bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18851: Effect of Diabetes Mellitus Treatment Type in Patients Undergoing Percutaneous Coronary Intervention
Authors: Upahyay Rani Y , Cortes Guillermo A , Tun Han , Rad Nazila Z , Mehra Anilkumar , Shavelle David M. M , Matthews Ray V , Clavijo Leonardo C
Published: April 2024

Background:
Patients with type 2 diabetes mellitus have a higher risk of cardiovascular events than those without diabetes. The effect of specific oral treatment type for diabetes on cardiovascular events remains unclear.
Objective:
The goal of this study is to investigate baseline risk factors, angiographic characteristics, interventional procedural information, and hospital outcomes in non-diabetic and diabetic patients who undergo percutaneous coronary intervention (PCI). Diabetic patients were divided into insulin treated diabetics and oral medication treated patients. Oral medication treated patients were subdivided according to oral medication drug class.

Methods:
We performed a retrospective analysis of 1,381 patients treated with PCI at the Los Angeles County Hospital + USC Medical Center and Keck Medical Center of USC between January 2008 and June 2011. Patients were divided into two groups: non-diabetic (ND, n= 645) and type-2 diabetes mellitus (DM, n= 704). Diabetic patients were further divided into those treated with insulin (IDM, n= 414) or oral medication (ODM, n= 290). Additional comparisons of ODM patients according to medication class were performed between sulphonyurea, biguanide and thiazolidinediones.

Results:
IDM patients were more likely than ODM patients to present with an acute coronary syndrome (56.2% vs. 43.8%) and suffer in hospital mortality (1.01% vs. 0%, p=0.03). Acute renal failure (6.10% vs. 1.99% vs. 1.37%, p<0.000), intra-aortic balloon pump-IABP (12.53% vs. 6.01% vs. 6.27%, p=0.0008), and MACE (13.77% vs. 8.39% vs. 8.99%, p=0.02) rates were higher in IDM than ODM and ND. Among ODM, biguanide treated patients compared to sulphonylurea and thiazolidinediones were more likely to present with an ACS (77.3% vs. 19.3% vs. 3.4%). There were no differences between groups on infract size and post-procedure success rate or TIMI flow.

Conclusion:
Insulin and biguanide treated diabetic patients are more likely to present with an acute coronary syndromes than non-diabetic and other orally treated diabetic patients. The outcome of insulin treated diabetic patients after PCI is worse than any other group with higher mortality, renal failure, IABP use and MACE.
Abstract 18870: Direct Reprogramming of Cardiac Fibroblasts to Cardiomyocyte: Insight into Mechanisms and Feasibility in Human
Authors: Kirste Imke , Jayawardena Tilanthi M , Mirotsou Maria , Dzau Victor J
Published: April 2024

Introduction:
Direct conversion of injured heart tissue to functional cardiomyocyte in situ represents an exciting approach for cardiac regeneration. We have recently shown that the combination of miRNAs 1, 133, 208 and 499 were able to reprogram mouse cardiac fibroblasts in vitro and in vivo to cardiomyocyte like cells. Here, we investigate the mechanisms involved in these processes as well as explore the feasibility of this approach in reprogramming human fibroblasts towards the cardiomyocyte fate.

Methods and Results:
Expression analysis miRNA transfected fibroblast demonstrated rapid induction (1-2 days) of primitive cardiac mesodermal marker Mesp2 but no change in the pluripotency markers Oct4 and Nanog suggesting that reprogramming results from a direct switch to cardiomyocyte progenitor state. Further microarray analysis using the Affymetrix GeneChip Mouse Genome 430 2.0 Array revealed that 1200 genes were differentially regulated between miRNA treated and control cardiac fibroblasts (P<0.01). This list was highly enriched for transcription factors and chromatin remodeling modulators (125 genes). HDAC2, a histone deacetylase that was recently associated with reprogramming of fibroblasts to iPS cells, was the only histone deacetylase that showed significant change upon treatment with the miRNA combination (decreased nearly 95%). These results were corroborated by qRT-PCR. Clustering analysis consistently altered expression of a sub-cluster of 5 genes (with functional relevance to HDAC2, further highlighting the potential importance of HDAC in modulating the miRNA effects directly and/or indirectly. Finally, to explore the feasibility of the miRNA approach to reprogram human fibroblasts, we transiently transfected BJ cells with the microRNA combination. Our preliminary results indicate that combination microRNA treatment of human fibroblasts results in the upregulation of early cardiomyocyte markers such as Mef2.

Conclusion:
Our data provide insights into the mechanisms of microRNA mediated cardiac reprogramming, indicating direct conversion and the potential role of epigenetic modulation.
Abstract 18981: Diagnostic Utility and Safety of Contrast Enhanced Gated Multislices Cardiac Computed Tomography (CT) for Evaluation of Patient s with Left Ventricular Assist Device (LVAD)
Authors: Chang Su Min , Kassi Mahwash , Abu Sharifeh Tareq M , Wang HaoJie , Elias Barbara A , Bhimaraj Arvind , Estep Jerry
Published: April 2024

Background
Visualization of the entire LVAD and surrounding cardiovascular structure is paramount for comprehensive assessment of LVAD-patients. Transthoracic echocardiogram is often limited by the artifacts and acoustic window. We studied the diagnostic utility and safety of Cardiac CT for evaluation of patients with LVAD.

Method
Between 2010-2012, 16 consecutive LVADs-Pts ( 14 Heart-Mate II) underwent 64 slices cardiac CT. The primary clinical indications were : 6 suspected cannula malposition ( frequent LVAD alarm, low output , recurrent VT, and hemolysis ), 5 source of emboli/infection, 3 effusion/hematoma, and 2 LV function/aortic valve assessment . Abnormal finding were defined as presence of inflow cannula (IC) malposition , significant outflow cannula (OC) kinking , mass/clot in the LVAD or heart/aorta or large effusion/hematoma . CT was considered diagnostic if the finding answered the clinical indications as determined by the LVAD/transplant cardiologist. CT-related complication was defined as worsened heart failure (HF) , anaphylaxis or contrast induced nephropathy (CIN : creatinine increase over 25 % at 7 days post CT ) . Beta-blocker was given prior to CT in 12 pts. Median contrast volume was 120 ml.

