bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18676: Early Changes of Pulmonary Vascular Remodelling After Pulmonary Thrombendarterectomy Measured by Cardiac MRI
Authors: Rolf Andreas , Rixe Johannes , Kim Won , Liebetrau Christoph , Szardien Sebastian , Koerlings Nils , Kramm Thorsten , Guth Stefan , Hamm Christian , Mayer Eckhard
Published: April 2024

Purpose:
Chronic Thrombembolic Hypertension (CTEPH) occurs in about 3.8% of patients with acute pulmonary embolism. The longterm prognosis is poor, however pulmonary thrombendarterectomy (PEA) offers a potential cure with excellent outcome. Several surrogate markers of pulmonary vascular remodelling have been defined. The max. PA velocity and acceleration time (AT) or its equivalent normalised over ejection times (AT/ET) reflect pulmonary pressure, the relative area change of the PA (RAC) and PA-flow-contour analysis derived dicrotic notch are indicative of changes of pulmonary vascular resistance (PVR). All these parameters can be measured excellently by cardiac magnetic resonance (CMR). In the present study we sought to quantitate surrogate markers of pulmonary vascular remodelling and reverse remodelling before and after PEA by CMR.

Methods:
patients underwent CMR 2 ± 1 day before and 10 ± 2 days after PEA. Flow/Time curves, PA area and PA max. velocity were derived from Phase-Contrast velocity encoded gradient echo sequences. The temporal resolution was adjusted to 11 ms, sequences were acquired with three signal averages in free breathing to allow for longer acquisition times needed for increased temporal resolution. All numerical data are presented as means ± SD, differences were tested with t-test for paired data, differences in frequencies were tested with McNemar's test.

Results:
65 patients were included, mean age 56 ± 16, 28 females. PA peak velocity improved from 61 ± 17 cm/s to 74 ± 19, p = 0.001, AT/ET improved from 0.32 ± 0.06 to 0.36 ± 0.09, p = 0.002, RAC showed a trend to lower values and decreased from 29 ± 1.9% to 25 ± 1.2%, p = 0.1, a diastolic notch was found in 51 of 65 patients before PEA and only in 12 of 65 patients post surgery, p = 0.0001. In those patients in which the notch persisted, there was a trend to smaller notch ratios post PEA 1.37 ± 0.17 vs. 1.12 ± 0.24, p = 0.06.

Conclusion:
CMR is an excellent tool to monitor pulmonary vascular remodelling after PEA for CTEPH. We were able to demonstrate improved surrogate markers of PA pressure and resistance as early as 10 days after PEA in a large series of 65 patients.
Abstract 18696: Feasibility of Transcatheter Closure of Secundum Atrial Septal Defect with Deficient Rims Other than the Antero Superior
Authors: Fraisse Alain , Kammache Issam , Assaidi Anass , Aldebert Philippe , Mancini Julien , Habib Gilbert
Published: April 2024

Introduction. Transcatheter closure of secundum atrial septal defect (ASD) with deficient rims is usually contraindicated except in cases with a deficient antero-superior rim in whom percutaneous closure is well demonstrated. Our goal was to assess the feasibility of transcatheter closure for secundum ASD with deficient rims (<5 mm) other than the antero-superior.

Method. Between January 1st, 2008 and december 31, 2011, 192 patients underwent percutaneous closure of ASD in our institution under transesophageal echocardiography guidance in children and intracardiac echocardiography guidance in adults. Amplatzer devices (Amplatzer Septal Occluder or Cribriform) were used in 191 whereas one case without deficient rim was closed with intrasept ASD occluder. We retrospectively analyzed the outcomes of the 43 patients (22.4%, 26 children) with one or more deficient rim.

Results.The median age and weight was 16(1.1 to 85) years and 56(8.8 to 99)Kg, respectively. Deficiency of the inferior (toward the AV valves, n= 11), inferior- posterior (toward the inferior vena cava, n=15), and the superior -posterior rim (toward the superior vena cava, n= 17) was confirmed by transesophageal echocardiography in all the cases. Transcatheter closure was successfully accomplished in 37 (86%) of the cases with a median device size of 28(10 to 40) mm. A modified method of implantation (sizing balloon technique) was used in 30 patients (70%).In 6 patients (5 children) the ASD could not be closed. Four children experienced device embolization few hours after successful transcatheter closure and underwent surgical ASD closure without further complication. By Fisher’s exact test, deficiency of the inferior-posterior rim was associated with failure or embolization(p = 0.05)and there was a trend for adult age to be associated with a low risk of embolization or failure (p= 0,06).

Conclusion. Transcatheter closure of secundum ASD is feasible in patients with deficient rims. However, this cannot be recommended because of an intolerable rate of embolization. Possibly, transcatheter closure of such secundum ASDs with deficient rims may be more successful in the adult population.
Abstract 18704: Late Blockade of Wnt/frizzled Signaling Pathway with UM206 Halts Further Dilatation of the Left Ventricle Following Myocardial Infarction
Authors: Daskalopoulos Evangelos P , Hermans Kevin C , Janssen Ben J , Blankesteijn W. M
Published: April 2024

Purpose:
Current pharmacotherapy cannot stop left ventricular (LV) dilatation that occurs after myocardial infarction (MI). Recently we have shown that in the MI mouse model, LV dilatation can be prevented by pharmacological blockade of Wnt/frizzled signaling with UM206. In these studies UM206 treatment was started immediately after induction of MI. The subject of the current study was to investigate if similar beneficial effects could be obtained with UM206 when treatment was started 3 weeks after the MI induction, when adverse LV dilatation has become manifest.

Methods:
Swiss male mice were subjected to MI by occlusion of the left anterior descending artery. At 3 weeks post-MI, UM206 administration (Alzet osmotic minipump, 6µg/kg/day) was initiated and animals were sacrificed at 8 weeks post-MI. The results were compared with vehicle (saline)-treated animals (treatment between weeks 3-8) that were also sacrificed at weeks 8 post-MI. Cardiac geometry and function parameters were obtained using 3D-echocardiography (Vevo 2100, Visualsonics, Toronto, Canada).

