bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18847: Visualization of Inflammation and Characterization of Lesions in Viral Myocarditis Mouse Model by Combined 19F-MR Cell Tracking and 1H Cardiac MRI
Authors: Ye Yuxiang , Helluy Xavier , Sauter Martina , Basse-Luesebrink Thomas C , Kampf Thomas , Hiller Karl-Heinz , Yilmaz Ali , Sechtem Udo , Bauer Wolfgang R , Kandolf Reinhard , Klingel Karin , Jakob Peter M
Published: April 2024

Introduction
Myocarditis is a challenging disease for diagnosis and treatment. Recently, we have established a non-invasive cellular 19F-MR method to visualize inflammation of myocarditis in mice [1]. In this study, we correlated detection of inflammation by 19F-MR and tissue characterization by 1H-MR in viral myocarditis mouse model.

Methods
Viral myocarditis was induced by infecting ABY mice (n=5 infected+3 control) with CVB3. 19F-perfluorocarbon emulsion (PFC) (150μl) was injected i.v. 13 days post-infection to label monocytes and macrophages in blood. The labeling efficiency was examined by FACS in blood samples. 19F/1H-images were acquired at a 7T MR. 19F-MRI was superimposed on 1H-Cine to localize inflammation in myocardium. Lesions were characterized by T2WI, T2*WI and Gd-DTPA enhancement. MR findings were examined by Histology and immunohistochemistry (IHC).

Results
Blood FACS and confocal microscopy on IHC revealed that the 19F-MR signal in myocardium was due to internalized PFC in macrophages. 19F-MR detected macrophage infiltrating myocarditis lesions. Edema and Gd enhancement could be found in some lesions. Interestingly, most patchy 19F signal co-localized with T2* hypo-intense signal in lesions, which has been reported in various mouse strains post CVB3 infection [2]. Necrosis, T cells, fibrosis, and mineral deposition were found in lesions by histology and IHC.

Conclusion
19F-MRI unambiguously detected active recruitment of macrophages to myocarditis lesions. On T2*WI signal voids in lesions were closely related to 19F signal in location and volume, which indicates its association to inflammation. Caution should be taken to apply iron oxide particles to visualizing inflammation in viral myocarditis, while the significance and mechanism of this contrast, especially its existence in human, need further investigation. 1. Ye et al ISMRM proceeding 2012. 2. Helluy et al. ISMRM proceeding 2011. This work was supported partly by BMBF 01EZ0816.
Abstract 18899: Distribution of Low CT Number Area is Dominant and Wide in Vessel Containing Vulnerable Plaque - Vessel-wide Cross-sectional Scannning by Multi-detector Row Computed Tomography
Authors: Komatsu Sei , Imai Atsuko , Takewa Mitsuhiko , Minamiguchi Hitoshi , Ohara Tomoki , Kodama Kazuhisa
Published: April 2024

Introduction.
Lipid-rich plaque is shown to be dominant in the culprit by intravascular ultrasound and multidetector row computed tomography in acute coronary syndrome (ACS) than in stable angina pectoris (SAP). However, there were few reports compared the disposition of lipid-rich plaque in vessel-wide.

Hypothesis
We assessed the hypothesis that lipid-rich plaque is dominantly located in ACS patients by our original vessel-wide cross-sectional scanning.

Methods
One hundred eight patients (32 acute coronary syndrome (ACS), 38 stable angina pectoris (SAP), and 38 patients without plaque) underwent 64-slice computed tomography angiography. Cross-sectional images for 1mm-intervals were analyzed containing culprit lesion from the ostium. Areas and ratio of 0-50, 50-100, 100-150, 150-200, 200-250, 250-300, 300-350, 350-400, 400-450, >450HU surrounding vessel were calculated for each cross-sectional images and continuously demonstrated as a graph (see figure).

Results
Analyzed cross-sectional images were averaged 52±18 images for 76 vessels. Fifty cross-sectional images for 38 vessels in patients without plaque were analyzed as control. The ratios of 0-50, 50-100 HU were statistically dominant in ACS patients compared to SAP patients or without plaque (34.7±14.4% vs. 19.6±4.1% vs. 14.8±3.6%, P<0.0001; 22.3±5.5% vs.15.4±3.4% vs. 14.6±2.0%; P<0.0001). The number of slices in which 0-50HU were dominant were higher in ACS than SAP (18±6 vs 12±4 slices, p<0.01). The number of positive remodeling in the vessel was higher ACS than SAP (3.6±0.9 vs. 1.5±0.8, p<0.001). The slices of 64 culprits (91%) were not the most distributed by 0-50HU in the vessels.

Conclusions.
In ACS patients, lipid-rich component, demonstrated as the area 0-50HU, distributed dominantly and wide on the vessel including the culprit.
Abstract 189: Characterizing Continuous Capnography at the Onset of Return of Spontaneous Circulation
Authors: Bluhm David C , Yuen Trevor C , Edelson Dana P
Published: April 2024

BACKGROUND: Manual pulse checks are often unreliable and result in prolonged pauses in chest compressions, which may be deleterious to patient outcomes. Capnography has the potential to minimize these pauses, but the threshold for determining a pulse is not known.

METHODS: We conducted a prospective study of consecutive, adult, in-hospital cardiac arrests with documented return of spontaneous circulation (ROSC) at a single academic center between April 2006 and March 2012. CPR parameters and capnography were recorded using a CPR-sensing defibrillator equipped with sidestream capnography (HeartStart MRX with QCPR, Philips Healthcare; MicroStream, Oridion). All cases with continuous capnography and compression data for at least 2 minutes preceding ROSC were included in the analysis. End-tidal carbon dioxide (ETCO2) values were extracted electronically using custom software and the nadir and peak surrounding the last chest compression were manually identified.

