bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19369: Relation Between Sedative and Outcomes in Patients Undergoing Mild Therapeutic Hypothermia Following Cardiac Arrest
Authors: Baker William L , Geronila Giovanni , Kallur Ramya , Noyes Adam , Lundbye Justin B
Published: April 2024

Introduction:
Great variability in sedation protocols currently exists in treating patients undergoing mild therapeutic hypothermia (MTH) following cardiac arrest. Even though sedation may confound outcome prediction, the optimal agent to use remains unknown.

Methods:
We retrospectively collected data on 201 consecutive adult patients admitted to Hartford Hospital who survived a cardiac arrest and were admitted to our cardiac intensive care unit (CICU). Use of sedatives, including propofol, midazolam, and lorazepam, was collected. The main outcome of interest was survival with good neurologic outcome defined using the Pittsburgh cerebral performance category (CPC) scale of 1-2. Multivariate logistic regression was used to control for potential confounders and identify independent predictors of good outcome.

Results:
Of the 201 patients (mean age 61 ± 15 years), 99 (49.3%) had VF or VT and 102 (51.7%) had PEA or asystole. During their CICU stay, 172 (85.6%) patients received propofol, 134 (66.7%) received midazolam, and 111 (55.2%) received lorazepam. A positive correlation was seen between rate of survival with good neurologic outcome in patients who received propofol (p=0.01) or midazolam (p=0.021) while a negative correlation was seen with lorazepam (p=0.01). Multivariate analysis showed that propofol use (p=0.001) was a positive independent predictor of survival with good neurologic outcome during hospitalization in our population whereas lorazepam use (p=0.004), history of diabetes (p=0.004), and either asystole (p=0.004) or PEA (p=0.002) were negative predictors.

Conclusions:
In our population, use of propofol or midazolam during MTH following cardiac arrest was positively associated with a good outcome while lorazepam use had a negative association. Direct head-to-head studies are required to identify the most appropriate sedation strategy to use in this population.
Abstract 19376: Coronary CT Angiography Performed in the Emergency Department in Chest Pain Patients is Effective in Identifying Patients who Require Revascularization
Authors: Prakash Sheena , Shaker Ahmad , Lingam Veena , Gopal Arun , Reilly Robert , Jeremias Allen , Voros Szilard , Poon Michael
Published: April 2024

Introduction:
The high sensitivity and negative predictive value of coronary CT angiography (CCTA) has been demonstrated in several multi-center studies; however little is known about downstream evaluation and revascularization in patients admitted to the hospital based on CCTA. We hypothesized that CCTA would be an effective testing modality in identifying patients with obstructive coronary artery disease (CAD) requiring revascularization.

Methods:
We performed a retrospective study of consecutive low-risk patients (TIMI risk score 3 or less) undergoing CCTA in the ED for chest pain during a 6-month period. CCTA was performed using institutional protocols; stenoses were graded semi-quantitatively as none, mild, moderate or severe; most severe lesion per patient was recorded. Downstream non-invasive and invasive evaluation and revascularization via either percutaneous coronary intervention or coronary artery bypass graft was extracted from charts.

Results:
There were 902 patients who had a CCTA study performed in the ER, of which 105 (11.6%) were admitted for further testing. Non-invasive testing was the initial strategy in 60% and angiography in 40% of patients (Figure). Of those with normal or mild stenosis, only 2 of 11 had revascularization. Of those with intermediate stenosis, 14 out of 65 (21.5%), and of those with severe stenosis, 22 of 29 (75.9%) required revascularization. In multivariate analysis, clinical characteristics did not, but stenosis severity by CCTA predicted revascularization (OR 3.53, 95% CI:1.59-7.80).

Conclusion:
CCTA appears to be an effective tool in triaging low-risk patients for downstream evaluation and revascularization procedures.
Abstract 19382: Ablation of the Cardiac-Specific Gene Leucine-Rich Containing 10 (lrrc10) Results in Dilated Cariomyopathy
Authors: Brody Matt , Hacker Timothy A , Sadoshima Junichi , Tevosian Sergei , Lee Youngsook
Published: April 2024

Dilated cardiomyopathy is the most common form of cardiomyopathy and is a leading cause of heart failure. Leucine-rich repeat containing 10 (LRRC10) is a cardiac-specific protein containing leucine-rich repeat motifs ideal for protein:protein interactions. We have previously shown that LRRC10 is essential for proper cardiac function in developing zebrafish. However, the role of LRRC10 in mammalian cardiac physiology remains unknown. To determine if LRRC10 is critical for mammalian cardiac function, Lrrc10-null (Lrrc10-/-) mice were evaluated by echocardiography. Lrrc10-/- mice exhibit prenatal systolic dysfunction and progressive dilated cardiomyopathy in postnatal life. Importantly, Lrrc10-/- mice have diminished cardiac performance in utero, prior to ventricular dilation observed in young adults. Gene expression profiling revealed that cardiac muscle contraction and oxidative phosphorylation are the most upregulated pathways in adult Lrrc10-/- hearts. We demonstrate that LRRC10 physically interacts with α-actinin and actin isoforms by coimmunoprecipitation, GST pulldown, and yeast two-hybrid screening, suggesting that LRRC10 may provide a link between the myofilament Z-disc and the actin cytoskeleton. Interaction of LRRC10 with α-actinin and actin positions it in ideal location in the cardiomyocyte to sense or transduce signals in response to biomechanical stress. To test the role of LRRC10 in response to biomechanical stress, transverse aortic constriction (TAC) was performed. Lrrc10-/- mice exhibit exacerbated and accelerated cardiomyopathy in response to 28 days of TAC with markedly greater left ventricular (LV) chamber dilation and severely compromised systolic and diastolic function relative to controls. Moreover, endogenous Lrrc10 expression is downregulated in controls in response to TAC, suggesting an important role for LRRC10 in cardiac adaptation to biomechanical stress. In summary, we identify the cardiac-specific factor Lrrc10 as a novel dilated cardiomyopathy candidate gene. LRRC10 is essential for normal cardiac function and is indispensible for proper adaptation of the mammalian heart to biomechanical stress.
Abstract 19398: Diastolic Dysfunction and Deposition of Fibrosis in Pressure Overloaded Hearts is Dependent on Pentraxin3
Authors: Carnevale Daniela , Fardella Valentina , Mascio Giada , Cifelli Giuseppe , Fardella Stefania , Pallante Fabio , Garlanda Cecilia , Mantovani Alberto , Lembo Giuseppe
Published: April 2024

