bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18299: Prevalence of and Correlates with QRS Prolongation in Heart Failure with Preserved Ejection Fraction: Data from the KaRen Study
Authors: Lund Lars H , Donal Erwan , Oger Emmanuel , Hage Camilla , Persson Hans , Simonsson Moa , Haugen-Löfman Ida , Daubert Jean-Claude , Linde Cecilia
Published: April 2024

Background:
QRS ≥ 120 ms is present in 1/3 of patients with heart failure with reduced ejection fraction, favorably treated with cardiac resynchronization therapy. In heart failure with preserved ejection fraction (HFPEF), the prevalence of and correlates with QRS prolongation are largely unknown.

Methods:
KaRen is a multicenter prospective registry of HFPEF (ClinicalTrials.gov
NCT00774709
). Inclusion criteria are Framingham symptoms and signs of heart failure together with NT-proBNP >300 ng/L and LVEF ≥45%. In patients with sinus rhythm and with atrial fibrillation / flutter (AF), the prevalence of and association between QRS prolongation and clinical characteristics was assessed with uni- and multivariable linear regression, with 10 clinical variables, ejection fraction, and EKG parameters (10 in sinus rhythm; 6 in AF), using backward step-wise selection based on p < 0.10.

Results:
We studied 382 patients, mean (SD) age 77 (9) years, 56% women. QRS < 120 ms, 120-149 ms, ≥ 150 ms, LBBB, and ventricular-paced EKG was present in 78, 11, 3, 3 and 8% respectively. One-hundred twenty-six patients (35%) had AF. AF was not associated with QRS width. The table lists variables independently associated with QRS in ms, their baseline values and Beta coefficients, separately among patients in sinus rhythm and AF, excluding ventricular-paced patients.

Conclusions:
In HFPEF, QRS prolongation and LBBB are less common than in reduced ejection fraction. QRS prolongation is associated with other EKG pathology and with B-blocker use. The rarely measured parameter “P-wave duration” may reflect the same underlying global conduction delay as QRS duration.
Abstract 18311: Metabolomic Signatures of Right Ventricular-Pulmonary Vascular Dysfunction
Authors: Lewis Gregory D , Farrell Laurie , Domos Carly , Dhakal Bishnu , Shi Xu , Sinha Sumita , Semigran Marc J , Wang Thomas J , Sabatine Marc S , Clish Clary B , Gerszten Robert E
Published: April 2024

Impaired performance of the right ventricular-pulmonary vascular (RV-PV) unit is an important determinant of reduced exercise capacity, morbidity and mortality. We sought to determine comprehensive plasma metabolite signatures of RV-PV dysfunction.

Methods/Results:
We studied subjects who underwent incremental cycle ergometry cardiopulmonary exercise testing with simultaneous hemodynamic monitoring to evaluate the etiology of dyspnea on exertion. In derivation and validation groups (n=71 and n=52, respectively) we performed multi-site blood sampling from the pulmonary and radial arteries to determine plasma concentrations of 130 metabolites using targeted liquid chromatography/mass spectrometry. Indicators of abnormal RV-PV function (i.e. elevated resting right atrial pressure, mean pulmonary arterial pressure [mPAP], pulmonary vascular resistance [PVR], as well as PVR and PAP-flow response [PQ] during exercise) were associated with levels of multiple groups of metabolites (
Table
), including arginine- nitric oxide (NO) pathway intermediates, indicators of oxidative stress, TCA cycle metabolites, and indoleamine 2,3-dioxygenase (IDO)-dependent tryptophan metabolites (TMs). Higher levels of IDO-TMs were the leading predictors of resting mPAP and PVR and exercise PVR and PQ. Transpulmonary release of IDO-TMs localized metabolic changes to the pulmonary circulation. Multivariate regression adjusting for age, gender, BMI, cystatin C, and NT-BNP did not attenuate the relationship between IDO-TMs and indices of RV-PV dysfunction.

Conclusion:
Metabolic profiling identified signatures of RV-PV dysfunction. These signatures consisted of metabolites known to be associated with RV-PV dysfunction (i.e. NO pathway intermediates, indicators of oxidative stress) and metabolites not previously associated with RV-PV dysfunction (i.e. TCA cycle metabolites and IDO-TMs), which represent potential novel biomarkers of RV-PV dysfunction.
Abstract 18322: A Ligand of Scavenger Receptor Class A Causes Vascular Relaxation Through an Activation of Endothelial Nitric Oxide Synthase in Rat Aorta
Authors: Iesaki Takafumi , Takeuchi Tomoaki , Okano Megumi , Hashimoto Ryota , Kakigi Ryo , Ishii Yuko , Okada Takao
Published: April 2024

The class A scavenger receptor (SR-A) are implicated in the development and progression of atherosclerosis. In addition to modified low-density lipoprotein, a diverse group of polyanionic compounds are listed as ligands for SR-A. Fucoidan is a natural sulfated polysaccharide obtained from brown marine algae and is a well-defined nonlipoprotein ligand for SR-A. It is attracting attentions due to its wide variety of biological effects including anticoagulant and antithrombotic activities, however, its effects on vascular tone are not fully elucidated. In the present study, we examined the effects of acute administration of fucoidan (10 μg/ml to 1 mg/ml) to isolated rat thoracic aorta (RA) and explored the mechanism(s) of action. Fucoidan caused RA relaxation in a dose-dependent manner, and this relaxation was significantly attenuated by the removal of endothelium; 88.4±5.8 % (mean±SEM, n=17) in the presence and 24.6±7.5 % (n=10) in the absence of endothelium at 1 mg/ml fucoidan. Fucoidan-induced relaxation was also significantly inhibited by both a nitric oxide (NO) synthase (NOS) inhibitor 300 μM L-NAME (N(G)-nitro-L-arginine methyl ester, 37.8±13.1 %, n=6) and a selective inhibitor of soluble guanylyl cyclase 10 μM ODQ (1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one, 33.0±5.6 %, n=8), but not affected by a cyclooxygenase inhibitor 10 μM indomethacin or various kinds of K
+
channel blockers including 10 mM tetraethylammonium, 10 μM glibenclamide and a combination of 0.1 μM apamin plus 0.1 μM charybdotoxin which is thought to block endothelium-derived hyperpolarizing factor-mediated reaction. NO production measured by Griess method in cultured human aortic endothelial cells (HAEC) was dose-dependently increased by fucoidan. Western blotting analyses revealed that fucoidan phosphorylated endothelial NOS (eNOS) at Ser-1177 and also phosphorylated protein kinase Akt at Ser-473 in a dose-dependent manner in HAEC, indicating an activation of eNOS. These results indicate that fucoidan, a ligand of SR-A, causes vascular relaxation through an endothelium-dependent and, at least in part, NO/cGMP-mediated mechanism through an activation of eNOS.
Abstract 18324: The Innate Immune System, Nlrp3 Inflammasome is Intensified in Epicardial Adipose Tissue around Coronary Arterial Lesions: Evidence from Biopsied Adipose Tissue in Coronary Artery Bypass Surgery
Authors: Sato Hiromi , Shimabukuro Michio , Hirata Yoichiro , Tabata Minoru , Munkhbaatar Dagvasumberel , Fukuda Daiju , Kurobe Hirotsugu , Soeki Takeshi , Takanashi Shuichiro , Kitagawa Tetsuya , Sata Masataka
Published: April 2024

