bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11027: Elevated Serum Testosterone Levels are Associated With Adverse Events in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia
Authors: Akdis Deniz , Saguner Ardan Muammer , von Eckardstein Arnold , Chen HS Vincent , Brunckhorst Corinna , Duru Firat
Published: April 2024

Introduction:
Sex hormones have been reported to play a role in the pathophysiology of ventricular arrhythmias.

Hypothesis:
We hypothesized that there may be a relationship between sex hormones and cardiovascular adverse events in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D).

Methods:
Serum levels of testosterone, dehydroepiandrosterone, sex steroid-binding globulin, androstendione, estradiol, and progesterone were measured along with routine biochemical markers in 44 patients (33 male) from the Swiss ARVC/D Registry with a definite (n=29) or borderline (n=15) diagnosis of ARVC/D. Sex hormone levels were correlated with major adverse cardiovascular events (MACE), defined as the occurrence of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia or arrhythmogenic syncope.

Results:
Twenty-four patients experienced MACE within the last six months prior to determination of sex hormone levels. Testosterone levels were significantly higher in patients with MACE (mean±SD: 14nmol/l±9.6 versus 8.6nmol/l±5.9;p=0.03). In male patients with MACE, testosterone levels (18.7nmol/l±5.8 versus 11.3nmol/l±3.8; p=0.001) and sex steroid-binding globulin levels (48.9nmol/l±20.8 versus 32nmol/l±12.2; p=0.01) were significantly increased, whereas dehydroepiandrosterone levels were significantly decreased (4.0 micromol/l±2.6 versus 7.0 micromol/l±4.4; p=0.03). In females estradiol was lower in patients with MACE (14.1pmol/l±3.8 versus 396.6pmol/l±336.2; p=0.007). In bivariable analysis after adjusting for confounders such as body mass index, sports activity, and reduced RV/LV function, increased testosterone levels remained a significant independent predictor of MACE in males (odds ratio 1.4 per 1 nmol/l increase, 95% confidence interval 1.1-1.8,
p=
0.005). A cut-off value for testosterone at 13.45 nmol/l predicted MACE with a sensitivity of 0.8 and a specificity of 0.7.

Conclusion:
In conclusion, our study suggests that sex hormones, in particular testosterone, are associated with adverse clinical events in patients with ARVC/D, and therefore, may play a role in risk stratification of this disease.
Abstract 11063: Evaluation of Different Energy Drinks and Coffee on Endothelial Function
Authors: Somberg John C , Molnar Janos
Published: April 2024

Background:
Endothelial function is an important component of vascular health. There have been differing reports on the effect of energy drink on endothelial function. The aim of this study was to evaluate the effect of 3 commonly consumed energy drinks on endothelial function. As the main active ingredient of energy drinks is caffeine, a comparison was made to coffee, a drink with substantial caffeine content. The hypothesis tested was that energy drinks differ in effect on endothelial function due to differing ingredients.

Methods:
Endothelial function was evaluated in 16 healthy volunteers employing an EndoPAT device (Itamar Medical, Israel) that measures digital peripheral arterial tonometry and reports endothelial function as the Reactive Hyperemia Index (RHI). Volunteers (Age: 25±5 years, 7 females, 9 male, weight: 72±11 kg, height: 169±10 cm, systolic blood pressure: 121±7 mmHg, and diastolic blood pressure: 80±6 mmHg) received the energy drink sequence (3) or coffee (16). Energy drink or coffee were given at least 2 days apart. Drinks studied were 250 mL Red Bull containing 80 mg caffeine, 57 mL “5-hour Energy” containing 230 mg caffeine, a can of 355 mL “NOS” energy drink containing 120 mg caffeine and a cup of 473 mL coffee containing 240 mg caffeine, taken in a random order. Studies were performed before drink (baseline) at 1.5 and 4 hrs. post drink.

Results:
Two of the energy drinks (Red Bull and 5-hour Energy) significantly improved endothelial function at 4 hrs. post drink, while one (NOS) as well as coffee did not change endothelial function significantly. RHI increased by 40±7% (p=0.01) and 48±12% (p=0.019) following 5-hour Energy and Red Bull respectively. RHI decreased following NOS by 13±8% (p=0.101) and increased by 7±30% (p=1.000) following coffee.

Conclusion:
Improvement in endothelial function as measured by RHI is seen with some but not all energy drinks. Coffee does not show a significant improvement in endothelial function as measured by RHI.
Abstract 11279: A Rapid Method to Evaluate Cardiac Repolarization Changes: The Effect of Two Coffee Strengths on the QT interval
Authors: Jaffrani Danial N , Somberg John C , Molnar Janos
Published: April 2024

Background:
Coffee is a widely used beverage, consumed for its stimulant effect, which is attributed to caffeine. Controversy exists about the acute and chronic cardiovascular effects of coffee in man including potential arrhythmogenicity. Surprisingly, very few studies with conflicting results have evaluated the effect of coffee or caffeine on ventricular repolarization. This is especially important in that prolongation in ventricular repolarization may lead to ventricular arrhythmias. The primary objective of this study was to assess the effect of coffee on ventricular repolarization as measured by the QT/QTc interval obtained from the body surface ECG.

Methods:
Fifty four healthy volunteers (34 males, 20 females, age: 23±5 years) received 1 cup coffee (caffeine: 120 mg) and 11 volunteers received 2 cups. Blood pressure (BP) and heart rate (HR) were measured prior to coffee and every hour thereafter for 5 hours. A 12-lead digital Holter was recorder continuously. The Holter analysis system automatically generates a representative median QRST complex for each 1 minute segment of the recordings and measures RR and QT intervals. The position of cursors indicating the beginning of the QRS complex and the end of the T wave were visually evaluated and their positions adjusted (as needed). The system has been validated for QT/QTc analysis. RR, QT and QTc intervals were tabulated every 30 minutes. The QTc intervals were calculated by the Fridericia formula.