Results:
UM206 late treatment had a beneficial effect on both End diastolic volume (EDV, saline: 278 ± 24 mm3, UM206: 202 ± 13 mm3; p<0.01) and End systolic volume (ESV, saline: 250 ± 27 mm3, UM206: 151 ± 15 mm3; p<0.01). Ejection Fraction (EF) was also improved in UM206-treated animals (saline: 11.0 ± 3.2 %, UM206: 23.2 ± 2.6 %; p<0.05), while increased lung weights (an indication of heart failure development) were found in the saline-treated animals only (saline: 319 ± 42 mg, UM206: 214 ± 6 mg, p<0.01).

Conclusion:
In the MI mouse model, administration of UM206 starting at week 3 post-MI, halts further increases in EDV and ESV while preserving the EF, resulting in improved overall cardiac function and prevention of heart failure development. The results show that pharmacotherapy targeting the Wnt/frizzled signaling can be beneficial in preventing heart failure after MI, even after adverse LV remodeling has been initiated.
Abstract 18722: Cardiac Stimulation Occurs with Electronic Control Devices and is Dependent Upon Subject Size, Dart Location, and Device Characteristics
Authors: Flaker Greg C , Koerber Scott M , Ardhanari Sivakumar , Chockalingam Anand , Zymek Pawel , McDaniel Wayne
Published: April 2024

Introduction
Electronic control devices (ECDs) are weapons used to incapacitate violent subjects. Subjects have died suddenly after ECD application but since cardiac arrhythmias have been inconsistently observed during ECD application to animals, the cause for death is uncertain. We hypothesized that cardiac stimulation, if apparent during ECD application, could be detected by transesophageal echocardiography (TEE) and, if present, could be related to the model of ECD.

Methods
Four Yorkshire pigs were anesthetized, paralyzed with vecuronium, and restrained in a supine position. A GE 6T echo probe was placed in the esophagus to directly visualize left ventricular function. M-mode echocardiography was used to estimate heart rate. Two dart locations, chest and abdomen, were assessed. ECD energy application was delivered from one of 5 commercially available devices (Taser X26, Singer S200 AT, Taser M 26, Taser X-3, and Taser C2, all with different waveform characteristics) in random order to each pig, 4 times in each orientation.

Results
Cardiac stimulation, characterized by an abrupt increase in heart rate, reduction in myocardial contractility and mitral valve standstill, was detected with chest dart application in small pigs with all devices except the Taser X3 and in large pigs only with the S200 AT device (Table 1). Cardiac stimulation did not occur with abdominal dart application. VF was not observed.

Conclusion
Cardiac stimulation occurs during ECD application in pigs. Stimulation is dependent upon dart orientation and pig size. Refinement in waveform characteristics may result in ECD’s with a lower risk of cardiac stimulation. Table 1: Heart Rate Response During ECD Stimulation *P < 0.0001 comparing cardiac heart rate with abdominal heart rate (Group 1)
Abstract 18745: Triglyceride-Rich High-Density Lipoprotein Composition as Residual Risk Biomarker of Coronary Artery Disease Including Reduced eGFR and Pre-diabetes
Authors: Nohara Atsushi , Inazu Akihiro , Noguchi Tohru , Inoue Takeshi , Mori Mika , Nakanishi Chiaki , Kawashiri Masakazu , Yagi Kunimasa , Kobayashi Junji , Yamagishi Masakazu , Mabuchi Hiroshi
Published: April 2024

Beyond LDL, HDL is the urgent target for atherosclerosis; few data exist regarding how compositional changes in HDL can affect coronary artery disease in which the anti-atherogenic quality of HDL is not simply defined by the plasma HDL-C level. Therefore, we determine the roles of HDL composition, closely related with VLDL metabolism, in angiographically evaluated coronary artery disease.

Methods:
A total of 365 patients (202 males, mean age of 58±13) suspected coronary artery disease were enrolled, and coronary stenosis index (CSI) was estimated with angiography in 210 patients (134 males, mean age of 61 ± 11). Fasting lipid profiles without lipid drugs at least 4 weeks were analyzed by ultracentrifugation, and free cholesterol, cholesterol ester, triglycerides (TG) and phospholipids (PL) levels in each fraction were determined. Pre-diabetes was defined as fasting glucose 110-125 mg/dL or impaired glucose tolerance with 75gOGTT.

Results:
Mean CSI was 10.8 and median was 8.0. CSI showed weak positive association with plasma TG (
p
<0.05, R
2
2%), and negative association with HDL-C (
p
<0.01, R
2
5%). In HDL composition, HDL-TG/PL ratio showed strong positive association with CSI (
p
<0.0001, R
2
8%) and number of coronary vessel with significant (>75%) stenosis (p<0.0005, R
2
6%). HDL-TG itself was weakly associated with CSI (
p
<0.05, R
2
2%). HDL-TG/PL was positively associated with CETP mass (
p
<0.01, R
2
5%). HDL-TG/PL showed no gender difference. CSI did not show significant association with LDL-C in this study; presumably most of patients with high LDL-C levels had been treated with statins already. CSI showed strong negative associattion with eGFR (
p
<0.0005, R
2
9%). eGFR showed weak negative association with HDL-C, but positive association with HDL-TG/PL (both
p
<0.05). Pre-diabetes patients showed higher CSI than normal group (14.7±13 vs. 8.9±9,
p
<0.005), and also higher HDL-TG/PL (
p
<0.05).