On the basis of the underlying pathophysiology, it is possible to distinguish two major forms of heart failure (HF): HF owing to reduced left ventricular (LV) systolic function and HF owing to LV diastolic dysfunction. In both cases, chronic remodeling processes in the myocardium antedate overt HF by many years. Inflammation has a pivotal role in cardiac remodeling, and circulating markers of systemic inflammation are independently associated with risk of developing HF and with prognosis after onset. However, the pathophysiological role of many inflammatory biomarkers in HF is poorly understood. In this context, the relationship between circulating levels of pentraxin 3 (PTX3), a novel marker of inflammation, and the presence of diastolic dysfunction and/or overt HF has been emerging. PTX3 belongs to pentraxins, members of a superfamily of multimeric pattern-recognition proteins that can be short (such as CRP) or long (the prototype of this group being PTX3), with important roles at the interface of innate immune response, inflammation, and extracellular matrix remodeling. To dissect the pathophysiological role of PTX3 in the two forms of HF, we subjected mice with a genetic ablation for PTX3 to chronic pressure overload. Both echocardiographic analysis and PV loops revealed an early and sustained protection from LV diastolic dysfunction. As regard the process of cardiac remodeling to pressure overload, absence of PTX3 resulted in reduced recruitment of monocyte and deposition of fibrotic tissue. The systolic function was not affected by the absence of PTX3 and both WT and KO mice developed a comparable systolic dysfunction over time. In conclusion our data fully support the clinical association among PTX3 levels and the presence of diastolic dysfunction and candidate this molecular target as a novel therapeutic approach for HF owing to LV diastolic dysfunction.
Abstract 19408: Noninvasive Electrocardiographic Imaging Demonstrates Early Structural and Functional Changes Associated with Paroxysmal Atrial Fibrillation in Humans
Authors: Agrawal Arpit , Vijayakumar Ramya , Cuculich Phillip S
Published: April 2024

BACKGROUND:
Atrial fibrillation (AF) causes and perpetuates with a remodeling process that involves both functional (ion channel, connexin) and structural (fibrosis) changes to atrial tissue. Presently, there is no noninvasive method to study this process in humans. Noninvasive electrocardiographic imaging (ECGI) could provide insight into remodeling processes associated with early AF.

METHODS:
Noninvasive ECGI was performed during sinus rhythm on 20 patients with a history of paroxysmal AF undergoing pulmonary vein isolation procedure after antiarrhythmic drug washout period. Eight patients with no history of AF and normal ventricular function were used for controls. For functional analysis, total atrial conduction time (TACT) and left atrial conduction time (LACT) were measured. For structural analysis, left atrial posterior wall (LAPW) voltage was measured. To account for patient-specific torso variability, this value was indexed to the maximal left atrial appendage voltage (indexed LAPW).

RESULTS:
Compared to controls, patients with AF had longer TACT (100 vs. 79 ms control, p<0.005) and longer LACT (55 vs. 39 ms control, p = 0.034, top left figure). There were no differences in raw LAPW voltage (0.40 vs. 0.47 mV control, p = 0.53), but significant differences existed after adjusting for patient-specific torso variability (0.36 vs. 0.64 mV control, p < 0.020, top right figure). These differences were strongly associated with duration of PAF diagnosis. Subtle functional differences were observed early in AF, while significant functional and structural changes were seen with AF diagnosis of longer duration (5+ years, see bottom figure).

CONCLUSIONS:
Very early in human AF, functional effects of ion channel and connexin remodeling are evident with delayed global and regional electrical activation. With longer AF, more pronounced delay and measurable decrease in electrogram voltage are likely a combined effect of ion channel adaptation and early fibrosis.
Abstract 19419: Algorithm-Based Vendor Selection for Implantable Cardiac Devices Reduces Costs and Avoids Appearance of Conflict of Interest
Authors: Henrikson Charles A , Stecker Eric C , Stajduhar Karl , Clark Thomas , Kron Jack
Published: April 2024

Introduction:
In most hospitals, device vendor selection for an individual case is at the discretion of the implanting physician. This exposes the physician to the appearance of conflict of interest and may increase device costs.

Methods:
At a single academic center, implanting physicians and electrophysiology lab staff constructed and implemented a device selection algorithm based on referring provider request, device features, and equal distribution of cases among the four vendors in our geographic area. Costs for comparable devices were also incorporated into the algorithm, and lower cost devices were selected if all other factors were equal. For each individual case, the algorithm was followed by technical and administrative staff who selected and notified the vendor. Information was solicited from the implanting physicians to inform algorithmic selection. The selection algorithm could be overruled at discretion of implanting physician on clinical grounds. When manufacturer-specific features were selected or non-algorithmic clinical factors incorporated into the decision, the rationale was documented.

