‘other’ category. PPV for cases with > 1 unique CHD code was 73.1% (920/1259) vs. 41.5% (100/241) for cases with only 1 unique CHD code. Characteristics of cases with and without CHD are in Table 1. ICD code 745.5/Q21.1 in isolation was present in 2.2% of cases with confirmed CHD vs. 19.4% of cases without CHD (p< 0.0001). Median number of encounters with a CHD code was higher in cases with CHD (6) vs. without CHD (2), p< 0.0001. Patent foramen ovale was present in 65.8% of false positives (316/480).

Conclusion:
There is significant variability in the PPV of individual and groups of CHD codes for detection of CHD. The presence of a code for severe CHD is associated with high PPV for true CHD. Use of administrative data for CHD surveillance may require the development of algorithms to improve the accuracy of case detection.
Abstract 10469: Time Averaged Lipoprotein(a) Reduction With Sln360, a Novel Sirna Targeting Lp(a,) in Healthy Adults With Elevated Lp(a)
Authors: Rambaran Curtis , Wilson Rosamund J , Swerdlow Daniel I , Campion Giles V , Scrimgeour Alison C , Nissen Steven E
Published: June 2023

Introduction:
Lipoprotein(a) [Lp(a)] is an important risk factor for atherothrombotic cardiovascular disease for which there are no approved drugs. SLN360 is a short interfering RNA (siRNA) designed to reduce hepatic production of apolipoprotein(a). Primary safety, tolerability and Lp(a) lowering effects have previously been reported in a phase 1 single ascending dose study.

Methods:
Adults with Lp(a) plasma concentrations ≥ 150 nmol/L at entry and no clinically overt cardiovascular disease were randomized to receive a subcutaneous dose of SLN360 or placebo. The primary efficacy evaluation was percent reduction in Lp(a). Time-averaged reductions were determined to further inform dosing frequency and better evaluate potential clinical benefits.

Results:
Thirty-two adults received study drug in 4 cohorts. Large, dose-dependent reductions in Lp(a) were observed. For the top 2 doses (300 mg and 600 mg), median (IQR) maximal reductions of 96% (89%, 98%) and 98% (97%, 98%), with reductions of 71% and 81% persisting to day 150, respectively. The time-averaged effect from administration to 150 days, including the time to reach the Lp(a) nadir, was 82% and 87% for the 300 mg and 600 mg groups, respectively. To reflect the anticipated effects of repeat dosing, additional analyses excluded the time to achieve Lp(a) nadir (the first 30 days). This analysis showed 85% and 92% time-averaged median reductions in the 300 mg and 600 mg doses, respectively.

Conclusions:
In adults with elevated Lp(a), single doses of SLN360 substantially reduced Lp(a) with observed median maximal percent lowering of >95% for doses of 300mg and above, with effects persisting for 150 days. Median time-averaged reductions during 150 days of follow up exceeded 80% in 300 mg and 600 mg treatment groups. Infrequent SLN360 dosing has the potential to substantially reduce Lp(a) to clinically meaningful levels.
Abstract 10470: Projected Lifetime Benefits of Alirocumab in Patients After Acute Coronary Syndrome
Authors: Budaj Andrzej , Elbez Yedid , Schwartz Gregory G , Bhatt Deepak L , Bittner Vera A , Chua Terrance Sing Jin , Diaz Rafael , Goodman Shaun G , Harrington Robert A , Jukema J Wouter , Kedev Sasko , Laucevicius Alexander , MORAIS JOAO , MURIN Jan , Parkhomenko Alexander , Pordy Robert , Scemama Michel , Szarek Michael , White Harvey D , Steg Philippe G
Published: June 2023

Introduction:
In the ODYSSEY OUTCOMES trial, alirocumab improved cardiovascular outcomes and reduced death after acute coronary syndrome (ACS). Median follow-up was 2.8 yrs (range 2-5). The effects of alirocumab on long-term survival are unknown.

Objective:
To calculate projected life span and potential survival gains with alirocumab vs placebo after ACS using validated nonparametric age-based methods.

