bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 1525: High Density Lipoprotein Cholesterol is Protective Against the Development of Cardiac Rhythm Disturbances in the Non-ST Segment Elevation Acute Coronary Syndrome
Authors: Kalayeh Nick , Kahn Yosef , Yarkoni Alon , Gonzalez Francisco J , Loli Akil , Cardello Frank , Halligan Robert E , Gerkin Richard , Desser Kenneth B
Published: July 2021

INTRODUCTION: Many studies have demonstrated that reduced high-density lipoproteins (HDL) levels and elevated triglyceride (TG)/HDL ratio correlate with the development of chronic ischemic heart disease. The role of HDL and the development of cardiac rhythm disturbances in the non-ST segment elevation acute coronary syndrome (ACS) is unclear.

HYPOTHESIS: We assessed the hypothesis that HDL might be protective against development of cardiac rhythm disturbances. Additionally, any protective effect was compared with TG/HDL and LDL/HDL in this setting.

METHODS: A total of 6881 patients who presented during 2000–2003 with non-ST segment elevation ACS had fasting lipid panels collected within the first 24 hours of admission. Patients were followed for the development of rhythm disturbances of up to 6 years after initial presentation, with a mean of 1269 days. These patients were further separated into diabetic and nondiabetic groups.

RESULTS: After adjustment for ischemic heart disease, congestive heart failure, stroke, peripheral vascular disease, hypertension, low density lipoprotein cholesterol, triglycerides, age, and body mass index, higher HDL levels were found to be independently protective against developing atrial fibrillation and other cardiac rhythm disturbances. TG/HDL and LDL/HDL were also protective of cardiac arrhythmias but not with the same power as low HDL (HDL > 31mg/dl, HR = 3.69, 95% CI=3.01– 4.53, P < 0.05).

CONCLUSIONS: Based on the above results, patients with lower HDL levels during hospitalizations with non-ST segment elevation ACS have a greater chance of developing cardiac rhythm disturbances independent of other risk factors. Although higher TG/HDL and LDL/HDL are also predictive, lower HDL is associated with highest OR for the development of cardiac arrhythmia among diabetic and non-diabetic patients with non-ST elevation with ACS.
Abstract 1527: Impact Of Glomerular Filtration Rate On Outcome In Consecutive Patients With Stemi In Clinical Practice: Results Of The Acos-registry
Authors: Gitt Anselm K , Wienbergen Harm , Towae Frank , Gottwik Martin G , Senges Jochen
Published: July 2021

Background: Patients with renal failure have a higher cardiovascular morbidity and mortality. Little is known about the impact of renal failure on the acute outcome of ST-elevation myocardial infarction (STEMI) in clinical practice.

Methods: Between 2000 and 2002 a total of 8303 consecutive patients with STEMI were enrolled into the multicenter ACOS-registry in Germany. We examined the impact of the glomerular filtration rate (GFR) on hospital outcome in clinical practice. GFR was calculated using the Cockroft-Gault-Formula.

Results: Patients with reduced GFR were older, more often female, more often had prior myocardial infarctions and coronary interventions, a higher prevalence of concomitant diseases and a worse TIMI-risk score. than patients with GFR >90 ml/min. Patients with impaired GFR did receive acute reperfusion therapy significantly less often. After adjustment for these differences by multivariate regression analysis, renal failure was associated with significant higher hospital mortality (GFR 30–59 ml/min: OR 2.38; GFR < 30 ml/min: OR 5.18, p<0.01).

Conclusion: In consecutive STEMI-patients severe renal failure (GFR<30 ml/min) was independently associated with a more than 5-fold increased hospital mortality in clinical practice.
Abstract 1544: Early Statin Therapy Reduces Risk Of ICD Shocks In Patients With An Implantable Cardioverter-defibrillator Undergoing Ablation For Ventricular Tachycardia
Authors: Bunch T. J , Friedman Paul A , Gersh Bernard J , Asirvatham Samuel J , Brady Peter A , Cha Yong-Mei , Jahangir Arshad , Hammill Stephen C , Monahan Kristi , Munger Thomas M , Rea Robert F , Shen Win K , Tabatabaei Niloufar , Packer Douglas L
Published: July 2021

Background
: Lipid lowering therapy reduces mortality in patients with both ischemic and nonischemic cardiomyopathies and recently has been shown to decrease ICD shocks. Radiofrequency ablation (RFA) of recurrent VT in patients with an ICD also reduces shocks following intervention. It is unclear if statin therapy after VT RFA will further impact ICD shock rates.