Results:
Following coffee, maximum changes were noted at 1.5 hr in RR which increased from 802±102 to 873±126 ms (p=0.001), and QT increased from 359±26 to 367±27 ms. The QTc shortened from 387±21 to 381±23 ms at 30 minutes (p=0.001) with no significant changes noted at the other time points. The HR decreased from 73±9 to 69±11 bpm at 1 hr. (p=0.018). There were no significant changes in BP. The effects of 1 or 2 cups coffee did not differ on QTc (p=0.663), HR (p=0.161), diastolic (p=0.250) or systolic BP (p=0.168). Caffeine users and caffeine naïve subjects did not differ in QTc effect (p=0.971). Females had longer QTc at each time point than males (p=0.037) but neither had QTc prolongation following coffee.

Conclusion:
Neither 1 nor 2 cups of coffee prolonged ventricular repolarization as measured by the QTc interval.
Abstract 11586: Pulse-based Arrhythmia Discrimination Using a Novel Smartphone Application
Authors: Napolitano Craig A , Chong Jo Woon , Saczynski Jane S , Esa Nada , Darling Chad E , Boyer Edward , Rosen Rochelle K , Floyd Kevin C , Chon Ki H , McManus David D
Published: April 2024

Introduction:
Screening for atrial fibrillation (AF) normally involves the use of expensive and cumbersome outpatient monitoring equipment. Currently, smartphone based detection allows for assessment of heart rate alone or requires additional hardware which has limited its widespread use in screening for AF. We describe the use of the first smartphone based monitor that has the ability to discriminate AF from ectopy (including PACs and PVCs) without the need of additional hardware.

Methods:
We analyzed 219 2-minute pulse recordings from 121 study participants with AF (n=98), PACs (n=15), or PVCs (n=15) using an iPhone 4S. We obtained pulsatile time series recordings in 91 participants after successful cardioversion to sinus rhythm from pre-existing AF. The PULSESMART app conducted pulse analysis using 3 methods [Root Mean Square of Successive RR Differences; Shannon Entropy; Poincare plot]. We examined the sensitivity, specificity, and predictive accuracy of the app for AF, PAC, and PVC discrimination from sinus rhythm using the 12-lead EKG or 3-lead telemetry as the gold standard. We also administered a brief usability questionnaire to a subgroup (n=41) of app users.

Results:
The smartphone-based app demonstrated excellent sensitivity (0.970), specificity (0.935), and accuracy (0.951) for real-time identification of an irregular pulse during AF. The app also showed good accuracy for PAC (0.955) and PVC discrimination (0.960). The vast majority of surveyed app users (83%) reported that it was “useful” and “not complex” to use.

Conclusion:
A smartphone app can accurately discriminate pulse recordings during AF from sinus rhythm, PACs, and PVCs without the need of additional hardware.
Abstract 11587: Excessive NaCl Intake Aggravates Aortic Dissection Through IL-17 Pathway
Authors: Nishida Norifumi , Aoki Hiroki , Ohno Satoko , Nishihara Michihide , Furusho Aya , Hirakata Saki , Hayashi Makiko , Ito Sohei , Yasukawa Hideo , Fukumoto Yoshihiro
Published: April 2024

Excessive NaCl intake is an established risk factor of cardiovascular events, although the molecular mechanism has not been fully understood. Aortic dissection (AD) is one of the fatal cardiovascular events, in which proinflammatory response is proposed to be important. In this study, we investigated the effect of excessive NaCl intake on a mouse AD model that was induced by continuous infusion of beta-aminopropionitrile (BAPN), a collagen/elastin crosslink inhibitor, and angiotensin II (AngII). BAPN+AngII caused thoracic and suprarenal AD in most of the mice within 2 weeks. Excessive NaCl intake was achieved by giving 1% NaCl as drinking water (Hi-Na) 1 week prior to and during the BAPN+AngII infusion. The lesion length of AD was significantly longer in Hi-Na group than in normal water group, even though systolic blood pressure or pulse rate showed no significant changes. Because recent studies have demonstrated that excessive NaCl activates TH17/IL-17 pathway that is central to the inflammatory response, we examined the involvement of IL-17 in AD using IL-17 knockout mice (IL17-KO). Deletion of IL-17 gene abolished the exacerbating effect of NaCl on the severity of AD. Transcriptome analysis of aortae before AD onset showed that strong induction of proinflammatory genes and suppression of extracellular matrix (ECM) genes precede the AD development in this model. Although IL-17 is central to inflammatory response in general, alteration of inflammatory response was not prominent in IL17-KO aorta. Instead, genes of ECM was upregulated in IL17-KO at the baseline. With BAPN+AngII and excessive NaCl intake, expression of ECM genes were higher in IL17-KO compared to wild type aorta. Picrosirius red staining showed that the amount of medial collagen fibers, the major ECM to support the physical strength of aorta, was increased in IL17-KO compared to wild type mice without NaCl overload or BAPN+AngII administration. These data uncovered the unexpected role of IL-17 to suppress the ECM deposition in aorta. Because ECM is essential to maintain the physical strength of aortic walls, the increase of ECM would explains why IL17-KO aorta is protected from dissection. NaCl intake and IL-17 may represent important therapeutic targets for AD.
Abstract 11669: Pulse Pressure and Risk of Cardiovascular Events in Patients With Atherothrombosis: Findings From the REACH Registry
Authors: Selvaraj Senthil , Steg Philippe , Elbez Yedid , Sorbets Emmanuel , Feldman Laurent J , Eagle Kim , Ohman E. Magnus , Blacher Jacques , Bhatt Deepak
Published: April 2024

Background:
Pulse pressure (PP) provides valuable prognostic information in specific populations, but few studies have assessed its prognostic value on cardiovascular outcomes in a broad, worldwide population.