Result
The mean age was 55 +-14 yrs , 50 % male and history of ischemic cardiomyopathy in 10 pts. Abnormal findings were present in 11 cases including 6 IC malposition , 1 IC malposition plus significant OC kinking , 1 clot in the aortic root and 3 large effusion/hematoma . In 11 pts (70 %) , the CT findings were considered diagnostic for the primary clinical indication . And in 9 pts (55%) , therapeutic changes were made according to the CT findings . Four were medical ( LVAD speed or anticoagulation changes ) and 5 were surgical ( 1 transplant, 3 LVAD exchange and 1 surgical evacuation of mediastinal hematoma with RV collapse) . There were no cases of worsened HF , anaphylaxis after CT. The mean GFR pre CT was 1 +-0.4 mg/dl . Eight pts was in stage 2 or 3 chronic kidney disease. CIN developed in only 1 pt with creatinine increased from 0.8 to 1.1 mg/dl.

Conclusion
For evaluation of pts with LVAD, cardiac CT appeared to be safe, had good diagnostic utility and often lead to therapeutic changes . However, the impact on outcomes remains to be determined.
Abstract 19028: Ablation of the Calpain-Targeted Site in Cardiac Myosin Binding Protein-C is Cardioprotective
Authors: Barefield David , Ji Xiang , Zhu Guangshuo , Takimoto Eiki , Luther Pradeep K , Dobrev Dobromir , Kass David A , Sadayappan Sakthivel
Published: April 2024

Rationale:
Cardiac myosin binding protein-C (cMyBP-C) phosphorylation is essential for normal heart function. We recently demonstrated a direct correlation between cMyBP-C dephosphorylation and its degradation during ischemia-reperfusion (I-R) injury. Strikingly, cMyBP-C phosphorylation protects the heart from I-R injury. However, the mechanism of cMyBP-C-mediated cardioprotection is unknown.

Objective:
To determine if preventing cMyBP-C proteolysis and cleavage confers cardioprotection during I-R injury.

Methods and Results:
cMyBP-C is a substrate for calpain and dephosphorylation makes cMyBP-C more susceptible to proteolysis. In patients with congestive heart failure, increased calpain activity was associated with cMyBP-C degradation. During ischemia proteolysis leads to the cleavage and release of the predominant N-terminal fragment (40 kDa) in association with increased calpain activity. MS/MS analysis identified a motif in the cMyBP-C M-domain responsible for the release of the 40 kDa fragment, 272-TSLAGAGRR-280, which we term the calpain-targeted site (CTS). Next, we used cardiac-specific transgenic mice expressing an ablated CTS (cMyBP-C[[Unable to Display Character: ∆]]CTS) which were bred into cMyBP-C null (t/t) mice. We hypothesized that ablation of the CTS would confer resistance to calpain-mediated proteolysis and protect the heart from I-R injury. An animal that transgenically expressed the normal cardiac isoform, cMyBP-CWT, served as a control. Histological, electron microscopic and immunofluorescence analyses confirm that cMyBP-C[[Unable to Display Character: ∆]]CTS incorporates normally into the cardiac sarcomere and results in rescue of the cMyBP-Ct/t phenotype compared to control. Echocardiography and in vivo hemodynamic studies revealed that cMyBP-C[[Unable to Display Character: ∆]]CTS mice have normal cardiac function similar to control mice. Altogether, these data suggest that cMyBP-C[[Unable to Display Character: ∆]]CTS is benign. Compared to cMyBP-CWT, cMyBP-C[[Unable to Display Character: ∆]]CTS protein is protected from calpain-mediated degradation. Finally, we determined that ablation of the CTS preserved cMyBP-C stability and cardiac function during I-R injury.

Conclusions:
Our data suggest that preserving cMyBP-C stability by thwarting calpain-mediated proteolysis protects the heart from I-R injury.
Abstract 19051: Accuracy and Internal Consistency of Cardiac Magnetic Resonance Imaging in Measuring Branch Pulmonary Arterial Flows in Conotruncal Anomalies Patients with Branch Pulmonary Arterial Stents
Authors: Harris Matthew A , Fogel Mark A , Gillespie Matthew J , Fu Gregory L , Kim Daniel W , Dori Yoav A , Keller Marc S , Whitehead Kevin K
Published: April 2024

Introduction
Conotruncal Anomalies patients may require branch pulmonary arterial (BPA) stent implantation. These ferromagnetic stents generate localized artifact that may affect phase contrast magnetic resonance (PCMR) imaging. There is little data on PCMR measurements in the presence of a BPA stent.

Hypothesis
PCMR acquired measurements away from the BPA stent artifact are accurate and internally consistent.

Methods
We retrospectively reviewed 43 consecutive repaired Conotruncal Anomalies PCMR and cine MR studies between 2005 and 2012. All patients underwent either left (30) pulmonary artery (LPA) or right (20) pulmonary artery (RPA) stent placement. Three different methods of measuring flow through the stented artery were compared: 1) main pulmonary artery (MPA) - unstented artery, 2) direct PCMR of the stented artery away from the artifact, and 3) pulmonary venous (PV) flows (see Figure). Where available, pulmonary radionuclide scintigraphy (PRS) was compared to each method. Significance was P < 0.05.