Background:
The emergence of chronic inflammation could enhance obesity-induced insulin resistance and atherosclerosis, but the underlying mechanisms remain unclear. The Nod-like receptor (NLR) family of innate immune cell sensors, such as pyrin domain-containing-3 (NLRP3) inflammasome are implicated as one candidate to elicit nonmicrobial originated signals in atherosclerosis. Objectives: We determined association between the NLRP3 inflammasome signals in epicardial adipose tissue (EAT) and coronary atherosclerosis in human.

Method:
Pair samples were obtained from epicardial and subcutaneous adipose tissue during elective cardiac surgery for coronary (CAD, n=40) or non-coronary artery disease (non-CAD, n=40). Expression of NLRP3 in EAT was analyzed by immunohistochemical staining using antibodies against NLRP3, CD68 and IL18. Expression of pro- and anti-inflammatory adipocytokines in EAT was evaluated by quantitative real-time polymerase chain reaction (qPCR).

Results:
By immunohistochemical staining, NLRP3 signals were well detected in EAT of the CAD group, but rarely in EAT of the non-CAD group. The signals was co-localized with macrophages in EAT determined by anti-CD68 or anti-F4/80 immunostaining. By qPCR, signals of NLRp3, TLR1, TLR2, TLR4, but not TLR3, TLR5 and TLR9, were increased in EAT of the CAD group as compared to that of the non-CAD group. Signals of MyD88, but not MD-2, were also enhanced in EAT of the CAD group. Signals of IL-18 and adiponectin were decreased in EAT of the CAD group.

Conclusions:
We, for the first time, showed that NLRP3 inflammasome signals were enhanced, but signals of IL-18 and adiponectin were decreased, in EAT of the coronary atherosclerotic lesions. We conclude that atherogenesis in human coronary arteries may be caused in part by NLR signals in infiltrating macrophage of epicardial adipose tissue.
Abstract 18342: Electrocardiographic Screening of One-month-old Infants with High Risk for Sudden Infant Death in Japan
Authors: Yoshinaga Masao , Ninomiya Yumiko , Tanaka Yuji , Tanoue Kazuyuki , Nuruki Norito , Sonoda Masahiro
Published: April 2024

Backgrond:
Sudden infant death syndrome (SIDS) is one of the major causes of death in infancy with the highest prevalence at about 2 months of age. Genetic studies have shown that about 10% of cases diagnosed as SIDS carry functionally significant mutations in long QT syndrome (LQTS) genes. In Japan, medical examinations at one month of age are performed for all infants currently.

Aim:
We assessed the hypothesis that electrocardiographic screening of one-month-old infants is able to screen infants with LQTS and those with risk of sudden death other than LQTS.

Methods:
The study was conducted in eight areas in Japan. Twelve-lead electrocardiograms were recorded and the QT/RR intervals of three consecutive beats were measured. Our prospective study showed that a formula to minimize the effect of heart rate for infants was QTc=QT/RR
0.43
and a provisional criterion of a QTc≥0.44 was appropriate. To assess the validity of the criterion, all infants with a QTc ≥0.43 were followed.

Results:
Of 4,319 infants who participated, 6 infants had a QTc value of ≥0.44 at one-month-old. From the follow-up ECGs, four infants were diagnosed as LQTS clinically. Two infants showed progress prolongation of the QTc intervals; propranolol and mexiletine were administered when their QTc values exceeded ≥0.50
0.43
. Genetic testing revealed a
KCNH2
mutation (3065 delT, L1021fs+34X) in one of these two infants. Remaining two infants with a QTc ≥0.44 had been following without medication. All 10 infants with the QTc values between 0.43 and 0.44 showed decline in their QTc values during follow-up. The study also screened infants with WPW syndrome in 3, VPC in 9, CRBBB in 5, and situs inversus totalis in 1. Among 3 infants with WPW syndrome, 1 infant was diagnosed as noncompaction with heart failure (ejection fraction of 50% at the 1
st
visit). A sharp drop of the ejection fraction to 28% emerged a few weeks later and medication was started.

Conclusions:
Electrocardiographic screening of one-month-old infants is successful in preventing deterioration of infants with risk and may prevent sudden infant death.
Abstract 18375: Prognostic Value of Unipolar vs Bipolar Electroanatomic Voltage Mapping in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy/dysplasia
Authors: Migliore Federico , Zorzi Alessandro , Silvano Maria , Bevilacqua Michela , Perazzolo Marra Martina , Bauce Barbara , Rigato Ilaria , Tarantini Giuseppe , Basso Cristina , Thiene Gateano , Iliceto Sabino , Corrado Domenico
Published: April 2024

Background:
electroanatomic voltage mapping (EVM) allows to identify and quantify low-voltage right ventricular (RV) areas, which may represent the electroanatomic scar substrate of life-threatening RV tachyarrhythmias. We prospectively assessed the prognostic value of EVM in a consecutive series of patients witharrhythmogenic right ventricular cardiomyopathy (ARVC).

