bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12362: Increased Cardiovascular Mortality Rates Within Historically Redlined Neighborhoods
Authors: Dilci Elise , Dilci Demir , Ho Vivian , Bozkurt Biykem
Published: June 2023

Introduction:
Redlining maps were developed by the Home Owners’ Loan Corporation (HOLC) in 1933 to depict perceived level of risk in home loans with ratings of best”, “still desirable”, “declining”, and “hazardous”. Neighborhoods that were “all-white” were rated as “best”, colored green, whereas Black neighborhoods were automatically assigned “hazardous” investment and colored in red, hence the term “redlining”. (Figure 1A) Living in historically redlined areas has been associated with disparities and adverse outcomes; however, their association with cardiovascular mortality rates has not been described. We sought to compare the cardiovascular mortality rates in historically redlined neighborhoods with others in Houston, Texas.

Methods:
Demographics and cardiovascular mortality rates reported by Department of Health and Human Services between 1999-2003 were compared between historically redlined neighborhoods and neighborhoods outside the limits of the HOLC maps in Houston, Texas.

Results:
Super-neighborhoods within historically redlined zones categorized as “hazardous” when compared with neighborhoods not in HOLC map zones, had a significantly higher proportion of Black residents (41.4 vs 21.1%, p=0.01), a higher proportion of residents with income less than twice the poverty level (28.1 vs 21.6%, p=0.04), significantly higher age adjusted mortality rates per 100,000 population for heart disease (304.65 vs 254.3, p=0.01), stroke ( 92.2 vs 70.5, p=0.001) and coronary heart disease (196.9 vs 164.4,p=0.01), and significantly higher years of potential life lost due to heart disease (905.6 vs 681 age-adjusted annual years of life lost per 100,000 population for <age of 65;p=0.03). (Table and Figures 1B &C)

Conclusions:
Living in historically redlined areas is associated with increased cardiovascular mortality rates. Future research should examine strategies to improve cardiovascular health in historically redlined neighborhoods.
Abstract 12367: Tavr Outcomes in Overweight and Obese Patients: Systematic Review and Meta-Analysis
Authors: Gupta Rahul , Behnoush Amir Hossein , Khalaji Amirmohammad , Mahmoudi Elham , Maitz Theresa , Goel Akshay , Malik Aaqib H , Bandyopadhyay Dhrubajyoti , Aronow Wilbert S , Vyas Apurva , Patel Nainesh
Published: June 2023

Introduction:
In recent years, the “obesity paradox” has been shown in studies demonstrating better outcomes in overweight and obese patients undergoing percutaneous or surgical cardiovascular procedures. This study compares the effect of body-mass index (BMI) on outcomes in patients undergoing transcatheter aortic valve replacement (TAVR).

Methods:
A comprehensive systematic search was conducted in PubMed, Web of Science, and Cochrane library for relevant studies. Studies were included if they had categories for BMI (normal-weight, overweight, and obese) and reported the outcomes of TAVR in each group. Random-effects using STATA was performed for the meta-analysis.

Results:
34 studies with 96,093 patients were included in our study. Overweight and obese patients had a significantly lower rate of 1-year all-cause mortality, long-term all-cause mortality and moderate to severe aortic regurgitation compared to normal-weight patients (Figure 1). Incidence of 30-day myocardial infarction was lower in overweight patients, and 1-year stroke incidence was significantly lower in obese patients compared with normal cases. In contrast, permanent pacemaker implantation was more observed in overweight and obese patients. There was no significant difference in outcomes in underweight patients compared to normal-weight ones except for a higher rate of major vascular complications in underweight cases.

Conclusions:
Our analysis showed improved outcomes in terms of all-cause mortality and aortic regurgitation in overweight and obese patients undergoing TAVR compared to normal-weight patients.
Abstract 12376: Is Supraventricular Tachycardia a Potential Complication of Bronchoscopic Lung Volume Reduction
Authors: Abdelhabib Mohamed , Rabulinski Daniel , Mayberry Daniel , Khoury Fadi , Rangan Pooja , Alalawi Raed
Published: June 2023

Introduction:
Endobronchial valve (EBV) placement is one technique to attain bronchoscopic lung volume reduction (BLVR). This procedure has shown clinical benefits in terms of lung function, symptoms, and quality of life. A few complications have been reported including pneumothorax, dislocation or migration of the valve, hemoptysis, COPD exacerbation, and pneumonia. However, supraventricular tachycardia (SVT) was not seen as a potential complication within 45 days of the procedure.

Hypothesis:
SVT is a complication of EBV placement to attain BLVR.

Methods:
We conducted a retrospective chart review of consecutive patients who underwent EBV placement between January 2018 and December 2021. Patients who developed SVT were compared to patient who did not get SVT.

Results:
A total of 94 cases were identified. The incidence of SVT was 18 (19.15%) cases post EBV placement. The patients who developed SVT were older (median [IQR]: 74 [69-76], 72.2% males and all were whites (100%). The time to develop SVT ranged between 2.5 hours and 118 hours with median 40.5 hours. 13 (72.2%, P= 0.007) of patients who developed SVT had an electrolyte imbalance post EBV placement. Electrolyte imbalance was an independent factor for predicting SVT on multiple regression after controlling for age, BMI, gender, and location of valve placement (adjusted OR, [CI 95%] 4.64, [1.41 - 15.29], P = 0.012). Placement of EBV in the lingula and left upper lobe (LUL) have higher incidence of SVT (5 (27.8%, P = 0.049) and 12 (66.7%, P = 0.071), respectively). Table 1 and Table 2 further summarizes the result from the study.