Results
For the entire study population, the mean age and body surface area were 12.0 ± 7.0 yrs (range 1.5 - 33.2 yrs) and 1.2 ± 0.5 m2. There was good agreement without significant difference between the mean PRS and MPA derived stented artery flow (method 1) (37 ± 17 and 35 ± 21 %, r=0.731, ICC=0.8403, p=0.627) There was even better agreement between PRS and direct measurement (method 2) (39 ± 20 and 40 ± 22%, r=0.888, ICC = 0.943, p=0.757). The greatest agreement was found between method 2 and PV flows (method 3) (48 ± 17 and 47 ± 14%, , r=0.939, ICC=0.961, p=0.837). As another check for internal consistency, there was excellent correlation between the PCMR and cine MR right ventricular stroke volume 70.2 ± 40.4 and 74.0 ± 41.4 cc, r=0.983, ICC=0.989.

Conclusion
In the presence of a ferromagnetic BPA stent, accurate measurement of the net fractional flow ratio is feasible. PCMR adjacent to the stent artifact or pulmonary venous flows provide the most internally consistent data.
Abstract 19053: Embolic Particles Show Surprising Size Dependent Predilection for Cerebral versus Peripheral Arteries: Results from Computational Fluid Dynamic Modeling
Authors: Shadden Shawn C , Nemoto Naohiko , Pedersen Wesley R , Lesser John R , Schwartz Robert S
Published: April 2024

Background:
Embolic particles originating at the aortic valve or ascending aorta can have devastating consequences if they enter the cerebral circulation. Little is known about anatomic embolic origin and cerebral events, as this relationship is difficult to observe. To better understand emboli arising from procedures such as TAVR, we built a computational fluid dynamic (CFD) model of cerebral emboli originating at the aortic valve and ascending aorta.

Methods:
An exact computer model of a human aorta and arteries to the brain was derived from CT angiography. Blood flow was modeled by the Navier-Stokes equations using pulsatile inflow at the inlet and physiologic Windkessel models at the outlets. Embolic particulate was injected at the level of the aortic valve and tracked using modified Maxey-Riley equations.

Results:
Aortic emboli that entered the cerebral circulation through the carotid or vertebral arteries were localized to specific locations of the proximal aorta, most closely in the region of the right and non-coronary aortic valve cusps. The percent of released particles embolic to the brain was markedly dependent on particle size. Particles 1.0 mm diameter had a 28% chance of reaching the brain, whereas particles 2.5 mm dia or greater had 5% chance of reaching the brain.

Conclusions:
Embolic particles reaching the brain appear have specific anatomic locations of origin, and may exhibit a strong size-destination relationship, with larger particulate (greater than 2.5 mm dia) less likely to traverse the cerebral vessel by a factor of 5 or greater. Particles less than 2 mm dia and originating from the right and noncoronary cusps appear more likely to cause cerebral injury according to this model. These data are consistent with sparse literature based on transesophageal echo observations. This CFD modeling method may prove useful for limiting aortic emboli to the brain during cardiovascular procedures.
Abstract 19081: 5-lipoxygenase Inhibitor Via-2291 (atreleuton) Reduces Inflammation and Coronary Necrotic Core Plaque and Improves Left Ventricular Function in Patients After an Acute Coronary Syndrome
Authors: Ahmadi Naser , Nabavi Vahid , Ram Reuben J , Flores Ferdinand , Baskett Michael , L'Allier Philippe L , Pressacco Josephine , Tardif Jean-Claude , Budoff Matthew
Published: April 2024

Background:
The 5-lipoxygenase inhibitor VIA-2291 effectively lowers production of leukotriene metabolites. This study investigates the relations between inflammation, coronary plaque characteristics and left ventricular function in response to treatment with VIA-2291 (Atreleuton) in patients after an acute coronary syndrome (ACS).

Methods:
Fifty six post-ACS patients who participated in a randomized trial evaluating the effects of VIA-2291 vs. placebo and underwent cardiac computed tomography angiography were studied. Leukotriene E4 (LTE4), high-sensitivity C-reactive protein (hs-CRP), coronary plaque volume (PV) with vulnerable characteristics (Necrotic Core) and left ventricular ejection fraction (LVEF) were measured at baseline and at 6-month follow-up. The relation of changes in LTE4, hs-CRP, PV and LVEF in response to VIA-2291 was analyzed using conditional logistic regression analyses.

Results:
From baseline to 6 months, after adjustment for risk factors, significant reductions in LTE4, hs-CRP and VP, and an increase in LVEF with VIA-2991 as compared to placebo were noted (p<0.05, Table).After adjustment for risk factors, there were strong associations between the decrease in LTE4, the decrease in necrotic core PV and the increase in LVEF (Table); 71% and 79% of the variance in PV and LVEF was explained by the decrease in LTE4 in response to VIA-2991 (p<0.05). The maximum improvement in LVEF was noted with maximum decrease in LTE4 and PV.

Conclusion:
This study documented a strong relation between decreases in LTE4, decreases in necrotic core coronary plaque volume and improved LV function in response to VIA-2291.
Abstract 191: Community Uptake of a Smartphone Application to Recruit Bystander Basic Life Support for Victims of Out-of-Hospital Cardiac Arrest
Authors: Brooks Steven C
Published: April 2024

Background:
PulsePoint is a smartphone application that links bystanders with the 911 response to cardiac arrest. The application facilitates bystander basic life support while EMS personnel are en route. After community members download the free software to their smartphones, they can receive automated alerts directing them to nearby public location out-of-hospital cardiac arrests and public AED locations.

Objective:
To quantify the uptake of the PulsePoint application in two Californian communities.
Methods:
PulsePoint was launched in San Ramon December 2011 and in San Jose February 2012. Promotional efforts in both communities included mass media campaigns, public service announcements in theatres and the use of social media outlets (e.g. Twitter and Facebook). Data from iTunes, Android Market and the PulsePoint enterprise server were collected to document uptake.