RESULTS: A total of 69 cases met inclusion criteria. The median ETCO2 nadir was 14 mmHg (range 2 - 23), which rose to a median peak of 43 mmHg (range 21 - 98), yielding a median relative rise of 215% (range 44-1944). The figure displays the changes in ETCO2 before and after the peak. The median time from nadir to peak ETCO2 was 108 s (range 24 - 501), and the median rise was 0.25 mmHg/s (range 0.05 - 0.92). The peak occurred a median of -4.4 s relative to the last chest compression. At the end of chest compressions, the median ETCO2 was 29 mmHg (range 13 - 58), without a significant drop-off when compressions were held. At the end of chest compressions, the median ventilation and heart rate were 14/min (range 6 - 34) and 126/min (range 36 - 225), respectively.

CONCLUSION: In this sample, we found that ROSC was accompanied by an abrupt increase in ETCO2. This rise has the potential to be used as a pulse detector. Future work should assess whether the failure of this rise obviates the need for a pulse check.
Abstract 18915: Modulation of Exosomal Pro-angiogenic MicroRNAs from CD34+ Progenitor Cells by Hypoxic-Preconditioning Enhances its Angiogenic Potency and Post-ischemic Tissue Repair
Authors: Sahoo Susmita , Gupta Rajesh , Thorne Tina , Misener Sol , Losordo Douglas W , Vaughan Douglas E
Published: April 2024

Exosomes, membrane bound nano-vesicles secreted by the cells, has great potential to advance cell-based therapies for ischemic cardiovascular diseases by overcoming its limitations- such as viability and retention, difficulty in isolation of adequate number of cells, or, appropriate storage of the cells. Recently, we have discovered that adult human CD34+ stem cells, one of the most successful cell types for treating cardiovascular diseases, secrete exosomes (Exo) that mediates most of the angiogenic and therapeutic activity of the stem cells via transfer of pro-angiogenic microRNAs. We hypothesize that the regenerative efficacy of the cell-free Exo derived from human CD34+ cells can be improved by hypoxic pre-conditioning, modulating its pro-angiogenic miRNA content.

Methods and Results:
CD34+ Exo isolated from hypoxic human CD34+ cells were significantly proliferative, anti-apoptotic and angiogenic both in vitro and in vivo, as compared to CD34+ Exo from normoxic cells. Treatment of hypoxic Exo significantly improved perfusion and prevented ischemic limb amputation, compared with normoxic Exo, in a mouse model of hind limb ischemia. We investigated the possibility of involvement of proteins by comparing the total proteins from hypoxic and normoxic Exo using 2-D differential gel electrophoresis and mass spectrometry; we did not detect any difference in the proteins expressions quantified. Interestingly, bioanalyzer analyses indicated that hypoxic cells and Exo were enriched for miRNAs. The differential expression of miRNAs between hypoxic and normoxic Exo are profiled using miRNA microarray and validated by qRT-PCR. We detected significantly high expression of proangiogenic miRNAs in hypoxic Exo. Flow cytometry and in vitro trafficking by confocal microscopy demonstrates transfer of Cy3 labeled miRNA to recipient endothelial cells. We are studying the involvement of transferred pro-angiogenic miRNAs on hypoxia-Exo-induced angiogenic activity and modulation of target endothelial cell gene expression by loss of function-gain of function studies.

Conclusion:
Our results demonstrate that hypoxia modulates the miRNA content of adult human CD34+ progenitor cell derived exosomes improving its angiogenic and therapeutic potency.
Abstract 18936: Kidney Injury Molecule-1 (KIM-1) is a Promising Urinary Biomarker to Detect Cardiorenal Syndrome in Children with Dilated Cardiomyopathy (DCM)
Authors: Kaddourah Ahmad , Goldstein Stuart , Jeffries John
Published: April 2024

Background:
Type II cardiorenal syndrome (CRS) describes renal dysfunction in the presence of chronic heart dysfunction. Novel urinary acute kidney injury biomarkers (NUB) have not been studied in children with DCM. We aim to 1) Evaluate the correlation between four NUB and severity of LV dysfunction, and 2) Determine the best marker to detect CRS in children with DCM.

Methods:
We are conducting a cross-sectional study in children with DCM and LV dysfunction. Enrolled children had an echocardiogram to measure the LV ejection fraction (EF). Urine samples were collected at the same visit to measure the NUB: KIM-1, NGAL, IL-18, and L-FABP. NUB levels were adjusted for each mg of urinary creatinine. Glomerular filtration rate was estimated using modified Schwartz formula (eGFR) when Creatinine level (Cr) is available. Univariate analysis was conducted between patients (pts) with EF< 45% and EF ≥ 45%. ROC analysis was performed for all NUB and GFR. 2x2 tables were constructed from NUB cutoffs to maximize specificity for EF <45%.

Results:
30 pts (14.2 ±6.4 years old) have been enrolled to date. 13 (43%) had EF<45%. Although all NUB levels were higher in pts with EF <45%, only KIM-1 was significantly higher [836.5 (±844.1) vs. 442.8 (±249.5) pg/mg
cr
, P
one-tailed
=0.04]. Area under the curve for KIM-1 was 0.61 to predict EF <45%, compared to 0.53 for eGFR. A KIM-1 cutoff of 900 pg/mg
cr
yielded highest correct EF classification (38% sensitivity, 94% specificity). 6/30 (20%) pts had KIM-1 >900; 5/6 (83%) had EF of <45% vs. 8/24 (33%) with KIM-1<900 (P
one-tailed
=0.03).