Hypothesis:
PP is associated with adverse outcomes independent of mean arterial pressure.

Methods:
We examined participants from the REACH (Reduction of Atherothrombosis for Continued Health) registry, an international study of individuals with atherothrombotic disease or risk factors for its development. We excluded those with incomplete four-year follow-up or PP data (final N=45,087). Univariable and multivariable regression analyses (using stepwise modeling) were performed to determine the association between PP and cardiovascular outcomes, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, cardiovascular hospitalization, and a combined outcome. Model 1 covariates included sex, age, smoking status, hyperlipidemia, diabetes mellitus, aspirin use, statin use. Model 2 further adjusted for history of atherothrombosis. Model 3 additionally adjusted for blood pressure medications. Model 4 finally adjusted for mean arterial pressure.

Results:
The mean age of the cohort was 68±10 years, 35% were female, and 81% were treated for hypertension. The mean blood pressure was 138±19/79±11 mmHg (mean PP of 49±16 mmHg). On univariable analysis, increasing PP quartile was associated with worse outcomes (p<0.05 for all comparisons). The Figure displays hazard ratios per 10 mmHg increase in PP, and shows an increased risk of the combined outcome. Similar findings were demonstrated for non-fatal myocardial infarction and cardiovascular hospitalization (p<0.01).

Conclusions:
In a large international cohort of high-risk individuals, PP, a readily available hemodynamic parameter, is associated with multiple adverse cardiovascular outcomes and provides prognostic utility beyond that of mean arterial pressure.
Abstract 11679: Similarities Between the Villi of the Jejunum and the Human Artery Wall May Contribute to Diet-Induced Dyslipidemia and Systemic Inflammation in LDLR Null Mice
Authors: Chattopadhyay Arnab , Navab Mohamad , Hough Greg P , Reddy Srinivasa T , Fogelman Alan M
Published: April 2024

In early atherosclerosis, LDL in the human artery wall is seeded with reactive oxygen species resulting in the formation of oxidized phospholipids that promote infiltration of monocytes, which convert into macrophages. We recently reported that supplementing standard mouse chow with lysophosphatidylcholine (LysoPC) 18:1 caused dyslipidemia and systemic inflammation in LDLR null mice. We now report that feeding chow supplemented with LysoPC 18:1 (1 mg LysoPC 18:1 per gram chow) or feeding a Western diet (WD) to LDLR null mice results in an increase in oxidized phospholipids in the villi of the jejunum as detected with the E06 antibody. On a diet of standard mouse chow, 2.2 ± 0.2% of the area of the villi of the jejunum stained positively for oxidized phospholipids. After two weeks of feeding standard mouse chow supplemented with LysoPC 18:1 or feeding WD, the area staining positively for oxidized phospholipids increased to 4.0 ± 0.5%, and 7.3 ± 0.8%, respectively (p = 0.0043, and p < 0.0001, respectively). If 0.06% by weight of a concentrate of transgenic tomato expressing an apoA-I mimetic peptide (Tg6F) was added to the chow supplemented with LysoPC 18:1 or was added to WD, the area staining positively for oxidized phospholipids decreased to 2.1 ± 0.3%, and 2.3 ± 0.4%, respectively (p = 0.0029, and p <0.0001, respectively). Concomitant with the increase in oxidized phospholipids there was a significant increase in macrophages as detected by F4/80 staining. On chow 0.8 ± 0.2% of the area of the villi of the jejunum stained positively for macrophages. After two weeks of feeding chow supplemented with LysoPC 18:1 or feeding WD, the area staining positively for macrophages increased to 1.6 ± 0.2%, and 4.4 ± 0.4%, respectively (p = 0.0095, and p < 0.0001, respectively). If 0.06% by weight of Tg6F was added to the chow supplemented with LysoPC 18:1 or was added to WD, the area staining positively for macrophages decreased to 0.9 ± 0.2%, and 3.0 ± 0.3%, respectively (p = 0.0169, and p < 0.0001, respectively). These data support the hypothesis that LysoPC 18:1 and WD lead to a sequence of events in the villi of jejunum that is very similar to that seen in the human artery wall, and may contribute to diet-induced dyslipidemia and systemic inflammation in LDLR null mice.
Abstract 11773: N-3 Polyunsaturated Fatty Acids Inhibit Inflammatory Responses in Macrophages by the Reduction of Toll-like Receptor 4 Expression in Lipid Rafts, Leading to the Suppression of Atherogenesis in Apolipoprotein E Deficient Mice
Authors: Takashima Akira , Fukuda Daiju , Tanaka Kimie , Higashikuni Yasutomi , Hirata Yoichiro , Yamada Hirotsugu , Soeki Takeshi , Wakatsuki Tetsuzo , Shimabukuro Michio , Sata Masataka
Published: April 2024

Introduction:
Macrophages promote inflammatory responses, contributing to the development of atherosclerosis. Lipid rafts in macrophages facilitate inflammatory responses by gathering inflammatory molecules such as toll-like receptor 4 (TLR4). Whereas, n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), incorporated into the plasma membrane cause functional alteration of lipid rafts. Here, we tested the hypothesis that n-3 PUFAs decrease macrophage activation by the reduction of TLR4 expression in lipid rafts and attenuate atherogenesis in apolipoprotein E knockout (ApoE KO) mice.