Results:
As of May 27, 2012 there were 23,069 PulsePoint application downloads (18,000 iOS, 5,069 Android). Figure 1 shows the cumulative installations of the PulsePoint application over time. The number of devices registered on the PulsePoint server is 11,167, accounting for users who removed the application from their device after installation. Of those devices registered, only 30% (3,350/11,167) have settings configured to receive cardiac arrest alerts. To date, there have been 64 suspected cardiac arrest incidents associated with a PulsePoint alert.

Conclusion:
There has been significant uptake of the PulsePoint application in San Ramon and San Jose with an increasing number of users over time. Future work should focus on methods to maximize the number of users configuring the cardiac arrest alerts feature to be active, to encourage retention of the application and determining the effectiveness of the application with respect to increasing bystander CPR, AED use and survival for out-of-hospital cardiac arrest victims in the community.
Abstract 19141: Comparison of Long-term Clinical Outcome Between Chronic Kidney Disease stage3a and stage3b in Patients with Acute Coronary Syndrome
Authors: Iwasaki Yusuke , Yamada Takahisa , Morita Takashi , Furukawa Yoshio , Kawasaki Masato , Kikuchi Atsushi , Naito Takashi , Fujimoto Tadao , Ozu Kentaro , Kondo Takumi , Sengoku Kaoruko , Yamamoto Hironori , Fukinami Masatake
Published: April 2024

Backgruond:
Chronic kidney disease (CKD) is highly prevalent and associated with an increase of risk to major adverse cardiac and events (MACE) in patients with acute coronary syndrome (ACS). However, there is little information available on the prognostic significance of the difference between whether CKD stage 3a (mild to moderate stage; estimated glomerular filtration rate (eGFR): 45-59 ml/min/1.73m
2
) and CKD stage 3b (moderate stage; eGFR: 30-44 ml/min/1.73m
2
) in patients with ACS. Therefore, we assessed to whether the CKD stage might affect the prognosis in patients with ACS.

Methods and Results:
We followed up 209 patients (72.7% men, mean age 70±11 yrs) with ACS. Patients were classified into 4 groups according to eGFR [groupA: CKD stages 1 and 2, eGFR ≧ 60 ml/min/1.73m
2
(n=82); group B: CKD stage 3a (n=53); group C: CKD stage 3b (n=30); group D: CKD stages 4 and 5, eGFR < 30 ml/min/1.73m
2
(n=44)]. There were no significant differences in baseline clinical characteristic among the four groups. During the follow up period (550±359days), MACE including all-cause mortality, myocardial infarction, and target vessel revascularization were compared among each group. Kaplan-Meier analysis revealed that patients in group C had a significantly higher risk of MACE than those in group B (46% vs 21%, p=0.024). Hazard ratio (HR) for MACE was 5.81(95%CI, 2.59 to 13.31) in group D, 3.95(95%CI, 1.57 to 9.71) in group C and 1.22(95%CI, 0.48 to 2.79) in group B, compared to group A. Notably, patients with group C had a significantly higher risk of MACE than those in group B (HR 3.34; 95%CI,1.25 to 8.87).

Conclusion:
Patients with moderate CKD (stage 3b) had a higher risk of MACE than those with mild to moderate CKD (stage3a). Thus, we should sub-divide CKD stage 3 into early (3a) and late (3b) components at the evaluation of the subsequent risk of MACE in patients with ACS.
Abstract 19154: A Combinatorial Approach for Bone Marrow Stem Cell Mobilization, Homing-in and Retention for De Novo Cardiac Regeneration: Gcsf Treatment Combined with Ex Vivo Transgenic Sdf-1α Delivery in the Heart
Authors: Jiang Shujia , Caudill Christy M , Ahmed Rafeeq P , Khawaja Haider H
Published: April 2024

Objective:
We have already shown that bone marrow stem cells (BMC) mobilized into the infarcted heart developed into mature cardiomyocytes and improved the heart function. Granulocyte colony stimulating factor (GCSF) reduces stromal cell derived factor-1 α (SDF-1α) in the bone marrow to support extravasation of BMC from their niches. We hypothesized that GCSF treatment combined with a favorable SDF-1α gradient in the infracted heart would promote homing-in and retention of mobilized BMC for angiomyogenic repair of the infracted myocardium.

Methods and Results:
Radiomyoabalated young female Fisher 344 rats received 1×10
6
BMC from transgenic GFP
+
male rats. Two month later, animals were used to develop experimental model of acute LAD artery ligation. The animals were grouped (n=16) to receive following intramyocardial injection of 70μ l DMEM without cells (G1) or containing 1×10
6
wild type BMC with (G2 and G3) or without SDF-1α overexpression (G4). Besides G1 and G3 had intraperitoneal injection of DMEM without GCSF whereas G2 and G4 received 10µg/kg body weight GCSF treatment starting 3 days prior to and until 2 days after intramyocardial injection of cells. Animals were harvested 4 days and 4 weeks after their respective treatment and the hearts were removed for molecular and histological studies. SDF-1α expression was higher in G2 and G4 animal hearts (
p
<0.05
vs
all groups) on day 4 with. Highest mobilization of GFP
+
BMC was observed in and around the infarcted myocardium in G2. GFP
+
BMC were also identified by immunostaining for ckit, CXCR4 and CD44 which showed highest propensity in G2. Fluorescence immunostaining for GFP and cardiac actin at 4 weeks showed that mobilized cells extensively differentiated into mature muscle fibers. Similarly, vascular density was markedly increased in G2 (
p
<0.01
vs
all groups) in peri-infarct area. Infarct size was significantly attenuated with improved LV contractile function in G2 (
p
<0.05
vs
all groups).

Conclusions:
Concomitant
ex vivo
expression of SDF1α in the infarcted heart combined with intraperitoneal GCSF treatment is more effective and efficient approach to mobilize BMC for participation in myocardial repair. Mobilized BMC homed-in to the infarcted heart and supported extensive angiomyogenic repair.
Abstract 19176: Mapping of Electrogram Morphology Recurrence Patterns during Atrial Fibrillation
Authors: Ng Jason , Gordon David , Sehgal Vinod , Arora Rishi , Goldberger Jeffrey J
Published: April 2024

Introduction:
Electrograms during atrial fibrillation (AF) are complex and seemingly chaotic. It is still unknown how to best analyze and utilize AF electrograms.