Conclusions:
Our pilot data suggest DCM pts with EF<45% tend to have higher NUB urinary levels indicating worse CRS than pts with EF≥45%. Urinary KIM-1 may be the most predictive test to detect CRS compared to other NUB and eGFR. We anticipate confirming this finding by increasing the study’s power.
Abstract 18974: A Pilot Study of the Effects of Ranolazine on Right Ventricular Structure and Function, Exercise Capacity, and Symptoms in Pulmonary Arterial Hypertension
Authors: Shah Sanjiv J , Cuttica Michael J , Beussink Lauren , Mkrdichian Hamorabi , Sarnari Roberto , Benefield Brandon , Selvaraj Senthil , DeMatte Jane E , Lee Daniel C
Published: April 2024

Introduction:
Right ventricular (RV) failure is a major cause of death in pulmonary arterial hypertension (PAH). RV ischemia, which is common in PAH, plays a major role in the development of RV failure. We hypothesized that ranolazine, a late Na+ current inhibitor, would be beneficial in patients with PAH by increasing RV perfusion.

Methods:
We prospectively enrolled 10 patients with World Health Organization (WHO) Group I PAH and symptoms of angina (or anginal equivalent) in an observational, 3-month study of the effects of ranolazine (1000 mg PO BID) in PAH. All patients were on chronic pulmonary vasodilator therapy. At baseline and 3 months, patients underwent functional class assessment, 6-minute walk test, bicycle echocardiography with speckle-tracking for assessment of RV mechanics, right heart catheterization, and adenosine perfusion cardiac MRI. Data was compared at baseline vs. 3-months using paired t-tests.

Results:
The mean age was 47±13 y, and 80% were female. At baseline, patients had moderate or greater PAH (Table 1) with evidence of RV dysfunction (7/10 patients had reduced RV fractional area change [<0.35], and all patients had septal flattening indicative of RV overload). Ranolazine was well tolerated in 90% of patients (7 patients tolerated the full dose and 2 patients required a dose reduction due to side effects, after which the drug was well tolerated). Ranolazine was discontinued in 1 patient due to a medication interaction. After 3 mo. of ranolazine therapy, symptoms improved, exercise capacity increased, RV size decreased, and tricuspid annular plane systolic excursion (TAPSE) increased (Table 1). There were no changes in invasive hemodynamics, and no major adverse events.

Conclusions:
Ranolazine is well tolerated and safe in patients with WHO Group I PAH. After 3 mo. of therapy, ranolazine improved RV size and function and resulted in symptomatic improvement. These findings support the development of clinical trials for ranolazine in PAH.
Abstract 18985: K-Ras Activates Mammalian Hippo Signaling to Promote Ischemia/Reperfusion Injury in the Heart
Authors: Del Re Dominic P , Matsuda Takahisa , Zhai Peiyong , Sadoshima Junichi
Published: April 2024

Acute myocardial ischemia and reperfusion (I/R) cause damage to the heart, thereby impairing its ability to function effectively. Therapies aimed at preventing I/R injury are limited and a better understanding of the mechanisms involved remains critical. In hearts of mice subjected to I/R we found differing kinetics of H- and K-Ras activation, and only K-Ras modification following oxidative stress was observed. Expression of active H-Ras12V caused increased phosphorylation of AKT (1.8±0.3-fold vs LacZ) and ERK1/2 (3.3±0.3-fold vs LacZ) and protected cardiomyocytes against apoptosis, whereas K-Ras12V activated mammalian sterile 20-like kinase 1 (Mst1)(2.1±0.1-fold vs LacZ), which led to myocyte death. Endogenous K-Ras, but not H-Ras, was detected at mitochondria and associated with Ras association domain family 1 isoform A (RASSF1A) in both cardiomyocytes and mouse hearts. Genetic disruption of RASSF1A prevented K-Ras-induced Mst1 activation and inhibited Mst1 translocation to mitochondria in response to oxidative stress. Mass spectrometry analysis revealed that active Mst1 phosphorylates Bcl-xL at Ser14, a previously unreported residue, in cardiomyocytes and mouse heart, and mediates Bcl-xL phosphorylation in response to I/R in vivo. Ser14 phosphorylation attenuated Bcl-xL-Bax binding and the phosphomimetic Bcl-xL S14D mutant showed a weakened protective capacity against apoptotic insult (cell viability; LacZ + H2O2 45±5%, XL WT + H2O2 76±4%, XL SD + H2O2 51±5%, p<0.05). Following in vivo I/R, Kras+/- mice had significantly smaller myocardial infarct size vs WT mice (22±4% vs 39±2%, p<0.05), while no significant difference in infarct size was observed in Hras+/- mice (37±3% vs 38±3%). Conversely, cardiac-specific K-Ras12V TG mice had increased Mst1 activation and significantly larger infarcts vs NTG mice (67±10% vs 36±2%, p<0.05). This myocardial damage was rescued in bigenic mice expressing both K-Ras12V and Dn-Mst1 (41±7%, p<0.05), implicating Mst1 as a critical mediator of K-Ras in vivo. Our work demonstrates a distinct role for K-Ras as an endogenous promoter of mammalian Hippo signaling, and identifies a novel mechanism involving phosphorylation of Bcl-xL by which Mst1 mediates cardiomyocyte apoptosis and I/R injury in the heart.
Abstract 18996: Comparison of Clinical Outcomes After Stent Implantation for Left Main Trunk Disease Between First- and Second-generation Drug-eluting Stent Eras
Authors: Hyodo Yusuke , Kadota Kazushige , Fuku Yasushi , Saito Naoki , Otsuji Hideaki , Otsuru Suguru , Hasegawa Daiji , Shigemoto Yoshikazu , Habara Seiji , Tada Takeshi , Tanaka Hiroyuki , Goto Tsuyosih , Mitsudo Kazuaki
Published: April 2024

Purpose: In Japan, zotarolimus-eluting stent (ZES) became available from May 2009 and everolimus-eluting stent (EES) from January 2010 in addition to the first-generation drug-eluting stents (DES). The aim of this study was to clarify the impact of second-generation drug-eluting stent (DES) on clinical outcomes in left main trunk disease (LMTD).