Results:
Over a three-year period of implementation, this algorithm resulted in a distribution of cases among vendors (15.4% Biotronik, 19.0% Boston Scientific, 35.4% Medtronic, and 30.0% St Jude Medical). Imbalances were due to referring provider preferences and the incorporation of cost considerations into the algorithm. In no instance did the implanting physician overrule the algorithm. There were no complaints from referring providers. As compared to prior to the implementation of the algorithm, approximately $750,000 was saved over three years, an 8.3% reduction in device costs. This was largely on the basis of algorithmic selection of less expensive (older generation) devices for appropriate patients. After two years, when vendor contracts were renegotiated, substantial further cost savings were realized.

Conclusions:
A device selection algorithm removes the daily task of vendor selection from the physician and removes the appearance of conflict of interest. The algorithm also results in a substantial cost savings for the hospital. We hope this model will find broad application in the electrophysiology community.
Abstract 19436: cAMP Regulation of Vascular Endothelial Ectoenzyme ENTPD1
Authors: Baek Amy E , Liao Hui , Visovatti Scott H
Published: April 2024

Ectonucleoside triphosphate diphosphohydrolase 1 (or CD39), an enzyme expressed on the plasmalemma of leukocytes and endothelial cells, serves as a potent antithrombotic agent by sequentially phosphohydrolyzing ATP and ADP, to generate AMP. CD39 is thus able to locally deplete levels of extracellular ATP and ADP, which would otherwise promote inflammation and platelet aggregation by binding P2X and P2Y classes of purinergic receptors found on leukocytes and platelets. The only known pathway for the transcriptional regulation of CD39 was described in recent work by this lab, which demonstrated that increased cAMP levels led to CD39 upregulation in murine macrophages through binding to the cAMP response elements (CRE) in the CD39 promoter with a consequent increase in CD39 transcription. Here, in contrast, we show that human endothelial cells (from umbilical vein; HUVEC) express less CD39 in response to elevated cAMP levels. Furthermore, we demonstrate that blockade of a major cAMP effector protein, protein kinase A (PKA), restores CD39 expression. Treatment of HUVEC cells with 250 μM 8-Br-cAMP, a cell permeable analogue of cAMP, led to a 2-fold decrease in CD39 protein from whole cell lysates in Western blots (18 hrs, p<0.001, n=5), and this pattern persisted in time course assays from 8 hours to 24 hours. This result was confirmed with immunoprecipitation for CD39 in HUVEC supernatants, where 8 hours of 8-Br-cAMP treatment at 250 μM led to a 2.2-fold decrease in CD39 protein. ELISA measurements of HUVEC treated with 20 μM of the PKA inhibitor H89 led to a 2.8-fold increase compared to control of CD39 protein from HUVEC supernatants (p=0.0021, n=6). This was confirmed by Western blot, where co-treatment with 250 μM 8-Br-cAMP and 20 μM H89 for 8 hours led to a 50% increase measured by Western blot in CD39 protein compared to control in whole cell lysates (p<0.05, n=3). Together, these data demonstrate that endothelial expression of CD39, a potent antithrombotic and anti-inflammatory enzyme, is modulated by the cAMP/PKA pathway, and contributes to basic understanding of the regulatory pathways governing CD39.
Abstract 19456: Does Choice of Neuromuscular Blocker Affect Outcomes in Patients Receiving Therapeutic Hypothermia Following Cardiac Arrest?
Authors: Baker William , Geronila Giovanni , Kallur Ramya , Noyes Adam , Lundbye Justin B
Published: April 2024

Introduction:
It is well recognized that the actions of neuromuscular blockers are enhanced in patients undergoing mild therapeutic hypothermia (MTH) following cardiac arrest. Little data on the association between various NMB agents and outcomes are available.

Methods:
We retrospectively collected data on 201 consecutive adult patients (mean age 61 ± 15 years) admitted to Hartford Hospital who survived a cardiac arrest and were admitted to our cardiac intensive care unit (CICU). Of the 201 patients, 99 (49.3%) had VF or VT and 102 (51.7%) had PEA or asystole. Use of neuromuscular blockers, including cisatracurium and vecuronium, was collected. The main outcome of interest was survival with good neurologic outcome defined using the Pittsburgh cerebral performance category (CPC) scale of 1-2. Multivariate logistic regression was used to control for potential confounders and identify independent predictors of good outcome.

Results:
During their CICU stay, 60 (29.9%) patients received cisatracurium and 36 (17.9%) received vecuronium. A positive correlation was seen between rate of survival with good neurologic outcome was seen in patients who received cisatracurium (p<0.001) but not in those receiving vecuronium (p=0.183). Neither agent was correlated with length of stay in the CICU. Multivariate analysis showed that cisatracurium use (p=0.014) was a positive independent predictor of survival with good neurologic outcome during hospitalization in our population whereas history of diabetes (p=0.004), and either asystole (p=0.006) or PEA (p=0.002) were negative predictors.

Conclusions:
In our population, use of cisatracurium during MTH following cardiac arrest was positively associated with a good outcome while vecuronium did not seem to affect this outcome. A prospective direct head-to-head study is required to better characterize potential differences between neuromuscular blocking agents.
Abstract 19457: Succesfull Heart Transplantation after Twelve Hours of Cold Ischemic Storage in the Novel Organ Preservation Solution, Custodiol-N
Authors: SzabÓ Gábor , Radovits Tamás , Veres Gábor , Schmack Bastian , Weymann Alexander , Korkmaz Sevil , Karck Matthias , Horkay Ferenc , Merkely Béla , Hartyanszky Istvan
Published: April 2024

Objective:
We currently developed a novel HTK based solution Custodiol-N which includes iron chelators to reduce oxidative injury and amino acids, in particular L-arginine, to improve endothelial function. We investigated the effects of Custodiol-N, on ischemia/reperfusion injury in a canine orthotopic heart transplant model.

