bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12318: Echocardiographic or Blood Pressure Screening of Women With Past Pre-Eclampsia and Gestational Hypertension: The Western Health Survey of Heart Failure Risk After Pregnancy Hypertension Pilot Survey
Authors: Sen Jonathan , Dixon Jordan , Smith Emma , Banks Sam , Sherriff Ashleigh-Georgia , Lynch Lee-Anne , Wright Leah , Oreto Marc , Said Joanne , Marwick Thomas
Published: June 2023

Introduction:
Pre-eclampsia (Pec) and gestational hypertension (GHT) are potential explanations for the female preponderance of heart failure with preserved ejection fraction. How and when to use this information clinically is unclear.

Hypothesis:
We hypothesized that subclinical disturbances of left ventricular (LV) structure and function (stage B heart failure, SBHF) are more common at 5-10 years post-partum in women with a history of Pec compared with women with GHT or uneventful pregnancies.

Methods:
The proportion of SBHF were compared between 25 women with Pec, 16 with GHT or normal pregnancy. Sub-group analysis comparing patients with and without hypertension at follow-up were also conducted.

Results:
Among 41 participants (age 40±6 years), followed at 9 years, SBHF was reported in 35% participants with Pec and 53% with GHT (
p
=0.32). Diastolic blood pressure was significantly higher in patients with SBHF than without (94±21 vs. 81±13 mmHg, p=0.035), and a similar trend was observed with systolic blood pressure (147±42 vs. 128±22mmHg, p=0.099). SBHF was observed in 6 (55%) of 11 pts with hypertension at follow-up, but only in 7 (32%) of 22 without (
p
=0.27). Mean LV end-diastolic volume (117.2±19.1 vs. 93.3±13.1mL,
p
=0.03), LV end-systolic volume (51.9±7.5 vs. 42±7 mL,
p=
0.04), LV mass index (73±8.6 vs. 67.3±14.6mmHg, p=0.41), E/e’ (Sept: 9.7±2.7 vs. 7.5±1.7,
p
=0.009; Lat: 7.4±2.6 vs. 5.5±1.7,
p
=0.02) were higher in participants with hypertension than without.

Conclusions:
9 years after pregnancy, SBHF was prevalent in pts with both previous Pec and GHT, but was not significantly different between the entities. Echocardiographic screening may add little to blood pressure follow-up in the identification of HF risk.
Abstract 12335: Increasing Awareness About Appropriate High Sensitivity Troponin Use in the Acute Care Setting: Is a Web Based Training Interface the Solution?
Authors: Ansari Umair , Daloya Jordan , perera rohan
Published: June 2023

Introduction:
High sensitivity troponin (hs-cTnT and hs-cTnI) aimed to reduce costs, observation times and hospital stays. However, since their implementation in many hospital systems across the US many healthcare professionals still struggle in regards to their appropriate utility and interpretation.

Hypothesis:
We assessed the hypothesis that a web-based training interface is an effective tool to increase education about the proper utility and interpretation of High sensitivity troponin in an acute care setting.

Methodology:
A web-based training interface was designed with 2 pre-education questions, a slide show based on the 2021 guidelines for chest pain (ie ordering troponin based on presentation, 0+1/2/3 hour) and 2 post-education questions. This interface was sent out to healthcare professionals in a community hospital through email bursts and QR codes. 52 providers participated in the training interface: Internal Medicine residents (n=24), Hospital medicine attendings (n=13), Cardiology Attendings (n=3), Emergency medicine attendings (n=3) and Advanced practice providers (APPs), included nurse practioners and physician assistants (n=9). We measured change in awareness of appropriate and inappropriate troponin use. Fisher's exact test was performed to compare all subgroups. P value <0.05 was considered significant.

Results:
Our study showed that a web-based training interface increased awareness in the proper usage of high sensitivity troponin across all provider subgroups, with statistically significant results seen among APPs and Resident physicians [Figure].

Conclusion:
In conclusion, web-based training applications are a good tool to use when providing information to large numbers of people about high yield topics such as the proper use of and interpretation of High sensitivity troponin and can increase awareness when used appropriately.
Abstract 12352: Left Ventricular Chordal Aberrancy: The Case of a Friend Turned Foe
Authors: Sawhney Aanchal , Finkel Jonathan
Published: June 2023

Introduction:
Aberrant cardiac structures reported on echocardiography include aberrant papillary muscles, accessory chordae tendineae, ventricular bands, and accessory mitral valve tissue. These usually present with conduction abnormality, obstruction, and heart failure. We report a diagnostic dilemma with a structurally anomalous chord noted on the echocardiogram presenting as recurrent stroke.

Case:
A 70 year old man presented with complaints of left facial droop, confusion and slurred speech, currently on aspirin and clopidogrel. CT head and MRI brain revealed right middle cerebral artery occlusion and acute on chronic infarcts in multiple vascular territories. Past medical history of recurrent strokes involving the right frontal, occipital lobes, and thalamus suggested embolic aetiology. Transthoracic and Transesophageal Echocardiographic (TEE) examination revealed an anomalous redundant chordal tissue attached to the papillary muscle with no distal attachment, normal mitral valve function without left ventricular outflow tract obstruction. This anomalous chord was present on TEE done 1 year prior but not well visualised at that time.

Differentials included ruptured aberrant ventricular band, ruptured chordae tendineae, ruptured papillary muscle with a thrombus or vegetation formation. Due to the chronicity of the condition and negative blood cultures, vegetation was less likely. Recurrent mural thrombus associated with the aberrant chord was identified as the culprit and patient was started on anticoagulation to prevent stroke.

Results:
All of the aberrant structures reported in current literature have been characterized based on their distal attachment. We excluded accessory papillary muscle and chordae tendineae from the list of differentials as its rupture presents as mitral regurgitation and acute heart failure. The most plausible explanation includes a ruptured false tendon serving as a nidus for thrombus formation with no prior echocardiographic evidence of distal attachment of the fibrous chord.

