bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19101: Increased Sympathetic Nervous System Activity in Refractory Hypertensive Patients in Contrast to Controlled and True Resistant Hypertensive Patients
Authors: Dudenbostel Tanja , Acelajado Maria C , Oparil Suzanne , Calhoun David A
Published: April 2024

Within the population of patients with resistant hypertension (RHTN), a unique phenotype with unexplained mechanisms of treatment failure has been identified. This phenotype remains uncontrolled despite optimal medical therapy who we refer to as having refractory hypertension (RefHTN) in contrast to true or controlled RHTN. The current study prospectively compared biochemical parameters, indices of arterial compliance, endothelial function and cardiohemodynamics in patients with RefHTN and a matched cohort of controlled and true resistant hypertensive patients. From 2009 to 2012, refractory patients were identified in a referral hypertension clinic using the following criteria: uncontrolled blood pressure (BP) on 5 or more antihypertensive medications (including chlorthalidone and spironolactone) after ≥ 3 visits within a minimum 6-month follow-up period. All 40 patients underwent measurement of 24-hr BP, heart rate (HR); pulse wave analysis (PWA); augmentation index (AIx75); aortic pulse pressure (APP); pulse wave velocity (PWV); arterial flow-mediated dilation (FMD), electrocardiogram, and impedance cardiogram. Baseline characteristics were similar; although, refractory patients were younger and were treated with an average of 7 different antihypertensive classes. ABPM confirmed a difference in systolic (177±29 vs 133±6 mm Hg, p<0.001) and diastolic BP (101±17 vs 79±10 mm Hg, p< 0.001) in the true or controlled vs refractory groups. Average 24-hr HR was higher in patients with RefHTN (78±8 vs 69±7 bpm, p=0.039) despite being on more β-blockers. PWV was greater(12±3 vs 10±3 m/s, p=0.044), as was AIx75 (31±7 vs 17±12 %). Brachial artery FMD was more reduced in patients with RefHTN (6.6 vs 9.4%). Impedance electrocardiogram showed significantly increased systemic vascular resistance(supine 3876.4 vs 1372.9 , p<0.001 and standing 1980.1 vs 1197.7 dyne sec cm-5,p=0.037). Patients with RefHTN have increased arterial stiffness, central blood pressure,systemic vascular resistance, and endothelial dysfunction compared to patients with controlled and true RHTN, consistent with higher sympathetic activity in his group suggesting that increased adrenergic output contributes importantly to antihypertensive treatment failure.
Abstract 19127: First Simultaneous Assessment of the Effects of Fish Oil Supplementation on Lipid and Thrombogenicity Profiles
Authors: Bliden Kevin , Singla Anand , Tantry Udaya , Jeong Young-Hoon , Ens Gordon , Gurbel Paul A
Published: April 2024

Background: Fish Oil supplementation may have anti-atherosclerotic effects by reducing triglycerides, improving endothelial function, and reducing inflammation. However, inconsistent results have been reported on the effects of fish oil on platelet function. We aimed to determine if fish oil supplementation reduced the atherothrombotic risk profile by measuring lipids and thrombogenic factors simultaneously .

Methods: Patients with suspected coronary artery disease with (n=79) and without (n=324) fish oil supplementation were enrolled in the Multi-Analyte, Thrombogenic, and Genetic Markers of Atheroclerosis (MAGMA) study. The lipid profile was determined by vertical density gradient ultracentrifugation technique, and thrombogenicity by thrombelastography immediately prior to elective coronary angiography. Urinary 11-dehydrothromboxane B
2
and AtherOx were performed by immunoassay. ADP and collagen-induced platelet aggregation were measured in aspirin+ clopidogrel- treated patients.

Results: Baseline demographics and cardiac risk factors were similar between groups. Fish oil supplementation was associated with significantly lower triglycerides, VLDL, remnant lipoproteins, and AtherOx levels and increased HDL levels (p<0.05). Among patients on aspirin + clopidogrel therapy, fish oil supplementation was associated with lower collagen-induced platelet aggregation (p=0.05, Table).

Conclusion: This is the first study to simultaneously examine the influence of fish oil supplementation on lipid and thrombogenicity profiles. Our study supports prior evidence of an improved lipid profile and suggests an enhancement of the anti-platelet effects of DAPT. Prospective studies are needed to determine the contribution of each of these effects of fish oil supplementation on thrombotic event occurrence.
Abstract 19135: Safety and Efficacy of Intramyocardial Delivery of Stem Cells in Ischemic Heart Failure: An Individual Patient Data-Based Meta-Analysis
Authors: Gyöngyösi Mariann , Pokushalov Evgeny , Bergmann Martin W , Kastrup Jens , Atsma Douwe , Sylven Christer , Maurer Gerald
Published: April 2024

Background. Intramyocardial stem cell delivery mode might be the choice for regeneration of chronic myocardial ischemia and/or left ventricular (LV) dysfunction.

Methods. Individual patient data-based meta-analysis includes data of 383 patients (part of MESS database, clinicaltrials.gov
NCT01098591
) with ischemic cardiomyopathy (iCMP) and treated either with autologous stem cell (SC) (bone marrow mononuclear or mesenchymal stem cells) using percutaneous 3D NOGA-guided delivery (n=290) or randomized to controls (n=93), data received from 5 European centers.