Conclusion:
We propose HDL-TG/PL as residual risk biomarker also reflecting chronic kidney disease and pre-diabetes beyond LDL-C.
Abstract 18772: Combined Therapeutic Effect of Probucol and Cilostazol on Endothelial Function in Patients with Silent Cerebral Lacunar Infarcts and Hypercholesterolemia
Authors: Takase Bonpei , Higashimura Yuko
Published: April 2024

Flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NMD) in brachial artery is excellent modality for evaluating endothelial function (ECF), and silent lacunar cerebral infarcts (SLCI) detected by MRI complicated with hyperlcholesterolemia is associated with untoward prognosis for cardiovascular events through impaired ECF. To investigate if combined therapy of probucol and cilostazol can ameliorate ECF in SLCI with mild hyperlcholesterolemia (MH; LDL-c> 100 mg/dL), we measured FMD and NMD by UNEXEF18G before and after 4-weeks combined treatment of probucol (500 mg/day) and cilostazol (200 mg/day) in 24 patients with SLCI and MH (72±7 years old) with impaired ECF (FMD<6%). Patients were randomly allocated into two treatment arms such as aspirin (100 mg/day) with behavioral modification such as diet and/or exercise therapy (A-group, n=17) and probucol and cilostazol treatment (PC-group, n=17) with behavioral modification. Although baseline FMD were not different between two treatment arms (2.7±1.5 vs. 2.6±1.5%, NS), PC-group significantly improved FMD (from 2.6±1.5 to 3.5±1.7%, P<0.05) whereas A-group had no effect on FMD (from 2.6±1.2 to 2.9±1.4%, NS).There were no different effects in NMD in two groups. Effects of treatments on lipid profiles were more profound in PC-group. Conclusions; Combined treatment of probucol and cilostazol can subacutely ameliorate ECF detected by FMD in SLCI with MH. This combination therapy possibly prevents further cardiovascular events through improving both ECF and lipid profiles.
Abstract 188: Neuroprognostication After Pediatric Cardiac Arrest
Authors: Kirschen Matthew P , Illes Judy , Topjian Alexis A , Berg Robert A , Nadkarni Vinay M , Abend Nicholas S
Published: April 2024

Objective:
Management decisions and parental counseling following pediatric cardiac arrest depend on the ability of physicians to make accurate and timely predictions regarding neurological recovery. This study examined the level of agreement in neuroprognostication among neurologists and among intensivists, and prediction accuracy in terms of time post cardiac arrest.
Methods:
Pediatric neurologists (N=10) and intensivists (N=9) each reviewed 18 cases of children successfully resuscitated from a cardiac arrest and managed in the pediatric ICU. Cases were sequentially presented in three sections: Day 1, Days 2-4, and Days 5-7 post arrest, with updated examinations, neurophysiologic data, and neuroimaging data as available. At each time point, physicians predicted outcome by Pediatric Cerebral Performance Category (PCPC). Predicted PCPC (p) vs. actual hospital discharge PCPC (a) outcomes were compared. Prediction accuracy was defined as Exact Accuracy (p-a = 0) and Close Accuracy (p-a = ±1). Descriptive statistics, Kappa coefficients (Κ) and generalized estimating equation were performed.
Results:
Agreement among neurologists improved over time (Day 1 Κ 0.27, Days 2-4 Κ 0.43, Days 5-7 Κ 0.62), as did agreement among intensivists (Day 1 Κ 0.30, Days 2-4 Κ 0.44, Days 5-7 Κ 0.57). For all physicians, prediction accuracy did not improve from Day 1 to Days 2-4, but did improve from Days 2-4 to Days 5-7 (p=0.001) [Exact Accuracy Days 2-4 and Days 5-7: 35% vs. 43%; Close Accuracy Days 2-4 and Days 5-7: 77% vs. 89%]. Prediction accuracy did not differ significantly between physician groups at any time point (p=NS). At Days 5-7, 16 of 19 physicians predicted PCPC = 5-6 at least once when actual PCPC ≤ 4. All physicians predicted PCPC ≤ 4 at least once when actual PCPC = 5-6.
Conclusions:
Inter-rater agreement among neurologists and among intensivists improved over time and converged to moderate-good levels at later time points. For all physicians, prediction accuracy improved over time; however, even at later time points, incorrect outcome predictions occurred. The ethical implications of these findings for clinical decision-making and allocation of health care resources after pediatric cardiac arrest are considerable.
Abstract 18800: Feeding Modifies the Relationship Between Glucose Metabolism, Inflammation and Outcomes After Pediatric Heart Surgery
Authors: Floh Alejandro A , Nakada Masayuki , La Rotta Gustavo , Manlhiot Cedric , McCrindle Brian W , Van Arsdell Glen S , Schwartz Steven M
Published: April 2024

Introduction:
We have previously shown that a low post-operative glucose:insulin ratio (GIR), which suggests insulin resistance, coupled with inflammation is associated with poor clinical outcomes in children following cardiac surgery. The purpose of this study was to determine if glucose infusion rate and enteral feeding alters this relationship and the association of these factors with morbidity following cardiopulmonary bypass (CPB).

Methods:
Subjects included children, age 0-18y, undergoing cardiac surgery with CPB. Blood samples were collected at baseline and every 6 hours for up to 72 hours. Feeding regimens included NPO with glucose infusion, low volume feeds (<20mL/kg/day) and liberal feeding. Clinical outcomes were measured with a composite morbidity-mortality endpoint reflecting organ failure. Regression models adjusted for repeated measures were used to determine associations between GIR, inflammation and outcomes in those subjects who were NPO or on low volume feeds and those being fed more liberally.

Results:
We studied 132 subjects with a median (IQR) age of 200 days (54, 1132) and weighing 6.79 kg (4.57, 14.7). The median (IQR) time of CPB and aortic cross clamp were 107 (71.5, 158) and 77 (54,112) minutes respectively. Median glucose infusion (IQR) rate was 1.44 (0.89-2.17) mg/kg/min. Most subjects (80%) had enteral feeds during the study, of which 29% were low volume feeds. Feeds were started on average at 30±16 hours post-surgery. A lower GIR was associated with increased TNF-alpha (EST: -0.066 (0.011)/0.1, p<0.001) and IL-6 (EST:-0.456 (0.127)/0.1, p=0.001. In children who were NPO or on low volume feeds, a low GIR was associated with increased IL-6 (EST: +0.215 (0.575)/0.1, p<0.001) and higher risk of reaching the composite morbidity outcome (OR: 1.24 (1.08-1.41), p=0.002). This relationship was not observed in subjects who were fed more liberally (EST: +0.198 (0.689), p=0.77).