Conclusions:
Our case illustrates a very rare entity of an idiopathic primary rupture of a left ventricle false tendon serving as a nidus for clot formation leading to recurrent stroke warranting anticoagulation.
Abstract 12361: Efficacy and Safety of NOACs vs. Warfarin Across the Continuous Range of Body Mass Index and Body Weight: Insights From COMBINE-AF
Authors: Patel Siddharth M , Steffel Jan , Boriani Giuseppe , Palazzolo Michael G , Bohula Erin A , Carnicelli Anthony , Connolly Stuart J , Eikelboom John W , Gencer Baris , Granger Christopher B , Morrow David A , Patel Manesh R , Wallentin Lars C , Ruff Christian T , Giugliano Robert P
Published: June 2023

Introduction:
The efficacy and safety of non-vitamin K oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) at the extremes of body mass index (BMI) and body weight (BW) remains uncertain, leading to concerns regarding use in these populations across clinical practice guidelines.

Methods:
This analysis of the COMBINE-AF database pools individual patient-level data from the 4 pivotal RCTs of NOAC vs. warfarin in AF: RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48. Pts randomized to low-dose NOACs not globally approved for clinical use were excluded. The primary efficacy and safety outcome was stroke/systemic embolic event (S/SEE) and major bleeding, respectively, with intracranial hemorrhage (ICH) being a secondary outcome. Outcomes were assessed across BMI and BW using a Cox model stratified by trial, with interaction testing for NOAC vs. warfarin. Restricted cubic splines were used to display the hazard ratio of NOAC vs. warfarin for each outcome across BMI.

Results:
For 58,464 pts, the median BMI was 28 (25
th
-75
th
%ile: 25-32) kg/m
2
,
with the top 5% (n=2,924) having a BMI ≥ 40 kg/m
2
. For patients randomized to warfarin, the risk of each outcome was lower with increasing BMI (HR per 5 kg/m
2
increase: S/SEE 0.79 [95% CI 0.75-0.84]; major bleeding 0.91 [95% CI 0.87-0.95]; ICH 0.72 [95% CI 0.66-0.80]; p<0.01 for each). There was no significant treatment interaction for NOAC vs. warfarin by BMI for S/SEE (p-interaction = 0.71;
Fig 1A
), major bleeding (p-interaction = 0.15;
Fig 1B
), or ICH (p-interaction = 0.84;
Fig 1C
), such that there was consistent reduction in S/SEE and ICH (
Fig 1A and 1C, respectively
) across the range of BMI with NOAC vs. warfarin. Similar results were seen for each outcome when assessed by BW (median [25
th
-75
th
%ile]: 81 [70-94] kg; 5
th
-95
th
%ile: 55-119 kg).

Conclusions:
In this pooled analysis of the pivotal AF trials, use of NOAC was associated with a consistent reduction in S/SEE and ICH compared with warfarin across the range of BMI and BW.
Abstract 12368: Results From the DoPING-HFpEF Trial: A Double Blind, Placebo-Controlled Randomized Cross-Over Trial Investigating Trimetazidine in Heart Failure With Preserved Ejection Fraction
Authors: Van De Bovenkamp Arno A , Bakermans Adrianus J. J , Geurkink Kiki J , Oosterveer Frank T , De Man Frances S , Kok Wouter E , Nederveen Aart J , van Rossum Albert C , Handoko M. Louis L
Published: June 2023

Introduction:
Due to mitochondrial dysfunction, cardiac energy homeostasis is compromised in heart failure with preserved ejection fraction. As left ventricular relaxation is an active and energy consuming process there is a clear relationship between the impaired cardiac metabolism and diastolic dysfunction. Here, we investigate whether trimetazidine, a fatty acid oxidation inhibitor, can improve cardiac energy homeostasis and consequently improve diastolic function.

Methods:
This was a single-center, double-blind, placebo-controlled randomized cross-over trial consisting of two treatment periods of three months with a 2 week washout period in between. Patients (N=25) were treated with 20mg trimetazidine or placebo t.i.d. or b.i.d. (based on kidney function). The primary endpoint was change in pulmonary capillary wedge pressure (PCWP) measured with right heart catheterization at multiple stages of exercise. Secondary endpoint was change in phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio, an index of the myocardial energy status, measured with phosphorus-31 magnetic resonance (MR) spectroscopy.

Results:
All included patients had invasively proven heart failure with preserved ejection fraction. There was no effect on the primary outcome PCWP at multiple levels of exercise (
P
=0.60). Myocardial PCr/ATP in the trimetazidine arm was similar to placebo (
P
=0.08). There was no change by trimetazidine in the exploratory parameters 6-minute walking distance, NT-proBNP, overall quality of life, or other parameters for diastolic function measured with echocardiography and cardiac MR, or additional metabolic parameters. Trimetazidine plasma level are currently being assessed and will be available at the moment of presentation.

Conclusion:
Trimetazidine did not improve diastolic function or myocardial energy homeostasis in patients with HFpEF.

Disclosure of unlabeled use:
Trimetazidine was not labeled for use in HFpEF.
Abstract 12381: Elevated Serum Carboxy-Terminal Telopeptide of Type I Collagen is Associated With Clinical Outcomes in Patients With Stable Angina Pectoris Undergoing Percutaneous Coronary Intervention
Authors: junya sato , Otaki yoichiro , Watanabe Tetsu , Tachibana Shingo , Kobayashi Yuta , Aono Tomonori , Saito Yuji , Goto Jun , Toshima Taku , Takahashi Tetsuya , Hashimoto Naoaki , Wanezaki Masahiro , kutsuzawa daisuke , Kato Shigehiko , Tamura Harutoshi , Nishiyama Satoshi , Takahashi Hiroki , Arimoto Takanori , Watanabe Masafumi
Published: June 2023

Background:
Despite high risk of developing cardiovascular events, it was reported to be difficult to predict clinical outcomes in patients with stable angina pectoris (AP). Serum carboxy-terminal telopeptide of type I collagen (I-CTP), a marker of collagen degradation, was reportedly associated with clinical outcomes in patients with acute coronary syndrome. However, clinical usefulness of I-CTP has not yet been elucidated in patients with stable AP. The aim of this study was to examine whether I-CTP can predict clinical outcomes in patients with stable AP.