Hypothesis:
We hypothesize that the frequency and patterns of AF electrogram morphology recurrence determined by a modified recurrence plot (RP) analysis will show differences based on region in this pilot study.

Methods:
AF electrograms (>16 s) recorded from documented left atrial (LA) and right atrial (RA) sites in 13 patients (10 male, 59±10 years old) prior to AF ablation were analyzed. A 100 ms window for each automatically detected activation was extracted and cross-correlated with every other activation in a 30-sec recording. The result was a set of NxN cross-correlation (CC) values, where N is the number of detected activations. These values were displayed in a two-dimensional RP. A recurrence index (RI), the percentage of the most common morphology, was also computed. A high RI likely indicates consistent activation directions at the site of bipolar electrogram recording.

Results:
Figure A is a RP example. The checker board pattern of alternating high and low CC values indicates periodic recurrences in morphologies (RI=70% for this example). The mean RI for all sites and all patients was 38±25%. The highest RI was found in the left superior LA in all 4 paroxysmal AF patients (85±18%, see Figure B). For 9 persistent AF patients, the highest RI was found in the RA (91±10%) in 5 patients and in the left superior LA (95±6%) in 4 patients. The persistent AF patients had higher maximum RIs in the RA than the paroxysmal AF patients (87±16 vs. 51±15%, p=0.01).

Conclusion:
Electrogram morphology with highest recurrence rates were most frequently found in the left superior LA, a common location for AF triggers. Further work is needed to determine whether high electrogram repeatability reflects AF driver activity and whether RPs could be used as part of an ablation strategy.
Abstract 19222: Persistence of Late Potentials Found during Repeat Ablation of Ventricular Tachycardia: A Mechanism for Recurrence?
Authors: Tung Roderick , Hayase Justin , Yu Ricky , Boyle Noel , Shivkumar Kalyanam
Published: April 2024

Background:
Recurrence of scar-mediated ventricular tachycardia (VT) approaches 50% in patients at 6-12 months. Outcomes from multiple procedures are not well characterized. Changes in electroanatomic substrate and the persistence of late potentials (LP) during a repeat procedure have not been reported.

Methods:
Patients who underwent both initial and repeat VT ablation between 2004-11 at Ronald Reagan UCLA Medical Center were analyzed. Electroanatomic maps (NAVX, St. Jude Medical, Minneapolis, MN and CARTO, Biosense-Webster, Diamond Bar, CA) from both the initial and repeat ablation procedures were analyzed for LP, defined as low-voltage electrograms with onset outside of the QRS complex. All studies were adjudicated by a second observer.

Results:
23 patients underwent both initial and repeat ablation at our institution, of which 16 patients had electroanatomic maps from both studies available for analysis. There were 3 patients who underwent 3 ablations, and the rest underwent a single repeat procedure. Substrates included 10 non-ischemic cardiomyopathy (NICM), 4 ischemic cardiomyopathy (ICM), and 2 arrhythmogenic right ventricular dysplasia (ARVD). The overall success rate, defined as no VT recurrence at 1 year, was 25% (4/16) (ARVD=2, ICM=2). All patients (13/13) who had LP identified on initial procedure had persistence of LP on repeat procedure. The remaining patients (3/3) who had no LP identified on initial procedure, again had no LP targets on repeat ablation.

Conclusions:
In this retrospective consecutive series of patients with recurrent VT, those with LP identified on the initial procedure exhibited persistence of LP during repeat mapping and ablation. This may be an important mechanism of recurrence, suggesting that more extensive substrate modification of all late activity is necessary. In patients without LP identified on the initial procedure, no LP were identified on repeat mapping. In patients that require repeat ablation, 25% experience freedom from VT recurrence at 1 year after their last procedure.
Abstract 19241: Characteristics of No-Reflow Phenomenon in STEMI Patients Post Thrombectomy: A Multiethnic Group Analysis
Authors: Jaiswal Abhishek , Leighton Harmony J , Moustakakis Emmanuel , Buda Andrew J , Park Chong H
Published: April 2024

Objective:
There is limited data about the characteristics of the no-reflow phenomenon in STEMI patients since the introduction of routine thrombectomy. We aimed at studying the characteristics of the no-reflow in multiethnic STEMI patients who underwent primary PCI with thrombectomy.

Methods:
All patients underwent primary PCI within 6 hours of their presentation. Pre-discharge LVEF was assessed by TTE (3+/-2 days post- MI).

Results
were then compared between patients who achieved TIMI II and III flow post PCI and the no-reflow group (TIMI 0 and I flow). Results: The 313 patients consisted of (57.2%)Caucasians,(18.5%) Asians,(12.1%) Hispanics,(8.6%) South Asians, and (3.5%)Blacks. No-reflow was seen in 14%(43/313) of patients. Gender distribution (males: 84% vs 79%) and mean age (62.8+/-5.9 yrs vs 61.7+/-6.8 yrs) were similar between the groups. Distribution of traditional risk factors: smoking (44% vs 56%), HTN (72% vs 75%), dyslipidemia (58% vs 71%), DM (30% vs 36%) and incidence of prior CAD (26% vs 25%) were similar in both groups. There were no differences in the distribution of infarct related arteries (prox. and mid LAD-58% vs 48%, RCA-28% vs 37%, LCx-5% vs 9%) in both groups. The no-reflow group had significantly higher serum CPK level on presentation (2154.8 ng/dl vs. 1465.8 ng/dl, p<0.04) and lower LVEF post PCI (44.5% vs 50.3%, p<0.003). However, patients with no-reflow did not have a higher incidence of cardiogenic shock (7% vs 9%), VT/V-fib (2% vs 5%), or IABP requirement (23% vs 21%). Of the ethnic groups, South Asians had significantly higher incidence (16% vs 9%, p<0.05) of no-reflow. In addition, they also presented later (469 minutes vs 179 minutes, p<0.007) and frequently presented with epigastric burning.