Conclusion:
A low GIR is associated with increased inflammation and worse outcomes in children who are NPO or are receiving only low volume feeds after CPB, but not in children receiving more liberal enteral feeds. This study suggests early feeding might be a way to modify outcomes after pediatric heart surgery.
Abstract 18853: Rivaroxaban is Associated with Higher Incidence of Major Bleeding Compared to Low Molecular Weight Heparin for Venous Thromboembolism Prophylaxis.- A Meta-analysis
Authors: Opina Angeline , Golwala Harsh , AbuFadel Mazen , Tafur Alfonso
Published: April 2024

Introduction:
The American College of Physicians guidelines for venous thromboembolism (VTE) prophylaxis stresses bleeding risk assessment before VTE prophylaxis. Rivaroxaban has recently been accepted for VTE prevention. However most of the publications heavily focus on the thrombosis rate. Hypothesis: The rate of major bleeding in patients receiving Rivaroxaban is higher than those receiving LMWH for VTE prophylaxis.

Methods:
MEDLINE, EMBASE, Cochrane Register of Randomized Controlled Trials as well as abstracts presented at national meetings [AHA, ACC, ASH]. We included all prospective experimental trials which declared and counted major bleeding criteria and utilized Rivaroxaban in primary VTE prophylaxis, published from 1-1-06 to 12-21-11. The data was abstracted by 2 independent reviewers in accordance with PRISMA guidelines. We used R [R Meta package v 0.8-2] for analysis. The OR estimates were done with Mantel-Hanzel fixed estimates method and with random effect model by DerSimonian and Liard.

Results:
We identified 335 records, screened 15 and 9 trials (n=21,035) were included in the analysis. There were 3 knee replacement, 5 hip replacement, and 1 medically ill prophylaxis trials. All compared to LMWH prophylaxis. Although no heterogeneity was detected [I2=0%, p=0.9], we present a conservative random effect model. The odds of major bleed were 1.98 [95%CI 1.3-3.0] times higher for Rivaroxaban compared to LMWH. Individual omission of each of the publications had no significant effect on the overall significance of the findings. When only those manuscripts using a Rivaroxaban dose of 10 mg daily were analyzed, the major bleeding OR was 1.98 [95%CI 1.3-3.1].

Conclusion:
Rivaroxaban is associated with a higher incidence of major bleeding compared to LMWH when used for VTE prophylaxis. This information will be instrumental in calculating risks and benefits of patients who need VTE prophylaxis.
Abstract 18906: Congenital Right Ventricular Hypertrophy Compensation is Characterized by Sustained Angiogenesis
Authors: Dromparis Peter , Sutendra Gopinath , Paulin Roxane , Zhao Joanne , Sandha Jaskiran , Rebeyka Ivan M , Ross David B , Michelakis Evangelos D , Nagendran Jayan
Published: April 2024

The right ventricle (RV) is hypertrophied at birth and in the neonatal period. The RV regresses to a normal phenotype in the first month of life correlated with a concomitant drop PVR over that time. The RV may remain hypertrophied and compensated in response to maintained afterload in patients with congenital heart disease (CHD) for decades; whereas the hypertrophied RV acquired in adulthood from pulmonary arterial hypertension (PAH) quickly transitions to failure, and remains their primary determinant of mortality in PAH. Potentially, the transition from RV compensation to failure has been attributed to ischemia from deficient capillary density from inadequate angiogenesis in RV hypertrophy. Angiogenesis is largely regulated by the transcription factor hypoxia-inducible factor 1a (HIF1a), which governs the transcription of proangiogenic signaling effectors. Two such effectors strongly promoting angiogenesis under HIF1a regulation are vascular endothelial growth factor (VEGF) and stromal derived factor 1 (SDF1), which promote endothelial cell survival/proliferation and recruitment of CXCR4+ stem cells, respectively. We hypothesized that sustained HIF1a-driven angiogenesis maintains adequate RV vascularity in hypertrophy, thus preventing the transition from RV compensation to failure in CHD patients. The free walls of neonatal rat RVs had elevated levels of HIF1a (immunoblot and nuclear localization) compared to those of adult RVs, adult LVs, and neonatal LVs. This was associated with increased VEGF and SDF1 expression (Immunoblot and ELISA), which correlated with increased angiogenesis (matrigel assay) and CXCR4+ stem cell recruitment (Boyden chamber migration assay). Neonatal RVs had elevated expression vascular density (CD31 expression) and tissue perfusion (Lectin) compared to adult RVs, further supporting proangiogenic signaling. Human compensated RV hypertrophy myocardium from CHD patients had elevated SDF1 and CXCR4 expression compared to normal adult RV and LV myocardium (immunoblot), suggesting HIF1a driven angiogenic pathways are maintained in CHD tissues. Therapies that maintain HIF1a signaling may delay the transition from compensation to failure in adults with acquired PAH.
Abstract 18920: Tricuspid Valve Dysfunction in the Setting of Left Heart Valve Disease Begins with Annular Shape Distortion Prior to Dilatation
Authors: Nemoto Naohiko , Pedersen Wesley R , Lesser John R , Rutten-Ramos Stephanie , Schwartz Robert S
Published: April 2024

Introduction:
Tricuspid Valve (TV) integrity is a potent predictor of poor prognosis in left heart valve dysfunction (LVD) and is independent of TR severity. Early stages of TV dysfunction prior to regurgitation are important since percutaneous therapies may soon permit early TV intervention. We examined the Tricuspid annulus major/minor axes, annulus area, and right atrial (RA) major/minor axes to detect the earliest stages of TV compromise.