Methods:
In ODYSSEY OUTCOMES (NCT01663402), 18,924 patients with recent ACS and elevated atherogenic lipoproteins despite high-intensity or maximum-tolerated statin therapy were randomized to alirocumab or placebo. All-cause death was a secondary trial outcome. Age-based estimates of projected survival and event-free (all-cause death, nonfatal myocardial infarction, nonfatal ischemic stroke) survival were calculated. In each treatment arm at every year of age, lifespan was estimated from area under the survival curve, to a maximum of 85 yrs. Differences in areas under the survival curves provide an estimate of the benefit of alirocumab on survival.

Results:
Mean (SD) baseline age was 58.5 (9.3) yrs. Mean survival benefits with alirocumab vs placebo ranged from 0.03 to 1.62 yrs, decreasing with age and becoming neutral at age 80-85 yrs. For example, at age 40, estimated survival was another 37.5 yrs with alirocumab and 35.9 yrs with placebo (difference 1.62 yrs [95% CI, 0.30-2.94];
P
=0.016). At age 60, it was 20.5 vs 19.6 yrs (difference 0.88 [95% CI, 0.16-1.61];
P
=0.017); at age 75 it was 8.8 vs 8.3 (difference 0.57 [0.09-1.05];
P
=0.019); and at age 80, it was 4.5 vs 4.5 years (difference 0.03 [-0.28 to 0.35];
P
=0.83). Mean event-free survival benefit similarly ranged from 1.85 to 0.0 yrs.

Conclusions:
Modeling suggests that long-term treatment with alirocumab may result in a meaningful increase in survival among patients less than 80 yrs of age. This analysis may facilitate shared decision-making with patients.
Funding:
Sanofi, Regeneron Pharmaceuticals
Abstract 10476: Impact of C-Reactive Protein Levels on Lipoprotein(a)-Associated Coronary Artery Disease and Aortic Stenosis Risk in Apparently Healthy Individuals
Authors: Girard Arnaud , Gaillard Emilie , Paulin Audrey , Puri Rishi , Couture Christian , Wareham Nicholas J , Pibarot Philippe , Clavel Marie-Annick , Stroes Erik S , Mathieu Patrick , Theriault Sebastien , Boekholdt Matthijs , Arsenault Benoit
Published: June 2023

Introduction:
Elevated Lipoprotein(a) (Lp[a]) levels are strongly and linearly associated with coronary artery disease (CAD) and calcific aortic valve stenosis (CAVS). Observational studies in primary and secondary prevention settings revealed that Lp(a) and other CAD risk factors such as C-reactive protein (CRP) levels, a biomarker of systemic inflammation, may jointly predict CAD risk. Whether Lp(a) and CRP levels also jointly predict CAVS risk is unknown.

Methods:
We investigated the long-term associations of Lp(a) with CAD and CAVS according to CRP levels in the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Norfolk study. Lp(a) and CRP levels were measured in 18,459 participants who were followed for 20 years. During the follow-up, 3915 and 418 participants had incident CAD and CAVS, respectively.

Results:
As presented in Figure 1, in comparison to individuals with low Lp(a) levels (<30 mg/dL) and low CRP levels (<2.0 mg/dL), those with elevated Lp(a) (>30 mg/dL) and low CRP levels (<2.0 mg/dL) and those with elevated Lp(a) (>30 mg/dL) and elevated CRP levels (>2.0 mg/dL) had a higher CAD risk (hazard ratio [HR] = 1.38 [95% CI, 1.28-1.49] and 1.93 [95% CI, 1.74-2.13] , respectively), and a higher CAVS risk (HR = 1.46 [95% CI, 1.08-1.98] and 1.87 [95% CI, 1.40-2.49], respectively).

Conclusions:
Results of this study confirm the joint association of high Lp(a) and CRP levels on incident CAD and extend these joint associations to valvular diseases such as CAVS. Lowering Lp(a) levels may warrant further investigation in the prevention of CAD and CAVS, especially in the context of systemic inflammation.
Abstract 10491: Drug-Coated Balloon and Drug-Eluting Stent Safety in Patients With Femoropopliteal and Severe Chronic Kidney Disease
Authors: Hanna Jonathan , Smolderen Kim G , Castro-Dominguez Yulanka , Romain Gaelle , Lee Megan , Turner Jeffrey , Mena-Hurtado Carlos
Published: June 2023

Background:
Severe-stage chronic kidney disease (CKD) patients were excluded from femoropopliteal disease trials evaluating drug-coated balloons (DCB) and drug-eluting stents (DES) vs. plain balloon angioplasty (POBA) and bare metal stents (BMS). We examined the interaction between CKD status and device type for the association with 24-month all-cause mortality and major amputation risk.