Methods: A total of 238 patients (174 men, 64 women, mean age 70.8±10.1 years) who had undergone DES implantation for LMTD were classified into two groups: group A (first-generation DES era, 168 patients, March 2003 to April 2009, median follow-up period 1489 days, interquartile range [IQR] 1165-1967) and group B (second-generation DES era, 70 patients, May 2009 to December 2010, median follow-up period 608 days, IQR 450-721), and long-term clinical outcomes were assessed. Patients who had undergone percutaneous coronary intervention in the past were excluded.

Results: In group A, SES was deployed in 142 patients and PES in 3. In group B, ZES was deployed in 35 patients and EES in 18. Bifurcation lesion was significantly higher in group B (A, 75.6% vs. B, 88.6%, p=0.038). Syntax score showed no significant difference between groups (26.6±9.6 vs. 27.2±11.4, p=0.70). Stent strategy, either single- or two-stent, showed no significant difference (two-stent strategy: 30.4% vs. 28.6%, p=0.92). The Kaplan-Meier method revealed that the event-free survival rate of target vessel failure, defined as a composite of cardiac death, myocardial infarction, and target vessel revascularization, was significantly higher in group B (p=0.029).

Conclusion: Our data indicate that the outcomes of DES implantation for LMTD are more preferable in the second-generation DES era than in the first-generation DES era.
Abstract 18999: The Effects of the Connexin40 Mutations P88S and G38A on Cardiac Physiology in the Intact Animal
Authors: Kanthan Ajita , Fahmy Peter , Rao Renuka , Kizana Eddy
Published: April 2024

Introduction:
Prior patch clamping studies have revealed that the somatic human connexin40 mutations P88S and G38A, identified within the atria of patients with atrial fibrillation (AF), are associated with reduced gap junction conductances when compared to wild type connexin40 (wtCX40). Our aim was to phenotype the rat heart following expression of these mutations by somatic gene transfer.

Methods:
A mix of pluronic F127, trypsin, and 10
7
vector genomes of lentivirus was painted onto the left atrium of adult Sprague-Dawley rats via a left thoracotomy. Rats were randomised to receive lentivirus containing a transgene encoding either wtCX40, P88S, G38A or eGFP. Electrophysiology studies (EPS) consisting of surface and trans-oesophageal electrocardiograms (ECG) were performed under anaesthesia just prior to and 7 days after surgery. Following day 7 EPS, atria were excised, sectioned, and examined histologically with Sirius Red and Haematoxylin and Eosin. Data are expressed as means ± standard deviations.

Results:
At day 7, eGFP expression revealed approximately 5% heterogeneous atrial transduction. Rats transduced to express either P88S or G38A possessed significantly longer mean P wave durations and AF when compared to eGFP controls as shown in the table. There were no significant differences in all other characteristics.

Conclusion:
The human somatic connexin40 mutations P88S and G38A slow atrial conduction as evidenced by prolonged P wave durations at day 7. In addition, heterogonous expression of P88S and G38A within the atrial myocardium increases the propensity for inducible atrial fibrillation.
Abstract 19002: LRP6 Mutation (LRP6
R611C
) Leads to PDGF Dependent Vascular Smooth Muscle Cell Hyperproliferation and Atherosclerosis
Authors: Srivastava Roshni , Mani Arya
Published: April 2024

A loss of function mutation in the Wnt co-receptor Low Density Lipoprotein Receptor Related Protein 6, (LRP6
R611C
) causes early atherosclerosis and metabolic syndrome in humans. We have generated

LRP6
R611C

mice with homologous recombination. LRP6
R611C
mice demonstrate enhanced vascular smooth muscle cell (VSMC) proliferation, and exaggerated neointima formation upon carotid injury mice and on LDLR knockout background develop accelerated atherosclerosis compared to their respective controls. The aorta of LRP6
R611C
mice exhibits a highly proliferative media marked by an increases in PDGFRβ and ELK1 expression along with decreased myocardin expression. These findings correlate with reduced α-SMA and increased vimentin in the aortic media, indicating proliferative phenotype of VSMCs. Furthermore, in LRP6
R611C
mice the aortic adventitia is loaded with PDGFRβ positive cells along with abundance of Sca1 positive progenitor cells in the aortic intimal and adventitial layers.
Ex vivo,
cultured

LRP6
R611C

VSMCs exhibit increased expression of PDGF-BB and its transcriptional regulator SP1. These findings suggest
that
LRP6
R611C
promotes maintenance of progenitor cell

in the aorta and enhances VSMC proliferation through activated PDGF signaling. Interestingly, the levels of PDGF-BB were also significantly increased in the macrophages as well as plasma of the LRP6
R611C
mice. LRP6
R611C
macrophages exhibited increased uptake of ox-LDL and augmented expression of vimentin, a regulator of intracellular LDL transport
.
Thus,

LRP6
R611C
mutation indicates

a single gene defect in Wnt pathway leading to a major aberration in PDGF dependent signaling thereby predisposing to atherosclerosis.
Abstract 19036: Transgenic Mouse with Overexpression Hypoxamir-210: Implications on Infarct Size Attenuation and Preservation of Heart Function
Authors: Ahmed Rafeeq P , Jiang Shujia , Caudil Christy , Durrani Shazia , Haider Khawaja
Published: April 2024

Background.
Hypoxamir-210 (miR-210) is a universal responder to activation of HIF-1 signaling and plays a significant role in cell survival under ischemic stress. To assess the impact of constitutive over expression of hypoxamir-210 on infarct size expansion and preservation of cardiac function, we report the development of first transgenic (TG) mouse model with miR-210 overexpression (
210
TG).