Results. The average follow-up (FUP) was 6.4±2.2 months. The baseline end-diastolic volume (189±73 ml vs 201±71 ml) and ejection fraction (EF) (41.4±14.5% vs 42.5±18.7%) were similar in SC treated vs controls. Procedural complication occurred in 2.1% of patients, and 80.8x10^6 cells were delivered in 11.2±2.5 myocardial sites. Compared with controls, intramyocardial delivery of SC improved (p<0.001) LV EF (mean difference 4.6%; 95% confidence interval /CI/ 6.4% to 2.7%); reduced infarct size (-2.22%; 95% CI -3.54% to -0.90%) and size of stress-induced myocardial ischemia (-5.6; 95% CI -7.38% to -3.88%). The CCS angina status (-1.0; 95% CI -0.68 to -1.06) and NYHA (-0.74; 95% CI -0.54 to -0.93) improved significantly (p<0.001) post SC therapy as compared with controls. Kaplan-Meier analysis resulted in a significant better survival (98.8% vs 93.5%, p<0.01) and MACCE-free survival (97.9% vs 78.5%, p<0.001) rate in SC-treated patients vs controls. Multivariate analysis resulted in a lower baseline EF and higher total number of intramyocardial delivered SC as significant predictors for improvement in EF, while norminal regression analysis revealed SC therapy as significant predictor for MACCE-free survival in patients with iCMP.

Conclusion. Meta-analysis of 3D NOGA endocardial mapping guided transendocardial stem cell treatment proves the safety and efficacy of this cardiac regeneration strategy in patients with chronic ischemia and low EF.
Abstract 19264: Regression of Atherosclerosis is Characterized by Molecular Re-programming of the Transcriptome: Insights into the Identification of New Therapeutic Targets Against Cardiovascular Disease
Authors: Feig Jonathan E , Vengrenyuk Yuliya , Wu Chaowei , Aliferis Constantin , Statnikov Alexander , Garabedian Michael J , Puig Oscar , Fisher Edward A
Published: April 2024

Atherosclerosis is the leading underlying cause of strokes and myocardial infarctions worldwide. We reported a mouse model of atherosclerosis regression that involves transplanting an atherosclerotic aortic arch into a normolipidemic mouse. The CD68+ cell population (predominantly macrophages) in the regressing plaques exhibited migratory behavior. To identify pathways and factors responsible for the beneficial changes in macrophage content and phenotype in the regressing plaques, we performed microarray analysis on RNA purified from laser captured CD68+ plaque cells isolated from atherosclerosis progression and regression environments. This yielded two major findings. First, genes associated with the contractile apparatus (such as titin, actinin and myopalladin) that are responsible for cellular movement were differentially up-regulated under regression conditions (by 3-4 fold) with members of the cadherin family (serves in adhesion functions) being significantly down-regulated by 2-3 fold. Both changes are consistent with the macrophage migratory behavior we observed in the regression environment. Secondly, the most highly up-regulated gene under regression conditions was arginase I (~8 fold), a classical marker of the M2 alternatively activated macrophage. Further examination revealed that regression was characterized by macrophages displaying other M2 markers, such as CD163, C-lectin receptor, mannose receptor, and Fizz-1, consistent with a less inflammatory state in the regression environment. In addition, we applied recently introduced local causal pathway discovery methods to the microarray data that revealed that vinculin and ApoCII, known factors in cell adhesion and lipid metabolism, respectively, may be important regulators in the pathophysiology of atherosclerosis regression. Ultimately, the insights gained from the regression model and the different modes of global analyses should lead to new therapeutic targets against cardiovascular disease.
Abstract 19277: Neither Comorbidities nor Socioeconomic Differences Explain the Association Between Higher Altitude of Residence and Better Coronary Artery Disease Survival
Authors: McMurtry Michael Sean , Patel Alka , Lewin Adriane , Kaplan Gil , Ghali William , Knudtson Merril , Graham Michelle M
Published: April 2024

Background:
Previous studies have linked higher altitude of residence with lower mortality from coronary artery disease, but were limited by incomplete ascertainment of co-morbidities, including hypertension, dyslipidemia, diabetes, and smoking, as well as lack of adjustment for socioeconomic variables such as education status and household income.

Methods:
We tested whether comorbidities and socioeconomic variables alter the association between altitude of residence and both results of coronary angiography and survival of those with coronary artery disease using the APPROACH database, a prospective cohort of all subjects undergoing coronary angiography in the Province of Alberta. Co-morbidities and mortality are ascertained by periodic linkage with Alberta Health, the provincial repository of administrative health data. The population was stratified by altitude of residence into quartiles based on residence postal codes, and logistic regression was used to calculate odds ratios for high risk or left main disease at coronary angiography, with the lowest quartile the reference. A Cox proportional hazard model was used to calculate hazard ratios for mortality, with the lowest quartile the reference.

Results:
A total of 105,093 consecutive subjects referred for coronary angiography between 1995 and 2010 were included, spanning elevations between 210 meters to 2,164 meters. After adjustment for comorbidities and socioeconomic variables, the odds ratio for the highest quartile having high risk or left main coronary disease at angiography was 0.86 (0.82-0.90). Survival analysis was restricted to 78,349 subjects with at least one >50% coronary lesion. The hazard ratio for mortality for the highest quartile was 0.88 (0.84-0.93) adjusting for all variables except coronary anatomy, and 0.95 (0.90-0.99) after adjusting for all variables.

Conclusion:
Higher altitude of residence was associated with lower odds of having high risk or left main coronary artery disease at coronary angiography and better survival, even after adjustment for comorbidities and socioeconomic variables.
Abstract 19283: Low Density Lipoprotein Cholesterol is Associated with the Extent of Noncalcified and Soft Lipid Rich Coronary Plaque but Not Coronary Calcium in Apparently Healthy Individuals from High Risk Families
Authors: Kral Brian G , Becker Lewis C , Yanek Lisa R , Vaidya Dhananjay , Qayyum Rehan , Moy Taryn F , Fishman Elliot K , Becker Diane M
Published: April 2024

Background:
Low density lipoprotein cholesterol (LDL-C) is strongly associated with CAD events. Calcified coronary plaque (CCP) is a proxy of overall plaque burden but the relationship between LDL-C and CCP has been inconsistent. LDL-C likely plays a more putative role in the early stages of atherogenesis including the formation and progression of noncalcified coronary plaque (NCP), especially lipid rich plaque (LRP), than later processes of vascular remodeling with CCP. Thus, we examined the association of LDL-C levels with the extent and relative volumes of NCP in apparently healthy individuals from families with premature CAD.