Methods:
the study population included 69 consecutive patients (47 male; age 37±14 years) fulfilling the International Task Force diagnostic criteria. All patients underwent electrophysiological study and high density EVM (195±22 points), using both bipolar and unipolar map techniques. The extent area of confluent bipolar (<1.5 mV) and unipolar (<6.0 mV) low-voltage electrograms was calculated with the CARTO software.

Results:
Fifty-three patients (77%) showed ≥1 RV electroanatomic scar regions with an estimated burden of bipolar vs unipolar low-voltage areas of 25.5±12.7% and 66.5±18.4%, respectively (P<0.009). In all the remaining patients with normal bipolar-EVM (n=16; 23%) the use of unipolar EVM technique unmasked ≥1 region of low-voltage electrogram abnormality affecting 27.3±13.8% of RV wall. During 49±13 months of follow-up, 19 (27.5%) patients experienced major arrhythmic events, such as sudden death (n=1), appropriate ICD interventions (n=7) or sustained ventricular tachycardia (n=11). Univariate predictors of arrhythmic outcome included syncope (HR=2.4;95%CI:1.1-6.7;P=0.03), previous cardiac arrest (HR=3.7;95%CI:1.4-8.9;P=0.02), right precordial T-wave inversion (HR=9.3;95%CI:1.7-29) and extent of bipolar low-voltage areas (HR=1.7/5%;95%CI=1.5-2; P<0.001), while the only independent predictor was the bipolar low-voltage electrogram burden (HR=1.5/5%;95% CI:1.4-1.6;P<0.001). All patients with normal bipolar EVM had an uneventful clinical course despite the presence of unipolar scar areas.

Conclusions:
The extent of bipolar RV endocardial low-voltage area is a powerful predictor of malignant arrhythmic events in ARVC/D, independently of medical history and RV datation/dysfunction. Non-transmural RV electroanatomic scar involvement (abnormal unipolar/normal bipolar EVM) characterized a low-risk subgroup of patients.
Abstract 18376: Angiographic Graft Patency After Multivessel Minimally Invasive Coronary Artery Bypass Grafting: MICS CABG Patency Study
Authors: McGinn Joseph T , Shariff Masood , Lapierre Harry , Sohmer Benjamin , Goyal Nikhil , Ruel Marc
Published: April 2024

Objective:
Previous publications from our institutions have shown that minimally invasive coronary artery bypass grafting (MICS CABG) is safe, widely applicable, and associated with fewer infections, less transfusions, and better recovery than standard CABG. However, graft patency rates are unknown. The MICS CABG Patency Study prospectively evaluated angiographic bypass graft patency at 6 months after MICS CABG.

Methods:
In this dual-center study, 61 patients were prospectively enrolled and underwent MICS CABG through a 4-7cm left thoracotomy approach, where the left internal thoracic artery (LITA), the ascending aorta for proximal anastomoses, and all distal coronary targets were accessed without endoscopic or robotic assistance. The primary outcome was graft patency at 6 months, using 64-slice CT angiography. Secondary outcomes included conversions to sternotomy and major adverse cardiovascular events (MACE).

(

Clinical Trial Registration

Unique identifier:
NCT01334866
)

Results:
Mean age was 64.1±8.1 years, the mean ejection fraction was 48.8±10.4%, and there were 8 females in the study (13.1%). Surgeries were performed off-pump in 52 patients (85.2%). Complete revascularization was achieved in all patients, and the median number of grafts was 3. There was no perioperative mortality, no conversion to sternotomy, and 1 reopening for bleeding. Transfusion occurred in 15 patients (24.6%).The median length of hospital stay was 4 days, and patients were followed-up to 6 months, with no mortality or MACE. At 6 months, overall CT angiographic graft patency was 91.2% for all grafts, and 100% for LITA grafts.

Conclusions:
MICS CABG is safe, feasible, and associated with excellent rates of graft patency at 6 months post-surgery.
Abstract 18381: Ten Years Genetic Screening in a Large Cohort of Patients with Dilated Cardiomyopathy
Authors: van Tintelen Peter , Spaendonck-Zwarts Karin Y , van Rijsingen Ingrid A , Jongbloed Jan D , Lekanne Dit Deprez Ronald H , Post Jan G , van Mil Anneke , Christiaans Imke , Wilde Arthur A , van den Berg Maarten P , Pinto Yigal M
Published: April 2024

Introduction:
Idiopathic Dilated Cardiomyopathy (DCM) is familial in up to 35% of cases. Conventional genetic analysis of DCM is hampered by genetic heterogeneity because over 40 DCM related genes have been identified, most of them accounting for only a minority of cases. We hypothesized that conventional genetic screening in DCM index-patients lead to a modest mutational yield. Therefore we evaluated the results of genetic screening in DCM patients over the last 10 years.

Methods:
Clinical data, family history, and results of conventional genetic analyses in 418 DCM index-patients (224 familial, 173 sporadic and 21 with neuromuscular disease) were collected. We assessed the prevalence of mutations in DCM related genes and evaluated its clinical expression.

Results:
Thirty-five putative pathogenic mutations were identified in 82 of 418 DCM index-patients (20%). When analyzing subgroups, mutations were found in 25% of familial DCM, 8% of sporadic DCM, and 62% of patients with DCM and neuromuscular disease. Most prevalent were a
PLN
founder mutation (p.R14del) in 43 index-patients and 16 different
LMNA
mutations in 19 index-patients. The majority of these patients showed a gene-specific phenotype. Other genes involved were:
MYH7
,
DES
,
TNNT2
,
DMD
,
TPM1
,
DMPK
,
SCN5A
,
SCGB
, and
TNNI3
. Only one patient was double heterozygous. After a median follow-up of 40 months (interquartile range; 13 to 90 months), combined death from any cause, cardiac transplantation, and malignant ventricular arrhythmias in mutation carriers was worse compared to DCM patients without a known genetic cause (HR 2.0, 95% CI: 1.4-3.0). This seems to be mainly due to the arrhythmogenic phenotypes of
LMNA
and
PLN
mutation carriers.