Methods:
After 4, 8, and 12 hours of ischemic preservation, 36 orthotopic heart transplantations were performed. The hearts were preserved with either HTK (Custudiol, control) or Custodiol-N solution. The slope of the left ventricular pressure-volume relationships (Ees) was calculated before explantation and after 120 minutes of reperfusion. Coronary blood flow (CBF), endothelium-dependent vasodilatation to acetylcholine (ACH) and endothelium-independent vasodilatation to sodium nitroprusside (SNP) were also determined.

Results:
Custodiol-N led to significantly better recovery of Ees (91±5 vs. 49±8%, p<0.05). CBF was significantly higher in the Custodiol-N group (53±5 vs. 27±4, ml/min, p<0.05). While the vasodilatatory response to SNP was similar in both groups, ACH resulted in a significantly higher increase in CBF in the Custodiol-N group (72±8% vs. 29±7%, p<0.05). While none of the control animals could wean from cardiopulmonary bypass after 8 and 12 hours of ischemic preservation, all the animals could successfully weaned both after 8 and 12 hours in the Custodiol-N group. The recovery of Ees was 88±6% and 92±8%, respectively which did not differ significantly from baseline values.

Conclusions:
The novel organ preservation solution, Custodiol-N, reduces myocardial and endothelial reperfusion injury after orthotopic heart transplantation and successfully extends the safe hypothermic ischemic cardiac preservation times up to 12 hours.
Abstract 19466: Metabolomic and Gene Expression Changes in End-Stage Heart Failure are Reversed by Left Ventricular Assist Device
Authors: Gupte Anisha , Hamilton Dale J , Cordero-Reyes Andrea M , Youker Keith A , Loebe Matthias , Stevens Robert D , Wenner Brett , Ilkayeva Olga , Taegtmeyer Heinrich , Newgard Christopher B , Torre-Amione Guillermo , Hsueh Willa A
Published: April 2024

Introduction:
Heart muscle tissue in advanced heart failure (HF) is reported to be ‘energy-depleted’ and inflexible to metabolic changes. Left ventricular assist devices (LVAD) and ventricular unloading with LVAD is known to regress cardiac hypertrophy, reduce fibrosis and partially improve function. The metabolic alterations with HF and LVAD support are not fully understood. We hypothesize that HF is associated with metabolic changes that are reversible with LVAD placement.

Methods:
We analyzed gene and protein expression and performed metabolomics analyses in failing left ventricular (LV) tissue obtained at the time of heart explant or LVAD placement (HF, n = 13) and removal (post-LVAD, n = 7). Control LV tissue was procured from patients undergoing heart-lung transplantation for severe right HF (control, n = 4). P<0.05 was considered significant.

Results:
In HF samples, expression levels of mitochondrial transcription factors and coactivators were decreased, while LVAD increased expression of PGC1α, PGC1β, ERRγ and TFAM to levels of control samples. Gene and protein expression of mitochondrial complex subunits NDUFS6, SDHA, UQCRC1, Cox5a, ATP5a1 were reduced in HF, but increased after LVAD. LVAD rescued reduced expression of fatty acid oxidation genes CPT2, ACADvl, ACADm, HADHA and PPARα, as well as pyruvate and glucose metabolism genes ME3, MCT1, PDHB, GPT and PFK. Targeted metabolomics analysis showed a reduction in short- and medium-chain acylcarnitines (C2-C10) in failing LV indicating decreased substrate catabolism, with these analytes universally restored to normal post-LVAD. Pyruvate levels tended to increase (P=0.07), whereas all measured Krebs cycle intermediates including citrate, α-ketoglutarate, succinate, fumarate and malate were reduced in the HF samples compared to normal controls. LVAD normalized pyruvate levels, and normalized the levels of all Krebs cycle intermediates.

Conclusion:
Both the gene expression and metabolomics profiles for mitochondrial, fatty acid, pyruvate and glucose metabolism pathways indicate that HF is associated with a global defect in substrate utilization. Complete reversal by ventricular unloading demonstrates the reversibility of metabolic defects.
Abstract 19511: Progesterone Reduces Isoproterenol-Induced pVTs in Male Transgenic Long QT Syndrome 2 (LQT2) Rabbits
Authors: Kossidas Konstantinos , Zheng Zhe , Odening Katja E , Zehender Manfred , Schoffield Lorraine , Taylor Chantel , Yang Bryant , Pfeiffer Zachary , Choi Bum-Rak , Koren Gideon
Published: April 2024

Background:
During childhood, boys with long QT syndrome (LQT) have a higher risk than girls for developing ventricular arrhythmia and sudden cardiac arrest. We have previously shown a pro-arrhythmic effect of estrogen (EST) and an anti-arrhythmic effect of progesterone (PROG) in transgenic female LQT2 rabbits. Here we study the effects of sex hormones in male LQT2 rabbits; hypothesizing that orchiectomy (ORCH) will increase the arrhythmogenic risk as compared to treatment with PROG or dihydrotestosterone (DHT).

Methods:
Orchiectomized LQT2 males were implanted with 90-day release pellets containing PROG (n=6), DHT (n=5), or placebo (ORCH) (n=6). All groups underwent dual voltage-calcium optical mapping ex vivo after 8 weeks of hormone-treatment.