Methods:
We studied patients undergoing femoropopliteal interventions (9/2016-12/2018) from Medicare-linked VQI registry data. We compared outcomes for: (1) early-stage CKD (stages 1-3) receiving DCB/DES, (2) early-stage CKD receiving POBA/BMS, (3) severe-stage (4-5) CKD receiving DCB/DES, (4) severe-stage CKD receiving POBA/BMS.

Results:
We studied 8,799 patients (early-stage CKD: 94%; severe-stage: 6%). DCB/DES use was 57% vs. 51% in early-stage vs. severe-stage CKD patients. Twenty-four-month mortality risk for early-stage CKD patients receiving DCB/DES (reference group) was 21% vs. 28% (HR=1.47, 95% CI, 1.31-1.65) for those receiving POBA/BMS; severe-stage CKD patients: those receiving DCB/DES had a 49% (HR=2.61,95% CI, 2.06-3.31) mortality risk vs. 52% (HR=3.64, 95% CI, 2.91-4.55) for those receiving POBA/BMS (interaction P<0.001) (
Figure
). Adjusted analyses attenuated these results. For severe-stage CKD, DCB/DES vs. POBA/BMS mortality risk was not significant at 24 months (post hoc comparison P=0.06) but was higher for POBA/BMS group at 18 months (post hoc P<0.05). Early-stage CKD patients receiving DCB/DES had the lowest 24-month amputation risk (6%), followed by 11% for early-stage CKD-POBA/BMS, 15% for severe-stage CKD-DCB/DES, 16% for severe-stage CKD-POBA/BMS (interaction P<0.001). DCB/DES vs. POBA/BMS amputation rates in severe-stage CKD patients did not differ (post hoc P=0.820).

Conclusion:
DCB/DES vs. POBA/BMS use severe-stage CKD patients was associated with lower mortality and no difference in amputation outcomes.
Abstract 10530: Incidence and Electrocardiographic Predictors of Atrioventricular Conduction Recovery After Permanent Pacemaker Implantation in Transcatheter Aortic Valve Replacement
Authors: Feng Zekun , Choy Ho-hin , Shin Soomin , Vu Andrew , Schricker Amir , Hongo Richard , Daniels David , Woods Christopher E
Published: June 2023

Background:
High grade atrioventricular (AV) block (HGAVB) after transcatheter aortic valve replacement (TAVR) requiring permanent pacemaker implantation (PPM) is a well-established complication, but recovery of intrinsic AV conduction is not well studied. We assessed the incidence and electrocardiography (ECG) predictors of AV conduction recovery after PPM implantation post-TAVR.

Methods:
In this multicenter, retrospective study, consecutive patients undergoing TAVR between January 2015 to February 2019 were identified. All patients requiring PPM for HGAVB within 30 days after TAVR were included. Follow up ECGs, PPM checks, and clinic notes were reviewed to determine AV conduction recovery, defined as no need for ventricular pacing.

Results:
There were 533 TAVR patients, 443 with balloon expandable valves (BEV) and 90 with self-expanding valves (SEV). 5.1% of patients (n=27) required PPM for HGAVB, including 4.5% (n=20) from BEV group and 7.8% (n=7) from SEV group. Right bundle branch block (RBBB) was the most common baseline ECG finding (n=19). Mean time to PPM implant was 3.3±4.5 days. 11 patients received leadless and 16 received conventional pacemakers. At 6 months, 65% (n=13) of BEV group and none of SEV group had AV conduction recovery. BEV patients without AV conduction recovery had significantly longer baseline PR intervals compared to those with recovery (248±85 msec vs 169±22 msec; 95% CI 12.5-147.2; p=0.024). There were no significant differences in baseline QRS duration or presence of RBBB between those with and without AV conduction recovery.

