bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16902: The Effect of Kidney Function on Antithrombotic Regimen Among Patients With Atrial Fibrillation and Acute Myocardial Infarction: Insights From the National Cardiovascular Disease Registry’s Acute Coronary Treatment and Intervention Outcomes Network Registry
Authors: Wong Jonathan M , Rymer Jennifer A , Chen Anita Y , Wang Tracy Y , Shaw Richard E
Published: April 2024

Introduction:
The impact of kidney function in selecting antithrombotic therapy at hospital discharge for patients with atrial fibrillation (AF) who survive an acute myocardial infarction (AMI) is uncertain.

Hypothesis:
We hypothesized that kidney dysfunction is associated with decreased oral anticoagulant (OAC) use in AF patients who survive AMI.

Methods:
We studied 30,308 AF patients at 791 hospitals who survived AMI and were hospitalized between January 2015 and December 2017 (Acute Coronary Treatment and Intervention Outcomes Network Registry). We separated patients into 4 mutually exclusive groups: triple antithrombotic therapy (TAT), dual-antiplatelet therapy (DAPT), dual antithrombotic therapy excluding DAPT (DAT), and single therapy. Logistic regression was used to explore the trend for each antithrombotic strategy across CKD stage.

Results:
Of the 30,308 patients included in this analysis, 6,618 were on TAT (22%), 12,920 on DAPT (43%), 6,148 on DAT (20%), and 4,622 were on single therapy (15%). Overall, 46% of patients were discharged on an OAC (warfarin 22%; apixaban 14%; rivaroxaban 8%; dabigatran 2%). Patients with higher CHA
2
DS
2
-VASC scores (≥4) were more likely to be discharged on oral anticoagulation, except patients with GFR < 15 ml/min/1.73m
2
. Compared to patients with normal kidney function, patients with GFR < 30 ml/min/1.73m
2
had lower rates of TAT use (23% vs. 18%) despite higher warfarin use (20% vs. 27%). Within each antithrombotic discharge strategy, there was no significant trend across GFR strata among patients with in-hospital PCI (
Figure
).

Conclusion:
Significant heterogeneity in antithrombotic discharge strategy was seen among AF patients who survived AMI, however, the trend of each strategy across CKD stage was not significant among patients with in-hospital PCI. More research is needed to understand whether a particular antithrombotic strategy has improved outcomes in this population.
Abstract 16906: Cangrelor versus Standard Therapy in Patients With ST-Segment Elevation Myocardial Infraction
Authors: Abo-Aly Mohamed , George Bennett , Smyth Susan S , Abdel-Latif Ahmed , Ziada Khaled
Published: April 2024

Introduction:
ST-segment myocardial infraction (STEMI) is associated with intense platelet (PLT) activation resulting in microvascular obstruction, inflammation and myocardial damage.

Hypothesis:
The impact of intense PLT inhibition with cangrelor during primary percutaneous coronary intervention (PPCI) in STEMI patients on PLT mediated inflammatory response has not been studied.

Methods:
We randomized 20 STEMI patients undergoing PPCI and who received aspirin + ticagrelor to receive intravenous cangrelor (n=11) or placebo (n=9) prior to PPCI. PLT reactivity units (PRU) were evaluated at baseline (prior to randomization), 10 minutes after initiating therapy and at the end of PPCI. Circulating inflammatory cells and PLT-inflammatory cell aggregates (cells/μl of peripheral blood) were evaluated using flow cytometry.

Results:
Compared to placebo, cangrelor significantly reduced PRU starting 10 minutes after administration. Cangrelor significantly reduced classical (inflammatory) monocytes: CD14++/CD16- (1193 ± 205.7 vs. 2024 ± 312.8; p<0.05), classical monocyte-PLT aggregates: CD14++/CD16-/ CD42+ (334.1 ± 50.35 vs. 580.6 ± 112.2; p<0.05), granulocytes (11040 ± 1545 vs. 24991 ± 7511; p<0.05), and granulocytes-PLT aggregates (1646 ± 203.1 vs. 3949 ± 985.1; p<0.05) compared to the control group (
Figure
). Cangrelor was associated with a trend towards a reduction in cardiac enzyme and inflammatory cytokine levels.

Conclusion:
Adding Cangrelor to standard antiplatelets in STEMI patients undergoing PPCI provided more intense platelet inhibition and reduced inflammation. This strategy may result in less myocardial damage. The clinical impact of intense platelet inhibition is currently being evaluated in our full cohort (NCT0304327).
Abstract 16942: Reduced Gastrointestinal Bleeding in Patients With Improved Left Ventricular Function After Left Ventricular Assist Device Implantation
Authors: Mandawat Aditya , Mandawat Anant , Vijayvargiya Priya , Karra Ravi
Published: April 2024

Introduction:
Gastrointestinal bleeding (GIB) after continuous-flow left ventricular assist device (CF-LVAD) implantation is common, with an incidence estimated at 18-40% per year. While the pathophysiology of GIB in these patients is unclear, physiologic changes related to the absence of pulsatility may account for the high rates of GIB seen in these patients.

Hypothesis:
Improved left ventricular (LV) function (increased myocardial pulsatility) after LVAD implantation may be associated with decreased rates of GIB.

Methods:
We studied 119 consecutive patients with CF-LVADs implanted between March 2006-November 2016 who received serial transthoracic echocardiograms (TTE), including at least one pre-implant and one post-implant TTE. Left ventricular ejection fraction (LVEF) was assessed by experienced readers, with a kappa statistic between readers >0.90. Improved LV function was defined as an improvement of at least 7% between the pre-implant LVEF and the best post-implant LVEF obtained with 9 months of the implantation date. Similarly, worsening LV function was defined as a decrease of at least 7%. Primary GIB was defined using INTERMACS adverse event criteria. Patients were followed until transplantation, device complication requiring explantation, or death.