Methods:
Participants in GeneSTAR (N=561; mean age 51±10 years; 58% female, 37% AA) were screened for CAD risk factors and for coronary plaque using 256 multidetector dual-source CT angiography. Segmental CCP volumes (mm3) were measured using standard techniques and volumes of NCP and LRP defined as <30 HU were quantified (mm3) using an automated well-validated method. All plaque volumes were log transformed as log(plaque+0.05). Controlling for age, sex, and race, multivariate GEE regression analyses for the association of CAD risk factors, including LDL-C, hypertension, diabetes, and smoking, as well as statin medication use, were performed separately for transformed NCP, CCP, and LRP.

Results:
The prevalence of any coronary plaque was 45.6%. Multivariate regression demonstrated that LDL-C was significantly associated with the volume of NCP (p=0.02) and LRP (p=0.01) but not CCP (p=0.23). All other risk factors and statin use were significantly associated with all three plaque volumes. Additionally LDL-C was the only risk factor associated with the relative ratio of noncalcified to calcified plaque volume (p=0.02), consistent with a more putative role of LDL-C in earlier stages of plaque development and progression.

Conclusion:
This is the first study to show that LDL-C is more strongly associated with noncalcified and lipid-rich coronary plaque volumes than with the extent of coronary calcification in high-risk apparently healthy individuals. These findings suggest that early preventive therapies to lower LDL-C may have the greatest benefit prior to the detection of significant CCP.
Abstract 19316: Family History of Cardiovascular Disease in a First Degree Relative is Associated with High Risk Profile, but not Healthier Lifestyle
Authors: Mudd-Martin Gia , Chung Misook L , Frazier Susan K , Lennie Terry A , Biddle Martha J , Bailey Alison L , Casey Baretta , Novak M. J , Moser Debra K
Published: April 2024

Background:
Family history (FH) of premature cardiovascular disease (CVD) and stroke is a risk factor for personal CVD. Engagement in healthy lifestyle behaviors and preventative health screenings may lessen risk. Objective: To compare CVD risk profiles, lifestyle behaviors, and health screening practices of rural Kentucky residents with and without high-risk FH and examine the association of FH with personal CVD diagnosis.

Methods:
Data were obtained from 687 participants (77% female; age 49 ± 13 years) who completed a FH questionnaire. High-risk FH was defined as having one or more first degree relatives with a history of myocardial infarction (MI) or stroke before age 60 years. CVD risk profile was assessed using the Framingham 10-year risk score for CVD. MOS-Specific Adherence Scale items on activity and diet were used to assess lifestyle behaviors, with unhealthy behavior defined as the response “none of the time” on the 4-point Likert scale. Screening was determined by asking about frequency of blood pressure, glucose, and cholesterol checks by a health professional. Self-reported diagnosis of MI, heart failure, and stroke was used to assess personal CVD. Differences in CVD risk profile, lifestyle behaviors, and screening between those with and without high-risk FH were evaluated using independent samples t-test or Chi square tests. Logistic regression was used to assess the association of FH with personal CVD, controlling for gender, age, and diabetes.

Results:
A total of 36.8% had a high-risk FH. Those with a high-risk FH had significantly worse CVD risk profiles than those without (
p
= .001). The only significant difference in lifestyle behaviors was greater adherence to a low saturated/trans fat diet among persons with high-risk FH compared to those without (80.6% vs. 73.7%,
p
= .04); no significant differences in screening practices were found. Participants with high-risk FH had a 2.5 times greater odds of personal CVD diagnosis (95% CI 1.4 - 2.5,
p
= .002).

Conclusion:
Despite having greater personal risk and worse CVD risk profiles than those without, individuals with a high-risk FH of MI or stroke had similar lifestyle and screening behaviors. Robust preventative interventions are needed to promote effective risk-reduction for high risk individuals.
Abstract 19327: Reduced Handgrip Strength Predicts Clinical Outcomes in Patients with Advanced Heart Failure Undergoing Ventricular Assist Device Placement
Authors: Chung Christine J , Wu Christina , Ferreira Orlanda , Jones Meaghan , Kato Tomoko S , Takayama Hiroo , Naka Yoshifumi , Forman Daniel E , Mancini Donna M , Schulze Paul Christian
Published: April 2024

BACKGROUND: Heart failure (HF) is a systemic syndrome associated with derangement of skeletal muscle structure and metabolic function which contributes to diminished exercise tolerance, patient frailty and increased morbidity and mortality. The objective of this study was to evaluate handgrip strength as a marker of muscle function and frailty for prediction of clinical outcomes after ventricular assist device (VAD) implantation in patients with advanced HF.

METHODS: Handgrip strength was measured in 53 patients with advanced HF 2.6±5.2 days prior to VAD implantation and over 6 months following surgery. We analyzed dynamics in laboratory values, post-operative complications and 30-day mortality.

RESULTS: There was no difference in grip strength of the dominant versus non-dominant hands at baseline and up to 6 months after VAD implantation. Baseline handgrip strength correlated with levels of albumin (r=0.29, p=0.04). Handgrip strength progressively improved, with a statistically significant increase seen at four months and sustained at 6 months following VAD implantation (non-dominant hand: 13±28% increase at 4 months and 18±34% at 6 months, p<0.05 versus baseline). Receiver operating characteristic curve analysis determined that handgrip strength<30% of body weight distinguished patients with greater likelihood of early post-operative mortality with a sensitivity of 72% and specificity of 80% (area under curve 0.8). Patients with handgrip strength<30% of body weight had 83% survival during the first 30 days after VAD implantation compared to 100% in those with handgrip strength >30% of body weight.