Methods and Results:
Serum I-CTP levels were measured in consecutive 360 patients with stable AP undergoing percutaneous coronary intervention. All patients were divided into three groups according to serum I-CTP tertiles: low I-CTP group (≤4.4 ng/ml, n=120), middle I-CTP group (4.5-6.2 ng/ml, n=118), and high I-CTP group (≥6.3 ng/ml, n=122). The high I-CTP group was older and showed higher levels of brain natriuretic peptide (BNP) and lower levels of estimated glomerular filtration rate (eGFR) and left ventricular ejection fraction (LVEF) compared with other groups. During the median follow up period of 1,347 days, there were 68 cardiovascular events including all-cause deaths. Kaplan-Meier analysis showed that the high I-CTP group had the greatest risk for cardiovascular events among 3 groups. Univariate Cox proportional hazard regression analysis showed that age, multivessel disease, BNP, eGFR, LVEF, and I-CTP were significantly associated with cardiovascular events. Multivariate Cox proportional hazard analysis demonstrated that I-CTP was an independent predictor for cardiac events after adjusting for confounding risk factors.

Conclusion:
I-CTP could be the feasible marker for predicting cardiovascular events in patients with stable AP.
Abstract 12401: Short-term Pdl-1 and Ctla-4 Blocking Agent Therapy Reduces Myocardial Pampk and Il-10 Levels, Increases Vascular Nf-kb Expression and Serum Il-1 / Il-6 Levels
Authors: Maurea Nicola , De Lorenzo Claudia , Passariello Margherita , Buccolo Simona , Di Mauro Annabella , Cipullo Ciro , Bisceglia Irma , Caronna Antonietta , Quagliariello Vincenzo
Published: June 2023

Introduction:
Several strategies based on immune checkpoint inhibitors (ICIs) have been developed or are under investigation for cancer therapy, opening to advantages in cancer outcomes. However, several ICIs-induced side effects emerged in these patients, especially a rare but clinically significant cardiotoxicity with high rate of mortality.

Hypothesis:
We analyzed the differential vasculo and cardiotoxicity of Pembrolizumab, Nivolumab and Ipilimumab in preclinical models highlighting on the molecular pathways involved.

Methods:
C57 female mice were treated with Ipilimumab, Pembrolizumab or Nivolumab (15 mg/kg) through intraperitoneal injection for 10 days. pAMPK expression and vascular p65/NF-kB was analyzed through Immunohistochemistry. Cardiac and systemic levels of IL-1α, IL-1β, IL-2, IL-6 and IL-10 were quantified through ELISA method

Results:
In preclinical models, all ICIs increased p65/NF-kB expression in vascular endothelial cells of mice compared to saline group. IHC analysis indicates that ICIs reduced pAMPK expression in myocardial cells. Notably, tissue levels of IL-1α, IL-1β, IL-2, IL-6 were strongly increased in ICIs group vs saline (p<0.05 vs saline). On the other hand, levels of the anti-inflammatory cytokine IL-10 were strongly reduced ( overall reduction of 43.3-54.5 % vs saline)

Conclusions:
In preclinical models, a short treatment with ICIs is sufficient to confer a pro-inflammatory phenotype in the heart of mice. Furthermore, reductions in pAMPK indicate the inhibition of mitochondrial metabolism after ICIs. Furthermore ICIs induce chemokines involved in fibrosis, myocarditis and vascultitis. These results could indicate new therapeutic candidates aimed to prevent myocardial and vascular damages in cancer patients treated with ICIs
Abstract 12428: An Unwelcome House Guest: Coronary Aneurysms and Evolving Stemi
Authors: Holder Tara A , Cluckey Andrew , Fong Pete , Carr Jeffrey , Beckman Joshua A
Published: June 2023

Case Description:
54-year-old man presented to the Emergency Department (ED) three weeks after Covid-19 infection for progressively worsening dyspnea and hypoxemia. Dexamethasone and prophylactic apixaban (2.5mg twice a day) were initiated and he was discharged 48 hours later. A week after discharge he re-presented to the ED requiring 6L of oxygen (O
2
) despite uninterrupted dexamethasone and apixaban therapy. His past medical history was significant for quiescent IgG4 disease on Rituximab and Type 1 Diabetes. He was afebrile, tachycardic and tachypneic with decreased right lower lobe breath sounds. He had an elevated erythrocyte sedimentation rate and C-reactive protein, no leukocytosis and no pulmonary embolism of CT. He was admitted and vancomycin and cefepime antibiotic therapy for a superimposed bacterial pneumonia was begun. On day 12 of the hospital stay, he experienced new onset chest pain. Evaluation showed an elevated troponin and submillimeter ST segment elevation concerning for an evolving STEMI. Coronary angiography demonstrated an 90% diffuse mid LAD stenosis and two large coronary aneurysms of the left circumflex artery (LCx). The mid-LAD was stented using a 3.0 x 38 mm and 2.75 x 26 mm Onyx drug eluting stents with resolution of his chest pain. IgG4 serum level was normal and imaging did not demonstrate active IgG4 disease. He was discharged on aspirin and clopidogrel. Due to concern for a hypercoagulable state in the setting of Covid 19 infection, IgG4 disease and the large coronary aneurysms for thrombus formation, warfarin anticoagulation was also initiated. On review of his coronary imaging, the largest LCx aneurysm was 9mm on admission and 12mm three weeks later with evidence of diffuse coronary inflammation. CT Fractional Flow Reserve (abnormal ≤ 0.80) demonstrated decreased flow at the distal aneurysm with no focal stenosis to account for flow reduction.