Conclusion:
Given the results, SVT can be recognized as a potential complication of BLVR. Additional caution must be paid to patients who have EBV placed in the LUL and patients with electrolyte imbalance post procedure. Electrolyte imbalance post procedure was the only statistically significant independent predicting factor for SVT. A larger study is needed to determine the level of association.
Abstract 12382: The Significance of Cardiac Resynchronization Therapy in Eligible Patients Undergoing Transcatheter Edge-to-Edge Repair for Functional Mitral Regurgitation
Authors: Natanzon Sharon , Shechter Alon , Siegel Robert J , Kaewkes Danon , Koseki Keita , Solanki Aum , Koren Ofir , Schwartz Brandon , Patel Vivek , Chakravarty Tarun , Skaf Sabah , Makar Moody , Stegic Jasminka , Makkar Raj
Published: June 2023

Introduction:
Current guidelines prioritize the utilization of cardiac resynchronization therapy (CRT) over transcatheter edge-to-edge repair (TEER) in eligible patients with functional mitral regurgitation (FMR). However, the data in support of this recommendation are limited.

Objective:
To examine the effect of performing TEER for FMR in patients without prior CRT.

Methods:
This is a single-center, retrospective analysis encompassing 440 days (IQR, 135-915 days) of follow-up after TEER for FMR in patients who fulfilled guideline criteria for CRT. The study cohort was divided according to CRT status prior to the procedure. The primary outcome was the composite of all-cause mortality and heart failure hospitalization at one year. Secondary outcomes included components of the primary outcome, as well as 1-year all-cause hospitalization, and 1-month MR severity, indexed left atrial volume, and indexed left ventricular mass.

Results:
A total of 126 patients were included in the analysis, of whom 70 (56%) did not have CRT at the time of TEER. Baseline characteristics and immediate procedural success were mostly comparable between those with and those without CRT. The no-CRT group experienced higher rates of the primary outcome (43% vs 25%, p=0.041), which were accounted for by increased mortality (26% vs 11%, p=0.033). After multivariate analysis, the absence of CRT was associated with more than twice the risk of the primary outcome (HR 2.36, 95% CI 1.1-4.98, p=0.024). Secondary endpoints did not differ between the groups.

Conclusions:
In CRT eligible patients undergoing mitral TEER for FMR, 1-year outcome is less favorable when the procedure is not preceded by CRT.
Abstract 12393: Two-Year Clinical Outcome of Mid-Range Ejection Fraction at Admission in Patients With Acute Myocardial Infarction
Authors: Jeon Ho Sung , Kim Young In , Lee Jung-Hee , Cho Dong-Hyuk , Park Young Jun , Son Jung-Woo , Lee Jun-Won , Youn Young Jin , Ahn Sung-Gyun , Ahn Min-soo , Kim Jang Young , Yoo Byung-Su , Lee Seung-Hwan , Yoon Junghan , Kang Dae Ryong
Published: June 2023

Introduction:
The American Heart Association and European Society of cardiology guidelines reclassified heart failure according to left ventricular ejection fraction, recognizing patients with mid-range EF (mrEF; 40% to 49%) as a distinct group. However, studies on the clinical characteristics of mid-range EF patients and the occurrence of cardiovascular events in acute MI patients are insufficient.
Methods:
We categorized 6,553 patients with acute myocardial infarction (AMI) from the Korea AMI-National Institutes of Health between November 2011 and December 2015 into three groups (reduced EF ; LVEF < 40% at admission, mild-reduced EF ; LVEF 40 to 49%, preserved EF ;LVEF ≥50%). The primary endpoint was defined as any death at two-year. Secondary endpoints were defined as any myocardial infarction, any revascularization, patient-oriented composite outcome(POCE).

Results:
Compared to patients with other two groups, the reduced EF group had a highest overall mortality, POCE, and any MI (24.7% vs 8.3% vs 4.6%, p < 0.0001, 33.0% vs 15.6% vs 12.4%, p<0.0001, 3.9% vs 2.7% vs 2.6%, p<0.0046). When mid-range EF group was designated as a reference, in multivariate analysis including all variables, significant differences with HFrEF group was found. (Hazard ratio ). When compared with HFpEF, only Model 1 and Model 2 showed a significant statistical difference (Model 1 ; 0.65 (0.53-0.81), Model 2 ; 0.56 (0.56-0.86).

Conclusions:
Followed up for two years, significant differences in survival rates were observed between the mid-range EF, reduced EF, and preserved EF group. After adjusting for common prognostic factors affecting the overall mortality rate, the reduced EF group had a significantly higher mortality rate than mid-range EF group, but no significant difference was observed between the preserved EF and the mid-range EF group.
Abstract 12397: A First Case of Myocardial Infarction Due to Multisystem Inflammatory Syndrome After Sars-cov-2 Vaccination
Authors: Yanishi Kenji , Takigami Masao , Matoba Satoaki
Published: June 2023