Methods and Results:
ApoE KO mice were fed western-type diets supplemented with 2.5% EPA, 5% omega-3-acid ethyl esters which include 2.3% EPA and 1.9% DHA (EPA+DHA), or none of n-3 PUFAs (control group) from 8-week-old for 20 weeks. Blood pressure and plasma total cholesterol level did not differ in these groups. En face Sudan IV staining of the aorta revealed that n-3 PUFAs treatment significantly attenuated atherogenesis compared with control group, and the effect was enhanced in EPA+DHA group (P< 0.05). Histological or quantitative RT-PCR analyses demonstrated that EPA+DHA treatment decreased lipid deposition, MMP-9 expression, and macrophage accumulation in atherosclerotic lesions in the aorta compared with control group (P<0.05, P<0.01 and P<0.01, respectively). In vitro experiment using RAW264.7, a murine macrophage cell line, demonstrated that n-3 PUFAs attenuated the up-regulation of MMP-9 and MCP-1 induced by LPS. Isolation of lipid rafts from RAW264.7 by sucrose gradient ultracentrifugation demonstrated that n-3 PUFAs suppressed LPS-induced TLR4 expression in lipid rafts. Lipid raft disruption by methyl-β-cyclodextrin, the membrane cholesterol depleting agent, suppressed LPS-induced up-regulation of MMP-9 and MCP-1 in this cell type.

Conclusions:
N-3 PUFAs inhibited inflammatory responses in macrophages by the reduction of TLR4 expression in lipid rafts, leading to the suppression of atherogenesis in ApoE KO mice. Our results suggested that lipid rafts in macrophages may serve as a potential therapeutic target for atherosclerosis.
Abstract 11815: Prolonged Space Flight Induced Alterations in the Structure of Medaka Cardiac Muscle and Gene Expression
Authors: Enomoto Hirokazu , Mittal Nishant , Makino Shinji , Fukuda Keiichi
Published: April 2024

Introduction:
Cardiovascular deconditioning (reduction of ventricular mass and blood pressure) induced by prolonged spaceflight. Little has been reported about histology and gene expression pattern of heart after long time in the international space station (ISS). The purpose of this study is to examine how microgravity affects the structure and gene expression of medaka cardiac muscle.

Methods:
Fifteen medaka fishes were sent to ISS. The fish lived in a space aquarium of ISS. Control medaka lived in same aquarium on the ground. After 2 weeks and 2 months of swimming in microgravity, medaka fish (N=5, each) were fixed in 4% paraformaldehyde at ISS. Cardiac morphology and structure were assessed by hematoxylin and eosin (HE), Azan and immuno-staining. The remaining 5 medaka fish, after 2 months at ISS, were treated by RNAlater for preservation of RNA for RT-PCR and RNA-Seq analysis.

Results:
The fishes at ISS were swimming in loops rather than straight line and tend to standstill. The body sizes were normal. Spaceflight heart looked normal without apparent histological abnormalities in 2 weeks samples. However, 2 month sampled spaceflight heart showed thinner cardiac fibers, exhibited circular lacunas and higher cardiac fibrosis. Using RNA-seq and RT-PCR, mRNA expression of cardiac contractile genes (myosin heavy chain, myosin light chain II and troponin T) were decreased in spaceflight heart. Interestingly, autophagy related genes (atg3, atg4, atg14 and atg16) expression were higher in spaceflight heart. However, Atg genes expressions were not changed in skeletal muscle. Although, myocardium mass was lower in spaceflight heart, mRNA expressions of muscle-specific ubiquitin ligases (MuRF1 and Atrogin1) and brain natriuretic peptide (BNP) were normal. Immuno-staining showed increased ULK1 expression in 2 weeks and LC3-II level (autophagosomes formation subtype) in 2 months spaceflight samples. Prolonged weightlessness produced substantial loss of cardiac fiber mass by autophagy.

Conclusion:
Microgravity increases autophagy related genes and decreases sarcomeric protein gene expression, which lead cardiac atrophy after prolonged spaceflight.
Abstract 11981: Comparison of Long-term Effects of Atorvastatin versus Pravastatin on Serum Proprotein Convertase Subtilisin/kexin Type 9 Levels in Patients With ST-segment-elevation Myocardial Infarction
Authors: Kashima Yuichiro , Imamura Hiroshi , Izawa Atsushi , Ikeda Uichi
Published: April 2024

Introduction:
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of serum low-density lipoprotein levels and statins increase serum PCSK9 levels. Therefore, we investigated PCSK9 levels in ST-segment-elevation myocardial infarction (STEMI) patients who underwent PCI and were randomly allocated to atorvastatin or pravastatin therapy for 2 years.

Hypothesis:
Atorvastatin or pravastatin differentially influence long-term PCSK9 levels in STEMI patients.

Methods:
The present study is a subanalysis of the ALPS-AMI study and patients who were increased 10 to 20 mg of statin dose, and added ezetimibe during the study period were excluded from the ALPS-AMI study. PCSK9 levels were measured at 1 and 24 months in 225 STEMI patients who were randomly allocated to 10 mg/day of atorvastatin (n = 107) or pravastatin (n = 118) statin therapy.

Results:
No differences in 1-month PCSK9 levels between the atorvastatin and pravastatin groups were noted. However, the 24-month PCSK9 levels were significantly higher in pravastatin group (389.4 [interquartile range: 293.6-485.1] ng/mL than in atorvastatin group (314.5 [interquartile range: 235.4-375.8] ng/mL,
P
<0.001).