Results:
The study sample was 58±12 years old, 72% male, and 63% Caucasian. Hemoglobin at implantation was 11±2 g/dL. Maximum LV recovery was seen a median of 103 (IQR 49-158) days after LVAD implantation. Improved LV function occurred in 25 (21%) patients, while LVEF remained stable or worsened in 94 (79%) of patients. When compared with patients whose LVEF remained stable or worsened, patients with improved LV function were more likely to be female (p=0.05). GIB occurred in 29 patients (24%). Improved LV function was associated with a significantly decreased risk of GIB (Figure; p=0.05).

Conclusions:
Improved LV function is seen in one-fourth of patients and is associated with a significantly decreased risk of GIB following CF-LVAD implantation.
Abstract 16961: KLF15 Regulates the Circadian Susceptibility to Ischemia Reperfusion Injury in the Heart
Authors: Li Le , Li Hui , Tien Chih-Liang , Zhang Rongli , Liao Xudong , Jain Mukesh K. , Zhang Lilei
Published: April 2024

The onset and the injury of heart attacks show a circadian rhythmicity with a peak during the sleep to active transition. Studies using cell type specific clock mutant demonstrated the intrinsic varying susceptibility of the cardiomyocytes to the ischemia reperfusion (I/R) injury, however, the molecular mechanisms remain unclear. Recently, we show that transcription factor KLF15 coordinates the diurnal expression of catabolic genes in the heart during the active phase. Here we show that cardiomyocyte specific KLF15 deficient mice have exaggerated I/R injury in vivo during the sleep to active transition but not the active to sleep transition, demonstrating its critical role in governing the circadian rhythmicity of myocardial injury. We found acute KLF15 deficiency in the primary cardiomyocytes is associated with increased ROS and exaggerated susceptibility to oxidative stress, which can be rescued by a MnSOD mimetic Tempol. We further demonstrate that KLF15 deficiency in the cardiomyocytes in vitro and in vivo are both associated with increased acetylation of MnSOD
K122
, which leads to reduced MnSOD activity. There is no change in mitochondrial sirtuin SIRT3 level, the main deacetylase for MnSOD
K122
, however its co-enzyme NAD
+
level and NAD
+
/NADH ratio are drastically reduced with KLF15 deficiency. We show that NAD
+
precursor NMN rescues the increased susceptibility to ROS in KLF15 deficient cardiomyocytes in vitro in a SIRT3 dependent fashion and rescues the increased cardiac I/R injury of KLF15 deficient mice specifically at ZT14. We show that KLF15 directly regulates nicotinamide phosphoribosyltransferase (NAMPT), the rate limiting enzyme of NAD
+
salvage pathway and the NAD
+
determinant in the heart. We found a strong circadian rhythmicity of NAD
+
level and mitochondrial acetylation in the heart. The beginning of the active phase is associated with increased expression of KLF15, NAMPT, NAD
+
, and reduced acetylation at MnSOD
K122
. Collectively, our results demonstrate that KLF15 coordinates cardiac metabolism and ROS clearance in a circadian fashion through mitochondrial NAD
+
; loss of KLF15 expression in ischemic cardiomyopathy likely contributes to an enhanced susceptibility to additional I/R insult in a time-of-the-day dependent fashion.
Abstract 16972: Introducing Advance Care Planning Into the Transition Process: The ACHD Patient Perspective
Authors: Edwards Lindsay A , Hansen Katherine , Sillman Christy , Dong Emily , Scribner Caroline , Romfh Anitra , Lui George K , Fernandes Susan M
Published: April 2024

Introduction:
The goal of the transition process from pediatric to adult care for congenital heart disease (CHD) patients, in additional to uninterrupted care, is to educate adolescents and young adults (AYAs) about their health and encourage them to develop strong self-care, decision-making, and communication skills. Adults are expected to voice their own values, opinions, and healthcare goals, especially when it comes to end-of-life (EOL) care, and, thus, it has been suggested to introduce advance care planning (ACP) into the transition process. To help inform timing of first ACP, we asked ACHD patients to share their opinions.

Methods:
Patients seen in the outpatient ACHD clinic from April-May 2018 completed a survey assessing their ACP preferences. Disease severity was recorded as simple, moderate, or complex. Health literacy was assessed with The Newest Vital Sign tool. Mann-Whitney U and Fisher’s exact tests were used to evaluate associations between demographics, health literacy, disease complexity, perceived health status and ACP preferences.

Results:
Forty-five patients (median age 37.6y, range 19.8-71.9y; 58% female; 67% Caucasian) were included. Disease complexity was moderate in 51% and severe in 39%, and 82% enrollees considered themselves in good health. Most (76%) thought ACP was
moderately
or
extremely
important. Regarding timing of ACP, 76% thought ACP should be discussed
before getting sick, while healthy
or
when first diagnosed with a life-threatening illness
. Participants reported that in late adolescence (16+) or early adulthood, AYAs with CHD are capable of knowing their EOL care wishes (68%), and ACP discussions should be introduced (76%). While higher income was associated with ACP importance, no demographic or disease complexity associations were found for ACP preferences.

Conclusions:
Adults with ACHD report that ACP is of high importance and should be discussed early in the disease course; however, they believe that it is not until late adolescence or early adulthood that AYAs are truly capable of knowing what kind of EOL care they want, and that ACP discussions should be initiated at this age. This valuable insight informs provider understanding of when ACP conversations can appropriately be initiated.
Abstract 16974: Experimental Insights Into Transapical Neochordplasty: A Quantitative Examination of Neochord Placement Using an
Ex Vivo
Left Heart Simulator
Authors: Imbrie-Moore Annabel M , Paulsen Michael J , Bae Jung H , Farry Justin M , Wang Hanjay , Hironaka Camille E , Edwards Bryan B , Thakore Akshara D , Lucien Haley J , Deschamps Daniela M , Kulkarni Rohun , Cutkosky Mark R , Woo Y. J
Published: April 2024

Introduction:
Neochordoplasty is an important repair technique, though the optimal anchoring position is unknown. While typically anchored at papillary muscles, new percutaneous devices anchor the chordae at or near the ventricular apex, which we hypothesize will result in significantly higher forces on the chordae and neochord.