Conclusions:
These data support the hypothesis that the no-reflow phenomenon occurs in a significant proportion of STEMI patients despite primary PCI with thrombectomy. No-reflow resulted in a large infarct size as measured by serum CPK and less early LVEF recovery. However, no-reflow did not result in higher complications during hospitalization. Although no reflow was seen in all ethnic groups, South Asians have a higher incidence of no-reflow phenomenon. This may be attributed to their late presentation and atypical presenting symptoms.
Abstract 19437: Concomitant Overexpression of FGF2 and TGFbeta1 in Mesenchymal Stem Cells Improves Both Autocrine and Paracrine Properties Through Activation of Akt, ERK1/2 and SMAD2 Pathways and Upregulation of Soluble Factors
Authors: Mura Manuela , Pisano Federica , Malpasso Giuseppe , Danieli Patrizia , Cervio Elisabetta , Gnecchi Massimiliano
Published: April 2024

Background:
mesenchymal stem cells (MSC) repair infarcted hearts mainly through paracrine mechanisms. However, donor age negatively influences paracrine properties of bone marrow MSC (BM-MSC). We have shown that in BM-MSC from elderly patients both TGFβ1 (T) and FGF2 (F) expression is decreased. We hypothesized that overexpression of these two factors involved in cytoprotection and angiogenesis may improve MSC repair capacity.

Methods:
rat BM-MSC were transduced with control (GFP-MSC) or with a bicistronic (TF-MSC) lentivirus. Cytoprotection was evaluated in MSC (autocrine) or in H9c2 (paracrine) cells exposed to 24 hrs of hypoxia in the presence of either unconditioned (CTRL-M) or conditioned medium (GFP-CM or TF-CM). Viability was measured by MTS assay and apoptosis by caspase-3 activation. Angiogenesis was assessed by evaluating HUVEC tube formation on Matrigel. Transcriptional levels of the pro-survival gene Bcl2 and genes encoding soluble factors were measured by RT-PCR. Activation of the three main TF-related pathways (ERK1/2, Akt and SMAD2) was tested by western blot.

Results:
TF-MSC showed a marked reduction of apoptosis rate (-27% p<0.001) compared with GFP-MSC after 24 hrs of hypoxia. Furthermore, TF-CM increased H9c2 viability compared with CTRL-M (+46.3% p<0.001). Caspase-3 activation in H9C2 was reduced by 60.3% in the presence of TF-CM vs CTRL-M (p<0.001) and by 44.7% vs GFP-CM (p<0.05). HUVEC tube formation was significantly enhanced by TF-CM compared to both CTRL-M (+57.5%; p<0.001) and GFP-CM (+45.2%; p<0.001). Both in TF-MSC and TF-CM treated-H9c2 we observed a strong activation of Akt, ERK1/2 and SMAD2 pathways and enhanced expression of Bcl2. Finally, in TF-MSC the transcriptional levels of soluble factors such as PDGF-β, VEGF, Ang1, IGF1, BMP2, and IL11 was upregulated.

Conclusions:
TF overexpression increases both autocrine and paracrine properties of MSC through upregulation of several soluble factors and activation of pathways known to be involved in cytoprotection and angiogenesis. These results pave the way for further research on modification of MSC as effective strategy to improve efficacy of stem cell therapy.
Abstract 19523: Catheter-Based Renal Denervation for the Treatment of Patients with Drug-Resistant Hypertension: EnligHTN I: Three-Month Data of a First in Man Study Using a Multi-Electrode Radiofrequency Ablation Catheter
Authors: Papademetriou Vasilios , Worthley Stephen G , Tsioufis Costas , Worthley Matthew , Chew Derek , Sinhal Ajay , Meredith Ian , Malaiapan Yuvaraj
Published: April 2024

Introduction: Renal denervation has emerged as a novel approach for the treatment of patients with drug-resistant hypertension. To-date studies in humans have been done using a single-tip electrode radiofrequency ablation catheter to achieve circumferential sympathetic fiber interruption through the renal artery wall. We investigated the safety and efficacy of a multi-electrode catheter ablation system developed by St Jude Medical (EnligHTN).

Methods and results: The EnligHTN catheter has 4 electrodes attached on a basket mounted at the tip of the catheter. The basket is collapsed and can be expanded via an external mechanism once the catheter is placed in the desired location of the renal artery. The electrodes can then be activated sequentially to achieve the desired lesion pattern. In preclinical studies, in large animal models we found that using a predetermined algorithm, transmural lesions can be placed strategically in the renal artery so to achieve optimal renal denervation. In the present study we assessed the efficacy and safety of the EnligHTN catheter in 46 patients with drug resistant hypertension (av. age 60±10years, 33% women, BMI 32kg/m², 20% with CAD, 59% with hyperlipidemia , 33% with type II DM and 30% with sleep apnea). Patients were on an avg. of 4±0.6 antihypertensive medications at baseline. Bilateral renal nerve ablation was done using the femoral percutaneous approach. On av. 7.7±0.8 lesions were created in the right renal artery and 7.4±1.4 lesions in the left renal artery. The median procedure time was 34 minutes. At one month there was a 28/10 mmHg (n=46) reduction in BP (p<0.001) and at three months a 35/14mmHg (n=24) reduction (baseline BP of 176±16). There was no significant change in serum creatinine or eGFR. There were no significant procedure related complications. Small hematomas were noted in 4 patients, vasovagal reaction in 3 and transient bradycardia in 1.