Conclusions:
This is the first clinical trial to compare the long-term effects of atorvastatin and pravastatin therapy on PCSK9 levels in patients with STEMI, and demonstrates that pravastatin therapy was more increased serum PCSK9 levels than atorvastatin therapy.
Abstract 12055: Impaired Right Ventricular Function Affects Survival After Surgical Left Ventricular Reconstruction
Authors: Couperus Lotte E , Delgado Victoria , Palmen Meindert , Tops Laurens F , Van Vessem Marieke E , Verwey Hariette F , Klautz Robert J , Schalij Martin J , Beeres Saskia L
Published: April 2024

Introduction:
The determinants of survival after surgical left ventricular reconstruction (SVR) in ischemic heart failure remain not fully elucidated. Several left ventricular (LV) parameters have been associated with prognosis. The role of right ventricular (RV) function, however, remains to be determined.

Hypothesis:
Impaired preoperative RV function is associated with worse outcome in patients undergoing SVR.

Methods:
Consecutive patients (130 patients; age 62±10 years; 79% male; LV ejection fraction [LVEF] 27±7%; urgent surgery in 22%) underwent SVR between 2006 and 2012. Biventricular function was assessed by echocardiography before surgery. Parameters of impaired RV function were RV fractional area change (RVFAC) <35%, tricuspid annular plane systolic excursion (TAPSE) <16mm and RV longitudinal peak systolic strain (RV LPSS) ≥-19%. The independent association between these RV functional parameters and mortality was assessed in several non-nested multivariate analyses. Furthermore, the additive effect of multiple impaired RV parameters on mortality was assessed.

Results:
Survival 30 days after SVR was 89%. Impaired RVFAC (HR 3.59, 95%CI 1.21-10.68, p=0.02), TAPSE (HR 2.96, 95%CI 1.05-8.35, p=0.04) and RV LPPS (HR 3.78, 95%CI 1.11-12.85, p=0.03) were independently associated with 30 day mortality, after adjusting for LVEF, the need for urgent surgery and surgery time. Moreover, a higher number of impaired RV parameters per patient was independently associated with increased mortality (HR 5.57, 95%CI 0.94-32.85, p=0.06 for 1 impaired parameter; HR 6.90, 95%CI 1.20-39.76, p=0.03 for 2 impaired parameters; HR 21.27, 95%CI 3.11-145.56, p<0.01 for 3 impaired parameters). Survival curves for impaired versus normal RVFAC, TAPSE and RV LPSS respectively and for multiple impaired parameters are presented in the figure.

Conclusion:
Impaired pre-operative RV function is associated with increased 30 day mortality in patients undergoing SVR.
Abstract 12075: Telecommunicator CPR Intervention Improves Recognition of Cardiac Arrest and Time to First Chest Compression
Authors: Sutter John , Langlais Blake , Dameff Christian , Tully Jeffrey , Panczyk Micah , Chikani Vatsal , Vadeboncoeur Tyler F , Spaite Daniel W , Bobrow Bentley J
Published: April 2024

Background:
Bystander cardiopulmonary resuscitation (BCPR) significantly improves survival from out-of-hospital cardiac arrest (OHCA). Telecommunicator CPR (TCPR) has been shown to increase BCPR rates, yet TCPR performance varies widely. We assess whether a bundled TCPR protocol, training, and continuous quality improvement (CQI) intervention improves TCPR performance.

Methods:
The intervention was implemented at a regional 9-1-1 dispatch center and had three main components: (1) the installation of the AHA-recommended 2-question TCPR protocol, (2) training to enhance telecommunicator OHCA recognition and (3) CQI with system and case-level feedback. Training included a two-hour lecture, 30 minutes of video training, and one hour of simulation training. Audio recordings of suspected OHCAs from pre (P1, 10/5/10 - 11/6/11) and post-intervention (P2, 11/7/11 - 11/4/13) periods were collected by searching center archives for calls originally processed as cardiac arrests. Recordings were analyzed according to six key TCPR metrics. Times to telecommunicator recognition of cardiac arrest, start of TCPR instructions, and initiation of chest compressions were measured using a standardized timestamp format.

Results:
Rates of OHCA recognition (80% to 95%, p<0.0001), TCPR instructions started (32% to 72%, p<0.0001), and bystander chest compressions initiated (18% to 70%, p<0.001) all increased significantly. Reductions in the time from call receipt to the start of TCPR instructions (176s to 133s, p<0.0001) and to the start of compressions (265s to 162s, p<0.0001) were also observed.

Conclusion:
This bundled protocol, training and CQI intervention was associated with a significant increase in TCPR rates and a reduction in the time to first chest compression.
Abstract 12121: Right Ventricular Free-Wall Longitudinal Speckle-Tracking Strain in Patients With Pulmonary Arterial Hypertension Under Specific Treatment
Authors: Kemal Hatice S , Kayikcioglu Meral , Can Levent , Nalbantgil Sanem , Vuran Ozcan , Mogulkoc Nesrin , Kultursay Hakan
Published: April 2024

Introduction:
Pulmonary arterial hypertension (PAH) is a devastating disease of pulmonary vascular remodelling, right heart failure and limited survival. Although right ventricular (RV) dysfunction is a major determinant of outcome in patients with PAH, the optimal measure of RV function is poorly defined.

Hypothesis:
The objectives of this study were to test the utility of RV free wall speckle-tracking strain (RV-free) as an assessment tool for RV function in patients with PAH who are already under specific medical treatment compared with conventional echocardiographic parameters and to investigate the relationship of the findings obtained with RV-free with hemodynamic parameters of RV performance.

Methods:
Prospective RV- free measurement was performed on 92 PAH patients of different etiologies (49 PAH associated with congenital heart disease, 21 idiopathic PAH, 11 PAH associated with connective tissue disease and 11 chronic thromboembolic pulmonary hypertension) who were on PAH spesific treatment for at least 3 months. RV-free was calculated by averaging each of 3 regional peak systolic strain values. The mean follow-up was 222±133 days. Conventional echocardiographic parameters-RV FAC, TAPSE and Tricuspid S-, hemodynamic parameters -functional class, 6-min. walking distance, and NT-proBNP- were also studied.