Methods:
Porcine mitral valves were dissected (n=3) and mounted in a custom 3D printed left heart simulator generating physiological pressure and flow. Hemodynamic and echocardiographic data were collected, and chordal forces were measured using Fiber Bragg Grating (FBG) strain gauge sensors. Isolated MR was induced by cutting P2 primary chordae resulting in prolapse. Regurgitant valves were then repaired with a PTFE neochord with transapical fixation, followed by papillary fixation for comparison. In both cases, the neochord was anchored to a customized force-sensing post positioned to mimic in vivo placement (
Fig. A
).

Results:
Hemodynamic and echocardiographic data confirmed that both techniques resulted in elimination of MR in all valves and restoration of physiologic hemodynamics. Peak forces on the chordae and neochord were lower for papillary than the transapical fixation (p=0.04). Force tracings were compiled for each class of chordae at baseline, after prolapse, and after both repair techniques (
Fig. B
). The maximum dF/dt for the neochord suture was 30.6 N/s with the papillary fixation and 51.7 N/s with the transapical fixation. These may translate into increased stress on the mitral valve apparatus.

Conclusions:
Transapical fixation results in higher peak forces on the chordae and noechord suture as well as an increased rate of loading on the neochord when compared to the papillary muscle fixation and may influence repair durability.
Abstract 16981: Prevalence of Primary Severe Hypertriglyceridemia in Olmsted County, Minnesota: A Community-Based Study
Authors: Sandhyavenu Harigopal , Pasha Ahmed , Farwati Medhat , Bailey Kent , Kullo Iftikhar
Published: April 2024

Introduction:
Severe hypertriglyceridemia (SHTG), defined as plasma triglyceride (TG) level ≥ 500 mg/dl, is a risk factor for cardiovascular disease. In the NHANES dataset (2001 - 2006), the prevalence of SHTG was 1.7%. However, the prevalence of primary SHTG in the community is unknown. We conducted a community-based study to estimate the prevalence of primary SHTG, in Olmsted County, Minnesota.

Methods:
We used the Rochester Epidemiology Project (REP) records linkage system to identify individuals with TG ≥ 500 mg/dl between 1998-2015. Index date was defined as the first documentation of TG ≥500 mg/dl during the study period. We excluded individuals with mixed hyperlipidemia (TG ≥500 mg/dl and non-high density lipoprotein (HDL) cholesterol ≥190 mg/dl). HTG was defined as secondary in the presence of hypothyroidism, biliary obstruction, nephrotic syndrome, uncontrolled diabetes, pregnancy, liver disease, renal failure, BMI ≥35 and medication use (isotretinoin, tetracyclines, anti-retrovirals). Primary HTG was defined as absence of an identifiable secondary etiology. Characteristics of the primary SHTG individuals were ascertained from the electronic health record.

Results:
SHTG was identified in 3802 individuals of whom 2511 had mixed hyperlipidemia, 743 had a secondary cause for SHTG and the remaining 548 had primary SHTG. Using the 2015 population census of 151,436 for Olmsted County, the prevalence of SHTG was 2.5%, of secondary SHTG was 0.49% and of primary SHTG was 0.36%. Only half of the primary SHTG group had a diagnosis of dyslipidemia in the electronic health record and 44.3% were on lipid-lowering therapy on index date. Characteristics of individuals with primary SHTG are summarized in Table 1.

Conclusions:
These data highlight that primary SHTG is relatively common (≈1 in 300, similar to the prevalence of familial hypercholesterolemia), underdiagnosed and undertreated.
Abstract 16990: Impact of 2013 ACC/AHA Cholesterol Management Guidelines on Statins Use Among Nationally Representative Adult Populations in United States: Medical Expenditure Panel Survey (2010-2015)
Authors: Salami Joseph A , Saxena Anshul , Warraich Haider , Khera Rohan , Okunrintemi Victor , Valero-Elizondo Javier , Blaha Michael J , Blankstein Ron , Virani Salim S , Veledar Emir , Krumholz Harlan M , Nasir Khurram
Published: April 2024

Background:
The 2013 American College of Cardiology/American Heart Association (ACC/AHA) Cholesterol Management Guidelines recommended statin as the first-line lipid-lowering therapy (LLT) for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). We aim to examine the impact of the guidelineson statin use in the US.

Methods:
Using the2010-2015 Medical Expenditure Panel Survey (MEPS) data, we estimated trends in statin utilization in adults age 40-75 years in 4 defined groups: (1) All adults, adults with: (2) established ASCVD, (3) diabetes mellitus [DM] and no ASCVD and, (4) estimated 10-year risk >=7.5% in absence of ASCVD and DM. Joint-point regression (JPR) analysis was used to examine changes in statin use trend around the period of the guideline’s publication.

Results:
We found no statistically significant change in statin use. (Figure) The use of any statin therapy in 2010-2012 ranged from 24.6 to 25.1%, and 24.6 to 25.1% in 2014-2015 among all adults. Statin use among those with ASCVD ranged from 58.8 to 56.6% (2010-2012) and 56.7-57.8% (2014-2015). Similar trends were noted in our two other study groups. However, a significantly higher proportion of statin users among established ASCVD patients reported use of high intensity doses: 34.3 to 38.1% post- versus 29.6 to 31.6% pre-guideline publication with an average annual percentage change (AAPC) of 4.9 (95% CI: 2.9-6.9). (Figure) Joint point regression showed no statistically significant inflection in the trend line of all and high-intensity statin use in any of the study groups after guideline publication.

Conclusion:
There was a mild increase in high-intensity statin use after the 2013 ACC/AHA guidelines release, but no impact on overall statin use in US two years after publication. Barriers to guideline adoption and opportunities to increase the impact of guidelines on clinical practice need to be investigated.
Abstract 12369: Adolescents With Eating Disorders Undergo Cardiac Remodeling
Authors: Ross Samuel W , Fisher Martin , Kulkarni Aparna
Published: April 2024

Introduction:
Patients with eating disorders (ED) such as anorexia and bulimia nervosa are known to have increased cardiac mortality. The exact etiology of this predisposition is unclear.