Conclusion:
54-year-old man with IgG4 disease presenting with prolonged Covid-19 infection and acute NSTEMI. He was found to have large, flow limiting coronary aneurysms and inflamed coronary arteries all consistent with his IgG4 disease. Management of these aneurysms will be discussed.
Abstract 12440: Type 2 Diabetes, Chronic Kidney Disease, and 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:
Type 2 diabetes (T2DM) and chronic kidney disease (CKD) both confer a high risk of cardiovascular disease (CVD), and these conditions frequently coincide. The single and joint effects of T2DM and CKD on major cardiovascular events (MACE) in patients with established cardiovascular disease are unclear.

Hypothesis:
We hypothesize that T2DM and CKD are independent predictors of MACE in patients with established cardiovascular disease.

Methods:
We prospectively investigated 1738 patients with established cardiovascular disease - angiographically proven coronary artery disease (CAD) or sonographically proven peripheral artery disease (PAD) - over 10.0±4.7 years.

Results:
MACE occurred more frequently in T2DM patients (n=575) than in non-diabetic subjects (42.5% vs 29.8%, p<0.001) and in patients with CKD (eGFR <60ml/min/1.73m
2
; n=302) than in those who did not have CKD (52.2% vs 30.1%, p<0.001). When both, T2DM and CKD were considered, 996 subjects had neither T2DM nor CKD, 440 had T2DM but not CKD, 172 did not have diabetes but had CKD, and 130 had both T2DM and CKD. Compared to the incidence of MACE among patients with neither T2DM nor CKD (26.5%), MACE occurred more frequently in patients with T2DM who did not have CKD (38.2%; p<0.001) as well as in non-diabetic patients with CKD (48.0%; p<0.001); the incidence of MACE was highest in patients with both, T2DM and CKD (57.8%; p<0.001), in whom it was higher than in those with T2DM but not CKD (p<0.001) or those without T2DM but with CKD (p=0.007); the incidence of MACE was higher in non-diabetic CKD patients than in T2DM patients who did not have CKD (p=0.040). In Cox regression analysis, T2DM (HR=1.53 [1.29-1.83]; p<0.001) and CKD (HR=1.85 [1.51-2.26]; p<0.001) proved to be mutually independent predictors of MACE after adjustment for age, sex, BMI, hypertension, history of smoking, LDL-C, HDL-C and HbA1c.

Conclusions:
We conclude that T2DM and CKD in patients with established cardiovascular disease are mutually independent predictors of MACE. Cardiovascular disease patients with both CKD and T2DM are at an extremely high risk for MACE.
Abstract 12445: Association of Remnant Cholesterol With Incident Cardiovascular Disease Among Koreans: A National Population-Based Study
Authors: Lee Sang Jun , Kim Se-Eun , Go Tae-Hwa , Kang Dae Ryong , Kim Young-In , Jeon Ho-Seong , Cho Dong-Hyuk , Kim Jangyoung , Kim Sang Hyun , Ahn Sung Gyun
Published: June 2023

Aims:
We sought to investigate the association of remnant cholesterol (remnant-C) and low-density lipoprotein cholesterol (LDL-C) levels with incident atherosclerotic cardiovascular disease (ASCVD) in various subgroups among Koreans.

Methods:
National Health Information Database, collated by Korean National Health Insurance System, was used for analysis. Among the individuals between 40 and 70 years of age and without history of cerebro-cardiovascular disease, those who had twice or more health screenings between 2009 and 2011 were selected. All subjects were divided into 4 groups by LDL-C level of 3.4 mmol/L (130mg/dL) and remnant-C level of 0.8mmol/L (30mg/dL). The primary outcome was defined as the incidence of ASCVD.

Results:
3,686,034 individuals (45.6% women) fulfilled the study requirements. By the end of 2017, 144,004 ASCVD events occurred. High remnant-C and low LDL-C group was 19% of total. Compared with low remnant-C and low LDL-C group, the high remnant-C and high LDL-C group had highest ASCVD risk (HR 1.266, CI 1.243-1.289) and the high remnant-C alone group (HR 1.102, CI 1.087-1.118) had similar ASCVD risk to the high LDL-C alone group (HR 1.098, CI 1.083-1.113). The association of high remnant-C (≥0.8 mmol/L) with an increased ASCVD risk was consistent across various strata. Remnant-C levels remained significantly to associate with ASCVD after adjustment for several confounders, including LDL-C levels.

Conclusions:
Elevated remnant-C values, apart from LDL-C levels, were independently associated with a risk of incident ASCVD. Combination of high LDL-C and high remnant-C levels better predicted ASCVD incidence than each one alone. Therefore, we might take into account remnant-C measurement in risk stratification for primary prevention of ASCVD.
Abstract 12446: Effectiveness of a Digital Health Enabled Cardiac Rehabilitation Program in Reducing Recurrent Events For Private Health Insurance Patients in Australia
Authors: Braver Justin P , Yiallourou Stephanie R , Salim Agus , Keating Catherine , Carrington Melinda J
Published: June 2023

Introduction:
Secondary prevention programs are paramount to avoid cardiovascular disease morbidity and mortality. However, they are underutilized. Technology-enabled programs provide a new frontier to break down access barriers and enhance health service delivery. We implemented a telehealth program using a cardiac rehabilitation (CR) mobile app for privately insured patients following a hospitalization for coronary heart disease.

Hypothesis:
It was hypothesized that patients participating in a digitally-enabled CR program would have improved health behaviors and less recurrent events at 30-days to 12-months post discharge compared with propensity matched controls.