Methods:
We analyzed 220 patients by echocardiography and CT angiography. TR was classified into 2 groups, None/Mild (Group 1, n=193) and Moderate/Severe (Group 2, n=27). Group I was subdivided into those without LVD (Group IA, n=140) and those with LVD (Group IB, n=53). GroupIIwas similarly divided (GroupIIA, n=14 no LVD) and (GroupIIB, n=13, LVD). Major and minor tricuspid annulus diameters (TAD) and normalized BSA areas (nTAA) were measured.

Results:
Four results occurred in cross-group analyses. 1) Patients without TR had significantly longer minor axes when LVD was present, though TA major axes did not differ (Groups IA vs IB), indicating LVD is associated with TA circularization. 2) Major and minor axes were significantly larger when TR developed regardless of LVD (Groups IA/IB vs IIA/IIB), p<0.05. 3) The RA long axis may determine TR onset in the setting of LVD. 4) TA circularization by minor axis increase was responsible for significantly larger nTAA, with an optimal dilation threshold >928mm2/m2.

Conclusions:
This study suggests that 1. LVD plays a role in early TA deformation, rendering it more circular through minor axis increase alone. 2. RA long axis lengthening correlates with TAA and may cause minor axis lengthening. 3. If TR has developed, the TA major and minor axes, and nTAA are enlarged regardless of whether LVD is present. Early changes in the TA minor/major axes and RA long axis may play key roles in prognostication for patients with or without LVD.
Abstract 18935: Left Ventricular Remodeling Following Alcohol Septal Ablation in Patients with Hypertrophic Cardiomyopathy: Assessment by Cardiac Magnetic Resonance Imaging
Authors: Sagar Utpal N , Salcedo Ernesto , Groves Bertron , Messenger John , Quaife Robert A
Published: April 2024

Background:
Treatment of HOCM using percutaneous alcohol septal ablation (ASA) reduces left ventricular outflow tract (LVOT) gradient and symptoms. The question of whether reduced LVOT gradient translates into lower LV wall stress is still unanswered. We propose that that ASA results in decreased LVOT gradient, leading to favorable LV remodeling related to lower circumferential wall strain (CWS). This reduction in wall strain will decrease LV mass to a greater extent than the amount of myocardium involved in the infarct alone.

Methods:
Forty-two HOCM patients who underwent ASA between 2002-10 and had cardiac magnetic resonance (CMR) tagged imaging were included. LVOT gradients were assessed both by catheterization and echocardiography. CWS was assessed on CMR images using specialized software (HARP, Diagnosoft). LV mass and infarct size were independently determined using two separate software packages (ARGUS and Diagnosoft). Doppler echocardiography was used to evaluate both resting and peak LVOT gradients. Statistical T-test was performed for data analysis.

Results:
After ASA, peak LVOT gradients decreased significantly from 112.5±24.2 to 65.3±45.4 mm Hg, p <0.0001. Shown in the figure is the significant reduction in mean LV circumferential strain in these patients with a mean and maximum follow-up of 8 and 24 months, respectively. There was a significant decrease in LV Mass (225.5±79.5 to 205.1±78.7 g, p<0.0001). The mean LV mass post-ASA corrected for infarct size was 212.5±95 g. The mean decrease in LV mass was significantly greater than the mean infarct size (21.2±24 g vs. 13.0±10.3 g, p=0.02).

Conclusion:
ASA reduced LVOT gradient and resulted in reduced CWS by CMR, which resulted in favorable LV remodeling, as demonstrated by a decrease in LV mass greater than the infarct size alone.
Abstract 18939: Impact of LDL Pattern on Risk for CHD in the Framingham Offspring Population
Authors: Toth Peter P , Kulkarni Krishnaji R , Massaro Joseph M , D'Agostino Ralph B
Published: April 2024

Introduction

: Low-density lipoprotein (LDL) particles that are small and dense are characteristic of pattern B. It has been assumed that such particles are more atherogenic than larger, more buoyant particles indicative of LDL pattern A. Additionally, there is evidence from observational studies to support LDL pattern B as an emerging risk factor for coronary heart disease (CHD) with the incidence of CHD increasing as the proportion of type B to type A LDL particles increases.

Hypothesis:

In participants in the Framingham Offspring Cohort Study (FOCS), LDL pattern B is a significant and independent risk factor for incident CHD (inclusive of coronary death, myocardial infarction, coronary insufficiency, and angina pectoris) and hard CHD (CHD endpoints exclusive of angina pectoris).

Methods

: Vertical auto profile measurements were performed on 819 men and women on no lipid-modifying therapy as part of an exploratory analysis of the FOCS. The relationship between increasing LDL pattern type (A, A/B, and B) and 12-year risk for CHD and hard CHD was quantified using multivariable Cox proportional hazard regression for two models adjusted for known Framingham risk factors (model 1 adjusts for age, sex, systolic blood pressure and use of antihypertensives, prevalent diabetes, and smoking; model 2 adjusts for model 1 risk factors, HDL-C, and total cholesterol).

Results:
LDL pattern B is a statistically significant (
p < 0.05
) independent risk factor for 12-year incident CHD with hazard ratios of approximately 1.4 in models 1 and 2. For incident hard CHD, LDL pattern B is a more significant risk factor with hazard ratios greater than two and
p < 0.005
across both models. There was no effect modification by sex (
p > 0.7
).

Conclusions:

In this exploratory analysis, LDL pattern B is an independent risk factor for CHD and hard CHD after controlling for known Framingham risk factors in men and women on no lipid-lowering therapy.
Abstract 18941: Vasodilator Use Guided by Wireless Pulmonary Artery Hemodynamic Monitoring Reduces Heart Failure Hospitalizations in Both African American and Non-African American Heart Failure Patients: Results from the CHAMPION Trial
Authors: Costanzo Maria Rosa , Adamson Philip B , Abraham William T , Bradley Jeffries , Neville Susan , Cowart Pam , Henderson John , Yadav Jay S
Published: April 2024

Introduction:
It is unknown whether benefits produced by nitrates and hydralazine (HDZ) in African Americans (AA) also occur in non-African American (non-AA) patients. The CHAMPION Trial showed that, compared to usual care (UC) patients, those managed according to wirelessly measured pulmonary artery pressures (w-PAP) plus UC had a significant reduction in heart failure (HF) hospitalizations over 6 months. The current analysis evaluated pattern of use and effects of nitrates and HDZ in AA and non-AA CHAMPION trial subjects to determine if non-AA patients receiving these vasodilators according to w-PAP will have benefits similar to those occurring in non-AA.