A 22-year-old man without any medical history developed fever three days after receiving the first dose of the Moderna vaccine (mRNA-1273; Moderna, Inc., Massachusetts, United States), but his symptom was naturally improved. On the 12th day after the second vaccination, he developed fever, headache, and redness in both eyes. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction test result was negative, but his symptoms were gradually worsening. Blood examinations on admission (the 24th day after the second vaccination, Day1) showed an increasing of C-reactive protein and D-dimer. In addition, contrast-enhanced computed tomography (CT) revealed hepatosplenomegaly and a contrast-enhanced defective area in the kidney. Subsequently, his fever subsided, and he was discharged on Day23, but he was readmitted for chest pain on Day26. We diagnosed non-ST elevation myocardial infarction (MI), and coronary angiography (CAG) revealed total occlusion of the atrioventricular branch of the right coronary artery (RCA), and 90% stenotic lesions with >3 mm coronary ectasia in the left circumflex artery (LCx). The optical coherence tomography (OCT) findings showed blurring of vessel construction, intimal thickening, medial destruction, and thrombus in the RCA and LCx lesions. Based on the Brighton Collaboration Network definition, we diagnosed the condition as multisystem inflammatory syndrome (MIS) after SARS-CoV-2 vaccination (MIS-V), presenting with systemic vasculitis lesions. Following antithrombotic therapy with warfarin, aspirin, and prednisolone (60mg/day), his D-dimer levels and inflammatory response promptly improved. Furthermore, coronary artery irregularities, especially in the LCx lesion, showed improvement on CAG on Day43. Follow-up OCT showed resolution of the thrombus and healing of the medial destruction. The prednisolone dose was reduced, and the patient was discharged. Follow-up CAG and OCT after six months showed further improvements of initial findings. So, we decided to stop warfarin and prednisolone according to these results. His clinical course is very good without symptoms after that. This is the first report of MI due to MIS-V with longitudinal OCT findings.
Abstract 12402: Sacubitril-Valsartan Increases Pampk and Reduces Inflammasome, Myddosome, Il-6 and Galectin-3 Levels in Short-Term Doxorubicin-Treated Mice Improving Longitudinal Strain and Ejection Fraction
Authors: Maurea Nicola , Canale Maria Laura , Buccolo Simona , Bisceglia Irma , Paccone Andrea , Maurea Fabrizio , Scherillo Marino , Quagliariello Vincenzo
Published: June 2023

Introduction:
Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sacubitril-valsartan (LCZ 696) is a combination drug, made up of neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan, used for the treatment of heart failure in patients with a reduced ejection fraction.

Hypothesis:
We hypothesized that LCZ 696, administered during doxorubicin, could improve cardiac function
Methods:
Female C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n=6), LCZ-696 at 60 mg/kg (LCZ, n=6) or doxorubicin combined to LCZ-696 (DOXO-LCZ, n=6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, DAMPs (galectine 3 and calgranulinS100) , pAMPK, NF-kB, and 13 chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified through ELISA and western blot methods.

Results:
LCZ 696 improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88, DAMPs and NF-kB in cardiac tissues was seen in DOXO-LCZ group compared to DOXO mice (p<0.001). Cardiac expression of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with LCZ-696 indicating anti-inflammatory properties. Expression of pAMPK was strongly enhanced in LCZ-696-DOXO compared to DOXO group. Levels of Calgranulin S100 and galectine-3 were strongly enhanced in DOXO group; on the other hand their expression were reduced by 47.7 and 52.3% in LCZ-696-DOXO group vs DOXO (p<0.005).

Conclusions:
LCZ-696 is able to improve cardiac function and reduce biomarkers involved in heart failure and fibrosis. The overall picture of the study pushes the use of Sacubitril-valsartan in prevention of cardiomyopathies induced by anthracyclines in cancer patients.
Abstract 12406: Sglt2i Dapagliflozin Associated to Berberine Reduces Cardiac Cell Apoptosis and Necrosis During Exposure to Her-2 Blocking Agents Through Induction of Pampk and Reduction of Inflammasome, Il-6, Methylglyoxal and Leukotrienes-B4 Levels
Authors: Maurea Nicola , Buccolo Simona , Bisceglia Irma , Canale Maria Laura , Scala Sara , Paccone Andrea , Scherillo Marino , Quagliariello Vincenzo
Published: June 2023

Introduction:
Trastuzumab has improved the prognosis in patients with HER2-positive breast cancer, but it can induce left ventricular dysfunction with reduced ejection fraction or HF during treatment. Dapagliflozin is a SGLT2i with cardio-renal benefits. In DAPA-HF trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin decreased the risk of worsening HF events and cardiovascular death in patients with HF and reduced ejection fraction. Berberine is a nutraceutical compound characterized by multiple metabolic effects in patients with/without cardiovascular diseases.

Hypothesis:
To investigate on the potential cardioprotective properties of Berberine associated to SGLT2i Dapagliflozin against HER-2 blocking agent-induced cardiotoxicity

Methods:
Human fetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of trastuzumab (200 nM) alone or co-incubated with Berberine (200 mM) or Dapagliflozin (50 nM) or both in combination for 48 h. After the incubation period, we performed the following tests: cell viability, apoptosis, expression of NLRP3 inflammasome, methylglyoxal and leukotrienes-B4. Expression of pAMPK was analyzed through western blot. Moreover, quantification of IL-6 was performed

Results:
Berberine and Dapagliflozin increased significantly the cell viability of cardiomyocytes exposed to Trastuzumab. When combined, Berberine and Dapagliflozin increased synergistically cell viability of cardiac cells (p<0.001 vs Trastuzumab). Cell apoptosis was reduced of 32.5, 41.8 and 72.7% for berberine, dapagliflozin and both combined (vs trastuzumab group). Methylglyoxal,a marker of AGEs, was strongly reduced compared to untreated cells. Western blot analysis clearly demonstrate that pAMPK was induced by berberine and Dapagliflozin, improving mitochondrial metabolism. No significant changes in Leukotriene B4 expression were seen. Intracellular levels of IL-6 were reduced of 46.3, 62.7 and 86.3% for berberine, dapagliflozin and both combined (vs trastuzumab group).

Conclusions:
Berberine and Dapagliflozin in combination induces an anti-inflammatory phenotype to myocardial cells through the reduction of biomarkers involved in heart failure and apoptosis.
Abstract 12411: Validation of Academic Research Consortium for High Bleeding Risk (ARC-HBR) Definition in East-Asian Patients
Authors: Lee Jinho , Kim Min-ju , Kim Mijin , Park Jinsun , Kim Hoyun , Suji Cho , Yeonwoo Choi , Lee Junghoon , Kim Ju Hyeon , Sung Joo Cha , Kim Taeoh , Kang Doyoon , Lee Pil Hyung , Ahn Jung-Min , Park Seung-jung , Park Dukwoo
Published: June 2023

Introduction:
Clinical applicability of the Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria in East-Asian patients receiving potent antiplatelet therapy for acute coronary syndromes (ACS) is still undetermined

Methods:
Using individual patient data from the TICAKOREA trial, which is a multicenter trial randomly compared ticagrelor and clopidogrel in Korean patients with ACS, we determined the prognostic effect of ARC-HBR criteria on bleeding and ischemic events. The primary safety outcome was bleeding of academic research consortium (BARC) type 3 or 5 and primary efficacy outcome was major adverse cardiovascular events (MACE; a composite of cardiovascular death, myocardial infarction, or stroke).