Methods:
Eligible patients received the Smart-CR mobile app, supplemented with telehealth consultations. Clinical and lifestyle changes, psychological well-being, quality of life and medication adherence were assessed at the beginning and 8-weeks following participation in the program. Using propensity matching methods, we compared rehospitalization and mortality rates of the digital-CR group (n=160) with a traditionally delivered CR group (n=115) and patients who did not undertake any form of CR (n=266).

Results:
Among 160 patients (35% regional/remote, 70% male and 78% aged over 60 years), physical activity levels increased from 128 minutes/week to 300 minutes/week and systolic blood pressure decreased by 5 mmHg. There were improvements in most other clinical, behavioral and lifestyle risk factors, including functional capacity, depression, anxiety, and quality of life. At 60 days, digital-CR reduced cardiac-related readmissions by 52% (RR 0.48; 95% CI: 0.24 to 0.93) compared to no CR. At 90 days, traditional CR decreased all cause readmissions by 36% (RR 0.64; 95% CI: 0.44 to 0.94) compared to non-attendance to CR. There were no other pairwise differences between groups at 30, 60 or 90 days. Health economic analyses and extended outcomes to 12 months post hospitalization are in process.

Conclusion:
A remotely delivered, technology-enabled CR program was effective in reducing hospital readmissions and improving cardiovascular risk. A randomized controlled trial is underway to test the generalizability of these findings in community participants.
Abstract 12458: Limb and Cardiovascular Events at 6 Months Among CLTI Patients Receiving Routine Care at BEST-CLI Sites: An Interim Report From the BEST-Registry
Authors: Weissler Hope , Patel Manesh R , Shah Nishant , Patterson Abigail , Rymer Jennifer A , MENARD Matthew , Drew Laura A , Mark Daniel B , Mena-Hurtado Carlos , Brooke Benjamin , Molnar Robert , Zayed Mohamed , Shah Samir , Kashyap Vikram S , Beckman Joshua , Laskowski Igor , Rosenfield Kenneth , FARBER Alik , Vemulapalli Sreekanth
Published: June 2023

Introduction:
Chronic limb-threatening ischemia (CLTI) affects 1-2 million Americans yet remains understudied. Existing CLTI trials focus on endovascular procedures and surgeries, maintain strict inclusion criteria, and may not fully capture the breadth of the CLTI population. We aimed to build a robust understanding of current treatments, outcomes, quality of life, and healthcare utilization among a diverse cohort of CLTI patients from across the United States.

Methods:
Designed as a companion to the BEST-CLI randomized trial, the BEST-Registry will prospectively enroll >1,000 CLTI patients at 40 U.S. BEST-CLI sites and follow their clinical courses for 12 months. Though initially, only patients ineligible for BEST-CLI were to be enrolled, BEST-Registry enrollment did not begin until after BEST-CLI enrollment ended. Baseline data including demographics, medications, and available hemodynamic data are collected as well as wound care regimens, interventions, and quality of life (VASCUQOL-6, EQ-5D, and SF-12). The primary adjudicated endpoint is major adverse limb events (MALE) defined as above-ankle amputation or major revascularization. Secondary endpoints include mortality, hospitalizations, MALE-free survival, and quality of life.

Results:
We will present 6-month adjudicated outcomes of 534 participants. The median age is 70.0 years [IQR 62.0, 77.0] and 35% are female (
Table
). Documented rates of hypertension (89%), diabetes (67%) and hyperlipidemia (78%) are high at baseline. Only 46.6% of patients had hemoglobin A1c and 38.8% LDL-c lab values available within a year. However, control of these two lab values was relatively good (
Table
).

Conclusions:
Patients with CLTI enrolled in the BEST-Registry are diverse, have complex disease, many comorbidities, and receive a variety of treatments. Registry data at 6 and 12 months will provide important context for the BEST-CLI trial results and characterize contemporary management and outcomes in CLTI.
Abstract 12483: Accurate QT Correction for Reliable Cardiac Risk Assessment
Authors: Räsänen Esa , Pukkila Teemu , Kanniainen Matias , Kim Jiyeong , Aalto-Setala Katriina , Potapov Ilya
Published: June 2023

Introduction:
In the electrocardiogram (ECG), the QT interval is one of the most important cardiac risk measures. For reliable interpretation, the QT interval must be corrected for the heart rate. Several approximative QT correction (QTc) models and methods have been developed. The most commonly used methods are the power-law formulas of Bazett and Fridericia, which are known to fail in various situations. It is generally accepted that no universally applicable QTc formulas can be constructed.

Methods:
We have developed a model-free QT correction method that minimizes the information transfer from the RR intervals (heart rate) to the QT intervals. This yields a reliable estimate for the true QTc. The resulting QTc values are compared to the conventional methods including Bazett, Fridericia, Hodges, and Framingham, and the individual QT correction. We use the ECG data of PhysioNet and the Telemetric and Holter ECG Warehouse (THEW).

Results:
Our method provides superior reliability and stability for QTc assessment. For healthy subjects in the PhysioNet database, the proportion of false positives for all the QTc intervals is only 3% with our method (Bazett: 16%; Fridericia: 10%). The pooled standard deviation is only 13 ms (Bazett: 32 ms; Fridericia: 28 ms; individual QTc: 24 ms). The figure shows a combined point cloud of RR and QT(c) intervals for the six longest recordings of the PhysioNet database.