Conclusions: In conclusion this data indicates that the EnligHTN ablation system is safe and effective. Sympathetic renal denervation can substantially improve BP control in patients with drug resistant hypertension.
Abstract 19554: Cardiologist Involvement in Heart Failure Hospitalizations is Associated with Reduced Rates of Readmissions and Increased Severity of Illness
Authors: Griffin Anna , Strauss Craig , Rutten-Ramos Stephanie , Garberich Ross , Lawler Casey
Published: April 2024

Background:
Congestive Heart Failure (CHF) is the most common cause for hospital readmission in patients over the age of 65 years. Whereas, efforts to reduce readmission rates have focused on transitions of care and short-term outpatient follow-up, limited data exist on the impact of specialist care during the index admission in reducing readmission rates.

Methods:
All CHF admissions between January 1, 2009 and December 31, 2011 were identified retrospectively by primary discharge codes. Patient demographics, length of stay (LOS), time to readmission, all patient refined diagnosis related groups (APRDRG), hospital attending at time of discharge, and total hospital costs were abstracted and analyzed based on the attending provider at discharge. Because traditional methods for standardization/transformation of data were insufficient to adjust for patient APRDRG, bootstrapping was employed.

Results:
Among 2311 patients (median age 75, 49.9% male), 1505 (65%) patients were treated by a Hospitalist attending, whereas, the remaining 808 (35%) patients were treated by a Cardiologist attending. 535 (23.2%) patients were readmitted within 30 days of discharge. Readmission rates were significantly lower when the attending was a cardiologist as compared to a hospitalist (16.0% [95% CL: 12.3%, 20.8%] vs. 27.1% [95% CL: 24.9%, 29.4%]; p<0.001). The APRDRG geometric mean for patients with a cardiologist either as consultant or attending was 1.80 (95% CL: 1.74, 1.87) and 1.02 (95% CL: 0.98, 1.05) for those without (p<0.001), indicating cardiologists were seeing higher severity cases. Median LOS was similar between attending cardiologists and hospitalists (4.8 days vs. 4.2 days; p=0.60). Adjusting for APRDRG, mean total costs for patients treated by a cardiologist were higher than those treated by a hospitalist ($9850 [95% CL: $9614, $10093] vs. $7741 [95% CL: $7560, $7926]; p<0.001).

Conclusions:
Reduced rates of hospital readmissions despite an increased severity of illness among patients with a cardiologist as the attending compared to those with a hospitalist attending highlights the value of specialized care in heart failure treatment. Additionally, total costs for patients treated by cardiologists are likely over-stated due to interventional charges.
Abstract 19581: Embryonic Lethality of Mice Deficient for IRF2BP2: An Essential Ischemia-Inducible Transcriptional Coactivator of VEGFA
Authors: Ho Tiffany V , Yap Nida , Almontashiri Naif , Stewart Alexandre F
Published: April 2024

Background - VEGF (vascular endothelial growth factor) is a master regulator of angiogenesis is a major player in ischemic heart disease. In 2010, we found that IRF2BP2 (interferon regulatory factor-2 binding protein-2) coactivates VEGFA expression in muscle. IRF2BP2 protein levels show a 7-fold increase is ischemic muscle whereas its mRNA expression is not increased, indicating that IRF2BP2 is translational repressed in normoxic tissues and becomes translationally derepressed during ischemia.

Methods - To characterize the mechanisms repressing translation of IRF2BP2 mRNA in normoxic conditions and enabling derepression during ischemia, luciferase reporter plasmids were transiently transfected in cultured cells. In addition, we generated transgenic mice with targeted deletion of the IRF2BP2 gene and others with a floxed IRF2BP2 allele enabling tissue specific ablation by Cre-transgene expression.

Results - In the 3’UTR of IRF2BP2 mRNA, microRNAs miR-17 and -20a were found to differentially regulate translation. A common 9 nucleotide deletion polymorphism (rs3045215) disrupted the miRNA target sequence in IRF2BP2 mRNA and associated with coronary artery disease risk in the Ottawa Heart Genomics study (p<0.0045). The RNA binding protein Staufen-1 (Stau1) binds to the 3’UTR of IRF2BP2 mRNA and inhibits its translation. Stau1 levels increased during C2C12 skeletal muscle differentiation, coincident with the downregulation of IRF2BP2 protein levels. Of interest, IRF2BP2 knockout mice died during embryonic development. Out of 11 litters from hemizygous matings, 42 offspring were born: 15 wild type (35.7%), 25 hemizygous (59.5%), and 2 homozygous null (4.8%) mice, deviating from the expected Mendelian ratio of 25% wild type:50% hemizygous: 25% null. The 2 surviving IRF2BP2 null mice displayed severe growth retardation. We are currently characterizing the phenotype of embryonic lethality in these mice.

Conclusion - Translational derepression enables expression of IRF2BP2 protein in ischemic tissues, an emerging mechanism of gene regulation. Our data show the IRF2BP2 gene is critical for mouse development. These transgenic models will enable the elucidation of IRF2BP2 function in angiogenesis and the response to ischemia.
Abstract 19603: Disruption of βPDGF Receptor-Dependent PI3k and Plcγ Signaling Protects from Hypoxia-Induced Pulmonary Hypertension
Authors: Ten Freyhaus Henrik , Janssen Wiebke , Leuchs Maike , Zierden Mario , Berghausen Eva , Vantler Marius , Caglayan Evren , Schermuly Ralph T , Tallquist Michelle D , Rosenkranz Stephan
Published: April 2024

Background: Vascular remodeling is critical during the pathogenesis of pulmonary hypertension (PH). Growth factors, such as platelet-derived growth factor (PDGF), appear to be involved in these processes. With pharmacological inhibitors, we demonstrated previously that phosphatidyl inositol-3 kinase (PI3K) and phospholipase Cγ (PLCγ) are the critical mediators of βPDGF receptor (βPDGFR)-dependent proliferation and migration in pulmonary arterial smooth muscle cells (PASMC). Whereas expression data and data with the tyrosine kinase inhibitor imatinib suggest a role for PDGF in PH, data from genetic models is lacking.