Methods:
Retrospective comparison of changes in use of nitrates and HDZ in AA and non-AA subjects randomized in the CHAMPION trial and evaluation of the effects of these therapeutic changes on HF hospitalization rates.

Results:
Of 424 non-AA patients, 202 were assigned to w-PAP and 222 to UC. Of 126 AA, 68 were assigned to w-PAP and 58 to UC. Baseline nitrate and HDZ use was similar between w-PAP and UC for both non-AA and AA groups. At 6 months nitrate use increased more in the w-PAP than UC group in both non-AA [90 (44.6%) vs. 48 (21.6%); p< 0.0001] and AA [23 (33.8%) vs. 17 (29.3%); p=ns due to small sample size]. At 6 months HDZ use increased more in the w-PAP than UC group in both non-AA [39 (19.3%) vs. 27 (12.2%); p< 0.0452] and AA [22 (32.4%) vs. 15 (25.9%); p=ns due to small sample size] . Within the non-AA population nitrate dose increased at 6 months more in the w-PAP than in the UC group (20.43 mg vs. 4.21 mg; p= 0.05). HF hospitalization rates were significantly lower in w-PAP than UC subjects both within the non-AA (0.31 vs. 0.43 p = 0.0007) and the AA population (0.33 vs. 0.45 p=ns due to small sample size) and the magnitude of reduction in HF hospitalization was similar for non-AA and AA subjects.

Conclusions:
Greater utilization of nitrates and HDZ in HF patients managed with w-PAP produces significant and similar reductions in HF hospitalizations in non-AA and AA HF patients.
Abstract 18944: Decreased Postprandial Active Glucagon-Like Peptide-1 Levels Correlate with Coronary Spastic Angina
Authors: Akiyama Eiichi , Sugiyama Seigo , Konishi Masaski , Nozaki Toshimitsu , Ohba Keisuke , Matsubara Junichi , Sumida Hitoshi , Kaikita Koichi , Kimura Kazuo , Umemura Satoshi , Ogawa Hisao
Published: April 2024

Background:
Coronary endothelial dysfunction plays an important pathogenic role in coronary spastic angina (CSA). Glucagon-like peptide-1 (GLP-1), a gut-derived peptide hormone, has attracted remarkable attention from clinical practice for diabetes care. Vascular cells express a GLP-1 receptor and exogenous GLP-1 infusion improves endothelial function in human and animal models, however, impact of endogenous active GLP-1 (aGLP-1) in CSA have not been clinically examined. Aim of the present study was to investigate association between plasma levels of aGLP-1 and CSA.

Methods and Results:
At
fasting state or during 75g-oral glucose tolerance test (OGTT), we measured plasma levels of aGLP-1 sampled from peripheral vein in 33 CSA patients without obstructive coronary artery disease (age 58±16, female 48%), and 31 gender-, comorbidity-matched patients without ischemic heart disease (non-IHD, age 65±10, female 48%). There were no significant differences in clinical characteristics between CSA patients and non-IHD patients, except for age. The rate of patients with undetectable fasting aGLP-1 (<2.0 pmol/L) was similar between CSA and non-IHD patients [6 (18%) vs. 5 (16%), P=0.83]. Fasting aGLP-1 levels were similar between CSA and non-IHD patients (3.6 [2.7-4.7] vs. 3.9 [2.7-5.0] pmol/L, p=0.58). During 75g-oral glucose tolerance test (OGTT) in non-diabetic patients, the aGLP-1 levels after glucose ingestion were significantly lower in CSA patients (n=30) than non-IHD patients (n=26) (30 min; 6.7 [4.8-12.4] vs. 12.0 [8.4-18.5], p=0.03, 60 min; 5.3 [3.0-10.7] vs. 7.6 [6.2-10.1] pmol/L, p=0.04). Area under the curve of aGLP-1 during OGTT was significantly smaller in CSA patients than non-IHD patients (697 [436-1022] vs. 941 [815-1602] pmol/L*min, p=0.03). Multivariate logistic regression analysis revealed that the lower aGLP-1 levels at 30 minutes during OGTT (below median, 9.0pmol/L) were independently associated with the presence of CSA (odds ratio; 0.17, 95%-confidence interval 0.04-0.65, p=0.01).

Conclusions:
Plasma levels of aGLP-1 during OGTT were significantly reduced in CSA patients. Decreased postprandial levels of endogenous aGLP-1 might play a key role in pathogenesis of CSA.
Abstract 18972: A 36-Year-Old Man with Stroke and Severe Hyperlipidemia: From Phenotype to Genotype
Authors: Green Eric M , Hung Judy , Macgillivray Thomas E , Stone James R , Macrae Calum A
Published: April 2024