Hypothesis:
ED pts have changes in their cardiac structure and function in adolescence that may alter their outcomes.

Methods:
All ED pts who had an echocardiogram between Jan 2005 - Dec 2020 were included. Patients with congenital heart disease and with poor image quality were excluded. Measurements of systolic and diastolic indices, including mass and volume (5/6 area length method) were made. Standard statistics were performed and pts with BMI
<
5% (LBMI) (n=40) were compared to pts with BMI >5% (NBMI, n=36) using Student’s t test. A p value
<
0.05 was considered significant.

Results:
In all, 78/136 pt echos met inclusion criteria. The median age was 16 (12-20) years. The mean BMI was 16.8
+
2.8 kg/sq.m. (LBMI 14.7
+
1.7, NBMI 19.2
+
2.1, p <0.01). Overall, left ventricular mass indexed (LVMI) was 23.2
+
6.8 gm/^height*2.7 with lower LVMI in LBMI (21.8
+
8) than NBMI (24.5
+
5; p=0.05). LV diastolic volumes were higher in LBMI pts (92.1
+
28.9 ml, z score -0.5
+
1.2) than NBMI pts (106
+
26 ml, z score -1.01
+
1.33; p=0.05)(overall 99.4
+
28.2 ml). Concurrently, ejection fraction was higher in LBMI pts (62
+
7% vs NBMI 58
+
5%; p=0.02) (overall 60
+
6%). Diastolic function was within normal range but different between the groups, consisting of mitral valve E/A (LBMI 2.7
+
1.04 vs NBMI 2.3
+
0.7; p=0.05)(overall 2.5
+
0.9), lateral E/e’ (LBMI 5.5
+
1.5 vs NBMI 4.5
+
1.3; p <0.01) (overall 5.0
+
1.5). Left atrial indexed volumes were similar between the groups (LBMI 18
+
6.5 vs NBMI 17.7
+
6.8; p=0.44)(overall 17.9+6.6). Aortic root z scores were higher in LBMI pts (0.01
+
1 vs NBMI -0.4
+
0.8; p=0.03)(overall -0.2
+
0.9). Other abnormalities on echo included mitral valve redundancy/regurgitation in 18% (5 LBMI, 9 NBMI), mild aortic regurgitation in 7% (2 LBMI 4 NBMI) and hemodynamically insignificant pericardial effusions in 9% (6 LBMI, 1O NBMI).

Conclusions:
Myocardial remodeling occurs in LBMI pts with lower LV mass and higher volumes. Further quantification of myocardial function using speckle tracking and longitudinal follow up may help understand progression and determine the risk for sudden death in these pts.
Abstract 12397: Polygenic Risk Score and Deep Learning Using Chest Radiographs: Complementary Prediction of Incident Coronary Artery Disease
Authors: Paruchuri Kaavya , Raghu Vineet , Hoffmann Udo , Natarajan Pradeep , Lu Michael T
Published: April 2024

Introduction:
Individual genomic and phenotypic characteristics may improve cardiovascular risk prediction beyond traditional clinical risk factors such as age, sex, diabetes mellitus, hypertension, and hyperlipidemia. We assessed the prognostic value of a polygenic risk score (PRS) and a chest radiograph (CXR) based deep learning (DL) risk score to predict incident coronary artery disease (CAD).

Methods:
The Mass General Brigham (MGB) Biobank is a prospective cohort of adult patients within the MGB healthcare system. A 6.6M variant CAD PRS using externally derived weights and an externally derived deep learning model (CXR-Risk) predicting long term mortality from CXR images were calculated for individuals with array-derived genotypes and CXRs. International Classification of Disease code-based incident CAD outcomes were defined as the first event after CXR and assessed by Cox Proportional Hazards.

Results:
Of 7,237 patients without known CAD (mean age 63.4 [SD 8.0] years; 3,259 [45.0%] male), 585 (8.1%) developed incident CAD over median follow-up of 4.7 [IQR 2.7-7.2] years. Adjusted for traditional clinical risk factors (age, gender, diabetes mellitus, hypertension, hyperlipidemia) and the first five principal components of ancestry, both CAD PRS (HR 1.19 per SD, 95% CI 1.09-1.31, p<0.001) and CXR-Risk (HR 1.27 per SD, 95% CI 1.15-1.39, p<0.001) were independently associated with incident CAD. Incorporation of both improved incident CAD discrimination (c-statistic 0.67 vs 0.65, p<0.01) beyond traditional cardiac risk factors alone. CXR-Risk addition significantly improved a model with both traditional cardiac risk factors and CAD PRS (c-statistic 0.67 vs 0.66, p = 0.02).

Conclusions:
Advanced genomic (CAD PRS) and phenotypic (DL based CXR-Risk) measures independently predict and jointly improve risk prognostication for incident CAD.
Abstract 12406: Mitral Valve Prolapse: Immune Response as a New Player
Authors: delwarde constance , Aumond Pascal , toquet claire , Sizorn Melissa , Lauzier Benjamin , VEZIERS Joëlle , Blandin Stephanie , Kayvanjoo Amir H , Mass Elvira , Remy Severine , Anegon Ignacio , Schott Jean-Jacques , Le Tourneau Thierry , Merot Jean , Capoulade Romain
Published: April 2024

Introduction:
Mitral Valve Prolapse (MVP) is observed in 3% of the population. The pathophysiological mechanisms leading to MVP remain elusive and the only therapeutic option is to perform valve surgery. We previously identified FLNA as the first gene causing MVP and generated a unique knock-in (KI) rat model for the FLNA-P637Q mutation.

Hypothesis:
We assessed the hypothesis that MVP pathophysiology is multifactorial.