Results:
HBR patients compared with non-HBR patients had a higher incidence of BARC type 3 or 5 bleeding (10.0% vs. 3.61%; hazard ratio [HR], 2.98; 95% confidence interval [CI], 1.52 to 5.86) and MACE (14.3% vs. 6.1%; HR 2.35; 95% CI, 1.35-4.10). Among HBR patients, there was no significant difference in bleeding events between ticagrelor and clopidogrel (10.2% vs. 9.8%; HR 1.15; 95% CI, 0.38-3.44). However, the efficacy endpoint of MACE tended to be higher in the ticagrelor group than in the clopidogrel group (19.1% vs. 8.1%; HR 2.31; 95% CI, 0.91-5.83)

Conclusions:
In Korean patients with ACS intended to receive early invasive management, ARC-HBR criteria is sufficiently applicable to predict both bleeding and ischemic risk. We also observed differential safety and effectiveness of ticagrelor compared with clopidogrel according to presence or absence of ARC-HBR criteria.
Abstract 12416: Factors Associated With Somatic Symptoms Perception in Patients With Heart Failure
Authors: HAYASHI KANAKO , Okada Akiko , Ito Shinya , Tsuchihashi-Makaya Miyuki
Published: June 2023

Introduction:
Since symptoms as perceived by patients are subjective experiences, it is important to understand from the patient's perspective the symptoms that they perceive as distressing or unpleasant. Investigating the reality of such symptoms as perceived by heart failure (HF) patients and related factors will help to construct effective nursing interventions for symptom relief in HF patients.
Aim:
To clarify the factors related to the symptoms using the Heart Failure Somatic Perception Scale (HFSPS) of HF as perceived by HF patients.

Methods:
The study population consisted of outpatients with HF who were assessed for symptoms as perceived by HF patients by the HFSPS, as well as self-care behaviors and depression by a questionnaire. Multiple regression analyses were applied to the factors associated with the perception of HF symptoms for each HFSPS subscale.

Results:
A total of 315 patients (mean age 73 years, 72% male) were included. The mean score of HFSPS total was 11.7±12.3, and the scores of each subscale of the HFSPS were dyspnea (3.3±4.8), chest discomfort (1.3±1.7), early subtle (5.3±4.9) and edema (1.8±2.6). HFSPS total score was associated with severity of HF (standard partial regression coefficient (β) = 0.16, 95% confidence interval (CI) 0.62~5.51, p=0.014), depression (β = 0.28, CI=0.46~1.04, p<0.01), self-care maintenance (β=-0.27, CI=-0.31~-0.12, p<0.01), and symptom perception (β=0.20, CI=0.05~0.20, p<0.01). Dyspnea indicated severity of HF (β=0.18, CI=0.35~2.38, p<0.01), depression (β=0.28, CI=0.18~0.40, p<0.01), self-care maintenance (β=-0.15, CI=0.08~0.01, p<0.01), chest discomfort indicated self-care maintenance (β=-0.24, CI=-0.04~-0.01, p<0.01), symptom perception (β=0.27, CI=0.01~0.03, p<0.01), depression (β=0.34, CI=0.25~0.48, p<0.01) for early subtle, self-care maintenance (β=- 0.27, CI=-0.13~-0.05, p<0.01), symptom perception (β=0.18, CI=0.01~0.07, p<0.01), and depression (β=0.12, CI=0.01~0.14, p=0.03) were shown for edema.

Conclusion:
Assessing symptoms as perceived by the HF patient is expected to help the health care provider understand the patient's perceived symptoms and provide comprehensive treatment and care that is appropriate to the patient's characteristics.
Abstract 12418: Prevalence and Clinical Characteristics of Patients With Decompensated Heart Failure and Clonal Haematopoiesis of Indeterminate Potential
Authors: Mooney Leanne , Robertson Neil A , Terradas Maria T , Goodyear Carl S , Copland Mhairi , McMurray John J , Kirschner Kristina , Tamir Chandra , Petrie Mark , Lang Ninian
Published: June 2023

Introduction:
CHIP is associated with inflammation, atherogenesis and poor outcomes in patients with HFrEF. Although inflammation may be important in the pathophysiology of HFpEF, CHIP has not previously been assessed in patients with HFpEF. We examined the prevalence of CHIP and its associated clinical characteristics in patients with HFpEF or HFrEF.

Methods:
Error-corrected targeting sequencing of 75 known haematopoietic driver genes was performed on peripheral blood DNA from patients admitted to hospital with acute HF (HFrEF [LVEF<40%] and HFpEF [LVEF≥40%]). CHIP mutations and their associated clonal population size were analysed and associations with clinical phenotypes and inflammatory markers were assessed.

Results:
96 patients were enrolled; 48 had HFrEF and 48 had HFpEF. CHIP mutations with VAF ≥2% were detected in 5 patients with HFrEF (10%) and 8 patients with HFpEF (17%). CHIP mutations with VAF ≥1% were detected in 25 patients with HFrEF (52%) and 21 patients with HFpEF (44%). HFrEF patients with CHIP were a similar age to those without CHIP (71.1 ± 14.2yrs CHIP vs 68.9 ± 13.0yrs without CHIP; p=0.58) but HFpEF patients with CHIP were older than those without CHIP (80.1 ± 8.8yrs CHIP vs 70.0 ± 12.3yrs no CHIP; p=0.002). There was an age-dependent rise in CHIP prevalence which appeared greater in patients with HFpEF than HFrEF. DNMT3A was the most commonly mutated gene. Patients with CHIP had higher concentrations of pro-inflammatory interleukins but CHIP was not associated with previous MI or NT-proBNP.