Conclusion:
AV conduction recovery is more frequent after PPM implantation in TAVR patients receiving BEV (65%) compared to SEV (0%). Normal baseline PR intervals at baseline is associated with higher rate of AV conduction recovery among BEV patients. Temporary pacing with leadless pacemakers may be an alternative to conventional pacemakers in BEV patients without baseline first degree AV block.
Abstract 10538: Metabolite Profiling Highlights Links Between Healthy Diet and Greater Cardiorespiratory Fitness in the Community
Authors: Mi Michael Y , Gajjar Priya , Walker Maura E , Xanthakis Vanessa , Larson Martin G , Vasan Ramachandran S , Shah Ravi V , Lewis Gregory D , Nayor Matthew
Published: June 2023

Introduction:
Cardiorespiratory fitness (CRF) is a powerful predictor of health outcomes, but its determinants are incompletely understood at the population level. Prior studies have suggested associations between dietary components and CRF, but they have generally been limited by small sample sizes, reliance on estimated CRF, variable dietary instruments, and lack of molecular interrogation to support shared biology.

Hypothesis:
Shared metabolite associations across dietary quality and CRF will prioritize metabolites potentially responsible for linking dietary quality with improved CRF in the community.

Methods:
Framingham Heart Study (FHS) participants underwent maximum effort cardiopulmonary exercise tests for quantification of CRF by peak oxygen uptake (VO
2
) and completed food frequency questionnaires at a routine study visit. Dietary quality was assessed by the Mediterranean-style Diet Score (MDS), and fasting levels of 201 metabolites were quantified.

Results:
In 2380 FHS participants (age 54 ± 9 years, 54% women, BMI 28 ± 5 kg/m
2
), a 1-SD higher MDS was associated with 4.4% (3.5% - 5.3%, p < 0.0001) greater peak VO
2
in linear models adjusted for age, sex, cardiovascular risk factors, and physical activity. In a representative subsample that had metabolite profiling (N = 1154), 80 metabolites were statistically significantly associated with MDS, 57 with peak VO
2
, and 27 with both MDS and peak VO
2
in multivariable linear models (FDR < 5% for all, Figure). These metabolites included dimethylguanidino valeric acid, medium chain acylcarnitines, and C16 ceramide, which are markers of insulin resistance and increased risk for cardiovascular disease. Metabolites with less established functions include C38:7 plasmalogens, which correlate with fish intake and may have anti-inflammatory effects.

Conclusions:
Healthy diet is associated with greater CRF in the community and may be partially explained by favorable metabolic health.
Abstract 10549: American Heart Association's Life's Simple 7 and Major Bleeding in Atrial Fibrillation: A Multicenter Cohort Study
Authors: Leung Robert P , Visrodia Parth , Lessard Darleen , Ding Eric , Saczynski Jane , McManus David D , Wang Weijia
Published: June 2023

Background:
Stroke prevention with oral anticoagulation (OAC) is a mainstay therapy in atrial fibrillation (AF) but is associated with increased bleeding. Identifying health determinants that contribute to this risk is essential to minimizing these adverse events and evaluating the risk benefit of OAC in an individual patient. This study examines the association between the seven cardiovascular risk factors (blood pressure, cholesterol, smoking status, physical activity, glucose, BMI, and diet) from the American Heart Association’s (AHA) Life’s Simple 7 (LS7) and major bleeding in older individuals with AF on OAC.

Methods:
In this multicenter prospective cohort study, we enrolled 1064 patients who were 65 years old and above, had non-valvular AF, and on OAC and followed them for 2 years. Based on AHA’s LS7 criteria, each risk factor was graded on a 3-point scale: 0 points (poor), 1 point (intermediate), and 2 points (ideal). Patients were separated into poor (0-6 pts), intermediate (7-9 pts), or ideal (10-14 pts) cohorts based on their aggregate score. Cox models were used to assess the relationship between the aggregate cohort scores and major bleeding as well as each individual cardiovascular risk factor score and major bleeding.

Results:
Our 1064 patients were separated into poor (n=242), intermediate (n=581) and ideal (n=241) cardiovascular health cohorts. There was a total of 95 major bleeding events, 8.93% of patients who had a major bleed, and a crude rate of 4.68 major bleeding events per 100 person-years. Compared to the ideal group, patients in the poor (HR, 2.29; 95% CI, 1.13 to 4.65) and intermediate groups (HR, 2.17; 95% CI, 1.14 to 4.14) were more likely to have a major bleeding event. Additionally, patients with poor smoking status (HR, 2.78; 95% CI, 1.29 to 5.98) or physical activity (HR, 1.66; 95% CI, 1.07 to 2.59) were significantly more likely to have a major bleeding event than those in the intermediate and ideal categories.