Results:
The mean age was 41± 16 years and 67.4% were female. Mean RV- free of the study population was %-13.16 ± 6.3. There was a significant positive correlation between RV-free and functional class (r=0.312, p=0.01), NT-proBNP (r=0.423, p=0.0001), whereas negative correlation with FAC (r=-0.637, p=0.0001), TAPSE (r=-0.524, p=0.0001), Tricuspid S (r=-0.450, p=0.0001), 6-min. walking distance (r=-0.333, p=0.002). RV-free significantly correlated with all follow-up adverse events, death and clinical right heart failure (p=0.04, p=0.03, p=0.02, respectively). According to the ROC analysis, the cut-off value for the development of clinical right heart failure was -13.8% (sensitivity: 71%, specificity: 60%) for RV-free.

Conclusions:
Assessment of RV-free is a feasible, easy to perform method and maybe used as a predictor of right heart failure, clinical deterioration and mortality in patients under PAH specific treatment.
Abstract 12143: The Identification of Bone Marrow-derived Artery-resident Mesodermal Progenitor Cells and Dynamics in Atherosclerosis
Authors: Cho Hyun-Jai , Cho Hyun-Ju , Lee Choon-Soo , Lee Ho-Jae , Han Jung-Kyu , Kim Hyo-Soo
Published: April 2024

Background:
Cellular components and dynamics play a pivotal role in vascular diseases. A recent study identified bone marrow (BM)-derived calcifying progenitor cells. However, the nature of progenitor cells remains elusive. We here investigated the developmental hierarchy of progenitor cells and their dynamics in atherosclerosis.

Methods and Results:
We harvested cells from BM and artery of C57 mice. In BM, Lin-/CD29+/Sca-1+/PDGFRα- cells showed hematopoietic potential and differentiated into osteoclast (OC)-like cells.They also possessed mesenchymal stem cell property including osteoblastic (OB) differentiation. In contrast, Lin-/CD29+/Sca-1+/PDGFRα+ cells showed only OB potential. In vivo reconstitution assay demonstrated that Sca-1+/PDGFRα- cell was an ancestor of Sca-1+/PDGFRα+ cell, suggesting a mesodermal progenitor cell. Interestingly, BM-derived artery-resident, clonal Sca-1+/PDGFRα- cells maintained bi-potency (OB/OC) but lost hematopoietic nature. When we stimulated or knocked down PDGFRα, there was no alteration in OB or OC differentiation of Sca-1+/PDGFRα- cells and no effect on OB differentiation of Sca-1+/PDGFRα+ cells, indicating PDGFRα as a surface marker but not a functional player. In Apoe-KO mice compared with control, Sca-1+/PDGFRα- cells were less mobilized from BM to peripheral circulation and less infiltrated into atherosclerotic plaque, whereas Sca-1+/PDGFRα+cells were not significantly affected. Multiplex cytokine assay of serum and artery revealed that IL-1β was modestly increased and IL-5 was markedly decreased in atherosclerotic mice. IL-1β decreased the migration of Sca-1+/PDGFRα- cells by 5 folds compared with TNFα, and IL-5 increased the migration as much as TNFα. But the migration of Sca-1+/PDGFRα+ cells was not altered.

Conclusion:
We demonstrate that Sca-1+/PDGFRα- cell is a mesodermal progenitor cell that possesses both hematopoietic and mesenchymal potentials. The mobilization and infiltration of mesodermal progenitor cells into artery were regulated by atherosclerosis-related Inflammatory and anti-inflammatory humoral factors. These data may have implications for the pathophysiology of atherosclerosis and provide a novel therapeutic target for vascular diseases.
Abstract 12201: High-Density Lipoprotein Cholesterol Levels and Cardiovascular Outcomes in Japanese Patients After Percutaneous Coronary Intervention: A Report From the CREDO-Kyoto Registry Cohort-2
Authors: Izuhara Masayasu , Ono Koh , Shiomi Hiroki , Morimoto Takeshi , Furukawa Yutaka , Nakagawa Yoshihisa , Shizuta Satoshi , Tada Tomohisa , Tazaki Junichi , Horie Takehiro , Kuwabara Yasuhide , Baba Osamu , Nishino Tomohiro , Kita Toru , Kimura Takeshi
Published: April 2024

Background:
Low levels of HDL-C is associated with increased coronary risks in patients without known coronary artery disease (CAD) and high risks of cardiovascular events in patients with stable CAD. But it is still controversial whether low HDL-C influences cardiovascular outcomes, especially in patients with known CAD receiving current optimized treatments.

Objective:
We determined whether low HDL-C is a risk factor for adverse cardiovascular events in patients with known CAD who underwent percutaneous coronary intervention (PCI).

Methods:
We evaluated 10,391 patients who underwent PCI from January 2005 to December 2007. In total, 3,838 (36.9%) patients had low HDL-C (HDL-C <40 mg/dL in males and <50 mg/dL in females) and 6,553 (63.1%) patients had normal HDL-C based on measurements on admission.

Results:
The unadjusted 5-year incidence of major adverse cardiac events (MACE: composite of cardiovascular death, myocardial infarction or stroke) was significantly higher in the low HDL-C group than in the normal HDL-C group (17.6% vs. 14.0%, P<0.0001). However, after adjusting for confounders, low HDL-C was not associated with a higher risk of MACE (adjusted hazard ratio [HR] 1.07, 95% confidence interval (CI) 0.97-1.19; P=0.19). There was no significant interaction between the effect of low HDL-C on MACE and several subgroup factors including age, sex, clinical presentation of CAD, statins use, serum low-density lipoprotein cholesterol level, and serum triglycerides level.