CONCLUSION: Patients with advanced HF lose the difference in grip strength between the dominant and non-dominant hands seen in normal reference populations further supporting the existence of a global myopathy in advanced HF. Non-dominant handgrip strength less than 30% of body weight is associated with higher mortality in the early postoperative period following VAD implantation. These findings indicate that measures of skeletal muscle function and patient frailty may have important prognostic value in the pre-operative evaluation of patients with HF undergoing VAD placement.
Abstract 19333: Ectonucleoside Triphosphate Diphosphohydrolase-1 (ENTDP-1/CD39) Regulates the Inflammatory Response in a Murine Model of Venous Thrombosis
Authors: Kanthi Yogendra , Ray Jessica J , Dolgacheva Nataliya N , Hyman Matthew C , Fukase Keigo , Anyanwu Anuli C , Sutton Nadia R , Visovatti Scott H , Liao Hui , Baek Amy , Goonevardena Sascha N , Diaz Jose A , Wakefield Thomas W , Pinsky David J
Published: April 2024

Background:
Deep vein thrombosis (DVT) is a major health concern in the United States, carrying significant morbidity, mortality and socioeconomic cost. CD39 (ectonucleoside triphosphate diphosphohydrolase 1) is a circulating and membrane-spanning protein on the surface of endothelial and some leukocyte populations that is responsible for the phospohydrolysis of ATP to ADP and ADP to AMP. We hypothesized that CD39 plays a protective role in modulating inflammatory responses in a murine model of DVT.

Methods:
C57BL/6 (WT) and CD39-/- mice underwent inferior vena cava (IVC) ligation. IVCs were harvested at 48h and 6 days post IVC ligation. Vena cava and thrombi were characterized. Leukocytes infiltrating the vein wall were quantified per high power field (hpf) by H&E. Additionally, gene expression of macrophage markers was evaluated using qRT-PCR.

Results:
Thrombosed IVC weights were higher six days post IVC ligation in CD39-/- mice compared to IVC-ligated WT mice (35.6 mg ± 4.0 vs. 19.5 ± 2.6, n=3 per group, p<0.05, respectively). Additionally, CD39-/- mice had a trend toward increased leukocyte infiltration into the vessel wall at all timepoints with an 80% increase in total leukocytes at 48h (225 ± 26 cells/hpf, n=3 vs. 124 ± 29 cells/hpf n=4, p=0.061, respectively), driven by neutrophilic (PMN) predominance (181 ± 15 cells/hpf, n=3 vs. 103 ± 23 cells/hpf, n=4, p 0.046, respectively) followed by a later trend toward increased macrophage and lymphocyte infiltration in CD39-/- mice. Consistent with these findings, CD39 gene-deletion was associated with a >40-fold increase in mRNA expression of CCR2 (52.35 ± 0.73 vs. 1.17 ± 0.10, n=2 per group, p<0.0002, respectively), a marker of pro-inflammatory macrophages, in the vessel wall compared to WT 6 days post IVC ligation. CD39-/- mice also had 15-fold increased expression (9.62 ± 0.43 vs. 0.62 ± 0.56, n=2 per group, p=0.006, respectively) of CD301b versus WT mice 6 days post IVC ligation.

Conclusion:
CD39 appears to be a critical regulator of the early and late inflammatory responses in murine DVT with increased thrombus burden, leukocyte infiltration and inflammation-related gene expression in CD39 gene-deleted mice. CD39 may serve a previously unexplored, protective role in the pathophysiology of DVT.
Abstract 19352: Obstructive Sleep Apnea Impairs the Time Delay of the Baroreflex Control and the Oscilattory Pattern of the Sympathetic Activity in Patients with Metabolic Syndrome
Authors: Toschi-Dias Edgar , Trombetta Ivani C , Dias da Silva Valdo J , Maki-Nunes Cristiane , Cepeda Felipe X , Alves Maria Janieire N , Drager Luciano F , Lorenzi-Filho Geraldo , Negrão Carlos E , Rondon Maria Urbana P
Published: April 2024

Background:
Incidence and oscillatory pattern of muscle sympathetic nerve activity (MSNA) depends on the magnitude (sensitivity) and time delay of the arterial baroreflex. In metabolic syndrome (MetS), the obstructive sleep apnea (OSA) exacerbates the MSNA and baroreflex control of heart rate. Unknown is the impact of MetS and OSA on oscillatory pattern of MSNA and time delay of the baroreflex control of MSNA in MetS patients. We tested the hypotheses that: 1) MetS would impair these autonomic functions; 2) OSA would impair even further these autonomic functions.

Methods and Results:
Thirty-nine never-treated MetS patients (ATP III) were allocated in two groups according to the presence of OSA (MetS+OSA, n=17 and MetS-OSA, n=22). Twelve aged-paired healthy subjects were enrolled in the study as control group (C). OSA (apnea-hypopnea index>15 events/hour) was determined during a polysomnography. We recorded MSNA (microneurography), blood pressure (beat-to-beat basis) and HR (ECG), during 10 min. Oscillatory patterns of MSNA, HR and systolic arterial pressure were evaluated by autoregressive spectral analysis. The baroreflex control of MSNA (gain and time delay), were evaluated by bivariate autoregressive analysis. Patients with MetS+OSA had increased high frequency band of MSNA (HF
MSNA
, 60±3 vs. 49±2 and 37±2 n.u., P<0.001) and decreased low frequency band of MSNA (LF
MSNA
, 40±3 vs. 51±2 and 63±2 nu, P<0.001) compared to MetS-OSA and C. The gain of the baroreflex control of MSNA was lower in MetS+OSA compared MetS-OSA and C (13±1 vs. 30±3 and 43±3 a.u./mmHg, P<0.001). The time delay of the baroreflex control of MSNA was augmented in MetS+OSA compared to MetS-OSA and C (6±0.3 vs. 4±0.3 and 3±0.2 s, P<0.001). MetS-OSA patients showed increased HF
MSNA
(P<0.001) and decreased LF
MSNA
(P<0.001) compared with C. And, the gain of the baroreflex control of MSNA was lower in MetS-OSA than in C groups (P<0.001).