Conclusions:
We find excellent potential in our QT correction to become the method of choice in QTc assessment. The method is applicable to all the ECG monitoring devices for clinical use, and it can be utilized in all the phases of drug development involving QT measurements.
Abstract 12485: Amniotic Fluid Level of NTproBNP as a Novel Biomarker of Heart Failure in Neonates and Infants
Authors: Uchida Hidetoshi
Published: June 2023

Background and Aim:
Recent advances in fetal echocardiography technology and its widespread use have made it possible to evaluate fetal cardiac function and heart failure more accurately, although there is a paucity of clinically useful biomarkers for the diagnosis of heart failure in neonates. N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in blood is one of the established biomarkers for heart failure and is known to be reduced exponentially after birth in children born full-term but not in premature infants. Nearly all (95%) NT-proBNP in the blood is excreted in urine. All amniotic fluid is replaced by fetal urine after the second trimester. The aim of this study was to investigate whether amniotic fluid NT-proBNP could be a potentially useful biomarker to assess severity of heart failure in neonates.

Methods:
We conducted a retrospective cohort study of 13 neonates, including 1 congenital heart disease patient not affected by chromosomal anomalies. We collected peripheral blood, umbilical vein blood, and amniotic fluid to assess each correlations: 1) between levels of umbilical vein blood NT-proBNP (uvNT/cre) and serum NT-proBNP (sNT/cre); 2) between levels of NT-proBNP in amniotic fluid(aNT/cre) and umbilical vein blood NT-proBNP (uvNT/cre); 3) between levels of NT-proBNP in amniotic fluid(aNT/cre) and serum NT-proBNP (sNT/cre).

Results:
Average gestational age for the subjects was 36±2.0 weeks and average birth weight were 2321.9±557.3g. 2 patients need treatment for heart failure. Our data revealed that there were very strong correlations between uvNT/cre and sNT/cre (R=0.970, p<0.05) as well as between aNT/cre and uvNT (R=0.712, p<0.05), between aNT/cre and sNT (R=0.685, p<0.05) respectively, in neonates.

Conclusion:
Our data demonstrated that aNT/cre could be a useful biomarker for diagnosing heart failure in neonates/fetuses after the third trimester.
Abstract 12487: Ex Vivo Assessments of Human Nodular Calcification: Optical Frequency Domain Imaging and Histopathology
Authors: Imanaka Takahiro , FUJII Kenichi , Hoshina Rin , Tanaka Hirokazu , Yoshihara Nagataka , Kimura Toshio , Miki Kojiro , AKAHORI HIROKUNI , Kawakami Rika , Kawai Kenji , Hao Hiroyuki , Ishihara Masaharu
Published: June 2023

Introduction:
It has been reported that a nodular calcification is associated with a calcified nodule and the reappearance of in-stent failure after percutaneous coronary intervention.

Hypothesis:
This study evaluated characteristics of nodular calcification on optical frequency domain imaging (OFDI) image in comparison to histopathology.

Methods:
One hundred and seven matched OFDI and histopathological cross-sections from 13 coronary arteries of 5 human autopsy hearts were evaluated. In histopathological assessment, a nodular calcification was defined as a fragmented calcification with accumulated fibrin. In OFDI analysis, calcification arc, shape of luminal surface, lumen side shape of calcification, irregularity of lumen surface, and irregularity of calcification surface of lumen side were analyzed in each OFDI image.

Results:
There were 10 nodular calcifications and 97 non-nodular calcifications in histopathological slices. The calcification arc was significantly smaller in nodular calcification than in non-nodular calcification [89.5° (56.4-108) vs. 126° (82.0-190), p =0.02]. OFDI features of a nodular calcification were characterized by a convex shape of the luminal surface (90.0% in nodular calcifications vs. 6.2% in non-nodular calcifications, p <0.01), a convex shape of calcification (90.0% vs 18.6%, p <0.01), an irregular luminal surface (50.0% vs 0%, p <0.01), and an irregular calcification surface of lumen side (60.0% vs 3.1%, p <0.01).

Conclusion:
This study suggests that OFDI has a potential capability to distinguish between nodular calcification and non-nodular calcification based on angle of calcification, shape and irregularity of luminal surface and those of calcification.
Abstract 12499: Anomalous Coronary Arteries Are Associated With Ischemia in the Ischemia Trial
Authors: Jaspan Vita , Leipsic Jonathon A , Nemeth Hayley , Mancini G B , Budoff Matthew , Hague Cameron , Min James , Shaw Leslee J , Berman Daniel , Picard Michael , Chaitman Bernard R , Kwong Raymond Y , OBrien Sean , Hochman Judith S , Maron David J , Reynolds Harmony
Published: June 2023

Introduction:
Coronary anomalies are detected in 0.3-2.3% of patients undergoing coronary computed tomography angiography (CCTA). Data are scarce on atherosclerosis severity in anomalous arteries and relationship to ischemia on stress testing.

Hypothesis:
High risk features of anomalous coronary arteries are associated with ischemia, even in the absence of coronary stenosis on CCTA.

Methods:
5,903 participants enrolled in the ISCHEMIA trial program with site-determined moderate or severe ischemia underwent CCTA. A core laboratory assessed atherosclerosis severity and made note of anomalous coronary origin. A single reader at the CCTA core laboratory re-evaluated all identified anomalies to assess high risk features and origin, blinded to stress test results. Patients were excluded if stress test results were unavailable. We assessed the relationship between type of anomaly and vessel with ischemia in the subtended territory on stress imaging, and stenosis severity.

Results:
There was anomalous origin of a coronary artery in 56 of 5,903 CCTA cases (0.9%). Age, sex and CAD risk factors were similar between patients with vs. without anomalies. Anomalous origin affected the left circumflex (LCX) in 28, right coronary artery (RCA) in 21, left main (LM) in 4, and left anterior descending (LAD) in 3. Ischemia was severe on stress testing in 58.2%, moderate in 34.5%, mild in 3.6% and absent in 3.6%. High risk anomalies were present in 17/56 (30.3%, 16/21 RCA and 1/4 LM), including inter-arterial course in 28.6%, intra-mural course in 1.8%, and slit-like orifice in 12.5%. Most anomalous coronaries (82.9%) were associated with ischemia in the subtended territory. Among anomalies associated with ischemia, 37.9% had <50% stenosis and 62.1% had <70% stenosis (Figure). Of those with <70% stenosis, 27.6% had high risk features.