Conclusions:
Extensive genetic analysis in a large and well-defined DCM cohort shows that the yield of genetic analysis is high (62%) in DCM patients with neuromuscular disease, moderate (25%) in familial DCM, and low (8%) in sporadic DCM. When resources are limited, specific clinical characteristics can be used to select cases for DNA analysis. These results form a solid base to develop next generation sequencing for DCM that will provide high-throughput, rapid and affordable genetic analysis for DCM.
Abstract 18387: Interleukin 23-signaling Affects Infarct Healing and Promotes Wound Stabilisation in an Experimental Model of Myocardial Infarction by Controling the Function of Cardiac Fibroblasts
Authors: Savvatis Konstantinos , Pappritz Kathleen , Becher Moritz , Westermann Dirk , Schultheiss Heinz-Peter , Tschöpe Carsten
Published: April 2024

Introduction:
Interleukin-23 coordinates together with other cytokines the adaptive immune response and its presence is important for the action of neutrophils, Th17 and regulatory T cells. We sought to determine the role of IL-23 in experimental myocardial infarction.

Methods:
Myocardial infarction was induced by ligation of the left anterior descending artery in C57Bl6j and IL-23-knockout mice. Left ventricular function was examined by conductance catheter, expression of proinflammatory and antiinflammatory cytokines by PCR and inflammatory cells in the myocardium by immunohistochemistry after 4 and 30 days. Mortality was examined 30 days after myocardial infarction. Differentiation and phenotype of cardiac fibroblasts was assessed under basal conditions and after stimulation with interferon-γ (IFNγ).

Results:
Endystolic and enddiastolic LV-volumes were higher in the IL-23-knockout mice 4 days after myocardial infarction (30%, p=0.05 and 35%, p=0.02 respectively). Expression of IL-1β was upregulated by 50% (p=0.006) and IFN-γ by 100% (p=0.05) in the infarction zone in the IL-23-knockout mice. Migration of neutrophils and macrophages in the infarcted area was higher in the IL23-knockout mice (by 43%, p=0.04 and 41%, p=0.03 respectively). IL-23-knockout mice showed a lower 30-days survival rate due to increased ventricular rupture (63% vs. 24%, p=0.036). Expression of α-smooth muscle actin (α-SMA, 2fold increase, p<0.05), collagen I (2.1fold increase, p<0.05) and III (1.9fold increase, p<0.01) as markers of fibrosis and activation of myofibroblasts were significantly higher in the infarction area in the wild type mice 30 days after infarction. Cardiac fibroblasts isolated from the infarcted and non-infarcted zones showed a 50% lower expression of αSMA, 30% lower collagen I and 20% lower collagen III (p<0.05) in the IL23KO-mice. Stimulation of cardiac fibroblasts with IFNγ led to a downregulation of αSMA and collagen I and upregulation of the proinflammatory chemokines CCL2 and CXCL10.

Conclusions:
IL23 controls the expression of IFNγ in the heart after myocardial infarction and induces the differentiation of cardiac fibroblasts into myofibroblasts promoting healing and wound stabilization.
Abstract 18392: Latent Myopathy is More Pronounced in Low Flow Versus Normal Flow Aortic Stenosis Pre- and Post-aortic Valve Replacement in Patients with Normal Left Ventricular Ejection Fraction
Authors: Sanchez-Ross Monica , Marrero Daniel , Suma Valentin , Correa Amit K , Azari Bani M , Mohareb Sameh , Swistel Daniel , Balaram Sandhya , Sookhu Suraj , Chaudhry Farooq A
Published: April 2024

Background:
Strain assessment using speckle tracking echocardiography (STE) is more sensitive than 2D echocardiography to detect subtle changes in left ventricular (LV) function. Mid cavity fibrosis on MRI and low indexed stroke volume are independent predictors of mortality in severe AS with preserved LV ejection fraction (LVEF). The role of 2D STE to identify latent myopathy (fibrosis) in AVR and normal LVEF is limited.

Methods:
Demographic, 2D echocardiographic, and STE data were analyzed in patients with severe AS and preserved LVEF who underwent tissue AVR. Velocity vector imaging (VVI) 2D STE was used to assess global and regional peak systolic longitudinal strain and strain rate in both pre- and post-AVR echocardiograms. Basal and mid segment averages were compared to normal reference values. Low flow (LF) was defined as an indexed LV stroke volume <35ml/m2.

Results:
Between July 2009 to May 2012, 47 patients (76 ± 10 yrs, 42% male) who underwent tissue AVR had both a pre- and post-AVR echo within 6.3 ± 6.7 months of surgery. Compared with pre-AVR values, global longitudinal strain (-6.6 ± 4.9% vs. -10.3 ± 3.7%; p=0.002) and strain rate (-0.8 ± 0.3 1/s vs. -0.9 ± 0.3 1/s; p=0.03) improved within 3.2 ± 2.3 months post-AVR. Pre-AVR mid segments showed a worse myopathy than basal segments, with a decrement of -10.1 ± 1.6% vs. -8.8 ± 1.6% (p=0.0009) from reference values. Although, improvement was seen in both mid (-8.6 ± 5.6 % vs. -10.6 ± 4.3%; p= 0.04) and basal (-8.2 ± 5.5% vs. -10.8 ± 5.0%; p=0.02) segments post-AVR, the myopathy remained more pronounced in the mid segments. Overall, 21 (46%) patients were classified as LF with significant improvement in pre- vs. post-AVR strain (-5.3 ± 4.6% vs. -9.4 ± 4.1%; p=0.003). However, compared with normal flow (-8.6 ± 5.7%) LF had lower pre-AVR (-5.3 ± 4.6%; p=0.05) and post-AVR (-12.4 ± 3.4% vs. -9.4 ± 4.1%; p=0.02) longitudinal strain.