Conclusions:
MetS reduces the oscillatory pattern of MSNA and the gain of the baroreflex control of MSNA. OSA exacerbates these dysfunctions and further increases the time delay of the baroreflex control of MSNA in these patients. These central autonomic dysregulation of sympathetic modulation may have important clinical implications in patients with MetS+OSA.
Abstract 19358: Comparative Outcomes of Catheter-Directed Thrombolysis plus Anticoagulation versus Anti-Coagulation Alone in the Treatment of Lower Extremity Proximal Deep Vein Thrombosis
Authors: Bashir Riyaz , Zack Chad J , Gaughan John , Comerota Anthony J , Bove Alfred A
Published: April 2024

Background:
The role of catheter-directed thrombolysis (CDT) in treatment of acute proximal deep vein thrombosis (DVT) is controversial and national rates of in-hospital mortality and acute complications in these patients are unknown.

Methods:
We used the Nationwide Inpatient Sample (NIS) database from 2005 to 2009 to identify all patients admitted with a principal diagnosis of proximal or caval DVT. In these patients, we evaluated the trends in the utilization rates of CDT and in-hospital outcomes. We compared in-hospital outcomes between the matched groups treated with CDT plus anticoagulation (Group A - 10,730 patients) versus anticoagulation alone (Group B - 10,730). We used propensity scores and Elixhauser comorbidity risk index to match the two treatment groups.

Results:
Among a total of 368,974 patients admitted with lower extremity proximal or caval DVT, 3.7% (13,542) underwent CDT. The national CDT utilization rates gradually increased from 2.3% in 2005 to 5.1% in 2009. The groups that were less likely to be treated with thrombolysis included females (3.5% versus 3.9%; p <0.0001), patients greater than 65 years of age (3% versus 6.6%; p < 0.0001), and African Americans (2.9% versus 3.7%; p<0.0001). The outcomes analysis of the matched groups showed that in-hospital mortality was similar in the CDT group than in the anti-coagulation alone group (1.2% versus 0.9%; p= 0.287). In the CDT group, a decline in mortality was noted from 2.0% in 2005 to 0.6% in 2006. The rates of blood transfusion, pulmonary embolism, intracranial bleeding, and vena caval filter placement were significantly higher in the CDT group. The CDT group also had significantly increased length of stay (7±2.3 versus 4.9±1.9 days; P < 0.00001) and hospital charges ($85416 ± 67940 versus $26841 ± 43872; p<0.0001) than the anticoagulation alone group.

Conclusions:
In this observational study we found that in-hospital morbidity with catheter-directed thrombolysis remains higher than anticoagulation alone, however recently a significant improvement in in-hospital mortality has been noted.
Abstract 19380: Cardiac Contractile Protein Expression of the Right Ventricle in End Stage Human Heart Failure
Authors: Su Yan R , Chuisa Manuel , Friedman David B , Absi Tarek S , Lim Chee , Di Salvo Thomas G
Published: April 2024

Objectives:
Little is known about right ventricular (RV) remodeling in human end-stage heart failure (HF). We sought to study RV contractile protein expression in HF.

Methods:
Western Blot (WB) analyses were performed on protein samples prepared from the RV and left ventricle (LV) free walls of 10 explanted human hearts (5 ischemic, ISC; 5 non-ischemic, N-ISC) and two normal (NOR) donor hearts. Tissues were homogenized in lysis buffer, subjected to electrophoresis gel separation and immune-blotted with antibodies against Myosin Heavy Chain 7 (MHC), Myosin Light Chain 3 (MLC), Troponin I type 3 (TNI), Tropomyosin 1 alpha (TRP), alpha Actinin-2 (ACT) and Desmin (DSM). GAPDH served as an internal loading control. The fluorescent intensity of reactive bands was detected by Li-Cor and band densities were quantified using Image Studio software.

Results:
We previously identified distinct RV and LV proteomic signatures in ISC in HF and confirmed these results by WB (Figure 1). In this study focused on the RV alone, we compared contractile protein expression in NOR, ISC and N-ISC RV (Figure 2). Expression of MHC and TNI was decreased and expression of MLC, TRP and DSM increased in both ISC and N-ISC RV compared to NOR. Expression of ACT was decreased in N-ISC RV but increased in ISC RV compared to NOR.

Conclusions:
RV contractile proteins exhibit distinctive expression patterns in human ISC and N-ISC HF compared to normal expression patterns in controls. In HF, RV expression of MLC and TRP is significantly increased and RV expression of MHC is significantly decreased. ACT RV expression is decreased only N-ISC HF.
Abstract 19386: Adaptive Upregulation of MicroRNA-146b Following Surgical Ischemia-Reperfusion Attenuates Myocardial Inflammation
Authors: Friede Kevin A , Ma Qing , Phua Kyle K , Zhang Zhiquan , Smith Michael P , Leong Kam W , Ivan Mircea , Podgoreanu Mihai V
Published: April 2024

Introduction:
Using a comparative biology approach we prioritized microRNAs (miRs) deregulated by surgical myocardial I/R. We hypothesized that in vitro overexpression of miR-146b is cardioprotective following simulated I/R through attenuation of NF-kB mediated inflammation. Finally, we compared two delivery methods of miR modulators - chemical transfection versus nanoparticle-bound.