Conclusions:
Anomalous coronary arteries in stable patients are associated with ischemia, even in the absence of severe atherosclerotic disease.
Abstract 12509: Characterization and Risk Factors for Death or Transplant After Stage Ii/glenn Palliation in Infants With Single Ventricle Heart Disease
Authors: Bucholz Emily M , Lu Minmin , Vergales Jeffrey , Bingler Michael , Ronai Christina , Anderson Jeffrey B , Lihn Stacey , Lannon Carole , Bates Katherine E , Reynolds Lindsey , Sleeper Lynn A , Brown David W
Published: June 2023

Background:
Infants with single ventricle heart disease have a 20% mortality rate during the first year of life with most deaths occurring prior to Stage II/Glenn. Although the time after the Stage II procedure is believed to be a lower risk period, significant morbidity and mortality may occur during this time.

Methods:
Retrospective cohort analysis of infants enrolled in the National Pediatric Cardiology Improvement Collaborative who underwent staged single ventricle palliation from 2016-2021 and survived to Stage II operation. Multivariable logistic regression and classification and regression tree analysis were performed to identify risk factors for the composite of mortality or transplantation between Stage II surgery and the first birthday. Candidate variables (n=75) included sociodemographic, prenatal, birth, anatomic, stage I intra- and post-operative, interstage course, and Stage II operative characteristics.

Results:
Of the 1455 patients in the cohort who survived to Stage II, the overall event rate was 7% (76 (5%) died and 34 (2%) were referred for transplant). Overall event rates at 30 and 100 days after Stage 2 were 2% and 5%, respectively (
Figure 1A
). Independent risk factors for mortality and transplantation included shunt type and AV valve repair at Stage I, ECMO and reintubation after Stage I, pre-operative weight and ≥ moderate AV valve regurgitation prior to Stage II, Stage II cross-clamp time, and comprehensive Stage II surgery (
Figure 1B).
Patient race/ethnicity and socioeconomic status were not associated with worse outcome.

Conclusions:
Mortality rates after Stage II surgery to 1 year of age remain high ~5%. Some of the risk factors identified have been shown to also predict interstage mortality, whereas others (reintubation, pre-operative weight, and Stage II characteristics) may be unique to the period after Stage II. Further research is needed to understand whether risk factor modification results in improved transplant-free survival.
Abstract 12528: Variants in Solute Cation Transporters 3 Associate with High Lp(a) Levels Independent of Apo(a) Isoform Size
Authors: Ismail Lamia , Black Michael , Williams Michael , Coassin Stefan , Forer Lukas , Kronenberg F. , McCormick Sally
Published: June 2023

Introduction:
Lipoprotein (a) [Lp(a)] consists of a low-density lipoprotein (LDL) molecule attached to apolipoprotein(a) [apo(a)]. Apo(a) comprises two kringle domains (KIV and KV) derived from the plasminogen gene and an inactive protease domain. The KIV domain is subdivided into 10 subtypes (KIV1-10), with KIV2 occurring as a copy number variation (CNV) that varies among individuals. Elevated Lp(a) levels are a major risk factor for CVDs and are inversely correlated to the KIV2 CNV determining apo(a) isoform size.
Objectives:
This study aimed to identify variants associated with a high Lp(a) phenotype that were not linked to apo(a) isoform size.

Methods:
Illumina sequencing of 13 candidate genes was performed on a discovery set comprising 54 high Lp(a) European samples (>50mg/dL). The sequenced genes included LPA, adjacent genes, and those coding for receptors involved in Lp(a) uptake. Variants commonly found in high samples were genotyped in the Otago LPA European cohort (n=589) and their association with Lp(a) levels was checked via Kruskal-Wallis and linear regression statistical models. The associations were then replicated in the much bigger German Chronic Kidney Disease (GCKD) cohort (n=4930).

Results:
Nine variants were significantly associated with high Lp(a) levels. Two variants were in the LPA gene (rs3124784 and rs3798220) and seven were in neighbouring genes (rs2282143 in SLC22A1, rs3127592, rs3127593, rs3103353 and rs3127594 in SLC22A2 and rs1810126 and rs3088442 in SLC22A3). Interestingly, the minor allele of all nine variants was significantly associated with increased LPA expression in liver tissues in the GTEx database. Seven of the variants were significantly associated with small apo(a) isoform size (P=1x10-4 to 2.9x10-18), while rs1810126 and rs3088442 in SLC22A3 were not associated with the small isoform size (P=0.43 and 0.42).

Conclusion:
Nine variants in the LPA and nearby genes were significantly associated with elevated Lp(a) levels and increased LPA expression, with the majority being linked to a short apo(a) isoform. The association of two SLC22A3 gene variants with Lp(a) levels independent of apo(a) isoform size warrants further investigation to establish any functional connection between LPA and this gene.
Abstract 12535: Associations Between Apolipoprotein (b) and Lipoprotein (a) With Coronary Calcium Scoring
Authors: Hajj Ali Adel , Zheng Wynne , Nakhla Michael , Cho Leslie , Seballos Raul , Lang Richard S , Feinleib Steven , Flamm Scott D , SCHOENHAGEN Paul , Wang Tom Kai Ming K , Nissen Steven E , Desai Milind Y
Published: June 2023

Introduction:
Apolipoprotein B (ApoB) and Lipoprotein a (Lpa) are emerging as important markers of coronary artery disease (CAD). In subjects without documented CAD, we assessed the association between ApoB and Lpa with coronary artery calcium scoring (CACS).

Methods:
We included 5324 subjects (age 57±8 years ,76% male & 87% white) referred for CACS in a primary prevention clinic between 3/2016 and 10/2021. 10-year multiethnic study on subclinical atherosclerosis CACS (MESA-CACS) risk score was calculated as 0, 1-4.99, 5-9.99 and >10%. ApoB (mg/dl) was divided into <104, 104-127 and >127, while Lpa (mg/dl) was divided into≤40 and >40. Additionally, Lpa was divided based on 60, 70 and 90 mg/dl cutoffs.