Results:
During 8 weeks of hormone-treatment, no episodes of SCD occurred in any groups. Optical mapping revealed similar APD and APD dispersion in all groups (APD, ms, ORCH 239.9±29.2, DHT 251.4±15.7, PROG 253.0±19.9) (APD dispersion, ms, ORCH 30.7±6.8, DHT 33.1±5.70, PROG 34.1±6.0). Isoproterenol induced calcium and voltage oscillations during the second phase of the AP in all three groups (Fig.1), However, the duration of the induced pVT was longer in ORCH rabbits as compared to PROG (5.8±4.8 sec vs. 2.1±1.3 sec p<0.05, n=6). By contrast, DHT had no beneficial effect (3.2±1.1 sec p=0.131 ORCH vs DHT n=5). Western blot analyses revealed that male rabbit heart express PROG nuclear receptors.

Conclusion:
Orchiectomy sensitized male LQT2 rabbits to isoproterenol-induced arrhythmias. PROG reduced the duration of pVT, but did not uncouple calcium and voltage oscillations as it does in ovariectomized female LQT2 rabbits.
Abstract 19535: Constitutive Expression of a Dominant Negative TGF-β Type-II Receptor in the Posterior Left Atrium Attenuates NADPH Oxidase and Mitochondrial Superoxide Production and Decreases Atrial Fibrosis (Resulting in Decreased AF)
Authors: Kunamalla Aaron , Ng Jason , Gordon David , Browne Suzanne , Smeltzer Brandon , Knight Bradley , Passman Rod , Goldberger Jeffrey , Aistrup Gary L , Arora Rishi
Published: April 2024

Background:
Oxidative stress is an important mechanism in the creation of AF substrate, especially in the setting of heart failure (HF). This is in part through reactive oxygen species (ROS) leading to activation of TGF-β signaling, which results in creation of atrial fibrosis. ROS are also an important downstream mediator of TGF-β signaling. We therefore hypothesized that in a canine model of HF induced by ventricular tachypacing, decreasing TGF-β signaling via atria-targeted dominant-negative type II TGF-β receptor expression will attenuate both oxidative stress and atrial fibrosis, thereby leading to decreased AF.

Methods:
17 dogs underwent injection + electroporation in the posterior left atrium (PLA) of either a plasmid expressing a dominant negative TGF-β type II receptor (pUBC-TGFβdnRII) (N=8) or control vector (p-UBC-
LacZ
) (N=7), followed by 3-4 weeks of right ventricular tachypacing (240 bpm). A terminal study was performed to assess for AF inducibility. Tissue was assayed for changes in fibrosis (Trichrome staining) and oxidative stress (superoxide quantification via lucigenin chemiluminescence).

Results:
Downregulation of TGF-β signaling by TGFβdnRII significantly decreased fibrosis (
Figure 1a
, blue staining), attenuated NADPH- and mitochondrial-generated superoxide (
Figure 1b
) and significantly decreased AF duration (
Figure 1c
), as compared to control animals.

Conclusions:
Targeted non-viral gene-therapy approaches aimed at reducing TGF-β signaling in the left atrium results in a decrease in AF substrate, in part through the reduction of oxidative stress and the development of fibrosis. Further optimization of this gene therapy approach may translate into effective AF therapies.
Abstract 19557: Comparative In-Hospital Outcomes for Pericardiocentesis versus Surgical Pericardiotomy in United States
Authors: Bashir Riyaz , Hermany Paul L , Zack Chad J , McClurken James B , Bove Alfred
Published: April 2024

Background:
The national and comparative in-hospital outcomes and resource utilization for pericardiocentesis and surgical pericardiotomy are not known.

Methods:
The Nationwide Inpatient Sample (NIS) database was used to identify patients who underwent pericardiocentesis or pericardiotomy from 2005 to 2009 in the United States. We used propensity score matching and the Elixhauser index for comorbidity adjustment to compare in-hospital outcomes and resource utilization among matched groups of patients that underwent either pericardiocentesis or pericardiotomy.

Results:
Among a total of 131,945 patients who underwent either procedure during the study period, 17,565 patients were divided into two matched groups of pericardiocentesis (9,336 patients) and pericardiotomy (8,229 patients). The pericardiocentesis group had significantly higher in-hospital mortality than the pericardiotomy group (15.7% vs. 10.4%, p<0.001). Patients in the pericardiotomy group had a significantly higher rate of blood transfusions (22.6% vs. 19.5%, p<0.001), post-procedural respiratory complications (2.0% vs. 0.8%, p<0.001), iatrogenic pneumothorax (8.1% vs. 3.1%, p<0.001), post-operative hemorrhage (3.1% vs. 1.8%, p<0.001), and post-operative hematoma (1.5% vs. 1.0%, p=0.001). The average length of stay was longer in the pericardiotomy group than in the pericardiocentesis group (12.6 vs. 8.5 days, p <0.001). The average hospital charges were also higher in the pericardiotomy group than in the pericardiocentesis group ($108,624 vs. $75,690, p<0.001).

Conclusion:
In this observational study, we found that pericardiocentesis is associated with a significantly higher in-hospital mortality than surgical pericardiotomy while the latter is associated with higher rates of post-operative morbidity and resource utilization.
Abstract 19560: Etv2 Regulates Endothelial Development via Activation of Sox7
Authors: Zierold Claudia , Behrens Ann N , Ren Yi , Koyano-Nakagawa Naoko , Garry Daniel J , Martin Cindy M
Published: April 2024