Methods:
1) miR expression analysis - microarray of myocardium from 2 models of I/R: a) rats - cardioplegic arrest (CA) or deep hypothermic circulatory arrest (DHCA) and 24h reperfusion, or sham; 2 rat strains with different susceptibilities to myocardial I/R used - Brown Norway (BN) and Dahl Salt Sensitive (DSS); b) pigs - CA or DHCA and 6h reperfusion, or sham (N=4/group). Deregulated miRs (FDR <0.1) validated by qPCR. 2) miR-146b functional analysis- ARVCs transfected with miR-146b mimics or inhibitors, subjected to 2h OGD - 6h reoxygenation; target gene expression IRAK1 and TRAF6 qPCR and Western; necrosis and apoptosis assays. 3) Nanoparticle delivery - chemical or nanoparticle-mediated ARVC transfection monitored as above plus Cy3-miR. Nanoparticle-bound Cy3-miR administered to rats in cardioplegia; biodistribution by fluorescence microscopy.

Results:
Robust post I/R miR-146b upregulation conserved across species, experimental conditions, and reperfusion timepoints (Fig, A). Different miR-146b expression between rat strains (BN vs DSS) corresponded to severity of myocardial injury. miR-146b overexpression attenuated IRAK 1, TRAF6 and NF-kB p65 upregulation following simulated I/R (Fig, B), resulting in improved cardiomyocyte viability (Fig, C). Nanoparticles show superior transfection efficiency to chemical methods in vitro, and early extravascular myocardial distribution.

Conclusion:
miR-146b may exert inhibitory feedback on NF-kB activation through effects on key regulatory elements IRAK1 and TRAF6 with potential cardioprotective roles.
Abstract 19387: Targeted Deletion of Mmp9 Mitigates Autophagy Mediated Contractile Dysfunction in Insulin2 Mutant Diabetic Mice
Authors: Mishra Paras Kumar , Chavali Vishalakshi , Metreveli Naira , Tyagi Suresh C
Published: April 2024

Insulin mediated activation of MMP9 and myocardial autophagy fosters pathological cardiac remodeling, and targeted deletion of MMP9 improves contractility. We hypothesize that ablation of MMP9 mitigates autophagy mediated contractile dysfunction in diabetes. To test the hypothesis, we created Ins2+/- /MMP9-/- mice, where MMP9 gene is deleted from diabetic Ins2+/-. We measured the levels of LC3B-II and Atg3 (autophagy markers) in C57BL/6J, Ins2+/- and Ins2+/- /MMP9-/- hearts. The results revealed induction of both LC3B-II and Atg3 in Ins2+/-, which is mitigated in Ins2+/-/MMP9-/- (fold change in C57BL/6J, Ins2+/-, Ins2+/- /MMP9-/- for LC3B-II: 1; 4.5 ±0.3, 3.0± 0.2, and Atg3: 1, 2.5±0.2, 1±0.3, respectively). The down regulation of autophagy in Ins2+/-/MMP9-/- suggests that targeted deletion of MMP9 attenuates autophagy in diabetes. To assess the specific role of autophagy in contractility, we administered Mdivi-1 (autophagy blocker) into C57BL/6J (control) and Ins2+/- mice (50mg/Kg, i.p) for 7 days and determined the improvement in contractility (±dL/dt) of cardiomyocytes by Ion-Optics device. We found no significant difference in the rate of contraction (dL/dt) and relaxation (-dL/dt) in C57BL/6J untreated (dL/dt=160±13 and -dL/dt= -165± 15) and treated (dL/dt= 170±20 and -dL/dt= -165± 21) groups. However, there was significant improvement in ±dL/dt in Ins2+/- (untreated: dL/dt=100±10 and -dL/dt= -95± 12) and treated (dL/dt= 185± 17 and -dL/dt= -180± 14). These elicit a novel regulatory role of MMP9 in autophagy in diabetes. It also suggests that inhibition of autophagy improves contractility in diabetic hearts. In conclusion, targeted deletion of MMP9 mitigates autophagy mediated contractile dysfunction in diabetes.
Abstract 19395: Increased Multiple Firing of Single Muscle Vasoconstrictor Neurons during Lower Body Positive Pressure in Human Heart Failure
Authors: Millar Philip J , Murai Hisayoshi , Morris Beverley L , Floras John S
Published: April 2024

Introduction:
Functionally specific efferent renal sympathetic nerves fire selectively in response to distinct hemodynamic afferent inputs. Using norepinephrine spillover, our group detected a heart failure (HF)-specific cardio-cardiac sympathoexcitatory reflex stimulated by high atrial pressure. Efferent discharge directed at other vascular beds similarly activated by atrial stretch might not be detected by multi-unit sympathetic recordings.

Hypothesis:
In contrast to healthy controls (CON), in HF some muscle sympathetic fibers respond paradoxically (i.e. increase firing) to increases in filling pressure.

Methods:
Single-unit muscle sympathetic nerve activity (sMSNA; microneurography) and peripheral venous pressure (PVP; forearm catheter) were recorded from 11 CON and 10 treated HF (LVEF 27±6%) patients at baseline and during non-hypotensive lower body negative pressure (LBNP; -10mmHg) and non-hypertensive lower body positive pressure (LBPP; +10mmHg). sMSNA firing frequency and incidence, and the percentage of multiple within-burst firing was calculated for each condition.

Results:
PVP was reduced with LBNP (p<0.05) and increased with LBPP (p<0.05) in both groups, with PVP greater in HF across each condition (p<0.05). Blood pressure and heart rate were unchanged by LBNP or LBPP in both groups (p>0.05). We identified 26 and 22 single-units in CON and HF patients, respectively. sMSNA firing frequency was similar (p>0.05) in CON and HF at baseline (30±18 vs. 35±15 spikes/min) and during LBNP (45±24 vs. 42±23 spikes/min) but higher in HF during LBPP (28±17 vs. 40±22 spikes/min, p=0.05). sMSNA firing incidence was similar (p>0.05) in both groups across each condition. The percentage of within-burst multiple spike firing was similar (p>0.05) in CON and HF during baseline (24±9% vs. 24±7%) and LBNP (25±11% vs. 28±14%) but higher in HF during LBPP (17±8% vs. 34±16%, p<0.001).