Conclusions:
STE VVI can identify both global and regional latent myopathy in patients with severe AS and preserved LVEF undergoing AVR. The myopathy is more pronounced in low indexed stroke volume pre and post-AVR. Furthermore, the myopathy in normal flow and low flow patients is more pronounced in the mid segments both pre- and post-AVR.
Abstract 18456: Morphologic Predictors of Aortic Growth in Conservatively Treated Type B Aortic Dissection
Authors: Tolenaar Jip L , Jonker Frederik H , van Herwaarden Joost A , Verhagen Hence , Moll Frans L , Muhs Bart E , Trimarchi Santi
Published: April 2024

Purpose:

Conservative management of acute type B aortic dissection (ABAD) is often associated with aortic enlargement during follow-up, increasing the risk of aortic rupture. The goal of this study was to investigate whether morphologic characteristics of the dissection can predict annual aortic growth.

Methods:

All conservatively managed type B dissection patients of four referral centers were included (2000-2010). Aortic diameters were measured at 5 levels on the baseline and last follow-up CTA, and annual aortic growth rates were calculated for all segments. Linear regression was used to study the influence of aortic morphologic characteristics on aortic enlargement.

Results

: Sixty-two patients were included (41 male; mean age 60.3 ± 10.7 years). Among the 310 analyzed segments, 248 (80.0%) were dissected of which 211 (85.1%) showed aortic growth. Overall, the mean diameter increased from 36.1 ± 9.4 mm to 40.2± 11.1mm (p < 0.001) corresponding with a mean aortic growth of 3.1 ± 6.3 mm/year. Multivariate linear regression analysis showed male gender (95% CI 0.84 - 4.27;
p
= .004), detection of entry tears (95% CI 0.32 - 8.01; p = .034,) and a saccular false lumen (95% CI 1.50 - 7.28:
p
= .003) were associated with a significantly increased aortic growth rate. Increasing age (95% CI -0.24 - -0.5;
p
= .003), false lumen located on the convexity (95% CI -4.56- -0.64;
p
= .009) and a circular configuration of the true lumen (95% CI -5.04 - -0.02;
p
= .048) were associated with a decreased aortic growth rate.

Conclusions:

Age, gender, saccular false lumen, detection of entry tears, the presence of the entry tear in the oncavity of and configuration of the true lumen, appear to affect aortic growth rates in conservatively treated ABAD patients. Assessment of these characteristics may be useful in the selection of ABAD patients who might benefit from closer radiologic surveillance or early intervention.
Abstract 18479: The Level of Pre-discharge N-terminal Pro B-type Natriuretic Peptide and its Change During Hospitalization Can Predict Future Left Ventricular Functional Recovery in Acute De Novo Dilated Cardiomyopathy
Authors: Kim Kye Hun , Yoon Hyun Ju , Ahn Youngkeun , Jeong Myung Ho , Cho Jeong Gwan , Park Jong Chun , Kang Jung Chaee
Published: April 2024

Background:
To investigate the usefulness of N-terminal pro B-type natriuretic peptide (NT-proBNP) in the prediction of left ventricular (LV) functional recovery in acute de novo heart failure (HF) patients with dilated cardiomyopathy (DCMP).

Methods:
A total of 175 consecutive patients acute de novo DCMP and HF were divided into 2 groups; the recovered group (group 1, n=54, 54.3±18.5 years, 31 males) vs the non-recovered group (group 2, n=121, 60.5±15.1 years, 79 males). NT-proBNP was measured serially at admission, at discharge, at 3 months after discharge and compared.

Results:
NT-proBNP was 5465.2±5389.6 pg/mL at admission, and the level of NT-proBNP was significantly reduced after HF management (1805.1±2568.4 pg/mL at discharge, 1027.5±1394.9 pg/mL at 3 months after discharge, p<0.001). The level of NT-proBNP at admission was not different between the groups (5251.7±4297.7 vs 5602.7±6013.4 pg/mL, p=ns). However, the level of NT-proBNP at discharge (844.3±630.6 vs 2459.5±3132.8 pg/mL, p<0.001) and at 3 months after discharge (360.5±296.0 vs 1495.3±1652.2 pg/mL, p<0.001) were significantly lower in group 1 than in group 2. The decrease of the level of NT-proBNP from admission to discharge was significantly greater in group 1 than in group 2 (4407.4±4115.6 vs 2817.0±4532.9 pg/mL, p=0.032). The area under the curve to predict LV functional recovery by Receiver Operating Characteristic curve analysis was 0.702 for NT-proBNP change at discharge, 0.247 for the level of NT-proBNP at discharge, and 0.137 for the level of NT-proBNP at 3 months after discharge. The decrease of NT-proBNP > 1633.5 pg/mL from admission to discharge could significantly predict future LV functional recovery (sensitivity: 74.5%, specificity: 66.7%).

Conclusion:
The level of NT-proBNP at discharge, not at admission, and the changes of NT-proBNP at discharge were significant predictor of future LV functional recovery. The serial monitoring of NT-proBNP would be useful for predicting future outcomes in acute de novo HF patients with DCMP.
Abstract 18483: Absence of Chemokine (c-x-c Motif) Ligand 10 Diminishes Perfusion Recovery After Local Arterial Occlusion in Mice
Authors: van den Borne Pleunie , Haverslag René T , Hoefer Imo E , Pasterkamp Gerard , de Kleijn Dominique P
Published: April 2024

Background
In arteriogenesis, pre-existing anastomoses undergo enlargement into functional collateral arteries that are able to restore blood flow in ischemic tissues. Chemokine (C-X-C motif) ligand 10 (CXCL10) is secreted after Toll-like Receptor activation and involved in chemo-attraction of monocytes and T cells. Previously, we have shown that TLR2 and 4 are involved in arteriogenesis. In this study, we investigated the role of CXCL10 in the process of arteriogenesis.

Methods
Unilateral femoral artery ligation was performed in wildtype (WT) and CXCL10-/- (KO) mice and perfusion recovery was measured over 7 days using Laser-Doppler analysis. Histology was performed in hind limb muscles for vessel number and influx of inflammatory cells. Chimerisation experiments were performed to assess the role of bone marrow-derived CXCL10. See table below for all animal numbers per experimental group. Data are shown as mean±SEM.