Methods:
5 WT and 10 KI rats were morphologically, functionally and histologically evaluated at 3, 6 and 13 weeks based on 2D echocardiography, 3D micro computed tomography (μCT) and histology. Mitral valve (MV) RNA-sequencing was performed and metaclusters (MC) have been identified. Immunofluorescence and cytometry experiments on MV were used.

Results:
Echocardiographic and μCT imaging confirmed the presence of MV prolapse, elongated anterior leaflet (+12 to +14% for all time points p<0.01) and increased MV volume (+20 to +58% for all time points p<0.05) in KI rats vs WT. Histological analyses revealed a myxomatous remodelling in KI MV. 6 MC were identified by RNA-seq: chemotaxis, epithelial and immune cell migration, extracellular matrix, stress molecular pathways, endothelial to mesenchymal transition and oxidative stress (all GO-terms p<1x10-5). A higher proportion of CD45
+
leukocytes (20% vs 14%, p=0.002), as well as a trend for CD206
+
“resident macrophages” (28% vs 16%, p=0.09), and CD34
+
stem cell progenitors (8% vs 15%, p=0.10) were observed in KI compared to WT rats. CD45
+
and CD206
+
cells were located in the medial third and atrial border of the MV leaflet in WT rats, and more diffusely observed in KI.

Conclusions:
Our results establish the KI FLNA-P637Q rat as a model of myxomatous MVP, a complex and multifactorial disease. Among others, we have characterized an increase of distinct immune cells in MVP. The course of cell recruitment, the cell-specific activity, and causality with the other MC need to be further studied.
Abstract 12445: Association Between Leptin and Left Ventricular Diastolic Dysfunction in Patients With Type 2 Diabetes
Authors: Wu Meizhen , Ren Qing-wen , Tse Yi Kei , Yu Si-Yeung , Hang Long Li , Tse Hung Fat , Yiu Kai Hang
Published: April 2024

Background:
Type 2 diabetes (T2DM) is associated with left ventricular (LV) hypertrophy, diastolic dysfunction, and elevated circulating leptin levels. However, the relationship of leptin with LV hypertrophy and diastolic dysfunction is unclear in patients with T2DM.

Methods:
A total of 176 T2DM patients (mean age 60±10 years; women, 46.6%) without cardiovascular diseases (CVD) were recruited. Circulating leptin levels were measured and detailed transthoracic echocardiography was performed to all patients. Multivariable linear regression analyses were applied to assess the associations between circulating leptin levels and echocardiography parameters.

Results:
Patients were divided into four groups based on their circulating leptin level. Higher sex-specific leptin quartiles were associated with worsening of diastolic function, reflected as lower septal e’, lateral e’, and elevated average E/e’ (all P < 0.05). However, Leptin was not associated with LV mass index. Multivariable linear regression, after adjustments for age, sex, body mass index, hypertension, and creatinine level, showed that leptin in the highest quartile was independently associated with worsening of average E/e′ (β = 1.26, P < 0.05).

Conclusion:
Circulating leptin level was associated with LV diastolic dysfunction in diabetic patients without CVD.
Abstract 12454: Prognostic Value of Computational Pressure-Flow Dynamics Derived Fractional Flow Reserve in Non-Culprit Vessels Among Patients Presenting With Acute Coronary Syndrome and Multivessel Disease
Authors: Leung Ka Lam Calvin , Lam Lok Yee , LI Kwan Yu , Yu Shuk Yin , Wu Mei Zhen , Ren Qing Wen , Wong Pui Fai , Tse Yi Kei , Yu Si Yeung , Li Hang Long , Feng Yundi , Huo Yunlong , Tse Hung Fat , Yiu Kai Hang
Published: April 2024

Introduction:
Computational pressure-flow dynamics derived fractional flow reserve (caFFR) is a novel index developed to assess the severity of myocardial ischemia in patients with coronary artery stenoses, without the requirement of invasive pressure wire and hyperemic stimulus needed in fractional flow reserve (FFR) measurement. In patients presenting with acute coronary syndrome (ACS), the non-culprit vessels are often diseased concomitantly, and the ischemia status of such vessels may affect clinical outcomes. In this study, we aimed to evaluate the prognostic value of caFFR in non-culprit vessels among ACS patients with multivessel disease.

Methods:
Patients presented with ACS and at least two vessels having ≥50% diameter stenosis were included, and the culprit vessel was identified for each patient. Analyses of caFFR were performed for the two non-culprit vessels of every patient. Based on the threshold of 0.8 adopted from FFR studies, patients were stratified into ischemic group if any non-culprit vessel caFFR was ≤0.8, and into non-ischemic group if none of the non-culprit vessels had caFFR≤0.8. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of all-cause mortality, non-fatal myocardial infarction, and any subsequent revascularization.

Results:
A total of 293 patients (mean age 65.3±13.2, male 77.5%) were included, with 113 (38.6%) presented with STEMI, 119 (40.6%) presented with NSTEMI, and 41 (14.0%) presented with unstable angina. The ischemic group patients (n=176) had more obstructive lesions compared to non-ischemic group patients (n=117) (3.8±1.5 vs. 3.2±1.1, p<0.001). The MACE event rate at 3 years was higher in ischemic group compared to non-ischemic group (28.4% vs. 15.4%; adjusted hazard ratio, 1.92; 95% confidence interval, 1.10-3.36; p=0.023).

Conclusions:
In ACS patients with multivessel disease, myocardial ischemia in non-culprit vessels assessed by caFFR was associated with adverse clinical outcomes in terms of MACE.
Abstract 12455: Comparison of Clinical Symptoms and Bioimpedance to Pulmonary Capillary Wedge Pressure in Heart Failure
Authors: Alvis Bret , Polcz Monica , Breed Meghan , Case Marisa , Huston Jessica H , Leisy Philip , Schmeckpeper Jeffrey , Brophy Colleen , Lindenfeld Joann , Hocking Kyle
Published: April 2024

Introduction:
Clinical symptoms of heart failure commonly include fatigue, edema, and shortness of breath. Unfortunately, clinical monitoring has proven to be unreliable for the assessment of congestion and predicting the need for hospitalization. Biosensing wearables have been developed as a potential adjunct to clinical signs and symptoms.