Conclusions:
In older adults with AF on OAC, poor cardiovascular health, smoking, and poor physical activity are all associated with a higher risk of major bleeding. Further

investigation is needed to determine if smoking cessation and physical activity can lead to clinically meaningful reduction in bleeding events.
Abstract 10560: Cost-Effectiveness of AF Screening With 2-Week Patch Monitors: The Mhealth Screening to Prevent Strokes Study
Authors: Reynolds Matthew R , Stein Amy B , Hytopoulos Evangelos , Sun Xiaowu , Steinhubl Steven R , Cohen David J
Published: June 2023

Introduction.
The mHealth Screening to Prevent Strokes (mSToPS) study reported that, compared with standard care, screening older Americans for AF using 2-week Zio patch monitors increased AF diagnosis and oral anticoagulant prescription within one year. The monitored group was also observed to have fewer strokes and deaths at 3 years. The cost-effectiveness of AF screening in this manner has not been explored.

Methods.
We conducted a health economic analysis of AF screening with Zio patch monitors using patient-level data from the mSToPS study. Clinical outcomes and costs from the payer perspective were obtained from enrollment through 3 years using Aetna claims data. Individual costs, survival and quality-adjusted survival (QALYs) were projected over a lifetime horizon using regression modeling, US life tables and external literature where needed. Potential imbalances between groups were adjusted for with propensity score bin bootstrapping.

Results.
Study group participants (mean age 74 years, 41% female, median CHA
2
DS
2
-VASC score 3) wore an average of 1.7 two-week monitors at an average cost of $601/person. Over 3 years, monitored individuals were more likely than unmonitored to have outpatient visits, including to cardiology, but less likely to require emergency department visits or hospitalization (see Table). Pharmacy costs over 3 years were similar between groups. Total adjusted 3-year costs, including monitors, were slightly higher (difference $1,170, 95% CI -1315 to 3657) in the monitoring group. In patient-level projections, the monitoring group had slightly better total and quality-adjusted survival (11.91 vs. 11.82 life years, 9.38 vs. 9.30 QALYs) and slightly higher lifetime costs, resulting in an incremental cost-effectiveness ratio of $16,978/QALY gained.

Conclusions.
Based on lifetime projections derived from the mSToPS study, we found AF screening using 2-week Zio patch monitors to provide high value from a health economic perspective.
Abstract 10565: Personalized Virtual Heart Approach Representing Fatty Infiltration (inFAT) in Arrhythmogenic Right Ventricular (RV) Cardiomyopathy (ARVC) Predicts Ventricular Arrhythmia (VA) Reentrant Circuits and Ablation Targets: A Pilot Study
Authors: Zhang Yingnan , Prakosa Adityo , Sung Eric , Gasperetti Alessio , Carrick Richard , James Cynthia , Zimmerman Stefan , Tichnell Crystal , Murray Brittney , Calkins Hugh G , Tandri Harikrishna S , Trayanova Natalia
Published: June 2023

Introduction:
inFAT is a pathological hallmark in ARVC that is associated with pro-arrhythmic remodeling that contributes to the substrate for VA. Identification of the inFAT distribution on contrast-enhanced computed tomography (CE-CT), which is highly accessible and has reliable image quality, may be useful in pre-procedural planning for catheter ablation treatment of VA.

Objective:
We aimed to develop and validate a novel non-invasive CT-based computational approach for VA ablation targeting in ARVC.

Methods:
As a retrospective pilot study, we constructed 3D personalized computational models of ARVC patient hearts with implanted cardioverter defibrillators from CE-CT scans representing the patient-specific inFAT distribution in the RV (Fig A, B). Three patients were included. P1 and P2 had clinical VA and electrophysiological study with ablation. P3 did not present with clinical VA and did not have ablation. We evaluated the inducibility of each model via rapid pacing and compared the results to electroanatomic voltage maps (EAM). In-silico ablation was performed and compared to clinical ablation locations (Fig C).

Results:
For all 3 patients, heart model predictions corresponded well with clinical observations.In both P1 and P2, reentrant circuits’ locations matched clinical records (Fig C). Both reentrant circuits manifested at the border of inFAT and fat-myocardium admixture, where tissue heterogeneity was prominent. Regions of inFAT co-localized well with low-voltage areas on EAM. Predicted ablation sites successfully terminated VA and coincided with the clinical ablation locations. In P2, the predicted ablation yielded a much smaller lesion than clinical ablation. For P3, the model correctly predicted that VA could not be induced in the heart.