Results
At 4 and 7 days after operation, perfusion recovery was significantly lower in KO mice compared to WT (50%±13 vs 35%±5 at day 4; p=0.003, 92%±2 vs 76%±13 at day 7; p=0.005) as well as numbers of vessels in the hind limb muscle (α-SMA, 102±7 vs 67±5 at day 4, p<0.001 and 88±9 vs 60±6 at day 7 p=0.02; CD-31, 102±7 vs 67±5 at day 4, p<0.001 and 74±14 vs 109±18 at day 7, p=0.02). Local macrophage and T cell infiltration did not significantly differ between WT and KO. Compared to WT, chimeric mice (KO bone marrow in WT) showed significantly lower perfusion recovery (WT vs chimers: 50%±13 vs 44%±4 at day 4 p=0.046, and 92%±2 vs 61%±5 at day 7, p<0.001). Compared to KO, chimeric mice (WT bone marrow in KO) showed significantly higher perfusion recovery, only at day 4 (KO vs chimers: 35%±5 vs 63%±4 at day 4, p<0.001, and 76%±13 vs 74%±6 at day 7, p=0.24).

Conclusions
CXCL10 plays a critical role in arteriogenesis. Bone marrow-derived, as well as tissue derived CXCL10, plays a critical role in accelerating perfusion recovery after arterial occlusion in mice.
Abstract 18508: The Association of eNOS Gene Single Nucleotide Polymorphism rs1799983 with High-Sensitivity C-Reactive Protein and Early Recurrence of Atrial Fibrillation after Radiofrequency Catheter Ablation
Authors: Shim Jaemin , Park Jae Hyung , Mun Hee-Sun , Wi Jin , Uhm Jae-Sun , Kim Jong Youn , Joung Boyoung , Lee Moon-Hyoung , Pak Hui-Nam
Published: April 2024

Background:
Previous reports have demonstrated the association between single nucleotide polymorphism (SNP) of the eNOS gene and atrial fibrillation (AF). This study evaluated whether eNOS gene variants are associated with high-sensitivity C-reactive protein (hsCRP) and AF recurrence after radiofrequency catheter ablation (RFCA).

Methods:
A total of 500 consecutive patients (56±11 years, 77% male) with paroxysmal (68%) or persistent (32%) AF who underwent RFCA were included. Plasma hsCRP concentration was measured and SNP of the eNOS gene, rs1799983, was genotyped. A 24- to 48-hour Holter ECG recording was performed at 3, 6, and 12 months after the ablation.

Results:
When we compared the patients with rs1799983 variant allele (T, n=84) and those without T allele (n=416), rs1799983 variant allele carriers are more likely to have coronary artery disease or stroke (31.0% vs. 17.8%, p=0.004). The early recurrence (ER) of AF (within 3 months) was observed in 31.8%, whereas the clinical recurrence (CR) of AF (after 3 months) occurred in 24.8% of the patients during the median 17 months of follow-up. The patients with ER were more likely to have persistent AF (44.4% vs. 27.1%, p<0.001) and larger left atrium (42.8±6.4 vs. 41.2±6.2 mm, p=0.011) than those without the ER. Although rs1799983 variant was not associated with the CR, carriers of the variant allele had an increased risk of the ER (OR 1.717 for TT+GT vs. GG, 95% CI 1.059-2.785, p=0.028) and experienced recurrence earlier than those without variant allele (11±16 vs. 20±25 days, p=0.016). However, there were no significant differences in hsCRP between variant and non-variant patients (2.32±4.94 vs. 2.06±4.36 mg/L, p=0.618). A multiple logistic regression analysis showed that the rs1799983 variant (OR 1.714, 95% CI 1.045-2.812, p=0.033) and persistent AF (OR 1.905, 95% CI 1.234-2.939, p=0.004) were independent predictors of the ER.

Conclusions:
The rs1799983 variant of the eNOS gene was associated with early recurrence after RFCA, but not with hsCRP level. A study that further investigates the relationship between genetic variations of eNOS and post-ablation inflammatory process will be warranted.
Abstract 18512: Comparison of Carotid Intima-media Thickness, Plaque Score and Plaque Area Stenosis in Patients with Acute Myocardial Infarction with and without ST-segment Elevation
Authors: Park Sunyoung , Lee Seung-Hwan , Song Taeho , Seo Hyunji , Lim Su-Yeon , Kwon So Jin , Lee Jun-Won , Youn Young-Jin , Ahn Sung-Gyun , Yoo Byung-Su , Yoon Junghan
Published: April 2024

Background:
Increased carotid intima-media thickness (IMT) and presence of carotid plaques are being used for estimation of subclinical atherosclerosis but their role in established coronary artery disease remains uncertain. Therefore, we aimed to evaluate whether carotid parameters are correlated with extent and complexity of coronary atherosclerosis using SYNTAX score (SS). We also sought to compare carotid parameters between ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI).

Methods:
Of 1351 patients who consecutively received carotid ultrasound evaluation from Sep 2011 to May 2012, 137 patients diagnosed with STEMI (n=73) and NSTEMI (n=65) were enrolled (104 men and mean age 64.9±12.7 years). IMT, plaque score (PS) and % plaque area stenosis (AS) were compared between STEMI and NSTEMI. PS was computed according to the presence of plaque in 4 different locations. For the quantification of plaques, % AS was calculated by the ratio of the luminal stenosis area divided by the vessel area at the narrowest portion in short axis view. Clinical parameters and SS were also compared.

Results:
The prevalence of hypertension and diabetes was higher in NSTEMI group than STEMI group (65.6% vs. 39.7%, p=0.002 and 42.2% vs. 19.2%, p=0.003). A higher incidence of multi-vessel disease (≥2 vessels) and diffuse lesion was observed in NSTEMI group (69.6% vs. 45.1%, p=0.007 and 65.6% vs. 46.6%, p=0.038). NSTEMI group had significant higher SS (16.0±9.2 vs. 20.0±10.2, p=0.015), IMT values, PS and % AS. SS was correlated with mean IMT values and PS (r=0.182, p=0.033 and r=0.200, p=0.019). SS was higher in NSTEMI patients with increased IMT & plaque than those with normal carotid artery (22.2±9.9 vs. 10.3±6.1, p=0.001).