Conclusions:
There is a substantial prevalence of CHIP in patients admitted to hospital with HF. In this cohort, CHIP was uncommon in patients with HFpEF under the age of 70 years but was frequent in older patients. The association between age and CHIP was stronger in HFpEF than HFrEF. CHIP was associated with inflammation. Its potential role in the pathogenesis of HF warrants further exploration in larger groups, including in elderly patients with HFpEF.
Abstract 12422: Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Are Mutually Independent Predictors of Major Cardiovascular Events in Patients With Established Cardiovascular Disease
Authors: Sprenger Lukas , Maechler Maximilian , Vonbank Alexander , Larcher Barbara , Mader Arthur , Leiherer Andreas , Muendlein Axel , Drexel Heinz , Saely Christoph H
Published: June 2023

Introduction:
Non-Alcoholic Fatty Liver Disease (NAFLD) is associated with insulin resistance, type 2 diabetes (T2DM) and cardiovascular disease. However, data on NAFLD in patients with established cardiovascular disease (CVD) are scarce.

Hypothesis:
We hypothesize that NAFLD and T2DM are independent predictors of the incidence of major cardiovascular events (MACE).

Methods:
In a large series of 1517 patients with established CVD (1199 patients with angiographically proven coronary artery disease and 318 patients with sonographically proven peripheral artery disease), using the validated fatty liver index for the diagnosis of NAFLD.

Results:
At baseline, the prevalence of NAFLD was significantly higher in patients with T2DM than in non-diabetic subjects (61.3% vs. 39.8%; p<0.001) respectively. Prospectively, we recorded 498 MACE over a mean follow-up period of 10.0±4.5 years. The risk of MACE was higher in NAFLD patients than in those who did not have NAFLD (49.5 vs. 43.5%; p=0.020) and in patients with T2DM than in non-diabetic subjects (41.4 vs. 28.1%; p<0.001). Cox regression models adjusting for conventional cardiovascular risk factors proved NAFLD and T2DM to be mutually independent predictors of MACE, with adjusted hazard ratios of 1.34 [1.06-1.69] p=0.013 and 1.59 [1.32-1.92]; p<0.001, respectively.

Conclusions:
We conclude that NAFLD and T2DM are mutually independent predictors of MACE in patients with established CVD.
Abstract 12425: The Interplay Between Left Atrial and Mitral Valvular Remodeling in Subtypes of Mitral Regurgitation
Authors: Berg-Hansen Christian Engelsen , Bach Rasmus S , Grymyr Lisa M , Urheim Stig , Rogge Barbara P , Persson Robert M , Cramariuc Dana
Published: June 2023

Background:
The interaction between left atrial (LA) mechanics and mitral valve remodeling patterns in patients with mitral regurgitation (MR) is poorly described.

Objectives:
To assess three-dimensional (3D) LA volumes and strain in relation to 3D mitral valve morphology in patients with degenerative vs. functional MR.

Methods:
Patients included in the 3D-PRIME (3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation) study at our heart valve clinic between 2020-2022 and with moderate or severe MR by combined transthoracic/transesophageal assessment were examined. LA remodeling was assessed by 3D maximum and minimum LA volume, reservoir strain (LASr) and contraction strain (LASct). Mitral valve annulus area, anterior and posterior leaflet length and area, tenting volumes and non-planar angle were measured using dedicated 3D mitral valve software.

Results:
100 patients with moderate or severe MR were included. Patients with atrial functional MR (n=26) were older, more often women and had higher heart rate compared to degenerative MR (n=54) and ventricular functional MR (n=20) (p <0.05). They also had larger LA volumes and severely impaired LASr and LASct despite smaller MR regurgitation volumes compared to MR by other mechanisms (Figure). Mitral annulus area was comparable between groups, but anterior mitral leaflet was higher, with larger area and the non-planar angle wider in functional MRs (p <0.05). In multivariable analysis, low LASr (below median) was associated with larger LA volume, and higher anterior mitral leaflet height independent of age, sex, heart rate, left ventricular global longitudinal strain, and right ventricular stroke volume (Nagelkerke R
2
0.67, p <0.01). In a similar model, low LASct was only associated with larger LA volumes.

Conclusions:
Patients with atrial functional MR have large LAs with severely impaired LA function and a specific mitral valve remodeling pattern at lower MR regurgitation volumes.
Abstract 12431: Association of Obesity With Incident Atrial Fibrillation in Korea and the United Kingdom
Authors: Choi Sung Hwa , Yang Pil-sung , Kim Daehoon , Sung Jung-Hoon , Jang Eunsun , Yu Hee Tae , Kim Tae-Hoon , Pak Hui-Nam , LEE Moon Hyoung , Lip Gregory Y.H. , JOUNG BOYOUNG
Published: June 2023

Introduction:
Obesity has been linked to atrial fibrillation (AF) burden and severity, and epidemiological studies suggest that AF is more prevalent in whites than Asian or Afro-Caribbean populations. We aimed to investigate whether obesity mediates associations with AF in Europe and Asia using patient-level data comparisons of two cohort studies.

Hypothesis:
We therefore hypothesized that the difference in the distribution of BMI and WC can partially explain the ethnic differences in AF incidence

Methods:
Using Korean National Health Insurance Service’s Health Screening (NHIS-HealS) and U.K. Biobank data, we included 401,206 Korean and 477,926 British aged 40-70 years without previous AF who received check-ups. The incidence and risk of AF were evaluated regarding different body mass index (BMI) values.