Conclusions:
Low HDL-C, as compared with normal HDL-C, was not associated with higher 5-year risk of MACE in patients who underwent PCI.
Abstract 12241: Exploring the Interaction Between Nighttime Heart Rate and Heart Rate Variability on Future Cardiovascular Event
Authors: Negishi Keita , Hoshide Satoshi , Kabutoya Tomoyuki , Ogoyama Yukako , Eguchi Kazuo , Kario Kazuomi
Published: April 2024

Introduction:
High nighttime heart rate or heart rate variability assessed by ambulatory blood pressure monitoring (ABPM) has been reported to be risk for cardiovascular events. However, it is not clear whether these indices provide synergic risk for cardiovascular events.

Hypothesis:
The aim of this study is to explore the interaction between nighttime heart rate and heart rate variability on future cardiovascular event.

Methods:
We studied 1418 patients (average age 64.6±11.6 years, male 47.9%) from J-HOP study who were performed ABPM. We divided average nighttime heart rate (NHR) and nighttime heart rate variability (NHRV) defined as standard deviation of nighttime heart rate into decile groups, and defined the top decile group (NHR 70bpm, NHRV 9.7bpm) as abnormal group, respectively. The average follow-up period was 5.0 years and the incidence of cardiovascular event was 56 events.

Results:
Kaplan-Meier curve showed that the incidence of cardiovascular event with abnormal NHR and NHRV was higher than those without (Figure A and B). When we divided the patients into 4 groups according to those with or without abnormal NHR and with or without abnormal NHRV, the incidence of cardiovascular event for the group with both abnormal NHR and NHRV was the highest among 4 groups (Figure C). After adjustment for age, sex, body mass index, smoking, alcohol, past history of cardiovascular disease, diabetes, dyslipidemia and 24hr systolic blood pressure, abnormal NHR and NHRV, the presence of abnormal HHR and NHRV has a synergic risk for cardiovascular event (Odds ratio, 7.27; 95% confidence interval, 1.53 to 34.60, P<0.013).

Conclusions:
The presence of nighttime higher heart rate and heart rate variability obtained every 30 minutes by ABPM has a synergic risk for cardiovascular event.
Abstract 12269: Prognostic Role of Hemoconcentration in Acute Decompensated Heart Failure With Preserved and Reduced Ejection Fraction; an Analysis From Mode of Death
Authors: Yamada Takahisa , Morita Takashi , Furukawa Yoshio , Tamaki Shunsuke , Iwasaki Yusuke , Kawasaki Masato , Kikuchi Atsushi , Kondo Takumi , Hakui Hideyuki , Ishimi Masashi , Ozaki Tastsuhisa , Satoh Yoshihiro , Ikeda Iyo , Fukuhara Eiji , Fukunami Masatake
Published: April 2024

Backgrounds:
Hemoconcentration (HC) during heart failure treatment is known to be associated with improved clinical outcome in patients with acute decompensated heart failure (ADHF). There is a difference in mode of death (cardiac [sudden vs pump failure death] vs non-cardiac death) between heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF). However, there is no information available on the different impact of HC in the prediction of mode of death in ADHF patients, relating to HFpEF and HFrEF.

Methods and Results:
We studied 302 patients admitted with ADHF and discharged with survival (HFpEF(LVEF≥50%);n=139, HFrEF(LVEF<50%); n=163). HC was defined as an increase in hemoglobin level from admission to discharge. During a follow-up period of 5.1±4.3 yrs, 65 patients had cardiac death (sudden cardiac death in 37 and pump failure death in 27 patients) and 56 patients had non-cardiac death. HC was significantly associated with cardiac death in patients with HFrEF (p=0.02) but not in those with HFpEF, while there were no associations between HC and non-cardiac death in both patients with HFpEF and HFrEF. In patients with HFrEF, although there was no association between HC and sudden cardiac death, HC was significantly associated with pump failure death (adjusted HR 0.31 [95%CI 0.10-0.91], p=0.04), independently of relevant covariates such as systolic blood pressure and BUN. On the other hand, there was no association between HC and sudden or pump failure death in patients with HFpEF.

Conclusion:
HC was related to improve pump failure death but not sudden cardiac death in hospitalized ADHF patients with HFrEF, not in those with HFpEF. This finding about clinical implication of HC might provide a new insight to decongestive therapy of ADHF in terms of LVEF.
Abstract 12382: A Novel Angiogenic Adipokine Neuregulin-4 Preserves Metabolic Homeostasis by Regulating Adipose Tissue Angiogenesis
Authors: Nugroho Dhite Bayu , Ikeda Koji , Barinda Agian Jeffilano , Wardhana Donytra Arby , Hirata Ken-ichi , Emoto Noriaki
Published: April 2024

Adipose tissue angiogenesis is a crucial factor for the maintenance of adipocyte functions, impairment of which causes systemic metabolic disorders. Adipocytes produce various angiogenic factors; however the interactive communications between endothelial cells (EC) and mature adipocytes in the regulation of adipose tissue homeostasis remains largely unexplored. We searched for genes that is highly expressed in adipose tissue, and the expression of which is regulated by EC. We found several genes with unknown functions; one of which encodes neuregulin-4 (Nrg4), a latest member of neuregulin family that are part of the EGF family proteins. Here, we show that Nrg4 is a paracrine-acting adipokine that regulates adipose tissue angiogenesis through a communication between EC and mature adipocytes. Nrg4 is highly and preferentially expressed in mature adipocytes, while its receptor is expressed in EC but not in adipocyte. Nrg4 activated endothelial angiogenic functions and enhanced angiogenesis both in vitro and in vivo. Of note, Nrg4 expression was substantially reduced in white adipose tissue during diet-induced obesity. Furthermore, targeted activation of Nrg4 in adipocytes (aP2-Nrg4-Tg) led to significantly improved glucose tolerance and better insulin sensitivity comparing to those in WT mice after a high fat-diet, while their body weight was similar. Adipose tissue angiogenesis was enhanced in aP2-Nrg4-Tg mice, resulting in ameliorated adipose tissue hypoxia and inflammation. Interestingly, expression of Nrg4 in adipocytes was negatively regulated by EC and/or blood vessels, constituting a negative-feedback loop for adipose Nrg4. These data unveiled a significant role of interactive communication between EC and mature adipocytes in the regulation of adipose tissue angiogenesis, and shed light on Nrg4 as a therapeutic target for the treatment of metabolic disorders associated with obesity.
Abstract 12453: Over-expression of NDNF Rejuvenates Aged Human Mesenchymal Stem Cells and Improves Mouse Heart Function After Myocardial Infarction
Authors: Song Hui-Fang , Li Shu-Hong , Wu Jun , Guo Jian , Shao Zheng-Bo , He Sheng , Weisel Richard D , Li Ren-Ke
Published: April 2024