Results:
ApoB was significantly associated with MESA-CAC risk score (p<0.001); while Lpa had a borderline association (Table) (p=0.09). A significantly higher proportion of subjects with normal ApoB were in 0 MESA-CACS risk category (87%), with no difference in other risk categories (Figure 1A). Almost 25% patients with 0 MESA-CACS had Lpa of >40, with no significant difference between normal vs. elevated Lpa across MESA-CACS categories (Figure 1B). No significant difference was noted among the MESA-CACS categories with p-values of 0.284, 0.672 and 0.392 for Lpa cutoffs of 60, 70 and 90 mg/dl respectively. Despite a CACS of 0, 793 (15%) subjects had Lpa>40, while 690 (13%) had a CACS >75th percentile despite Lpa≤40.

Conclusions:
ApoB was significantly associated with MESA-CACS score, while Lpa only showed a weak association. Hence the addition of Lpa could add synergistic value to CACS in atherogenic risk. stratification

Fig1
Distribution of ApoB (A) and Lpa(B) across MESA-CACS groups
Abstract 12536: Type A Aortic Dissection in a Young Marfanoid Filipino Male Eventually Developing Fungal Mediastinitis: A Case Report
Authors: Perez Ray Z , Lasco Jun Maximo F
Published: June 2023

Introduction:
Aortic Dissection (AD) results from a tear between the layers of the aorta. This is often seen among older males or those with heritable connective tissue disorders, and it mostly presents as chest pain. Management involves surgical repair wherein post procedure complications are to be expected. Mediastinitis, or deep sternal wound infection, however, is likewise unusual.

Case Presentation:
We present a case of a 29-year-old Filipino male presenting with sudden diffuse abdominal pain; he had no comorbidities and had no significant history suggestive of connective tissue disorders. Physical examination was mostly unremarkable. CT Aortogram revealed presence of dissection from the proximal ascending aorta up to the common iliac arteries, with the entry tear measuring 8.5mm at the level of T5, with extension to the proximal branches of the aortic arch, both common carotid arteries, right renal, right internal and external iliac arteries. Echocardiogram also showed a normal aortic valve but with dilated sinus of Valsalva(4.5cm, z-score 5.13). The patient underwent a Modified Bentall Procedure with Cabrol Shunt, with delayed closure of operative site due to extensive bleeding. Cystic medial necrosis was not seen on biopsy. After developing persistent post-operative fever, repeat chest CT showed a fluid collection in the mediastinum encasing the ascending aorta and main pulmonary trunk; culture of abscess fluid was positive for
Candida tropicalis
. He was then given prolonged parenteral followed by oral antifungal therapy and subsequently discharged improved.

Discussion:
Vascular causes of abdominal pain should be considered in patients with scant history and physical findings. Major vascular surgery has expected complications such as bleeding and infection; the management of such complications should incorporate a multidisciplinary approach as in such cases, a trial of medical management may be safer than repeat surgery.
Abstract 12554: Hipsc Derived Cardiomyocytes for Mechanistic, Patient Tailored Treatment in a Novel Mutation Linked to Cpvt
Authors: Goehringer Noah , Stachelscheid Harald , El-Battrawy Ibrahim , Ludwik Katarzyna , Boldt Leif-Hendrik , Parwani Abdul , Pieske Burkert , Heinzel Frank , Hohendanner Felix
Published: June 2023

Background:
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a disease related to altered ryanodine receptor (RyR) mediated SR Ca
2+
leak and associated with sudden cardiac death in young adults. We recently identified a family with a mixed phenotype of CPVT and long-QT-syndrome (CPVT3*) related to a novel mutation in the trans-2.3-enyol-CoA reductase-like (TECRL) gene. Ventricular arrhythmia burden varies greatly between individual CPVT3* patients.

Methods/Results:
We generated human induced pluripotent stem cell derived cardiomyocytes (iPSc-CM) from a control and CPVT3* patient to explore underlying mechanisms and individualize pharmacological treatment. iPSc-CM were studied using confocal Ca
2+
imaging (fluo-4). Ca
2+
signaling during excitation-contraction coupling was studied in the presence of different clinically available modulators of RyR mediated SR Ca
2+
leak. In particular, cardiomyocyte function and arrythmias were tested upon addition of the class Ic antiarrhythmic flecainide (10μM), the RyR stabilizer dantrolene (1μM), the betablocker R-Carvedilol (1μM), the kinase inhibitor Rimacalib (10μM) and the RyR-Calstabin interaction stabilizer S107 (10μM). Under baseline conditions, CPVT3* iPSc-CM showed significantly decreased Ca
2+
transient (CaT) amplitudes and increased CaT duration. Upon addition of the beta-agonist isoproterenol (ISO, 100nM), CaT amplitudes and pro-arrhythmogenic Ca
2+
release (i.e. Ca
2+
sparks) significantly increased in CPVT3* as compared to control. All pharmaceuticals altered Ca
2+
signaling in CPVT3* in a substance dependent manner and pro-arrhythmogenic Ca
2+
release was particularly mitigated upon addition of flecainide. Treatment of the CPVT3* patient with flecainide significantly reduced ventricular premature beats as determined by 24 hour holter-ECG monitoring.

Conclusion:
We quantitatively assessed drugs targeting RyR mediated SR Ca
2+
leak in a CPVT3* patient with a novel TECRL mutation using iPSc-CM. Favorable in-vitro results of flecainide were mirrored in a significant reduction of ventricular arrhythmia in-vivo. Our results underscore the potential of iPSc-CM for the development of patient-tailored treatment in genetic arrhythmia syndromes.