Etv2 has recently been shown to be an important factor for the specification of the endocardial/endothelial and hematopoietic lineages. Transgenic embryos lacking Etv2 die between E9.0 and E9.5 due to absence of the endocardial/endothelial lineage and significant disruption of hematopoietic lineages. Sox 7, Sox 17 and Sox 18 comprise the Sox-F family which has been shown to be important in the regulation of hematopoietic cells and cardiovascular development. Therefore, we examined the hypothesis that the Sox family members were downstream targets of Etv2. Sox 7, Sox 17 and Sox 18 were found to be significantly downregulated in the Etv2 null mice compared to wildtype (WT) littermates at two developmental stages. WT embryoid body (EB) developmental expression profiles supported that Sox 7 and Sox 17, but not Sox 18, were direct downstream targets of Etv2. Studies performed using ES cells generated from the Etv2 null and WT littermate blastocysts confirmed the lack of the endothelial and hemogenic endothelium lineages in the absence of Etv2. The expression of all Sox F family members was also markedly altered in the Etv2 null EB system with a virtual absence of both Sox 7 and Sox18 expression in all developmental timepoints in the Etv2 null EBs when compared to WT controls. We utilized an array of molecular biological techniques to demonstrate that Etv2 is a direct upstream regulator of the Sox 7 gene. We also generated an inducible Sox7 overexpressing embryonic stem (ES) cell line and overexpression of Sox7 resulted in an induction of the endothelial molecular program with an increase in the percentage of Flk-1/Cdh5 double positive endothelial progenitor cells and increased expression of Pecam1 and Cdh5 in Sox7 overexpressing Day6 EBs. Collectively, these studies support the conclusion that Etv2 is essential for the endocardial/endothelial lineage including the hemogenic endothelium and Sox7 is an important factor in this developmental pathway. To further verify the role of Sox 7, we are undertaking rescue experiments of the Etv2 null ES cells by expressing Sox 7 under the control of an inducible lentivirus system. We anticipate that the induction of Sox 7 in Etv2 null EBs will reestablish expression of the endothelial and hemogenic endothelial molecular programs.
Abstract 19564: Role of Insulin Resistance and Excess Free Fatty Acids in Determining Endothelial Function in the Metabolic Syndrome
Authors: Perlstein Todd S , Buck J. S , Kadivar Samoneh , Beckman Joshua A
Published: April 2024

Introduction: It is hypothesized that insulin resistance and endothelial dysfunction are reciprocally linked, though clinical data are limited. In particular, impaired endothelial insulin signaling is thought to result in endothelial dysfunction. Excess circulating free fatty acids (FFAs) are hypothesized to impair insulin signaling and result in both insulin resistance and the associated endothelial dysfunction.

Aims: We examined the relationship between insulin resistance and endothelial function in the metabolic syndrome, a clinical state of insulin resistance. We also tested whether lowering of FFAs would improve endothelial function in persons with the metabolic syndrome.

Methods: A total of 70 adults, 39 with the metabolic syndrome and 31 healthy controls, were studied. Subjects underwent euglycemic hyperinsulinemic clamp to measure insulin resistance (‘M’, mg/kg/min) and insulin-stimulated, endothelium-dependent vasodilation (%), as well as ultrasound-measured brachial artery flow-mediated dilation (FMD, %) to measure endothelial function. Thirty-five subjects, 18 with the metabolic syndrome and 17 controls, completed a double-blinded, placebo controlled crossover trial to examine the effects of 7 days of FFA lowering with acipimox on endothelial function and insulin resistance.

Results: FFA levels were higher in the metabolic syndrome (p < 0.01). Persons with the metabolic syndrome were insulin resistant compared with control subjects (M 5.1 (1.4) mg/kg/min vs. 9.7 (3.9) mg/kg/min, p < 0.001), but FMD (10.9 (6.4) % vs. 10.7 (5.0)%, p = 0.92) and insulin stimulated vasodilation (36.9 (32.4) % vs. 86.6 (140) %, p = 0.31) were not different between groups. Acipimox therapy improved insulin resistance approximately 20% (p < 0.05) but did not alter FMD (p = 0.67) or insulin-stimulated dilation (p = 0.26).

Interpretation: These data demonstrate preserved endothelial function in persons with the metabolic syndrome despite severe systemic insulin resistance, and no effect of FFA lowering therapy on endothelial function despite improvement insulin sensitivity. Insulin resistance and elevated FFA levels may not be sufficient to cause endothelial dysfunction in humans.
Abstract 19572: Obese Female Patients Have Higher Rates of Lead Dislodgement After ICD or CRT-D Implantation
Authors: Kawata Hiro , Patel Jigar , Sawhney Navinder , Krummen David , Narayan Sanjiv , Feld Gregory , Birgersdotter-Green Ulrika
Published: April 2024

Background:
While there is significant data available regarding the effects of gender and obesity in cardiovascular disease, research focusing on defibrillators has been limited. Obese patients (pts) are considered at higher risk for complications of cardiac implantable electronic devices (CIED). However, no study has been published regarding the relationship between gender, obesity and risk of CIEDs implantation. The aim of this study was to evaluate complications of defibrillator implantation (ICD and CRT-D) and their rationship to gender and body mass index (BMI).

Methods:
We analyzed all complications related to ICD or CRT-D implantation from 2005 to 2012 at University of California San Diego Health System. Only ICD or CRT-D implants with a new lead were included in the analysis. Four hundred twenty nine consecutive pts were included. We divided these 429 pts into 4 groups based on gender and BMI (Group1=Male, BMI≥30, Group 2=Male, BMI<30, Group 3=Female, BMI≥30, Group 4=Female, BMI<30) and compared rate of complications among these 4 groups.

Results:
During 26.8±23.7 months follow-up, complications were observed in 75 patients (17.5 %). Lead dislodgement (32 patients), diaphragmatic pacing (9 patients), pocket hematoma or bleeding (8 patients), infection (8 patients) and pneumothorax (6 patients) accounted for >80% of all complications. Fifty-four of these 75 pts needed additional surgical procedures or eariler generator exchange. No significant differences were observed in overall complication rates among the 4 groups (15.6%, 16.1%, 24.6% and 31.3%). However, lead dislodgement occurred at a significantly higher rate (p<0.001) in group 4 (27.5%) compared to the other groups (5.7%, 6.7% and 7.7%).