A 36-year-old man with a history of hypertension and hyperlipidemia was admitted to the hospital with headaches, a left visual field deficit and a right occipital lobe infarct. Family history is notable for multiple maternal relatives with premature coronary artery disease and severe hyperlipidemia. Laboratory testing revealed an LDL level of 325 mg/dl. Echocardiography demonstrated a bicuspid aortic valve and two highly mobile thrombi at the sinotubular junction. Because there was no aortic false lumen and the clinical picture was most suspicious for a ruptured aortic root atheroma, we administered intravenous heparin with plans for aortic thrombectomy pending his hemodynamics, neurological status and changes in the echocardiographic apperance of the presumed thrombi. On day three, the patient experienced acute chest pain and ST elevation concerning for abrupt occlusion of the right coronary artery. He was taken emergently to the operating room where two thrombi_one of which was lodged in the right coronary ostium_were removed and aortic endarterectomy was performed. Histology of the aortic specimen showed atherosclerosis and inflammation but no evidence of medial degeneration. The histologic evidence of atherosclerosis focused attention on the patient’s personal and family history of severe hypercholesterolemia. To assess for a genetic defect in cholesterol metabolism, we directly sequenced the LDL receptor gene and identified a heterozygous missense mutation associated with familial hypercholesterolemia (FH). Aortic root disease is common in FH homozygotes, but its presence in a heterozygote suggests an additional inherited or acquired risk factor and prompts further investigation. The bicuspid valve raises the possibility of a subclinical aortic condition that may have contributed to this unusual syndrome. This case directly illustrates the consequences of aortic plaque rupture and emphasizes the multidisciplinary clinical approaches that are central to understanding the complex links between genotype and phenotype even in a well-characterized "simple" monogenic disorder.
Abstract 19009: Increased Endogenous C-kit
+
Cardiac Stem Cells Diminish Myocardial Infarction Damage in S-nitrosoglutathione Reductase Mice
Authors: Paulino Ellena C , Hatzistergos Konstantinos E , Takeuchi Lauro M , Kanashiro-Takeuchi Rosemeire M , Balkan Wayne , Hare Joshua M
Published: April 2024

Background.
Cardiac tissue has endogenous cardiac stem cells (CSCs), which proliferate after myocardial infarction (MI) to support cardiac repair. As mice deficient in S-nitrosoglutathione reductase (GSNOR
−/−
), an enzyme regulating S-nitrosothiol turnover, have preserved cardiac function after MI, we hypothesized that GSNOR
−/−
mice have higher levels of endogenous c-kit
+
CSCs post-MI.

Methods.
GSNOR

−/−

and WT (C57BL/6) mice were infarcted by permanent occlusion of the left anterior descending coronary artery. Cardiac performance was assessed by serial echocardiography. Histological sections were analyzed for infarct size and endogenous c-kit
+
/CD45
-
CSCs were quantified by immunostaining.

Results.
There was no difference in ejection fraction (EF%) or endocardial volume (EDV, ESV) at baseline or 1 week post-MI, but at 8 weeks, EF% was improved (30.4±2.2 vs. 21.4±2.8, p<0.05) and EDV and ESV were preserved in GSNOR

−/−

mice compared with WT (ESV 72.7±6.0 vs. 139.6±19.7 ul; p<0.001, and EDV, 102.1±7.0 vs. 169.7±19.0 ul; p<0.001, respectively). In addition, GSNOR

−/−

mice exhibited smaller scar size (34.6±2.8 vs. 62.2±7.9%, p<0.05). The number of c-kit
+
/CD45
-
CSCs was greater in post-MI GSNOR

−/−

hearts vs WT, independent of the zone analyzed (infarct+border zone: 6.3±0.8 vs. 2.3±0.9 cells/mm
3
, p<0.05; remote zone: 0.4±0.1 vs. 0.1±0.05 cells/mm
3
, p<0.05).

Conclusion.
Following MI, GSNOR

−/−

mice have preserved cardiac function, decreased remodeling and infarct size and increased c-kit
+
/CD45
-
CSCs population in cardiac tissue during the remodeling phase. Thus, c-kit
+
CSCs contribute to cardioprotection in GSNOR

−/−

mice following MI, and suggest that enhanced S-nitrosylation based signaling contributes to CSC function following injury.
Abstract 19012: Impact of Beta-Blocker on Angiographic and Clinical Parameters During Intracoronary Acetylcholine Provocation Test
Authors: Im Sung Il , Rha Seung Woon , Choi Byoung Geol , Choi Se Yeon , Kim Sun Won , Na Jin Oh , Han Seong Woo , Choi Cheol Ung , Lim Hong Euy , Kim Jin Won , Kim Eung Ju , Park Chang Gyu , Seo Hong Seog , Oh Dong Joo
Published: April 2024

Background:
Beta blockers (BB) are widely used to control hypertension. It is well known that BB may lead to significant vasospasm. However, the impact of chronic administration of BB on clinical and angiographic characteristics during acetylcholine (Ach) provocation test is not clarified yet.

Methods:
A total 3034 consecutive patients (pts) underwent coronary angiography with Ach provocation test from January 2004 to August 2010 were enrolled for this study. Ach was injected in incremental doses of 20, 50, 100μ g into the left coronary artery. Significant coronary artery spasm (CAS) was defined as focal or diffuse severe transient luminal narrowing (>70%) with/without chest pain or ST-T change on ECG. A total 1394 pts (45.9%) showed positive provocation tests. Among the (+) provocation test pts, we compared the clinical and angiographic characteristics of patients with beta-blocker to those without beta-blocker in pts with myocardial infarction.

Results:
The baseline clinical and procedural characteristics are well balanced between the two groups. There was no difference in the incidence of myocardial bridges, chest pain, ischemic ECG changes and atrioventricular (AV) block on ECG, incidence of baseline spasm, severe vasospasm, multi-vessel involvements during the Ach provocation test were similar in both groups

Conclusion:
The use of beta blocker in pts with vasospastic angina was not associated with worse clinical and angiographic parameters during the Ach provocation test. BB may be safely used in pts with vasospastic angina.
Abstract 19023: Distinct Remodeling of Mitral Valve Leaflets in Severe Myxomatous and Ischemic Mitral Regurgitation
Authors: Absi Tarek S , Galindo Cristi L , Petracek Michael R , Lenihan Daniel J , Leacche Marzia , Sawyer Douglas B , Byrne John G , Su Yan Ru
Published: April 2024

OBJECTIVES: The mitral valve (MV) leaflets in severe MR undergo structural remodeling associated with multiple degenerative and adaptive changes. We hypothesized that the gene expression profiles of MV leaflets from patients with severe myxomatous MR (MMR) are distinct from those with severe ischemic MR (IMR), reflecting different underlying pathophysiologic processes.