Methods and Results.
miR-210 transgenic mouse was generated at the University of Cincinnati transgenic core using the C57BL/6 mouse strain. Briefly precursor miR-210 along with H1 promoter (HmiR0167-MR01 vector from Genocopiea) was amplified and cloned into pShuttle vector (Stratagene) using restriction enzymes Not1 and Sal1. Amplified vector was digested, purified and used for microinjection into the pronuclei of single cell embryos derived from superovulated C57BL/6 females. The surviving embryos were implanted into foster female mice. TG mice were identified genotyping of the tail genomic DNA by PCR. As compared to control littermates (NTG),
210
TG had significantly higher miR-210 expression in different tissues and organs including the heart and the bone marrow. Molecular studies showed altered expression of miR-210 putative traget Dffb in
210
TG animals. Age and sex-matched mouse model of permanent LAD coronary artery ligation was developed in
210
TG(n=12 animals/group) using NTGas controls. Animals were harvested on day 7 (short term) and 28 (long term) after LAD ligation. Echocardiography performed prior to euthanasia showed that cardiac function was significantly preserved in
210
TG as compared to NTG as indicated by LVEF (45.2±1.06
vs
38.9±1
p
<0.001) and LVFS (18.3±1
vs
15±1), Histochemical studies showed preserved myocardial architecture and attenuated infarct size in
210
TG (
p
<0.05
vs
NTG). TUNEL combined with fluorescence immunostaining for cardiac troponin-1, smooth muscle actin and CD31 showed significantly reduced TUNEL positivity of cardiomyocytes, smooth muscle and endothelial cells in
210
TG heart at day 7 (
p
<0.05
vs
NTG hearts).

Conclusions.
Constitutive overexpression of hypoxamir-210 rescued global cardiac function after myocardial infarction by inhibition of cardiomyocyte apoptosis to attenuate infarct size in the heart.
Abstract 19041: The Effectiveness of Intensive Medical Treatment of Patients Initially Referred as Refractory Angina: Preliminary Results
Authors: Dourado Luciana O , Poppi Nilson T , Pereira Alexandre C , Cesar Luiz Antonio M , Krieger Jose Eduardo , Gowdak Luis Henrique W
Published: April 2024

Introduction:
Refractory angina is a major clinical challenge. Many patients (pt) may be erroneously diagnosed as refractory angina (RA), if not on intensive medical therapy. Objectives: To evaluate the impact of intensive medical treatment on angina functional class, angina episodes and nitrate consumption
per week
in pt initially diagnosed as RA.

Methods:
63 pt (68% male, 62±11 years) were included based on the following criteria: 1) disabling symptoms; 2) objectively documented myocardial ischemia; 3) coronary anatomy unsuitable for conventional myocardial revascularization procedures. Medical visits ocurred every 4 weeks during a 3-month period (V0 to V3). Pt were evaluated in each visit according to the functional class(CCS), and angina episodes and sublingual nitrate consumption
per week
were registered in pt's angina diary. Optimized medical therapy was strongly encouraged based on pt’s tolerance. Statistical analysis included the paired-sample T-test and logistic regression.

Results:
There was an overall improvement in CCS class between V0 to V3 of 0.89±1 (p<0.001), from 2.9±0.8 to 2.1±1.0; a decrease in angina episodes of 3.2±6.2 (p=0.007), from 6.9±7.6 to 3.7±4.5, and in sublingual nitrates
per week
of 2.2±4.7 (p=0.04), from 4.7±5.0 to 2.4±2.6. In V0 and V3, anti-ischemic drugs were used as follows (%), respectively: beta-blockers (89 vs. 95), calcium channel blockers (78 vs. 89), long-acting nitrates (92 vs. 100), and trimetazidine (36 vs. 95), aspirin (81 vs. 81), statins (97 vs.98). There were non-significant changes in: mean HR (bpm) from 65±11 to 63±10 (p=0.09), in mean SBP from 125±22 to 122±22 (p=0.24), and DBP from 72±12 to 70±13mmHg (P=0.18), in mean waist circumference (cm) from 104±11 to 104±10(p=0.67) and in mean weight (kg) from 79±17 to 80±16 (p=0.39). The only predictive factor of clinical improvement found was CCS (p=0.04).

Conclusion:
Pt enrolled in this clinical program, although initially diagnosed as refractory angina, experienced a significant improvement in their clinical presentation, although little medical management changes were made. We believe that the regular visits at shorter intervals may have led to a better treatment adherence, emotional easiness and self-confidence.
Abstract 19056: Left Ventricle Longitudinal Strain was Reduced in Subclinical Patienst with Repaired Tof
Authors: Nakamura Akihiro , Seo Yoshihiro , Ishizu Tomoko , Kato Yoshiaki , Takahashi Miho , Horigome Hitoshi , Sumazaki Ryo , Aonuma Kazutaka
Published: April 2024

Background:
Right ventricular (RV) dilation and dysfunction caused by residual pulmonary regurgitation afterh repaired tetralogy of Fallot (ToF) are associated with their prognosis. In contrast, left ventricular (LV) function has been focused as a novel determinant of prognosis in patients with repaired ToF. Although RV-LV interaction may be a cause of LV dysfunction, the reason of LV dysfunction in patients with repaired ToF was poorly understood. We aimed to assess LV regional myocardial function in consideration of interaction with RV properties.

Methods:
We studied subclinical 27 patients with repaired ToF (11 male, 17.1 ± 4.9yrs) and 10 control subjects (7male, 13.9 ± 5.5yrs). RV and LV ejection fractions (EF) and end diastolic volume index (EDVi, ml/m2) were measured with 3-dimensional echocardiographic sysytem (Tomtec imaging systems). Pulmonary regurgitation(PR) fraction was caliculated by volumetric method [RV stroke volume - LV stroke volume / RV stroke volume]. Tricuspid annular plane systolic excursion (TAPSE) was measured in assessing RV systolic function.Left atrium area(LA), transmitral mitral flow ratio(MVE/A), and velocity ratio of early mitral flow to mitral ring (MV E/E’) were measured for evaluation of LV diastolic function. Global LV and RV longitudinal strain (LS) were assessed by speckle tracking echocardiography. Ramp protocol cardiopulmonary exercise testing was performed to measure peakVO2 (ml/kg/min).