Conclusion:
NSTEMI was associated with increased CIMT, higher PS and % AS reflecting atherosclerotic burden. Carotid parameters provided additional information to predict the severity of coronary atherosclerosis in patients with NSTEMI.
Abstract 18562: Severity of Posterior Coaptation Displacement of the Anterior Mitral Leaflet Contributes to Irreversibility of Mitral Regurgitation Following Left Ventricular Assist Device Placement
Authors: Kitada Shuichi , Kato Tomoko S , Schulze P. Christian , Farr Maryjane , Conwell Suzanne D , Takayama Hiroo , Jorde Ulrich P , DiTullio Marco , Naka Yoshifumi , Mancini Donna M , Homma Shunichi
Published: April 2024

Background
The usefulness of concomitant mitral valve surgery at the time of left ventricular assist device (LVAD) placement has not been fully elucidated. We investigated factors associated with irreversibility of mitral regurgitation (MR) after LVAD surgery.

Methods
We reviewed 61 consecutive patients undergoing continuous-flow LVAD placement at Columbia University between 2007 and 2010. Echocardiograms within 2 weeks before and 1 week after surgery were analyzed. Irreversibility of MR was defined as the persistence of moderate or severe MR after LVAD placement. We evaluated clinical characteristics and echocardiographic parameters including left ventricular (LV) dimension, left atrial area (LAA), and the mitral leaflet configuration quantified by posterior (D
P
) and apical (D
A
) displacement of the coaptation point of anterior mitral leaflet (AML). (Figure) The change ([[Unable to Display Character: ⊿]]) of each parameter before and after LVAD placement was also calculated.

Results
Fifty-six patients (92.9%) showed a reduction of LV dimension after LVAD placement. Thirty-three patients (54.1%) had moderate to severe MR before surgery. Among those, 5 patients (5/33, 15.2%) underwent concomitant mitral valve repair at the time of LVAD placement, and 19 patients (19/33, 67.9%) showed only mild or less MR due to mechanical unloading by LVAD, but 9 (32.1%) still had at least moderate MR. The [[Unable to Display Character: ⊿]]LV end-diastolic dimension was correlated with [[Unable to Display Character: ⊿]]D
P
and [[Unable to Display Character: ⊿]]D
A
(r=0.408, p=0.002, r=0.468, p<0.0001, respectively). Pre-operative echo-parameters associated with irreversibility of MR were LV end-diastolic and systolic dimensions, LAA and D
p
.
Multivariate analysis revealed that only D
p
was significantly associated with irreversible MR (HR 1.278, 95%CI 1.015-1.610, p=0.037).

Conclusions
Pre-operative echocardiographic severe posterior coaptation displacement of the AML may predict irreversibility of MR following LVAD placement, and could help identify patients that might benefit from MV repair.
Abstract 18603: Estrogen Plays a Protective Role in Advanced Heart Failure by Regulating Target Genes of miR-129-5p Suppressing Cardiac Fibrosis
Authors: Sharma Salil , Iorga Andrea , Nadadur Rangarajan D , Eghbali Mansoureh
Published: April 2024

Background: Moderate cardiac fibrosis has been reported in advanced heart failure (HF) induced by pressure overload in mice. We have previously shown that short term estrogen(E2) therapy starting after the advanced HF can rescue HF. E2 has been shown to reverse fibrosis through estrogen receptor beta(ERb). Here, we explored whether E2 can suppress cardiac fibrosis by inducing miR-129-5p expression through ERb mediated mechanism and verified its key target genes.

Methods and results: We used transaortic constriction to induce HF in male mice, and once the ejection fraction (EF) reached ∼30%, one group of animals was sacrificed (HF group), and the other group received 17b-estradiol via a subcutaneous pellet implant (0.012mg/pellet, n=16) (E2 group) for 10 days. Sham-operated mice served as CTRL. Serial echocardiography was performed to monitor cardiac structure and function. Short-term E2 treatment rescued pressure overload-induced decompensated HF in mice by restoring the EF from 33.17±1.12% to 53.05±1.29(p <0.001). E2 also decreased both interstitial and prevascular fibrosis in HF. MicroRNA microarray analysis and qPCR validation revealed that miR-129-5p is upregulated ∼2 fold in E2 group compared to HF group. Interestingly, miR-129-5p showed no significant change in E2 versus CTRL suggesting altered miR-129-5p expression in HF was restored to CTRL group by E2 treatment. Treatment of HF with ERb agonist (DPN), but not ER-alpha agonist (PPT), also resulted in the upregulation of miR-129-5p indicating the estrogen mediated induction of miR-129-5p is possibly mediated through ERb. In vitro, angiotensin II treatment significantly downregulated miR-129-5p expression in fibroblasts which was restored by estrogen and DPN but not by ERb antagonist (PHPT) further confirming the role of ERb in regulating miR-129-5p. In vitro, over-expression of miR129-5p in fibroblasts resulted in the significant down-regulation of many potential pro-fibrotic target genes including COL1A, PDGFA, GREM1 and the transcription factor SOX4.

Conclusion:
Our data strongly suggests that estrogen treatment during HF induces miR-129-5p likely through ERb. Mechanistically, miR-129-5p represses fibrosis by targeting key component genes associated with cardiac fibrosis.
Abstract 18611: Transcatheter Aortic Valve Implantation Reduces Central Sleep Apnea in Patients with Severe Aortic Stenosis
Authors: Linhart Markus , Fistéra Rebecca , Pabst Stefan , Ghanem Alexander , Sinning Jan-Malte , Hammerstingl Christoph , Springmann Karin , Werner Nikos , Nickenig Georg , Skowasch Dirk
Published: April 2024

Introduction
While the association between congestive heart failure and central sleep apnea (CSA) is well described, the role of sleep disordered breathing (SDB) and particularly CSA in valvular heart disease is unclear. We evaluated 67 patients with high-grade aortic stenosis and high preoperative risk for the prevalence of SDB before and after transcatheter aortic valve implantation (TAVI).