Conclusions:
Our novel ARVC CT-based computational approach accurately predicts VA ablation targets and could potentially become a highly accessible tool in assisting ARVC ablation.
Abstract 10578: St-Elevation Myocardial Infarction With Complete Heart Block in the Setting of Vagally Mediated Coronary Vasospasm
Authors: Truglio Thomas S , Choi Esther , Henry Mariana L , Hennessey Kerrilynn
Published: June 2023

Introduction:
This case identifies vagal tone as a paradoxical cause of coronary artery spasm, coinciding with complete heart block. It will additionally identify proper management in these cases.

Clinical Presentation:
A 53 year old male with a medical history of HIV not of ART, acute, infectious COVID-19 and late, latent syphilis admitted for malaise, found to have DLBCL. Following a routine blood draw the patient experienced acute chest and abdominal pain. Minutes later, while having a bowel movement he experienced syncope with heart rates in the 30s. EKG showed ST elevations in leads II, III, and aVF. Troponin-T was elevated to 0.15. Echocardiogram showed inferior wall hypokinesis. Coronary angiography showed non-obstructive right coronary disease. Cardiac MRI demonstrated no evidence of infiltrative disease or myocarditis. The patient experienced a similar episode the following morning, during blood draw, EKG and telemetry demonstrated complete heart block with ST elevations (image). This suggested vagal mediated AV block with coronary artery spasm (CAS). He was started on the anticholinergic hyoscyamine and amlodipine for vasodilation. Following initiation of therapy, the patient had no further episodes of chest pain or bradycardia.

Discussion:
While acetylcholine causes vasodilation via endothelial NO, interestingly, it can also lead to CAS. In the setting of vascular smooth muscle cell (VSMC) hyper-reactivity or high vagal tone, VSMC muscarinic receptors are activated leading to vasoconstriction. Vagal tone can cause both CAS with resulting STEMI as well as AV blockade resulting in high degree heart block (image). When ischemic symptoms are accompanied by AV block in the setting of high vagal tone, consider vagal mediated CAS. Calcium channel blockers such as amlodipine are used to manage CAS. When the suspected mechanism is vagal tone, management includes avoidance of precipitating factors and or anticholinergic premedication.
Abstract 10586: CREG1-FBXO27-LAMP2 Axis Promotes Autophagy Function of Cardiomyocytes and Alleviates Diabetic Cardiomyopathy
Authors: Liu Dan , Xing Ruinan , Zhang Quanyu , Tian Xiaoxiang , Qi Yanping , song haixu , Liu Yanxia , Yu Haibo , Zhang Xiaolin , Yan Chenghui , Han Yaling
Published: June 2023

Introduction:
Diabetic cardiomyopathy is a chronic complication of diabetes in the absence of coronary artery disease, arterial hypertension and valvular disease. Autophagy plays an important role in the development of diabetic cardiomyopathy. Cellular repressor of E1A-stimulated genes 1 (CREG1) is an important myocardial protective factor. The aim of this study was to investigate the effects and mechanisms of CREG1 in diabetic cardiomyopathy.

Methods:
Male C57BL/6J mice, CREG1 transgenic mice, and CREG1 cardiac-specific knockout mice were used to establish a type 2 diabetic model. Small animal ultrasound, Masson’s staining, and western blotting were used to evaluate cardiac function, myocardial fibrosis and autophagy. Neonatal mouse cardiomyocytes (NMCMs) were isolated and cultured. NMCMs were infected with CREG1- overexpressing adenovirus or small interfering RNA, followed by stimulation with palmitic acid (PA), real-time PCR, western blotting and immunofluorescence staining were used.