Methods and results: We utilized βPDGFR F3/F3 (“F3”) mice that were generated by introducing point mutations of the PI3K and PLCγ binding sites into the βPDGFR locus by gene targeting. We isolated PASMC from F3 and wild-type (WT) mice. Co-immunoprecipitation experiments after PDGF treatment showed that PI3K and PLCγ did not bind to the activated F3 receptor, whereas overall phosphorylation and binding of RasGap and SHP-2 were unaffected. In line with these observations, PDGF-mediated phosphorylation of Akt and Erk 1/2 was inhibited in F3-PASMC compared to WT. To address, if cellular responses were altered, we analyzed βPDGFR-dependent proliferation (as BrdU incorporation) and migration (modified Boyden chamber). These experiments revealed that these responses were essentially completely blocked in F3-PASMC compared to WT. To analyze the development and severity of PH in vivo, we exposed F3 and WT mice to hypoxia for 3 weeks. Following this treatment, right ventricular systolic pressure (RVSP) was measured by right heart catheterization, and right ventricular (RV) hypertrophy was assessed as RV weight/left ventricular + septal weight (RV/LV+S). These analyses revealed that RVSP and RV/LV+S were significantly reduced in F3 compared to WT mice.

Conclusions: These data show that disruption of βPDGFR-dependent PI3K and PLCγ signaling blocks PDGF-dependent proliferation and migration of PASMC in vitro and protects from the development of hypoxia-induced PH in vivo. Consequently, these data support a critical role of PDGF during the pathogenesis of PH.
Abstract 19648: Exposure to Ionized Medical Radiation after Heart Transplant is Associated with Higher Risk of Malignancies
Authors: Uriel Nir , Pak Sang-Woo , Morrison Kerry , Garan Arthur R , Yuzefpolskaya Melana , Colombo Paolo C , Restaino Susan W , Einstein Andrew , Takayama Hiroo , Mancini Donna M , Naka Yoshifumi , Jorde Ulrich P
Published: April 2024

Objective Evidence on the increase cancer risk due to medical radiation is mounting. Heart transplant (OHT) patients are at high risk for cancer due to immunosuppression medications. In this study we shout to determine the correlation between the cumulative ionized medical radiations after OHT to the development of cancer.

Methods: Adult Patients transplanted between 1999-2010 without history of cancer in a large medical center were included in this analysis. Medical tests that expose the patients to radiation (i.e X-ray, Computer Tomography (CT), nuclear test and cardiac catheterization) were collected from the hospital database, and the amount of radiation was calculated based on a look up tables specified for our institution. The prevalence of cancer was recorded from electronical medical records.

Results: 891 patients were enrolled to the study. Age 52.3±13.0 years old, 677 (75.9%) were male. The mean follow up time post OHT was 6.9±3.3 years and 76 (8.5%) patients developed de-novo malignancy. Prostate cancer was the most common 20%, followed by lung 17% and hematologic malignancies 13%. The mean time for development of malignancy was 5.2±3.4 years. Patients that developed cancer were exposed to significantly more ionizing radiation 68.0 ± 65.9 mSv vs 54.4 ± 45.9 mSV (p=0.026) respectively. Cumulative radiation exposure was the only variable associated with the development of de-novo cancer in a multivariable regression model (for every increase of 10mSv the chance of cancer increase by 5.1% P=0.046). Patients in the higher tertile of radiation exposure had 40% more chance to develop cancer (Figure).

Conclusion High frequency of early post OHT malignancy was reported. There was a strong association between the amounts of medical ionizing radiation to the frequency of post OHT malignancy. This is the first study to report actual cancer percentage in relate to radiation exposure. Minimized the amount of radiation post OHT may reduce the frequency of cancer.
Abstract 19783: Performance of Ultra-Low Dose Tc-99m Sestamibi Myocardial Perfusion Imaging Using Solid-State SPECT: Comparison to Coronary Angiography
Authors: Taylor Matthew G , Bateman Timothy M , McGhie Arthur I
Published: April 2024

Introduction:
Ultra-low dose (ULD) SPECT is feasible using solid-state detector systems, with advantages of lower dosimetry and lower radionuclide costs. Thus far, there have been no studies validating accuracy of ULD SPECT against coronary angiography. We therefore performed a 2-expert consensus blinded review of 37 patients who had coronary angiography and ULD SPECT (D-SPECT, Spectrum Dynamics) within 30 days, with a stress-first protocol utilizing < 4 mCi Tc-99m sestaMIBI.

Methods:
Pts were imaged both supine & upright for ∼10
6
myocardial counts; rest images were acquired for equivocal or abnormal stress images using ∼4X stress dose. Mean stress dose was 3.9 mCi +0.47 mCi and mean rest dose was 14.8 mCi +1.8 mCi (n=23). Patient mean age was 62 yrs; 32% were female; 43% underwent pharmacologic stress. Each study was interpreted as ischemic vs non-ischemic, and also evaluated semi-quantitatively (4-point scale) for perfusion and function using a 17 segment model. Significant CAD was defined as a stenosis >70% on coronary angiography.

Results:
Coronary angiography was abnormal in 25 and normal in 12 pts; 11 had single vessel (SVD) & 14 had multi-vessel disease (MVD). ULD SPECT sensitivity was 88% (22/25), specificity was 92 % (11/12), PPV was 96%, and NPV was 79%. Sensitivity for detection of SVD was 91% and for MVD was 92%. Detection of a 2
nd
or 3
rd
diseased vessel in pts with MVD was 54%.

Conclusions:
The results of this study are encouraging that ULD-SPECT with patient dosimetry ∼10% of typical rest/stress SPECT is diagnostically accurate for identification of significant CAD. Correct identification of MVD is currently suboptimal.