Introduction:
The benefits of cell transplantation for cardiac repair are diminished in aged individuals and effective methods to rejuvenate aged stem cells are required to treat the increasing number of elderly patients with heart failure. Neuron-derived neurotrophic factor (NDNF) has biological effects which could restore stem cell activity. This study determined whether NDNF could regenerate aged human bone marrow mesenchymal stem cells (hMSCs) and improve their regenerative capacity after a myocardial infarction (MI).

Methods and Results:
hMSCs were harvested from young (24±7 years, n=9) and aged (72±8 years, n=13) patients after informed consent, evaluated and then transfected with a lentiviral expression vector carrying the NDNF gene. NDNF overexpression was confirmed by RT-PCR and Western blot. Aged hMSCs had 54% lower NDNF mRNA levels and 66% lower NDNF protein levels (relative NDNF protein expression: 0.26±0.06 in young and 0.09±0.05 in old patients, p<0.001). Proliferation (assayed by BrdU staining) was 54% lower and migration (by a scratch-wound assay) was 58% lower in aged compared with young hMSCs. Overexpression of NDNF in aged hMSCs increased cell proliferation and decreased apoptosis. The rejuvenation of the aged hMSCs was associated with a 45% decreased in p16 (a cyclin-dependent kinase inhibitor, relative protein expression: 0.55±0.34 in NDNF-transduced hMSCs and 1.00±0.30 in non-transduced hMSCs, p=0.04). Regucalcin (a senescence marker protein) was increased 2-fold in the NDNF-transduced aged hMSCs compared with empty vector-transduced aged hMSCs. In vivo implantation of NDNF-overexpressing aged hMSCs into a mouse cardiac infarct decreased scar size and preserved function at 28 days after MI compared with mice that received aged empty vector-transduced hMSCs (fractional shortening was 26±3% in the NDNF group and 20±3% in the empty vector group, p=0.04). Exploration of potential mechanisms revealed that phospho-Akt (Ser473), a key cell survival factor, was increased in mouse heart tissue after NDNF hMSC transplantation compared to the empty vector group.

Conclusions:
NDNF could be an important new target to rejuvenate aged stem cells that could then become potent vehicles for cardiac repair of the aged heart after injury.
Abstract 12533: First Noninvasive Visualization of Sinoatrial Node Fibrosis via High-Resolution 3D Gadolinium Enhanced MRI of Intact Human Hearts
Authors: Csepe Thomas A , Zhao Jichao , Hansen Brian J , Li Ning , Wang Yufeng , Bratasz Anna , Powell Kimerly A , Higgins Robert D , Kilic Ahmet , Raman Subha V , Simonetti Orlando P , Mohler Peter J , Janssen Paul M , Fedorov Vadim V
Published: April 2024

Introduction:
The normal adult human sinoatrial node (SAN) structure consists of 35-55% fibrotic tissue, which provides mechanical and electrical protection for the primary pacemaker of the heart. The level of fibrosis and its spatial density can significantly increase in disease conditions, leading to SAN dysfunction. We hypothesize that gadolinium enhanced MRI (GE MRI) can be used to identify and locate 3D SAN structure in the human heart.

Methods:
Explanted human hearts (n=5, 19-65 y.o., 507±135 g) were coronary-perfused and the SAN was functionally identified with an intramural optical mapping approach. After mapping, the preparations were formalin fixed and incubated in 0.2% gadolinium based contrast agent to perform GE MRI (9.4T Bruker BioSpin Spectrometer) with a spatial resolution of 78-175μm3. The entire SAN pacemaker structure was then sectioned at 5μm thickness and stained with Masson’s trichrome.

Results:
Percent fibrosis vs total tissue area was measured from 2D GE MRI sections by applying a fibrosis enhancement mask, which was based on signal intensity threshold differences of connective and muscular tissue and validated with 2D histology sections from the same locations (Figure). GE MRI vs histology percent fibrosis measurements of SAN (60±6% vs 63±1%), CT (16±6% vs 18±4%), RAFW (13±6% vs 14±2%) and septum (29±22% vs 28±7%) were strongly correlated (r = 0.87, p < 0.01). GE MRI allowed for the complete delineation of the 3D SAN structure (averaged SAN size 16.6±2.8 x 3.9±0.7 x 2.2±0.6 mm3) by distinguishing significant increased fibrosis in SAN compared to surrounding atrial tissue.

Conclusions:
Our integrative study for the first time demonstrated the application of GE MRI to resolve the intact 3D structure of the human SAN and estimate its fibrotic spatial density and distribution. Analysis of SAN fibrosis content with GE MRI supports further work to develop in vivo SAN fibrosis imaging in patients and help predict the need for pacemaker implantation.