Results:
CREG1 protein expression was decreased in the myocardium of diabetic cardiomyopathy. CREG1 deficiency in the heart aggravated cardiac dysfunction, cardiac hypertrophy, and fibrosis in mice with diabetic cardiomyopathy, accompanied by aggravated autophagy dysfunction. CREG1 overexpression improved cardiac function and ameliorated cardiac hypertrophy and fibrosis in diabetic cardiomyopathy, by improving autophagy. CREG1 protein expression was decreased in PA-stimulated NMCMs. CREG1 knockdown aggravated cardiomyocyte hypertrophy and inhibited autophagy, which were reversed by resveratrol treatment. Conversely, CREG1 overexpression inhibited cardiomyocyte hypertrophy and improved autophagy, which were reversed by chloroquine or bafilomycin A1 treatment. Overexpression of LAMP2 reversed the effect of CREG1 knockdown on the PA-induced inhibition of cardiomyocyte autophagy. CREG1 inhibited the LAMP2 protein degradation by inhibiting the expression of F-box protein 27 (FBXO27).

Conclusions:
CREG1-FBXO27-LAMP2 axis alleviated diabetic cardiomyopathy by promoting cardiomyocyte autophagy. Our findings might help clarify new roles of CREG1 in the development of diabetic cardiomyopathy.
Abstract 10588: Pre-Clinical Study of Induced Pluripotent Stem Cell-Derived Cardiomyocyte Sheet Transplantation for a Cynomolgus Macaque Model of Doxorubicin-Induced Dilated Cardiomyopathy
Authors: Mikami Tsubasa , Kawamura Takuji , Nakae Masaro , Suzuki Kota , Seiko Eiraku , Harada Akima , Miyagawa Shigeru
Published: June 2023

Introduction:
Due to the serious shortage of cardiac donors in Japan, there is a strong demand for an effective alternative treatment to heart transplantation (HTx) and left ventricular assist device for end-stage severe heart failure. We have conducted induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) sheet transplantation for ischemic cardiomyopathy as first in human clinical trial (jRCT2053190081), based on several pre-clinical studies suggesting both of angiogenic effects and mechanical contribution of iPSC-CMs. Then, we are next aiming to expand the indication for dilated cardiomyopathy (DCM), which is the most common indication for HTx worldwide. In this study, we established a cynomolgus macaque model of Doxorubicin (Dox)-induced DCM and performed the iPSC-CM sheet transplantation.

Methods:
Twelve male cynomolgus macaques were treated with Dox to induce DCM every two weeks for three consecutive days in three different doses. The cardiac function was assessed over time by transthoracic echocardiography (TTE) and the effect of doxorubicin on the myocardium was investigated with histological analysis.

After the establishment of animal model, we performed the iPSC-CM sheet transplantation and assessed the postoperative cardiac function by TTE and cardiac computed tomography (CT).

Results:
Each Two macaques treated with high (1.2 kg/mg/day) and medium (1.0 kg/mg/day) dose of Dox died before the establishment of animal model. Of the remaining eight macaques in the low dose (0.8 kg/mg/day) group, six had progressively decreased cardiac function. Histology revealed vacuolization in the left ventricle of the Dox-treated heart. Postoperative evaluation two weeks after iPSC-CM sheet transplantation revealed the improvement in cardiac function on TTE and cardiac CT (left ventricular ejection fraction: from 22 % to 31%, and from 19 % to 31 %, respectively).

Conclusions:
Three-month administration of low-dose Dox was able to create a cynomolgus macaque model of Dox-induced DCM with relatively high reproducibility. IPSC-CM sheet transplantation may have the possibility for improving cardiac function of DCM.
Abstract 106: Neurological Effects Of Methylene Blue In A Porcine Model Of Cardiac Arrest
Authors: Johannsen Cecilie M , Nørholt Casper , Baltsen Cecilie , Eggertsen Mark Andreas A , Magnussen Andreas , Vormfenne Lasse , Mortensen Signe Ø , Vammen Lauge , Andersen Lars W , Granfeldt Asger
Published: June 2023

Purpose
To investigate the neuroprotective effects of methylene blue (MB) in a clinically relevant porcine model of cardiac arrest.

Method:
40 anaesthetized pigs were subjected to myocardial infarction and seven minutes of untreated cardiac arrest. Animals were randomized into three groups: one group received saline only (control), one group received 2 mg/kg MB and saline (MB+saline), and one group received two doses of 2 mg/kg MB (MB+MB). The first intervention was given after the 3rd rhythm analysis, while the second dose was administered one hour after achieving return of spontaneous circulation (ROSC). The main investigator was blinded during resuscitation and the first hour after ROSC. Animals underwent intensive care and observation for 6 hours. Neurological outcomes were evaluated by cerebral microdialysis and serum-neuron specific enolase (NSE). Normality was assessed by qq-plot and histograms. Pointwise data were analyzed using Kruskal-Wallis test as data did not assume normal distribution. Data are presented as medians and 25
th
and 75
th
percentiles. A value of p<0.05 was considered statistically significant.