Results:
PR fraction (31±18%) was correlated with RVEDVi(r=0.532, p=0.001), however, not correlated with TAPSE, RVEF, and RV-LS. LV-LS was lower in patients with repaired ToF compared to control subjects (-29.1±5.7 vs -23.8±4.8 %, p=0.014). LV-LS was negatively correlated with PR fraction (r= -0.435, p=0.008), and RVEDV(r= -0.491,p=0.002). However, no correlation between RV-LS and LV-LS was observed. LV-LS was negatively associated with LA (r= -0.392, p=0.018), but not associated with MV E/A, MV E/E’ and peak VO2.

Conclusions:
Even in subclinical patienst with repaired ToF, LV-LS was reduced as comoared to normal subjects. The longitudinal dysfunction may be rather affected by dilated RV, and clininical significance with LV diastolic function and exercise capacity were not clear in this setting.
Abstract 19057: Functional Tricuspid Regurgitation is an Independent Predictor of Mortality and Morbidity in Patients with Aortic Stenosis Undergoing Valve Replacement
Authors: Tan Timothy C , Flynn Aidan W , Rincon Luis M , Nunes Maria P , Mehrotra Praveen , Agnihotri Arvind K , Shahian David M , Picard Michael H , Afilalo Jonathan
Published: April 2024

Background:
In patients with severe aortic stenosis (AS), pulmonary hypertension (PHT) and right ventricular (RV) dysfunction are predictors of adverse events. PHT and RV dysfunction can lead to progressive functional tricuspid regurgitation (FTR), which has an under-appreciated yet potentially devastating course. We describe the impact of FTR in patients with severe AS undergoing aortic valve replacement (AVR).

Methods:
We identified consecutive patients with severe AS who underwent AVR in 2009 and 2010. We excluded those with concomitant mitral or tricuspid valve replacement, organic tricuspid valve pathology, and those without an available echocardiogram (echo) within 3 months of surgery. A panel of quantitative echo parameters was measured according to American Society of Echocardiography guidelines. Clinical variables were extracted from the Society of Thoracic Surgeons (STS) database. The outcomes of interest were postoperative STS-composite mortality or major morbidity, and all-cause mortality over a mean follow-up of 1.8 years.

Results:
Of 207 patients studied, 21 (10.1%) had moderate-to-severe FTR. Moderate-to-severe FTR was associated with higher pulmonary artery systolic pressure (58 vs. 38 mmHg, P<0.001), worse RV myocardial performance index (0.57 vs. 0.42, P=0.003), lower RV fractional area change (38% vs. 47%, P=0.004), lower LVEF (48% vs. 58%, P=0.002), and higher left atrial volume index (56 vs. 42 cm2/m2, P<0.001), but not with aortic valve area (0.71 vs. 0.71 cm
2
, P=0.82) or peak aortic velocity (4.3 vs. 4.4 m/s, P=0.62). Patients with FTR were more likely to suffer postoperative in-hospital mortality or major morbidity (48% vs. 23%, P=0.02) and long-term mortality (17% vs. 9%, P=0.004). When echo parameters were entered in a multivariable model, optimal predictors of all-cause mortality were: FTR (HR 3.46, 95% CI 1.26, 9.49) and restrictive diastolic filling (HR 3.07, 95% CI 1.16, 8.11). Results were similar when adjusted for clinical covariates including chronic lung disease.

Conclusion:
In the setting of AVR, moderate-to-severe FTR is an independent predictor of postoperative mortality and major morbidity. FTR is prevalent in AS patients with PHT and poor right or left ventricular function.
Abstract 19068: Connective Tissue Growth Factor in Human Diastolic Heart Failure from the Taiwan Diastolic Heart Failure Registry and a Canine Model of Diastolic Dysfunction
Authors: Wu Cho-Kai
Published: April 2024

BACKGROUND:
Diastolic heart failure (DHF) is characterized by myocardial interstitial fibrosis and left ventricular hypertrophy. The study investigated the association between connective tissue growth factor (CTGF) and DHF from animal model to clinical indices.

METHODS:
The participants of current study were enrolled from the Taiwan Diastolic Heart Failure Registry (TDHFR). 1284 patients were screened and a total of 125 patients with a diagnosis of DHF confirmed by echocardiography were recruited. The severity of DHF was decided according to tissue doppler imaging (E/e’). Soluble plasma levels of CTGF were measured in all subjects and the associations with diastolic function parameters were calculated. Canine model of DHF was induced by aortic banding. Hemodynamic and echocardiographic data were obtained before and after pressure loading (at baseline and after 2 weeks). Myocardium tissues were collected, and western blotting was used to detect the protein expression of CTGF for each dog. The correlation between CTGF, the severity of diastolic dysfunction and hemodynamic changes was then calculated.

RESULTS:
Patients with severe DHF presented significantly higher plasma CTGF levels than the controls. Significant correlation were found for plasma CTGF and E/e’ (r = 0.80, p<0.001) in advanced DHF patients (E/e’ >15). After 2 weeks in canine models, the protein expression of CTGF from LV myocardial tissue was significantly increased (p<0.01) compared with the controls (shame dogs). Moreover, the expression of CTGF paralleled the severity of LV diastolic dysfunction parameters (r= 0.70, p= 0.03 for E/e’) and hemodynamic changes (r= 0.75, p= 0.02). After adjusting the possible confounding factors for diastolic dysfunction, CTGF levels were associated with diastolic parameters both in human and canine models (Plasma CTGF, B=0.064, p<0.001; tissue CTGF, B= 9.87, p = 0.05).