Conclusions:
In HF, increases in PVP with non-hypertensive LBPP cause a paradoxical increase in muscle sympathetic single-unit firing frequency and multiple within-burst firing, compared to CON. This provides evidence of a sympathoexcitatory cardiac-skeletal muscle vasoconstrictor reflex in human HF that may be attenuated by normalizing filling pressures.
Abstract 19420: Epicardial Paracoronary Chemical Ablations Using Endocardial Approach Preserve Coronary Patency
Authors: Dori Yoav , Kolandaivelu Aravindan , Beinart Roy , Halperin Henry R , Saman Nazarian , Zviman Menekhem M
Published: April 2024

Background:
Epicardial ablations are often neccesary to treat ventricular tachycardia (VT). However, this procedure carries significant risk of damage to coronary vessels. We hypothesized that paracoronary epicardial ablations can be performed safely using intra-myocardial injection of alcohol from the endocardial approach.

Methods:
5 swines underwent 3D rotational angiography guided intra-myocardial injection of 1 cc of ethanol at a depth of 5 mm into the myocardium. Lesions were placed at 1-3 locations under the LAD. The animals were survived for 3 days and then sacrificed and the myocardium stained with TTC. Hearts were excised and sectioned for lesion analysis and for histological evaluation.

Results:
Injections resulted in lesions that engulfed the coronary vessels, but by angiography and histology did not cause coronary stenosis. In 5/5 (100%) animals the lesions extended to the epicardial surface and were not transmural. Average lesion volume was 325.4 ± 73.5 mm3 and average epicardial scar area was 48.3 ± 23.9 mm2. Injections caused transient ST and blood pressure (BP) changes that return to baseline with a mean time to BP normalization of 159 ± 74 sec. Histological analysis demonstrated disruption of the paracoronary myocardium and the coronary tunica adventitia as well as partial disruption of the tunica media. There were no visible changes in the tunica intima.

Conclusions:
Paracoronary epicardial ablations can be performed safely using injection of alcohol from endocardial approach. This novel approach mitigates many of the risks of epicardial RF ablations and should be considered as an alternative to the current methods. Further studies are warranted to determine the long term efficacy of this method. Figure 1. Injection catheter was placed underneath the LAD (A) and alcohol mixed with contrast was injected. (B) Angiography shows that the arteries were patent post injection. (C) Epicardial view reveals epicardial lesions. (D) section through the LV wall
Abstract 19432: Exit Site of Ischemic Ventricular Tachycardia: Lessons from Simultaneous Multi-Electrode Mapping Era Applied to Sequential Mapping Era
Authors: Masse Stephane , Downar Eugene , Sevaptsidis Elias , Asta John , Harris Louise , Cameron Douglas , Nair Krishnakumar , Chauhan Vijay , Spears Dana , Ha Andrew , Nanthakumar Kumar
Published: April 2024

Background:
Ventricular tachycardia mapping in the sequential era is dependent on determining the exit site using entrainment mapping and or activation mapping. During entrainment mapping, VT has the potential of degenerating into ventricular fibrillation, requiring cardioversion that may distort the electroanatomic map. In addition entrainment may change the activation sequences and initiate another VT. Thus it is of importance to identify the exit site based on temporal characteristics of the activation map and characterize the exit site. In the era of point by point sequential mapping it is unclear how much time ahead of surface activation is the activation at the exit site. We sought to determine the temporal characteristics of the exit site where successful ablation was performed in relation to the surface activation.

Methods and Results:
Twelve patients with ischemic VT who had multi-electrode simultaneous endocardial mapping during ventricular tachycardia were retrospectively reviewed. 16 VTs induced in these twelve patients were analyzed and the activation sequence in systole, diastole, and the presystolic period was annotated. Activation time in relation to surface activation was characterized at the exit site where ablation was performed. Mapping was performed with a custom-made system consisting of a 112 electrode endocardial array with simultaneous uni and bipolar recording. Filter settings for uni was 0.1 - 200 Hz, bipolar 28 - 700Hz, sampling rate was 1 kHz for uni and 2 kHz for bipolar electrograms.The mean activation time at the exit site was 60 +/- 24 msec ahead of surface VT activation. The range of the timing of the activation at the exit site preceding surface activation was was 18 - 114 ms. The unipolar characteristic at the site was not useful in identifying timing on a consistent basis.

Conclusion:
The exit site of an ischemic ventricular tachycardia is on average 60 ms ahead of surface activation. This presytolic timing is earlier than what is generally believed in the current sequential mapping era of VT ablation. Our analysis suggests that catheter position at shorter activation times would indicate a location in the post exit site and unlikely to produce a useful outcome.
Abstract 19461: Endogenous Protein Kinase Inhibitor Peptide (pki) Regulates β-Adrenergic Responses of the Heart
Authors: Li Ying , Zhang Xioaying , Ai Xiajie , Szeto Christopher , Chen Xiongwen
Published: April 2024

Introduction:
Protein kinase inhibitor peptide (PKI) isoforms are endogenous inhibitors of PKA and existing in the heart. The physiological relevance of PKI has not been studied. Aims: We will determine the role of PKIα (one of the major PKI isoforms in the heart) in β-adrenergic regulation of the heart with PKIα knockout (KO) versus c57bl/6 control (CTR) mice.

Methods:
In vivo cardiac function was evaluated by conventional echocardiography (ECHO) in PKIα KO mice. In vivo cardiac β-adrenergic response was determined by intra-LV hemodynamic measurements in response to different doses of isoproterenol (10-16g/g BW∼10-5g/g BW). Isolated ventricular myocytes were used to determine cellular responses to β-adrenergic agonist, isoproterenol (ISO, 1nM, 10nM and 100nM). Western blotting was used to determine phosphorylation levels of PKA-targets in the heart.