Hypothesis:
This report hypothesis a correlation between clinicians’ signs and symptoms of heart failure along with bioimpedance measurements (ZOE
®
), and pulmonary capillary wedge pressure (PCWP).

Methods:
One hundred and fifty-five subjects undergoing right heart catheterization (RHC) at Vanderbilt University Medical Center (VUMC) were prospectively enrolled. A Zo value (ohms) was obtained, jugular venous pressure (JVP) was estimated, edema graded, and dyspnea assessed in all subjects. RHC was performed by scheduled cardiologist per routine. One-way ANOVA was performed to assess relationship between dependent and independent variables. A Pearson correlation coefficient was used to compare Zo value and PCWP.

Results:
Neither estimated JVP (cmH
2
O) (p = 0.65, n=110) nor edema scores (p = 0.12, n=110) demonstrated a significant relationship to PCWP (Figure 1). The presence of subjective SOB also did not demonstrate significant association with PCWP (p = 0.99, n=110; Figure 1). There was no correlation between ZOE
®
and PCWP (r = -0.08, p = 0.56, n=56; Figure 2).

Conclusions:
These findings support the idea that traditional measures for monitoring heart failure patients are limited.
Abstract 12465: Clinical Results of a Novel Chest-Based Wearable During Transcatheter Aortic Valve Replacement Surgery for Real-Time Remote Monitoring
Authors: Charalambides Alexi , Pillai Rohith Krishnan , Beri Maahin , Carpenter Jesse , Stancil Brian , Majidi Carmel , Leduc Philip , Rauso Louis , Kliner Dustin , Serna-Gallegos Derek , Toma Catalin , Sanon Saurabh , Sultan Ibrahim
Published: April 2024

Objective:
Transcatheter Aortic Valve Replacement (TAVR) is the most common strategy for treating stenotic aortic valves in older adults. However, up to 18% of patients in the US are readmitted within 30 days, with about a third of these patients readmitted due to cardiac issues [1]. It would therefore be desirable to monitor discharged patients remotely to catch early signs of deterioration before more serious complications occur, and thereby reduce hospital readmission rates. The current gold standard for arrhythmia monitoring involves a single-lead Holter monitor in the form of a wearable chest-based patch. However, these devices usually do not track cardiac rhythms in real-time, and are typically mailed in after the wear period is over resulting in further delays.

Methods:
A novel chest patch capable of single-lead ECG that achieves real-time monitoring via Bluetooth and smartphone communications was used. To validate, the patch was placed on the chest of patients undergoing a TAVR; ECG was recorded and compared to gold-standard equipment.

Results:
ECG rhythms were collected from four patients using the patch and compared to an institutional hemodynamic monitoring system (GE MACLAB). The ECGs from each system were time aligned using a Fourier Transform method [2], R-peaks were identified using the Pan-Tompkins algorithm, heart rates were calculated over the course of the procedure by averaging R-R intervals over a 10 sec sliding window, and lastly Pearson correlation coefficients were calculated between the patch and gold-standard equipment. Pearson coefficients ranged from 0.995 to 0.999 with a Mean Absolute Error of 0.55 BPM and Root Mean Square Error of 2 BPM (see fig).

Conclusion:
These early results suggest an excellent agreement and accuracy between the wearable device and gold-standard ECG equipment, and may pave the way for monitoring discharged patients remotely. [1] Kolte, Dhaval et al 2017 [2] Fridman, Lex et al 2016
Abstract 12484: Weekday 16:8 Time-Restricted Eating in Breast Cancer Survivors: Feasibility, Safety, and Effects on Cardiometabolic Health
Authors: Kirkham Amy A , Topolnyski Jordan , Haykowsky mark J , Paterson Ian , Prado Carla M , Joy Anil Abraham A , Boule Normand , Ford Katherine L , Andre Pelletier B , Ramos Da Silva Bruna , Pituskin Edith , Thompson Richard
Published: April 2024

Introduction:
Time-restricted eating (TRE) is a form of intermittent fasting involving ad libitum energy intake within a set time window, commonly 8 hours, followed by a water-only fast for 16 hours (i.e., 16:8 TRE). TRE is a practical approach to improve cardiometabolic health but has not been tested in cancer populations.

Hypothesis:
TRE is feasible (>85% adherence), safe (no major adverse events), and will improve cardiometabolic health in breast cancer survivors.

Methods:
Women who completed chemotherapy for early-stage breast cancer 1-6 years earlier, are ≥60 years, have a BMI >25 kg/m
2
, and not taking lipid or glucose-lowering medications were enrolled in a single-arm study of 16:8 TRE on weekdays for 8 weeks. Participants could eat ad libitum between 12-8 pm on weekdays and all weekend. No other dietary or physical activity instructions were given. Adherence was collected by twice daily text messages that asked participants to respond with the times that they started/stopped eating. The Framingham 10-year cardiovascular disease (CVD) risk score and heart age, and ectopic adipose tissue (3T magnetic resonance imaging) were assessed before and after 8 weeks of TRE.

Results:
Fifteen participants (66±4 years, 31±4 kg/m
2
) have completed the study. Participants responded to 99% of text messages and adhered to the 16-hour fast a median of 98% of days (range 93-100%). Reported symptoms were minor and transient. At baseline, 73% of participants were at ‘intermediate’ (10-19%) CVD risk, and pharmacological treatment was indicated. Among those at intermediate risk, 8 weeks of TRE decreased the absolute CVD risk by a median of 2% and heart age by 6 years, and reversed the need for pharmacological treatment (i.e., reclassification to ‘low’ risk) or metabolic syndrome in 45%. In all participants, visceral adipose tissue decreased by a median of 6% (p=0.018) and triglycerides by 17% (p=0.008). There were no significant changes in hemoglobin A1c, or ectopic adipose tissue in the liver or thigh.