CONCLUSIONS:
Both Plasma and myocardium CTGF levels had significant correlations to the severity of DHF. Our study offered the evidence to apply novel therapies for DHF patients aim to down-regulate the overexpression of CTGF.
Abstract 19075: Impact of LDL Apheresis on Lipoprotein Particle Concentrations
Authors: Lynch Donald R , Winegar Deborah A , Yancey Patricia G , Pourfarzib Ray , Fazio Sergio , Linton MacRae
Published: April 2024

Background:
Low-density lipoprotein (LDL) apheresis via dextran-sulfate-cellulose absorption lowers LDL cholesterol (LDL-C) levels (>60%) by removing apoB containing lipoproteins due to their positive charge. Although HDL is negatively charged LDL apheresis also causes small but significant reductions in HDL-C levels (10-15%). LDL particle number (LDL-P) has been associated more strongly with clinical atherosclerotic outcomes than LDL-C; however, the impact of LDL apheresis on lipoprotein particle concentrations as determined by nuclear magnetic resonance (NMR) has not been reported.

Objective:

To determine the effects of LDL apheresis on lipoprotein particle concentrations and to compare changes in lipoprotein particle concentrations to conventional serum lipid levels.

Methods:

Comprehensive NMR lipoprotein analysis was performed on serum obtained from five subjects prior to and following three occasions of LDL apheresis performed at two-week intervals. Three subjects had homozygous familial hypercholesterolemia (FH) and two had coronary artery disease (CAD) and mixed dyslipidemia with LDL-C > 200 mg/dL (one subject had pre-treatment triglyceride (TG) levels > 400 mg/d) prior to and following LDL apheresis

Results:

Mean LDL-P concentration was 2957+1024 nmol/L, HDL particle number (HDL-P) was 27+9 μ mol/L and TG was 224+208 mg/dL. LDL apheresis treatment reduced LDL-P by 67% (p < 0.0001) and decreased TG (43%, p = 0.153) to a lesser extent. All reductions were significant in subjects with pre-treatment TG levels < 400 mg/dL. The mean HDL-P increased slightly with treatment (29+7 mg/dL, p = 0.533), but the effect was not significant. There were no treatment-dependent changes in the size distribution of LDL particles, whereas HDL particle size shifted toward an increase in medium HDL-P in FH subjects.

Conclusion:

This is the first report on the effects of LDL apheresis on serum concentrations of lipoprotein particles as determined by NMR. LDL apheresis promoted dramatic reductions in both LDL-C and LDL-P, whereas HDL-P was unchanged to slightly increased despite a significant decrease in HDL-C.
Abstract 19115: Cardiac MR Evaluation of Diffuse Myocardial Fibrosis in Children and Young Adults with Congenital Aortic Stenosis
Authors: Dusenbery Susan M , Jerosch-Herold Michael , Geva Tal , Newburger Jane W , Powell Andrew J
Published: April 2024

Background:
Diffuse myocardial fibrosis (DF) in adults with aortic stenosis (AS) is associated with heart failure, arrhythmias, and mortality; however, little is known about its role in younger patients with congenital AS. Study aims were to apply for the first time a recently validated cardiac magnetic resonance (CMR) extracellular volume fraction (Vec) measurement technique to quantify DF in children and young adults with AS and to explore associations between DF and indices of diastolic function.

Methods:
All pts who had a CMR with myocardial T1 measurement, were <30 yrs, and had congenital AS with a peak Doppler gradient ≥20 mm Hg at any time prior to the CMR were included. The Vec, a measure of DF, was calculated in the mid-LV by measuring T1 values for blood pool and myocardium before and after gadolinium with a modified Look-Locker technique, and adjusting for hematocrit. Vec results were compared to published values in healthy volunteers (n=14).

Results:
Thirty-five pts met inclusion criteria with a median age of 15 yrs (1.7-27), peak AS gradient of 36 mm Hg (0-90), and aortic regurgitation (AR) fraction by CMR of 25% (0-48). Vec was significantly greater in AS pts than volunteers (0.29 ± 0.06 (range, 0.22-0.48) vs. 0.25 ± 0.02 (range, 0.22-0.28), p<0.001) with 13 pts (37%) having an increased Vec (>0.28). Factors associated with higher Vec included any AS intervention (p=0.031), late gadolinium enhancement (p=0.028), and younger age at CMR (r=-0.37, p=0.031). Vec was not significantly associated with AS gradient, AR fraction, indexed LV mass, mass/volume ratio, or ejection fraction at the time of CMR, or a history of cardiac surgery. Increased Vec was significantly correlated with echo indices of diastolic dysfunction: E’ (r=-0.55, p=0.002), E/E’ (r=0.62, p<0.001), and indexed LA volume (r=0.56, p=0.001). In the 24 pts with contemporaneous cath data, Vec did not correlate with LV end-diastolic pressure (r=0.09, p=0.72).

Conclusions:
In this cohort of children and young adults with congenital AS, an elevated Vec indicating DF was present in approximately one-third. Increased Vec was associated with aortic valve interventions, late gadolinium enhancement, and echo indices of diastolic dysfunction. For congenital AS, therapies to reverse DF may be warranted.
Abstract 19126: Cardiac AL Amyloidosis with or without Significantly-increased Left Ventricular Wall Thickness
Authors: Lee Ga Yeon , Choi Jin-Oh , Kim Kihyun , Kim Seok-Jin , Jang Hye Ryoun , Kim Hee-Jin , Lee Soo-Youn , Kim Byoung-Joon , Min Ju-Hong , Jeon Eun-Seok
Published: April 2024

Background:
Cardiac involvement is a major prognostic factor in AL amyloidosis. Poor survival of cardiac amyloidosis (CAm) have been reported previously. Recently, many data demonstrate methods detecting early CAm. However, data regarding the clinical meanings of early CAm without significantly-increased LV wall thickness (LVWT) are still lacking. So, we investigated clinical findings of early CAm.