Results:
(1) The loss of PKI did not change basal cardiac morphology, function and life span of mice; (2) ISO (2μ g/g BW) enhanced cardiac function more in KO mice than in CTR mice when evaluated by ECHO and intra-LV hemodynamic measurements; (3) The loss of PKIα sensitizes the heart in response to ISO (Log[EC50] shifted from -9.2 to -10.8) and the maximum dp/dt increases more (by 25%) in KO mice than in CTR mcie; (4) PKIa KO myocytes were more sensitive to ISO in that 10nM ISO increased myocyte contraction and Ca2+ transient amplitudes more in KO myocytes; (5). At the ISO concentration of 10-9M, ISO increased more phosphorylation of the Ser16 site (PKA site) on phospholamban.

Conclusion:
PKI plays an important role in regulating cardiac β-adrenergic responses by antagonizing PKA.
Abstract 19469: Outcomes in Extended-Criteria Caradiac Transplantation: A 10-Year Experience
Authors: Owen Ashleigh A , Samsky Marc , Patel Chetan , Hernandez Adrian F , Jentzer Jacob , Schulte Phillip , Felker G. M , Rosenberg Paul B , Milano Carmelo A , Rogers Joseph G
Published: April 2024

INTRODUCTION: Extended criteria cardiac transplant (ECCT) provides cardiac replacement therapy in patients (pts) with end-stage heart failure who are ineligible for standard criteria transplantation (SCCT). While ECCT provides lower survival, short term outcomes are adequate for pts with advanced age or comorbidities. Long term outcomes after ECCT have not been defined and determining clinical variables associated with improved survival after ECCT will improve risk stratification.

METHODS: 454 pts undergoing cardiac transplantation at Duke University Medical Center from January 2000 until December 2009 were retrospectively analyzed. Each patient was identified as either SCCT (n=370) or ECCT (n=84). Baseline clinical variables included demographics, renal function, and need for circulatory support prior to transplant. Comparisons were made between SCCT and ECCT patients pre-transplant and at years 1 and 5. Survival analysis was performed using standard Kaplan-Meier methods. A Cox proportional hazards model was developed to identify predictors of survival.

RESULTS: Significant differences (P<0.001) in clinical variables between SCCT and ECCT groups included age (53 y vs 66 y), presence of diabetes (25% vs 46%) and ischemic disease (43% vs 70%). Renal function was worse in the ECCT group when assessed by BUN (19 vs 25, p<0.001) but serum creatinine (Cr) was equivalent (1.2 vs 1.3, p=0.027). Mean follow up was 4.7 years and survival is shown in Figure 1. Only serum Cr prior to transplant had a statistically significant effect on survival regardless of the criteria used (p=0.001, HR 1.7, 95% CI 1.25, 2.30).

CONCLUSION: ECCT pts have lower survival than SCCT pts and this risk persists after adjusting for covariates. Serum Cr is an independent predictor of survival in all transplant recipients. Given the detrimental impact of transplant medications on renal function, consideration of Cr should be incorporated in to risk-stratification for patients undergoing ECCT.
Abstract 19509: Cardiomyocyte-Specific Overexpression of the E3 Ubiquitin Ligase Wwp1 Causes Altered Connexin 43 and 45 Expression Leading to Arrhythmias and Sudden Cardiac Death
Authors: Basheer Wassim , Harris Brett S , Matesic Lydia E
Published: April 2024

Rationale:
The electrical coupling between adjacent cardiomyocytes is tightly regulated by gap junctions (GJ) to ensure proper electrical conduction in the myocardium. We have recently shown that the ubiquitin ligase Wwp1 can interact with and ubiquitylate the GJ protein connexin 43 (Cx43) causing its degradation. All mice ubiquitously overexpressing Wwp1 develop left ventricular hypertrophy (LVH), a 90% decrease in Cx43 protein, and die from sudden cardiac death (SCD) around 8 weeks of age.

Hypothesis:
We hypothesize that the effects of Wwp1 overexpression are cell autonomous to cardiomyocytes and that some degree of compensation exists until 8 weeks of age in mice.

Methods:
Cardiomyocyte-specific overexpression of Wwp1 was achieved using a tamoxifen-inducible cre transgenic mouse line driven by the
α-MHC
promoter. LVH was assessed in animals overexpressing cardiac Wwp1 (n=8) relative to their wild type littermates (n=8) using echocardiography. Cx43 and Cx45 protein levels and localization within myocardial tissue was determined via Western blotting and multi-immunofluorescence staining in conjunction with laser scanning confocal microscopy. Susceptibility to arrhythmias was ascertained using ventricular burst pacing monitored by ECG.

Results:
Induction of cardiomyocyte-specific Wwp1overexpression at 4 weeks of age resulted in decreased Cx43 expression, ECG abnormalities, and inducible ventricular arrhythmias as early as 48h following induction. In contrast, protein levels of Cx45 were unaltered but showed mislocalization. Unpaced Wwp1 overexpressers (n=12) displayed progressive LVH and SCD at 8 weeks of age. Interestingly, induction of cardiac Wwp1 overexpression at 8 weeks of age or later resulted in similar Cx43 and Cx45 changes and associated ECG abnormalities. Spontaneous or induced ventricular arrhythmias were observed as early as 48h following induction with no associated LVH.

Conclusions:
Wwp1 exerts its effects on cardiac structure and function in a cell autonomous manner. There is some plasticity in the myocardium which provides protection against spontaneous arrhythmias up until 8 weeks of age in mice. This mechanistic insight highlights the potential for novel anti-arrhythmia therapeutics targeting Wwp1.