METHODS: MVs were obtained from 11 MMR patients (9 m, 2 f; age= 60.5±11.9 y, LVEF=58.2±4.6%) and 6 IMR patients (3 m, 3 f, age= 66.5±6.7 y, LVEF=33.3±16.3%) undergoing surgery for severe MR. Hemodynamic abnormalities were similar in the two groups. Tissue RNA was extracted and cDNA were hybridized to the Affymetrix Gene Chip 1.1. Normalization and two-way ANOVA analysis were performed by Partek Genomics Suite. Only genes that resulted in >1.5 fold difference and p <0.05 were considered significantly altered.

RESULTS: Of ∼29,000 genes examined, 453 (1.6%) were differentially expressed between the two groups. Hierarchical clustering of the normalized fluorescence signal values for these genes successfully differentiated all the MMR from the IMR samples (Figure 1). Based on functional analysis, the most statistically enriched biological processes were development (MYH11, ACTA2, ECM1, MMP19), cell growth (IGF1, IGFBP3, ADAMTSL2), adhesion (MCAM, PCDH10, COL4A1) and metabolic processes (ACOT7, CYP4A11) as shown in Table 1.

CONCLUSIONS: MV leaflets in severe MMR and IMR exhibit distinct gene expression patterns, suggesting different pathophysiologic mechanisms are involved in the leaflet remodeling processes. Understanding such adaptive mechanisms can potentially provide therapeutic opportunities.
Abstract 19034: microRNA-145 Regulates ABCA1, SR-B1, and Reverse Cholesterol Transport
Authors: Mutharasan R. Kannan , Zhang Heng , Ardehali Hossein , Thaxton C. Shad
Published: April 2024

Background - Reverse cholesterol transport, the process by which cholesterol is effluxed from cells to lipoproteins and subsequently delivered to the liver for clearance, is a promising pathway to augment for treating atherosclerosis. MicroRNA-145 (miR-145) plays a critical role in regulating smooth muscle proliferation, and has been implicated in atherosclerosis. However its function in regulating reverse cholesterol transport has not been investigated. Methods and Results - A bioinformatics screen was performed to find novel microRNAs predicted to regulate ATP-binding cassette transporter A1 (ABCA1), Scavenger receptor class B member 1 (SR-B1), and ATP-binding cassette transporter G1 (ABCG1), critical mediators of reverse cholesterol transport. Based on the results of this screen, miR-145 was further investigated. Overexpression of miR-145 in both the THP-1 macrophage cell line and the HepG2 hepatocyte cell line led to downregulation of ABCA1 and SR-B1 protein levels at 48 hours and 72 hours post-transfection, while no effect was seen on ABCG1. Conversely, knockdown of miR-145 using anti-miRs in HepG2 cells resulted in upregulation of ABCA1 protein levels. Finally, to assess the effects of miR-145 on reverse cholesterol transport, functional assays were performed using radiolabeled cholesterol in differentiated THP-1 cells and in HepG2 cells. These assays demonstrated that miR-145 overexpression in THP-1 cells reduced efflux of radiolabeled cholesterol to HDL, while miR-145 knockdown in HepG2 cells increased cholesterol efflux to the HDL acceptor. Conclusions - In summary, these results demonstrate a role for microRNA-145 in regulating ABCA1, SR-B1, and reverse cholesterol transport.
Abstract 19066: D-Dopachrome Tautomerase Provides a Novel Cardioprotective Mechanism Through its Modulation on AMPK Activation in Heart During Ischemia-reperfusion
Authors: Qi Dake , Atsina Kwame , Hu Xiaoyue , Wu Xiaohong , Leng Lin , Bucala Richard , Young Lawrence
Published: April 2024

Endogenously released cardiac proteins or cardiokines regulate intracelluar signaling pathway and cardiac injury in response to stress. Macrophage migration inhibitory factor (MIF) modulates AMP-activated protein kinase (AMPK) activation and limits cardiac injury during ischemia-reperfusion. Genetic deletion of the MIF receptor, CD74, has more profound effects on ischemic tolerance and AMPK activation, than deletion of MIF alone, suggesting the possibility of a second receptor ligand. We recently identified D-dopachrome tautomerase (DDT) as a homolog of MIF, and the purpose of this study was to determine the actions of DDT in the heart. DDT perfusion in mouse heart increased AMPK in a dose-dependent manner (from 10 to 50ng/ml) without alterations in LV contractile function. Immunohistochemistry showed that DDT was highly expressed in cardiomyocytes in the mouse heart. DDT release from perfused mouse hearts (baseline: 2 ± 0.5 ng/min; post-ischemia: 4.5 ± 0.7 ng/min, p<0.05) was triggered by brief episodes (15 min) of ischemia and the inhibition of DDT actions by perfusion with neutralizing antibody (anti-DDT vs. non-immune IgG) significantly attenuated AMPK activation during ischemia. Anti-DDT (100µg/ml) also resulted in more pronounced cardiac injury following ischemia-reperfusion. Parallel effects were observed in isolated rat heart papillary muscles: recombinant DDT treatment had a similar pharmacologic effect to induce AMPK activation in a dose-dependent manner. Hypoxia (15 min) also stimulated DDT release from rat papillary muscles and inhibition of extracellular DDT by DDT neutralizing antibodies impaired AMPK activation. These pharmacologic and physiologic effects of DDT were also observed in isolated rat cardiomyocytes, indicating that DDT has specific autocrine effects. DDT treatment (400ng/ml) increased intracellular calcium in cardiomyocytes and STO-609 (2µM), a calmodulin-dependent protein kinase kinase (CaMKK) inhibitor attenuated DDT induced AMPK phosphorylation, suggesting that DDT induced AMPK activation is mediated by calcium-CaMKK pathway. Thus, DDT is a novel endogenous cardiac protein that modulates cardiac stress response pathways and protects against injury during ischemia.