Results:
The obese proportion(BMI ≥ 30.0 kg/m
2
, 2.8% vs. 24.3%,
P
< 0.001) was higher in the U.K. than the Korean. In the Korean and U.K. cohort, the age- and sex-adjusted incidence rates of AF were 3.52 and 3.95 per 1,000 person-years among overweight individuals (BMI, 25 to <30 kg/m
2
), and 4.97 and 6.54 per 1,000 person-years among obese individuals, respectively. Compared to Koreans, the risk of AF was higher in the British population, with adjusted hazard ratios of 1.11 (95% confidence interval [CI], 1.04-1.19) and 1.16 (95% CI, 1.11-1.22) in overweight participants and 1.69 (95% CI, 1.57-1.83) and 1.45 (95% CI, 1.30-1.62) in obese participants, respectively (
P
for interaction < 0.05).

Conclusions:
Obesity was associated with AF in both populations. British subjects had a greater incidence of AF related to the high proportion of obese individuals, but the risk of AF was also increased when separating participants into overweight and obese categories.
Abstract 12435: A Rare Case of Pericarditis Following Varicella-Zoster Vaccination
Authors: Mears Dominic R , Hothi Sandeep S
Published: June 2023

Introduction:
We emphasise the role of imaging as illustrated by the case of a 71-year-old male who presented with acute pericarditis one day after receiving a Varicella Zoster Virus (VZV) Vaccination. Although active VZV infection itself is recognised as an uncommon trigger for pericarditis, and myopericarditis following several live attenuated vaccines, its occurrence specifically following VZV vaccination is rare.

Case Presentation:
This gentleman was previously fit and well prior with no significant comorbidity or drug allergies. Clinically, we suspected VZV vaccine-induced pericarditis in this case due to the short temporal relationship between vaccination and symptom onset and absence of other known infectious and non-infectious causes of pericarditis. This was in addition to characteristic chest pain, fever, sweating, electrocardiogram (clear PR depression and subtle concave ST elevation) and imaging (echocardiography and Cardiac MRI) features.

Imaging Results:
Pulmonary embolism was excluded by CT pulmonary angiography, but this scan did reveal a large, global pericardial effusion. Prompt transthoracic echocardiogram categorised the pericardial effusion as small and did not show any signs of cardiac tamponade. Cardiac MRI imaging demonstrated a large pericardial effusion but did not show any overt myocardial oedema, inflammation or fibrosis, consistent with a low high-sensitivity troponin I. Interestingly, the MRI did not reveal any convincing pericardial oedema or fibrosis acutely, which might be expected in pericarditis.

Transthoracic echocardiography was important in excluding features of tamponade and helped confirm the diagnosis of acute pericarditis by clearly demonstrating the pericardial effusion. A Cardiac MRI was essential in excluding co-existent myocarditis and infarction.

Conclusions:
Acute pericarditis should be considered in patients presenting with chest pain after receiving the VZV vaccination and patients should be made aware of this rare side effect prior to receiving their vaccination. The patient in this case study responded well to symptomatic treatment with analgesia and colchicine, suggesting that anti-viral therapy is not required for VZV related pericarditis.
Abstract 12457: Usefulness of Automatic Assessment for Longitudinal Strain to Diagnose Wild-Type Transthyretin Amyloid Cardiomyopathy
Authors: Usuku Hiroki , Yamamoto Eiichiro , Fujisaki Tomohiro , Egashira Koichi , Oike Fumi , Fujisue Koichiro , Sueta Daisuke , Takashio Seiji , Tsujita Kenichi
Published: June 2023

Introduction:
Despite obvious diagnostic usefulness, left ventricular (LV) apical sparing has not been widely accepted to diagnose transthyretin amyloid cardiomyopathy, because it is time consuming and requires a level of expertise. Automatic assessment may be the solution for these problems.

Methods and Results:
We enrolled 69 patients aged ≥ 70 years who underwent
99m
TC-PYP scintigraphy and transthoracic echocardiography (TTE) by EPIQ7G, and had enough information for two-dimensional speckle tracking echocardiography at Kumamoto University Hospital from January 2016 to December 2019. LV apical sparing was diagnosed as relative apical longitudinal strain (LS) index (RapLSI) >1.0. Measurement of LS was repeated using the same apical images with three different measurement packages as follows: (1) full-automatic assessment, (2) semi-automatic assessment, and (3) manual assessment. The calculation time for full-automatically assessment (14.8±1.5 sec/patient) and semi-automatically assessment (67.3±14.1 sec/patient) were significantly shorter than for manual assessment (211.1±60.5 sec/patient) (p<0.01 for both). Receiver operating characteristic curve analysis showed that the area under curve (AUC) of the RapLSI evaluated by full-automatically assessment for
99m
Tc-PYP scintigraphy positivity was 0.656 (best cut-off point; 1.12 [sensitivity 63%, specificity 68%]), by semi-automatic assessment was 0.806 (best cut-off point; 1.00 [sensitivity, 61%; specificity, 100%]) and by manual assessment was 0.806 (best cut-off point; 1.00 [sensitivity, 71%; specificity, 96%]).

Conclusion:
The diagnostic accuracy of semi-automatically assessed RapLSI to predict
99m
Tc-PYP scintigraphy positivity was as same as that of manual assessed RapLSI. Semi-automatically approach using novel automated software was useful to diagnose ATTR-CM in the terms of rapidity, reproducibility and diagnostic accuracy.
Abstract 12463: Low-Density-Lipoprotein Cholesterol and Mortality Outcomes Among Healthy Older Adults Not Taking Lipid-Lowering Agents: A Cohort Study With 12,334 Participants
Authors: Zhou Zhen , Tonkin Andrew M , Curtis Andrea J , Murray Anne , Zhu Chao , Reid Christopher , Williamson Jeff , Ryan Joanne , McNeil John J , Beilin Lawrence J , Ernst Michael E , Stocks Nigel , Lacaze Paul , Shah Raj , Woods Robyn , Wolfe Rory , Gall Seana L , Zoungas Sophia , Orchard Suzanne , Nelson Mark R
Published: June 2023

Introduction:
Clinical uncertainty remains about the relationship between cholesterol levels and risk of death in older persons.