Conclusions:
In our retrospective, single-center study there was a higher risk of lead dislodgement in obese female pts undergoing ICD or CRT-D implantation. Careful attention to lead and device anchoring, particularly with larger cardiac devices, may be more important in this group of pts to avoid lead dislodgement.
Abstract 19587: Clinical Predictors of Heart Failure Event or Death in Left Bundle Branch Block Patients from MADIT CRT Trial
Authors: Zareba Wojciech , Block Thomsen Poul Eric , Kutyifa Valentina , McNitt Scott , Moss Arthur J
Published: April 2024

Background:
Heart failure patients with left bundle branch block (LBBB) benefit the most from cardiac resynchronization therapy (CRT). However, cardiac events consisting of heart failure (HF) hospitalization or death continue to occur in CRT-treated LBBB patients. The aim of this study is to identify clinical variables associated with adverse outcome in CRT-treated LBBB patients.

Methods:
Study population consisted of 665 CRT treated LBBB patients enrolled in the MADIT-CRT. Echocardiographic data were available in 657 CRT-treated LBBB patients. HF event or death was the primary endpoint of the trial and of this analysis. Two predictive models were constructed: Model 1 without baseline echo variables and Model 2 with baseline echo variables. Patients who crossed-over at the beginning of the study from CRT-D to ICD (mostly due to inability to advance left lead) were excluded, therefore actually CRT-treated patients were only considered in the analysis.

Results:
Among 665 CRT-treated LBBB patients there were 101 (15.2%) with HF event or death, whichever came first. Echo-base cohort included 657 CRT-treated patients with 101 (15.4%) of them developing primary endpoints. The following clinical variables (Model 1) were predictive for HF or death in LBBB patients: male gender: HR=1.83; p=0.027, ischemic etiology: HR=1.53; p=0.049, QRS<=150ms: HR=1.69; p=0.015, prior HF hospitalization: HR=1.44; p=0.076. Figure below shows the risk of primary endpoint as a function of ischemic etiology and QRS duration. Among Echo parameters (Model 2) only left atrial volume index =>40 ml/m2 was predictive for endpoints: HR=2.90; p=0.002.

Conclusions:
LBBB patients with ischemic cardiomyopathy and QRS<=150 ms derive limited benefir from CRT. Ischemic and nonischemic cardiomyopathy patients with QRS>150 ms benefit the most. Increased left atrial volume indicates increased risk of cardiac events among CRT patients.
Abstract 196: Does Health Status Influence the Willingness to Provide Informed Consent? Results from a Cardiac Arrest Trial Conducted Under Waiver of Informed Consent
Authors: Frascone Ralph , Salzman Joshua , Yannopoulos Demetris , Mahoney Brian , Swor Robert , Domeier Robert , Wayne Marvin , Aufderheide Tom , Olinger Michael , Wewerka Sandi , Tupper David , Holcomb Richard
Published: April 2024

Background

Federal regulation 21 § CFR 50.24 allows an initial waiver of informed consent (IC) for treatment of certain medical emergencies but requires the consent process be initiated at the earliest feasible opportunity. In a recent out-of-hospital cardiac arrest (OHCA) trial conducted under 21 § CFR 50.24, data from public records were collected which shed light on whether the willingness to provide subsequent IC was associated with study outcomes. We hypothesized that IC was less likely to be obtained in subjects with significantly compromised health status.

Methods

A post-hoc analysis was conducted using data from a NIH-funded randomized, controlled OHCA clinical trial comparing active compression decompression CPR plus an impedance threshold device (ACD+ITD) with standard CPR. The primary endpoint was survival to hospital discharge (HD) with favorable neurologic function [Modified Rankin Scale (MRS) score <3]. The status of the consent process was tabulated for all subjects who survived to hospital admission. Unadjusted Fisher’s exact test and associated odds ratios were used to compare the MRS at HD by IC status.

Results

Among a total study population of 1655 subjects, 457 survivors were admitted to the hospital, and 440 had known HD status (see table).

Survival with a MRS≤3 was significantly higher in subjects where IC was given: 35.0% vs 4.1%, p < 0.001. Sixteen of the 17 cases with missing MRS outcomes were in the IC denied group. Even if all were considered to have favorable outcomes, the resulting rate (21.1%) was less than that seen among subjects with IC given (p = 0.015).

Conclusion

Subjects who denied IC were significantly less likely to have favorable outcome. These findings suggest that some resuscitation trials may unknowingly under-represent those subjects with the worst prognoses in a target study population despite pre-specified inclusion and exclusion criteria, due to the unwillingness or inability of the subjects or their families to provide IC.
Abstract 19618: Effect of Electroanatomically Guided versus Conventional Renal Sympathetic Denervation on Radiation Exposure and Blood Pressure in the SAVE Trial
Authors: Gangireddy Sandeep R , Neuzil Petr , Sennhauser Susie N , Reddy Vivek Y
Published: April 2024

Introduction:
SYMPLICITY -2 demonstrated that renal sympathetic denervation (RSDN) is effective in lowering blood pressure in patients with resistant hypertension. RSDN is typically performed using fluoroscopy. Our aim was to assess the clinical utility of electroanatomic mapping systems (EAM) on radiation exposure and treatment results in a prospective trial.