Methods 67 consecutive patients that were eligible for TAVI were underwent an overnight polygraphy (Embletta ® Device, Embla). Clinical, echocardiographic and invasive data were collected. SDB was defined as an apnea-hypopnea-index (AHI) >5/h. In 31 patients that to date performed the 3 months follow-up, monitoring was repeated and compared to the baseline status.

Results Prevalence of SDB was 61% with a clear predominance of CSA (43%, table 1). In the 3 months follow-up that was completed by 31 patients so far, significant improvement in AHI, AI central, LVEF, NYHA class and NT pro-BNP was seen (table 2). There was a highly significant inverse correlation of NT pro-BNP with LVEF (r=-0.72, p<0.001) but not with severity of CSA (r=0.19, p=0.13). 18 patients died before the 3 months follow-up.

Conclusion We can show a high prevalence of SDB, in particular of CSA, in this patient cohort. There is a highly significant improvement of sleep apnea in the CSA subgroup after TAVI, which is independent of left ventricular function and NT pro-BNP.
Abstract 18612: Intravenous Infusion of Ultrashort-acting Beta-blocker, Landiolol, for Prevention of Immediate Recurrence of Atrial Fibrillation after Catheter Ablation
Authors: Ishigaki Daisuke , Arimoto Takanori , Iwayama Tadateru , Yashiro Yoshinori , Kutsuzawa Daisuke , Tamura Harutoshi , Nishiyama Satoshi , Takahashi Hiroki , Shishido Tetsuro , Miyashita Takehiko , Miyamoto Takuya , Nitobe Joji , Aoyama Hiroshi , Watanabe Tetsu , Kubota Isao
Published: April 2024

BACKGROUND:
Immediate recurrence of atrial fibrillation (AF) after catheter ablation (CA) troubles with patients. We investigated whether intraveneous infusion of landiolol, an ultrashort-acting beta-blocker, could inhibit immediate AF recurrence after CA by randomized controlled trial.

METHOD:
atients with drug-resistant AF treated by CA were assigned to receive either landiolol or placebo after the procedure. In the landiolol group, landiolol was infused ntraveneously at speed of 1 μg/kg/min and continued for 3 days after the CA. The primary end point was occurrence/non-occurrence of AF, defined as supra-ventricular arrhythmia more than 5 min, up to 3-day after CA. Logistic regression analysis was performed to investigate risk factor.

RESULT:
31 and 24 patients were assigned to landiolol group and placebo group, respectively. There were no significant difference between both groups in systolic blood pressure (SBP) before CA, diastolic blood pressure (DBP) before CA and changes from pre-CA to post-CA of SBP and DBP. AF recurrence occurred in 5 patients (10%) in landiolol group versus 11 patients (45%) in the placebo group (P=0.016, Figure). Multivariable analysis revealed that landiolol infusion significantly reduced the risk of transient AF recurrence after procedure (Hazard ratio: 0.208, 95% confidence interval of hazard ratio: 0.048-0.897, P=0.035).

CONCLUSIONS:
Short-term landiolol infusion successfully decreased immediate AF recurrence after CA without changing SBP and DBP. Administration of landiolol may become a new strategy to facilitate management after CA.
Abstract 18631: The Histone Methyltransferase Smyd3 Modulates Growth and Differentiation of Human Cardiac Stem Cells
Authors: Gurusamy Narasimman , Kim Junghyun , Hosoda Toru , Fiorini Claudia , Sanada Fumihiro , Caballero Virginia , D'Amario Domenico , Zheng Hanqiao , Rota Marcello , del Monte Federica , D'Alessandro David A , Michler Robert E , Kajstura Jan , Anversa Piero , Bolli Roberto , Leri Annarosa
Published: April 2024

Stemness and pluripotency of embryonic stem cells (ESCs) are largely mediated by epigenetic modifications. The objective of this study was to determine whether growth and commitment of human cardiac stem cells (hCSCs) are similarly regulated. Discarded surgical specimens were enzymatically digested and c-kit-positive hCSCs were sorted by FACS. Genome-wide analysis of histone modifications documented that adult hCSCs are characterized by a bivalent chromatin configuration similar to that of ESCs with repressive and activating marks at lysine residues of histones H3 and H4. The high levels of di- (H3K4me2) and tri-methylation (H3K4me3) at lysine 4 of histone H3 prompted us to test the possibility that the histone methyltransferase Smyd3 is involved in the epigenetic control of hCSC function. Smyd3 downregulation by siRNA decreased the levels of H3K4me2 and H3K4me3 and resulted in a marked attenuation in hCSC replication and differentiation into myocytes and vascular cells. In contrast, Smyd3 overexpression led to a 1.6-fold increase in dividing hCSCs and a 2-fold increase in hCSCs committed to the myocyte lineage. Thus, we studied whether Smyd3 regulates a group of genes controlling the growth of hCSCs and their specification to the myocyte and vascular fate: telomerase (TERT), Nkx2.5, and GATA6. Downregulation of Smyd3 decreased the activity of telomerase, and the expression of Nkx2.5 and GATA6. By immunolabeling, Smyd3 co-localized with TERT, Nkx2.5 and GATA6 in hCSC nuclei. To document the role of Smyd3 in the transcription of TERT, Nkx2.5, and GATA6, ChIP assays with antibodies against Smyd3 and H3K4me3 were performed in hCSCs. Amplification and sequencing of the precipitated DNA fragments demonstrated that Smyd3 occupied the TERT, Nkx2.5, and GATA6 promoter regions in which its consensus sites are located. Gene reporter assays with plasmids carrying the 5’ flanking regions of TERT or Nkx2.5 containing mutated Smyd3 binding sites led to a marked decrease in promoter activity of the two genes. Importantly, high levels of expression of Smyd3 were found in the regenerated myocytes derived from hCSCs injected in immunosuppressed infarcted rats. Thus, Smyd3 plays a central role in the modulation of growth and differentiation of hCSCs in vitro and in vivo.