Methods:
Total 124 patients were diagnosed as AL amyloidosis by positive Congo red stain in tissue. Among them, 46(37.1%) patients satisfied the classic definition of CAm; mean LVWT>12mm without other cardiac cause. And, 19(15.3%) patients had LVWT≤12mm, but were diagnosed as CAm with cardiac biopsy or cardiac MRI. The number of patients without evidence of CAm was 51(41.1%). We compared the echocardiographic parameters as well as survival among three groups. Median follow-up duration was 14.5 months.

Results:
Mean LVWT was higher in the group of classic definition compared to the group of minor LVWT [14(13∼16) vs 11(9∼12)mm, p<0.003]. However, LV ejection fraction, LA volume index, and e’ were not different between the group of classic definition and of minor LVWT [55.3(46.5∼62.5) vs 54(48∼61)%, p=0.908, 44.0(36.7∼55.1) vs 45.9 (37.7∼58.6)ml/m
2
, p=0.486, 0.04(0.03∼0.06) vs 0.04(0.04∼ 0.05)m/sec, p=0.796]. These parameters were better in the group of no cardiac involvement [65(61∼69)%, 23.5(18.1∼29.7)ml/m
2
, 0.08(0.06∼0.09)m/sec, all p<0.003]. Overall survival rates showed similar pattern. The group of no cardiac involvement showed better prognosis compared to the other two groups (p<0.003). However, between the two groups of CAm, the survival curves were not different (p=0.361).

Conclusions:
The parameters in echocardiography and survival rates were different according to the presence of CAm, not by the degree of LVWT. The classic definition of cardiac involvement in AL amyloidosis may need to be re-evaluated to reflect more accurate clinical findings.
Abstract 19161: Pregnancy-Induced Disorders Identify High-Risk Women who Benefit from Cardiovascular Screening: Results from the Women's Heart Health Initiative, an OB/GYN Screening Pilot Program
Authors: Yu Jennifer , Johnson Jerri A , Theodoropoulos Kleanthis , Mungee Sudhir , Couri Michele A , Malasky Beth , Wild Robert A , Dobies David , Badin Auroa , Vadde Raj , Sartori Samantha , Sergie Ziad , Baber Usman , Mehran Roxana
Published: April 2024

Introduction
. Prior studies have suggested that pregnancy-induced conditions (PIC) such as hypertension, diabetes, and pre-eclampsia are associated with increased long-term cardiovascular (CV) risk. However, many women see their obstetrician/gynecologist (OB/GYN) as their primary care physician, and their CV risk factors may be underdiagnosed and undertreated. Our hypothesis was that women presenting to an outpatient OB/GYN clinic with a history of PIC would have a higher prevalence of CV risk factors and symptoms compared with women with no PIC. Methods. From May 2010 to January 2012, 2,236 patients in 16 OB/GYN centers completed a simple one-page CV survey. Blood pressure was measured in all patients with no prior screening. We compared responses in 295 patients with a history of PIC versus 1,939 patients with no PIC. Results. Compared to women with no PIC, women with PIC were younger but more likely to have hypertension, diabetes, a family history of premature coronary artery disease, and to be overweight (Table). Women with PIC were more likely to report CV symptoms such as exertional chest pain, dyspnea or claudications. A similar proportion of women with and without PIC considered their OBGYN their primary care physician (15.1% vs. 18.7%, p=NS). As a result of screening, 33.5% of women with a history of PIC (vs. 23.9% no PIC, p=0.006) were referred to another health care provider (e.g. primary care physician, cardiologist, endocrinologist). Conclusion. Amongst middle aged women screened in community OB/GYN clinics, PIC was associated with a higher prevalence of CV risk factors and symptoms, but with no difference in whether the OB/GYN was the primary care provider. Specific CV screening in this setting may improve the early diagnosis and treatment of CV risk factors and disease in this high risk group of patients.
Abstract 19162: Metabolites Reporting on Mitochondrial Function Predict Response to Biventricular Pacing
Authors: Shah Svati H , Thakkar Happy , Shah Asad A , Andersen Nicholas D , Bain James , Haynes Carol , Muehlbauer Michael , Stevens Robert , Nilsson Kent , Piccini Jonathan P , Koontz Jason , Sun Albert , Newgard Christopher B , Hranitzky Patrick M
Published: April 2024

Background.
Biventricular pacing has been shown to improve morbidity and mortality in patients with impaired systolic left ventricular function and congestive heart failure who have evidence of dyssynchronous ventricular contraction. However, a significant percentage of patients implanted with a biventricular pacer will not have a beneficial response. Novel molecular technologies may help identify biomarkers to better predict who will benefit most from this therapy.

Methods.
Individuals undergoing biventricular pacemaker implantation were selected from the ElectroPhysiology GENetics (EPGEN) biorepository (N=120). Targeted, quantitative mass-spectrometry based metabolomic profiling of 63 metabolites was performed on baseline, frozen, fasting plasma samples collected at the time of the index procedure. Positive response to pacing was defined as a 5% improvement in left ventricular ejection fraction or a ≥1 class improvement in New York Heart Association functional class at six months after device implantation. Principal components analysis (PCA) was used to reduce the large number of individual metabolites into a smaller set of uncorrelated factors. Logistic regression was used to test the association between PCA-derived factors and response.

Results.
A positive response to biventricular pacing was observed in 55 individuals at 6 months (N=65 showing no positive response). PCA identified 13 metabolite factors clustering in biologically plausible pathways. Of these, factor 1 (composed of medium and long chain acylcarnitines, medium and long chain dicarboxylacylcarnitines, ketones and β-hydroxybutyrate) was associated with positive response to pacing (p=0.007). Analyses of the individual metabolites composing this factor showed similar results (p=0.03-0.003).

Conclusions.
We have identified a cluster of metabolites, many of which are derived from mitochondrial metabolism, that predict a positive response to biventricular pacing. These novel biomarkers may assist in better risk stratification and patient selection for this therapy.