Results:
The proportion of animals achieving ROSC was similar across groups: 11/13 (85%) in the control group, 10/13 (77%) in the MB+saline group, and 12/14 (86%) in the MB+MB group (p=0.81). Cerebral lactate and pyruvate levels increased after ROSC in all groups. Lactate/pyruvate ratios were comparable between groups two hours after ROSC (control: 25 (22;31); MB+saline: 24 (22;36); MB+MB: 23 (20;28); p=0.43). Cerebral glycerol levels initially increased in all groups with the highest levels at two hours after ROSC (control: 454 μmol/L (319;507); MB+saline 351 μmol/L (241;420); MB+MB 347 μmol/L (256;478); p=0.35). Glycerol levels decreased over time with no difference 6 hours after ROSC (control: 210 μmol/L (138;293); MB+saline (146 μmol/L (61;156); MB+MB: 105 μmol/L (63;159); p=0.07). Serum-NSE levels 6 hours after ROSC were not different between groups (control: 0.9 μg/L (0.7;1.5); MB+saline 1.5 μg/L (1.0;2.0); MB+MB: 1.0 μg/L (0.7;1.2); p=0.13).

Conclusion
Contrary to previous publications the current porcine trial did not observe any neuroprotective effects of MB when evaluated by cerebral microdialysis and NSE levels.
Abstract 10602: The Relationship Between Layered Plaque and Plaque Volume in Patients With Acute Coronary Syndromes
Authors: Yuki Haruhito , Nakajima Akihiro , Araki Makoto , Naganuma Toru , Seegers Lena , Kinoshita Daisuke , Suzuki Keishi , McNulty Iris , Lee Hang , Kakuta Tsunekazu , Nakamura Sunao , Jang Ik-kyung
Published: June 2023

Introduction:
Layered plaque is a signature of previous subclinical plaque destabilization and healing, which can be identified by optical coherence tomography (OCT). Silent plaque rupture or erosion with formation of a layer might contribute to rapid step-wise progression of plaque. We examined the relationship between layered plaques detected by OCT and plaque burden detected by intravascular ultrasound (IVUS) in patients with acute coronary syndromes (ACS).

Methods:
Patients presented with ACS who underwent preintervention OCT and IVUS were included in the analysis. Layered plaque was identified by OCT, and plaque burden was measured by IVUS around the culprit lesion. IVUS findings were compared between patients with layered plaque versus those without layered plaque.

Results:
Among 150 patients, total atheroma volume (TAV) (183.27 mm
3
[114.2 mm
3
to 275.0 mm
3
] vs. 119.27 mm
3
[68.9 mm
3
to 185.5 mm
3
], p=0.004), percent atheroma volume (PAV) (60.06 % [54.7 % to 60.1 %] vs. 53.69 % [46.8 % to 60.6 %], p=0.001), and plaque burden (PB) (86.51 % [81.7 % to 85.7 %] vs. 82.58 % [77.9 % to 85.4 %], p=0.001) were significantly higher in patients with layered plaques than non-layered plaques (Figure). When multi, single, and non-layered plaques were compared, TAV (188.69 mm
3
[122.1 mm
3
to 293.6 mm
3
] vs. 137.85 mm
3
[100.1 mm
3
to 208.4 mm
3
] vs. 119.27 mm
3
[68.9 mm
3
to 185.5 mm
3
], p=0.021), PAV (62.12 % [56.8 % to 67.8 %] vs. 57.52 % [48.9 % to 60.1 %] vs. 53.69 % [46.8 % to 60.6 %] p<0.001), and PB (87.44 % [81.8 % to 89.3 %] vs. 84.7 % [77.9 % to 88.0 %] vs. 82.58 % [77.9 % to 85.4 %], p=0.018) were significantly greater in multi-layered plaques than others.

Conclusions:
This study demonstrates that layered plaques, compared to non-layered plaques, have significantly greater plaque burden in patients with ACS, indicating plaque disruption and healing process, rather than gradual smooth muscle proliferation, significantly contributes to plaque progression at the culprit lesion in patients with ACS.