Hypothesis:
Lower low-density lipoprotein (LDL) cholesterol level was associated with a decreased mortality risk from cardiovascular disease (CVD) and an increased mortality risk due to non-CVD causes in primary prevention older populations.

Methods:
We examined the relationship between LDL cholesterol levels and mortality outcomes in a cohort of older individuals aged ≥65 years enrolled into a clinical trial. At baseline, participants had no diagnosed dementia, physical disability or CVD events, and were not taking lipid-lowering agents. Multivariable Cox proportional-hazards models were used to examine associations of LDL cholesterol with all-cause, CVD, cancer, and combined non-CVD/non-cancer mortality. Restricted cubic splines were used to depict non-linear relationships.

Results:
Among 12,334 participants included in this analysis [mean (SD) age: 75.2 (4.6) years; 54% females], who were followed for a median of 6.9 (5.7-8.0) years, 1250 (10%) died (24% due to CVD, 43% cancer, and 33% non-CVD/non-cancer). There was a U-shaped relation linking LDL cholesterol and all-cause mortality (nadir: 3.3mmol/L) and a curvilinear relation for other mortality outcomes. Each 1-mmol/L higher LDL cholesterol was associated with a lower risk of all-cause mortality (HR=0.91, 95% CI 0.85-0.98), cancer mortality (0.83, 0.74-0.94) and non-CVD/non-cancer mortality (0.81, 0.71-0.93), but a higher risk of CVD mortality (1.19, 1.03-1.38). Reduced risks of all-cause and non-CVD/non-cancer mortality were only significant in males and but not females (P values for sex interaction <0.05). When deaths in the five years after baseline were excluded, the HRs for all-cause, cancer, non-CVD/non-cancer and CVD mortality were 1.03, 1.05, 0. 91 and 1.21 respectively (all P>0.10).

Conclusions:
Higher LDL cholesterol is associated with a greater risk of CVD mortality in older adults. Reduced risks for non-CVD mortality were likely driven by reverse causality, evidenced by the absence of associations after excluding deaths that occurred within the initial five years of follow-up.
Abstract 12469: Ras-Related Associated With Diabetes (RRAD) Regulates Cardiomyocyte Response to Cell Cycle Stimulation
Authors: Abouleisa Riham , Salama Abou bakr M , Miller Jessica , Abdulwali Fareeha , Hammouri dana , Ou Qinghui , andres douglas , Satin Jonathan , Hill Bradford G , Mohamed Tamer
Published: June 2023

Background:
Cardiomyocytes (CMs) lost during ischemic cardiac injury can't be replaced due to their limited proliferative capacity. Our laboratory has shown that overexpression of cyclin-dependent kinase 1 (CDK1), CDK4, cyclin B1, and cyclin D1 in combination (4F) promotes cell division in 10-20% of post-mitotic cardiomyocytes (CMs). Recently, we found that 4F overexpression transiently decreased CM contractility during the mitotic phase. Temporal bulk and single-cell RNAseq data from 4F-transduced human iPSC-derived CMs (hiPS-CMs) or P7 neonatal mouse CMs (NMCM) indicated a transient downregulation of contractile genes during the mitotic phase; among the most differentially regulated genes was Ras-Related Associated with Diabetes (RRAD), an endogenous inhibitor of the L-type calcium channel (LTCC).

Objective:
RRAD inhibition of LTCC primes CMs to respond to cell cycle stimulation through unloading CMs from their commitment to contractile function.

Methods and Results:
We used viral approaches to overexpress and knockdown
(KD)
RRAD in hiPS-CMs and NMCM. Functionally, RRAD overexpression abolished intracellular calcium transients’ amplitude while RRAD KD significantly increased calcium transients’ amplitude in response to electric stimulation in CMs. RRAD overexpression in hiPS-CMs or P7 NMCM augments the cell cycle induction following 4F transduction, while RRAD KD resulted in a decline in the cell cycle induction as indicated by cell cycle markers; EDU and PHH3 (PHH3(%): 4F 26.0± 1, 4F+RRAD 41.15± 6.7, 4F+KD 15.92± 2.6, P<0.05; EDU(%): 4F 29.9± 3.9, 4F+RRAD 61.04± 2.6, 4F+KD 16.8± 2.8; n=6, P<0.05). Nitrendipine, an LTCC blocker, and Mavacamten, which directly suppress cardiomyocyte contractility, reversed the inhibitory effect of RRAD KD on cell cycle induction. More interestingly, RRAD overexpression enhanced the cell cycle induction in presence of only 2 factors (CDK4 and CCND (2F)), which are known to induce S phase (PHH3(%): 2F 5.1± 0.4, 2F+RRAD 10.4± 6.7, 2F+KD 0.4± 0.1, EDU (%); 2F 38.6±15, 2F +RRAD 44.7± 18, 2F+KD 5.6± 2; n=6, P<0.05).

Conclusions:
These data suggest that RRAD modulation of contractile function modulates the response of CMs to cell cycle induction and can reduce the number of factors needed to induce cell cycle in CMs.
Abstract 12519: Derivation of Coronary Age Based on Coronary Artery Calcification Score Compared to Chronological Age
Authors: Hajj Ali Adel , Nakhla Michael , Cho Leslie , Seballos Raul , Lang Richard S , Feinleib Steven , Flamm Scott D , SCHOENHAGEN Paul , Wang Tom Kai Ming K , Desai Milind Y
Published: June 2023

Introduction:
Besides reporting conventional calcium score, coronary age was suggested as an original function of cardiovascular risk.