Conclusions:
Eight weeks of weekday 16:8 TRE is highly feasible, safe, and reduces CVD risk among older breast cancer survivors with overweight/obesity at moderate CVD risk. Improvements in glucose control and liver/thigh ectopic adipose tissue may require a longer intervention.
Abstract 12565: Rotational Atherectomy in the Left Coronary System
Authors: Rodriguez Barriga Erika A , Flores Galaviz Augusto A
Published: April 2024

It′s known that the Left Coronary Artery stenosis has greater mobility and mortality compared to the rest of the coronary tree, due to its size since the formation of plaques has a disseminated distribution, greater volume and severity of calcification. The use of rotational atherectomy (RA) has proven to be an effective tool to facilitate the sub-expansion of stents in atheromatous calcified lesions. We present a case study where plaque modification is performed by atherectomy and angioplasty in the Left Coronary system.A 62 years old female patient diagnosed with diabetes mellitus 2, systemic arterial hypertension and dyslipidemia. Antecedent of coronary angiography 10 days prior to admission due to chest pain and dyspnea, where found trivascular disease of left dominance with diffuse calcified lesion. She was programmed for RA with ROTABLATOR and ROTAWire system. It started by advancing the microcatheter on the angioplasty guide and exchanging for ROTAWIRE 0.009”. Subsequently, the 1.5 mm abrasive bur was advanced, rotating up to 6 times in the proximal and middle segment of the Anterior Descending Artery, proceeding to predilate with balloon noting a non-dilatable distal lesion, a 1.25 mm abrasive bur was passed, rotating up to 3 times, and it was decided to perform balloon predilatation and placement of spliced stents.Continuing with Circumflex Artery, an intermediate 0.014” Zinguer guide was advanced to the distal segment, spliced stents were placed in the proximal segment and it was dilated with a balloon to optimize results. It was decided to exchange guides and predilated the artery ostium, then it was decided to advance the stent using the Culotte bifurcation technique and a proximal optimization of the stent with a balloon was performed.Finally, a post-dilation was performed in the Anterior Descending Artery and the Left Coronary Trunk with a balloon to optimize a successful result (Figure 1), with no dissection image or thrombus. Final flow TIMI 3, TMP 3.
Abstract 12579: Empagliflozin and the Risk of Atherosclerotic Events and Hospitalization for Heart Failure: Updated Analysis From the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study
Authors: Htoo Phyo , Tesfaye Helen , Najafzadeh Mehdi , Schneeweiss Sebastian , Jawaid Dureshahwar , Wexler Deborah J , Glynn Robert , Koeneman Lisette , Deruaz Luyet Anouk , Paik Julie , Patorno Elisabetta
Published: April 2024

The EMPA-REG OUTCOME trial reported cardioprotective effects of empagliflozin (EMPA) in patients with established cardiovascular diseases (CVD). We evaluated the association between EMPA and the risk of cardiovascular events, versus GLP1 receptor agonist (GLP-1RA) or DPP4 inhibitor (DPP-4i) in the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) study of type 2 diabetes (T2D) patients in routine care, updating a prior analysis using data from 08/2014 through 09/2018. Using 2 commercial and Medicare claims databases, we identified 88,826 pairs of 1:1 propensity score-matched (PSM) T2D patients ≥18 years initiating EMPA or a GLP-1RA [Cohort 1], and 69,610 pairs initiating EMPA or a DPP-4i [Cohort 2]. Our outcomes were (i) a composite of atherosclerotic cardiovascular diseases (ASCVD): MI, stroke, unstable angina and coronary revascularization and (ii) heart failure hospitalization in primary discharge (HHF-Primary) or any position (HHF-Any). In each cohort, we estimated hazard ratios (HR) and 1-year numbers needed to treat (NNT), accounting for death as a competing risk, pooled across databases adjusting for >140 baseline covariates. After PSM, exposure groups had similar characteristics (Table 1). Compared to GLP-1RA, EMPA had a similar risk of ASCVD [HR (95% CI): 1.05 (0.96,1.15)] and a decreased risk of HHF-Primary: 0.64 (0.54,0.76) and HHF-Any: 0.83 (0.77,0.90). One-year NNTs for EMPA vs GLP-1RA were 235 for HHF-Primary and 133 for HHF-Any. Results for EMPA vs DPP-4i were similar: ASCVD [0.94 (0.85,1.03)], HHF-Primary [0.46 (0.38,0.55)] and HHF-Any [0.66 (0.60,0.72)]. One-year NNTs for EMPA vs DPP-4i were 100 for HHF-Primary and 52 for HHF-any. Results for the individual components of the ASCVD outcome were consistent. The updated analysis from EMPRISE showed that relative to GLP-1RA or DPP-4i, EMPA was associated with a similar risk of ASCVD and a reduced risk of HHF in routine care, with more precise estimates compared to prior analyses.
Abstract 12588: Biomechanical Analysis of Neochordal Mitral Valve Repair Geometry to Quantitate the Impact of Diastolic Phase Inversion During Static Left Ventricular Pressurization
Authors: Park Matthew H , Marin-Cuartas Mateo , Zhu Yuanjia , Wilkerson Robert , Pandya Pearly , Imbrie-moore Annabel M , Borger Michael , Woo Y J
Published: April 2024

Introduction:
Artificial neochord implantation is a common form of surgical mitral valve (MV) repair, and neochord length is commonly determined by static left ventricular (LV) pressurization in diastole. However, this causes a geometric phase inversion as the subvalvular apparatus will dilate when the LV would be contracting during systole in a beating heart. We hypothesize that static LV pressurization and the subsequent papillary muscle (PM) geometric shift affects the implanted neochord length, which may alter hemodynamic performance and chordal stresses.