Methods:
Pre-specified analysis of outcomes in both the non-randomized Impact of Renal Sympathetic Denervation on Chronic Hypertension (SAVE) trial (n=10), and the randomized Renal Sympathetic Denervation for the Management of Chronic Hypertension (RELIEF) trial (n=10). Both trials enroll patients with refractory HTN, defined as BP≥140/90 mmHg despite treatment with at least 3 anti-HTN drugs. Patients in the SAVE cohort underwent catheter based RSDN using EAM (NavX, CARTO), and were compared with case-matched controls in the RELIEF trial who underwent RSDN using fluoroscopy. All patients underwent bilateral renal angiography prior to RSDN, resulting in radiation exposure. Blood pressure was measured at 1 month post-procedure in an office setting.

Results:
Radiation exposure was significantly reduced in the EAM group (39,175 ± 14,463 mGycm2 vs 61,209 ± 22,259 mGycm2, P=0.0172). Total procedure duration was comparable between the EAM group (77.0 ± 35.5 min) and conventional group (75.6 ± 33.8 min, P=0.8837). The SBP at 1 month (147 ± 11 vs 156 ± 19 mmHg, P=0.3662) and DBP at 1 month (91 ± 11 vs 88 ± 15 mmHg, P=0.6998) were similar between the EAM and conventional group.

Conclusion:
The use of electroanatomic mapping systems during RSDN significantly reduces radiation exposure, without increasing procedure duration.
Abstract 19638: Watchman Left Atrial Appendage Closure in Atrial Fibrillation Patients with Contraindication to Oral Anticoagulation: The ‰ASA Plavix Registry” (ASAP)
Authors: Reddy Vivek , Neuzil Peter , Miller Marc , Schuler Gerard , Möbius-Winkler Sven , Wiebe Jens , Wunderlich Nina , Sick Peter , Sievert Horst
Published: April 2024

Background:
AF patients at the highest risk for embolic stroke also experience the greatest risk of hemorrhagic complications of anticoagulant use. The PROTECT AF trial revealed that LAA closure using the Watchman device was non-inferior to Warfarin for preventing stroke in AF pts with CHADS
2
≥ 1. However, these pts were treated with Warfarin post-implant until a TEE demonstrated LAA closure at 6 wks. Due to the pressing need for strategies that can prevent stroke in pts with contraindications to Warfarin, we performed a prospective study of Watchman implantation in Warfarin-contraindicated pts.

Methods:
Prospective registry of pts with non-valvular AF, a CHADS
2
score ≥1, and a contraindication to Warfarin use. The Watchman device was implanted in standard fashion. Post-implant, patients were discharged on 6 mo of clopidogrel and life-long aspirin. Follow-up TEE was performed at 3/12 months.

Results:
At 4 centers, 150 pts were enrolled. The mean age was 72.5 ± 7.4 yrs. The prevalence of stroke risk factors was: CHF in 29%, HTN in 95%, Age ≥ 75 in 43%, DM in 32%, and stroke/TIA in 41%. The mean CHADS
2
score was 2.8 ± 1.2. The reason for Warfarin contraindication was: hemorrhagic tendencies (26%), blood dyscrasias (7%), bleeding tendencies (67%), unsupervised pts with senility/high fall risk (4%), and other (5%). Watchman implantation was successful in 95% (142/150). At 14.2 ± 8.7 mo of follow-up, there were 4 strokes (3 ischemic) and 6 instances of device-related thrombus by TEE. The observed rate of ischemic stroke 1.7% represents 77% fewer events from that expected in pts with a similar CHADS2 score treated with aspirin alone (7.3%; Figure). Data from additional follow-up (to a total of >250 pt-yrs) will be available.

Conclusion:
Watchman implantation without a Warfarin transition is safe and effective in AF pts with contraindications to even short-term oral anticoagulation
Abstract 19639: Long-Term Change in Cardiovascular Risk Factor Profile at Baseline and 39-Year Follow-Up and Hs-C-Reactive Protein - - The Chicago Healthy Aging Study (CHAS)
Authors: Vu Thanh Huyen T , Pirzada Amber , Allen Norrina B , Garside Daniel B , Daviglus Martha L
Published: April 2024

Background:
High high-sensitivity C-reactive protein (hs-CRP) levels are associated with adverse levels of individual cardiovascular disease (CVD) risk factors and incident CVD events. However, little is known on the association of long-term changes in RF profile -- from young adulthood to older age -- with hs-CRP levels at older age.

Methods:
Using data from CHAS, we assessed association of changes in CVD RF status from baseline (1967-73) to follow-up (2007-10) with follow-up hs-CRP levels (see Table for definition of RF groups). Hs-CRP was dichotomized as >3 mg/l (cutpoint for high risk of developing CVD). Participants with hs-CRP >10 mg/l were excluded.

Results:
The study sample consists of 1,321 participants -- 27% women, 9% African American, baseline ages 25-44 years, free of major ECG abnormalities and MI (at baseline), mean follow-up age 71. After 39 years of follow-up, 17% of persons (117/681) with no adverse RFs at baseline remained RF-free at follow-up and 1.6% of persons with any 1+ RFs at baseline became RF-free at follow-up (62/640) (Group A). With adjustment for baseline age, sex, race, education, and current aspirin use, prevalence of high hs-CRP (>3mg/l) was lowest in Group A (11%) and higher in Group E (≥1 RF at both exams and not taking cholesterol-lowering medication) (34%) and in Group C (0 baseline RF status but ≥1 RF at follow-up) (26%). Further, within each risk category, persons who took cholesterol-lowering medication had a lower likelihood of high Hs-CRP than their counterparts not taking it (see Table).

Conclusion:
Long-term absence of RFs or, among those with baseline adverse risk factors, improvement in risk status to having no adverse RFs in older age is associated with lower prevalence of high CRP levels. RF burden in both young adulthood and older age were associated with substantially increased odds of having high hs-CRP levels at older ages, especially for those who did not take cholesterol-lowering medication.