Hypothesis:
In a primary prevention cohort, we sought to assess the reclassification provided by coronary arterial age derived from the Multi-Ethnic Study of Atherosclerosis- coronary artery calcification 10-year risk score (MESA-CACS).

Methods:
Consecutive patients (n=5324 ,age 57± 8 years ,76% male and 87% white) undergoing CACS screening in a primary prevention clinic between 3/2016 and 10/2021 were retrospectively included in this study. Coronary arterial age was calculated for the patients using the formula provided by Blaha M et al 2021 by solving for age from MESA-CACS 10-year risk = 1–0.99963exp(0.04555*Age+2.45).

Results:
The distribution of the difference between the calculated coronary age and the chronological age is presented in Fig 1a, with 1823 (62%) patients with CAC of 0 being downgraded by >20 years and 298 (29%) of patients with CAC >75
th
percentile being upgraded by >20 years. The average difference between coronary age and chronological age (years) across the CAC percentile groups is -23.7, -18.3, -7.4, -0.2 and +12.8 years for CAC of 0, 1-25, 26-50, 51-75 and >75
th
percentile, respectively (Figure 1b).

Conclusions:
The use of coronary age is a simplified method of explaining the MESA-CAC cardiac risk status for the patients. In our study, coronary age was lower by more than 20 years versus chronological age for CAC percentiles between 0 and 50, almost equal with CAC percentile 51-75 and greater than chronological age by more than 10 years for CAC percentile >75.

Fig 1A:
Distribution of coronary age classification compared to the chronological across the CACS percentiles
1B:
Mean difference between coronary and chronological age across the CACS percentile
Abstract 12562: To Call ‘911’ or Not: What Influences Decision Making in Patients With St-Elevation Myocardial Infarction (STEMI)?
Authors: Avery Lorraine , Marshall Kirsten , Nelson David , Liu Yixiu , Grierson Robert , Liu Shuangbo , Ducas John ,   Manitoba Acute Coronary Syndrome (ACS) Network
Published: June 2023

Introduction:
It is well-established that total ischemic time (TT) is related to mortality of STEMI patients treated with primary percutaneous coronary intervention (PPCI). TT is composed of the time from symptom onset (Sx) to first medical contact (FMC) and FMC to device. Shortest times are achieved when patients decide to call ‘911’, have a pre-hospital electrocardiogram and are transported directly for PPCI. Efforts have primarily focused on improvement of FMC-Device time. SxFMC time is less understood, collected and studied. Our goal was to identify factors that influence STEMI patients’ decision making to employ emergency medical services (EMS) vs self-presenting to an emergency department (ED).

Methods:
Between 1/1/2013- 12/31/2014, we collected data on 481 consecutive low risk STEMI patients, excluding cardiogenic shock, cardiac arrest and unsuccessful PPCI.

Results:
The median SxFMC was 53 minutes (interquartile range (IQR) 23-120) in EMS cohort versus 139 minutes (IQR 72-297) in ED group (p<0.001). EMS patients were more often older (median age 64, IQR 56-74 vs 60 IQR 52-68) vs ED, p<0.001. Presenting features such as sex, anterior STEMI, and Killip Class were not statistically different between EMS and ED. Risk factors (RF) for coronary disease including hypertension, dyslipidemia, diabetes, smoking, previous diagnosis of myocardial infarction (MI), previous PCI or coronary artery bypass grafting (CABG) were not statistically different between the groups. There was no difference in time of the day of symptoms onset between the groups.

Conclusions:
Accordingly, demographic, cardiac risk factors, time of onset of symptoms, location and severity of infarction are not associated with patient decisions to employ EMS. However, older patients were more likely to employ EMS. Further research is required to understand these decision-making processes to develop targeted public awareness interventions that are directed to improve SxFMC in STEMI patients.
Abstract 12595: De Novo Lymphoproliferative Disorders in Heart Transplant Recipients: Predictors and Clinical Outcomes
Authors: Kim Sang Hyun , Kim In-cheol , Rossano Joseph W , Lee Seonhwa , Kim Hyungseop , Kim Jin-jin , Jung Mi-Hyang , Cherikh Wida S , Vece Gabriel , Stehlik Josef , Youn Jong-Chan
Published: June 2023

Introduction:
Post-transplant lymphoproliferative disorder (PTLD) is an important cause of morbidity and mortality in heart transplant (HTx) recipients. However, clinical characteristics and predictors of PTLD in the real world have not been well studied.

Methods
We retrospectively analyzed clinical characteristics, predictors, and outcomes of PTLD, in 28,136 recipients of heart alone transplants between January 2000 and June 2015 from the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry.

Results
Ten-year incidence of PTLD after successful discharge from HTx during 2000-2007 was 3.8%. The adjusted overall risk of mortality was significantly higher in patients diagnosed with PTLD within 3 years after HTx compared to those without PTLD (HR 2.22, 95% CI 1.86-2.65, p<0.001). Bimodal age peak of the PTLD incidence within the 3 years of HTx and mortality after the diagnosis of PTLD was noted. Both adjusted risk of PTLD incidence and mortality were lower in recent HTx; lower incidence and mortality in era of 2008-2015, compared to 2000-2007 (Incidence: HR 0.75, 95% CI 0.57-0.98, p=0.038) (Mortality: HR 0.86, 95% CI 0.81-0.91, p<0.001). Age at transplant, male recipient, high risk Epstein-Barr virus (EBV) mismatch (donor positive and recipient negative for EBV) were independent risk factors, while primary maintenance therapy with cyclosporine (vs. tacrolimus) at initial discharge was a protective factor for PTLD within 3 years.

Conclusions
The incidence as well as mortality of PTLD has decreased in recent years of HTx, possibly with advances in changed pattern of immunosuppression according to patient profile. Clinical characteristics such as age, male gender, EBV status and rejection history are key factors for assessing the risk of PTLD, which can be detrimental in the course of post HTx care.