Methods:
Porcine MV (n=6) were explanted and mounted in an
ex vivo
heart simulator and PM were affixed to image-guided robots that accurately simulate PM motion (Fig A, B). Baseline valve hemodynamic and chordal strain data were collected, after which P2 chordae were severed to simulate posterior leaflet prolapse from chordal rupture and subsequent mitral regurgitation (MR) (Fig C). Neochord implantation was performed in both systolic and diastolic stationary PM configurations. Data is presented as mean ± standard error, and statistics were performed using two-tailed Student’s T-Tests.

Results:
While both repairs adequately reduced MR, we found that the systolic vs diastolic configuration repair resulted in marginally reduced MR and neochord lengths, 2.25±1.384% and 2.19±0.4 mm or 16.0±3.2%, respectively (
p=0.011
,
p=0.004
). Moreover, peak primary and secondary chordal forces were reduced by 14.4±7.0% (
p=0.07
) and 18.8±6.4% (
p=0.03
), respectively.

Conclusions:
By leveraging advanced
ex vivo
technologies and biomechanics analyses, we were able to quantify the impact of diastolic phase inversion on neochordal MV repair geometry. Our findings suggest that this technique may slightly overestimate the neochordal length and that marginal additional shortening of neochordae may positively affect MV repair performance and durability by reducing load on surrounding native chordae.
Abstract 12592: Acute Administration of N-Acytylcysteine Leads to Highly Specific Sub-Regional Changes in AF Electrogram Characteristics - A New Way to ‘Uncover’ Regions of High Oxidative Injury in the Fibrillating Atrium?
Authors: Rottmann Markus , Pfenniger Anna , Yoo Shin , Johnson David , Geist Gail E , Zhang Wenwei , Shanab Bassel , Mandava Suman , Burrel Amy , Wasserstrom Andrew J , Kim Susan , Knight Bradley P , Passman Rod S , Arora Rishi
Published: April 2024

Introduction:
It is currently not possible to measure and therapeutically target oxidative injury (OI) in the intact fibrillating atrium.

Hypothesis:
We postulated that measurement of AF electrogram characteristics after acute administration of a reactive oxygen species (ROS) scavenger can help ‘uncover’ regions of high OI in the fibrillating human atrium.

Methods:
We mapped in both atria pre/post NAC (intravenous, 100mg/kg) in 15 persistent AF dogs (3-14 weeks rapid atrial pacing) using a high-density epicardial mapping-plaque (6 atrial regions in both atria, 130 electrodes, electrode-distance 2.5mm) and in 4 patients using the HD-grid catheter. We quantified the OS-levels as ratio of oxidatively damaged nuclei (
Figure A
) against the total number in 8-OHdG staining (N=36) and the degree of dense fibro-fatty tissue in Masson’s trichrome stained tissue (N=24) using Qupath. We analyzed cycle length (CL) and dominant frequency (DF) in ‘hot spot’-sub-region sizes with >10% change pre vs. post NAC.

Results:
Oxidative stress (OS) levels, highest in the left atrial free wall, lowest in the appendages increased with increasing degree of fibro-fatty tissue (R=0.6,P<0.05) and with decreasing cycle length (R=0.5, P<0.05) in all regions (
Figure C
). NAC selectively reduced AF characteristics in ‘hot spot’-sub-regions (
Figure D
). OS level correlated with delta CL, delta DF, and delta Organization Index in delta maps (NAC - baseline) (R=0.5, P<0.05, all comparisons) (
Figure E)
. In patients, NAC (
Figure G)
reduced AF characteristics in subregions (
Figure H)
and increased cycle length from 210±50ms to 252±18ms (P<0.05) in the left atrium (
Figure I
).

Conclusions:
OS-level correlated with the degree of dense fibro-fatty tissue and with electrogram measures in both atria. Acute scavenging of ROS reduced AF characteristics in the left atrium in dogs and patients. We might have found a new way to target regions of high OS in the atrium in the individual patient.
Abstract 12594: GRK2 is a Novel Regulator of Cardiac Mitochondrial Bioenergetics
Authors: Ferrero Kimberly , Pfleger Jessica M , Chuprun Kurt , Gao Erhe , Koch Walter J
Published: April 2024

Introduction:
The GPCR kinase GRK2 is highly expressed the heart; during cardiac injury or heart failure (HF) levels and activity of GRK2 increase. While GRKs are canonically studied upstream of β-adrenergic desensitization, GRK2 has a large non-GPCR interactome and novel, noncanonical functions. We have discovered that in the heart, GRK2 translocates to mitochondria (
mtGRK2
) following injury and negatively affects cellular metabolism and substrate utilization. Thus, we have sought to identify the mechanism(s) by which GRK2 regulates mitochondrial function.

Hypothesis:
mtGRK2 phosphorylates proteins involved in mitochondrial bioenergetics, which may explain the altered metabolic phenotype seen following cardiac injury or HF.

Methods:
Stress-induced mitochondrial translocation of GRK2 was validated in rat ventricular myocytes, murine cardiac tissue and a cardiac-derived cell line. The mtGRK2 interactome was then via protein immunoprecipitation followed by liquid chromatography-mass spectroscopy (LCMS) analysis. Proteomics analysis identified mtGRK2 interacting proteins which were involved in mitochondrial dysfunction.

Results:
Complexes I, II, IV and V of the electron transport chain (ETC) were identified as mtGRK2 interacting partners. Several mtGRK2 interactions were increased following stress, particularly those with Complex V. We further established that mtGRK2 phosphorylates some of the subunits of Complex V, particularly the ATP synthase barrel which is critical for ATP production. Specific amino acid residues on these subunits have been identified using PTM-LCMS and are currently being validated in a murine myocardial infarction model. Additionally, alterations in either the levels or activity of GRK2 appear to alter the enzymatic activity of Complex V
in vitro
, thus regulating ATP production in cardiomyocytes.

Conclusions:
The phosphorylation of the ATP synthesis machinery by mtGRK2 may be regulating some of the phenotypic effects of injured or failing hearts such as reduced substrate utilization. Research is ongoing to further elucidate the novel role of mtGRK2 in regulating bioenergetics and cell death, uncovering a novel, treatable target for rescuing cardiac function in patients with injured or failing hearts.