Methods
: All patients from 1993–2005 who underwent a RFA procedure for recurrent VT at the Mayo Clinic with an ICD were included. Patient records were extracted for medical and procedural details and all ICD interrogations were reviewed for VT recurrence and therapies.

Results:
63 patients (age 62±15 years) were followed over 3.9±3.6 years. Comorbid diseases included: coronary artery disease 37(58%, 34 prior myocardial infarction), ARVD/C 6(10%), nonischemic dilated cardiomyopathy 7(11%), moderate-severe valve disease 14(22%), hypertension 34(54%), and hyperlipidemia 35(56%). Ejection fraction was <0.35 in 34(56%). VT was induced in all patients (LV 55 (LVOT 1), RV 8 (RVOT 3) with multiple inducible VTs in 21(33%). VT was noninducible after RFA in 39(62%) patients. Dismissal medications included: statins 19(30%), beta blockers 40(66%), ACE/ARB 37(61%), diuretics 34(55%), and digoxin 23(37%). 5-year overall survival was 63%(95% CI 55–71). Age, diabetes, and renal insufficiency were associated with increased post ablation mortality, with no medication improving survival. 5-year survival free of ICD shocks was 31%(95% CI 24–38). Only statin therapy at discharge was associated with a decreased risk of ICD shocks [5(26%) versus 26(59%), p=0.020]. 7 additional patients received statins during follow-up, but not at discharge, of these 5(71%) had shocks.

Conclusion
: Statin use at discharge in patients with an ICD undergoing RFA for refractory VT significantly reduced recurrent ventricular arrhythmias and ICD shocks. Although the mechanism underlying the effects of statins on arrhythmic recurrence early after RFA requires further study, these data support aggressive therapy of the underlying substrate responsible for the VT.
Abstract 1556: Esmolol As A Cardioplegic Agent; An Effect Beyond β-blockade
Authors: Fallouh Hazem B , McLatchie Linda M , Shattock Michael J , Chambers David J , Kentish Jonathan C
Published: July 2021

Esmolol, an ultra-short-acting β-blocker, is used in the treatment of hypertension and arrhythmias. We and others have shown that millimolar doses of esmolol is cardioprotective, and acts as a cardioplegic agent in both human and animal hearts.
In vivo,
the β-blocking effect explains the cardioprotective action but the mechanism for esmolol-induced arrest in isolated hearts is unknown. This study characterises the mode of action by which esmolol causes diastolic arrest at millimolar doses. Isolated rat ventricular myocytes were superfused with buffered Tyrode solution and electrically stimulated. We measured myocyte contraction by sarcomere shortening (SS) and calcium transient (Ca

tr

) by fluorescence microscopy using fura-2 (340/380 nm ratio). Additional studies of L-type calcium currents (
I

Ca,L

) using whole-cell voltage-clamping were conducted. Esmolol (0.3 mmol/L) decreased myocyte SS by 72% from 0.16±0.01 μm to 0.04±0.01 μm (mean±SE, n=7;
P
<<
med
>
0.0001). The corresponding
Ca
tr
fell from 0.13±0.02 to 0.07±0.02 (P<0.001), a decrease of 47%. Inhibiting the SR with thapsigargan (1 μmol/L) did not alter the effect of esmolol: the SS (in an elevated bathing [Ca] of 7 mmol/L) decreased from 0.16±0.007 to 0.05±0.002 μm, a drop of 69% (n=7), and Ca
tr
fell from 0.12±0.006 to 0.06±0.003 (50% decrease). This suggested that high dose esmolol inhibits the L-type Ca channels; this was confirmed by voltage-clamp studies (Fig

). In separate studies on skinned myocytes, esmolol had no effect on myofilament sensitivity to calcium. We conclude that high doses of the β-blocker esmolol (that are already used in cardiac surgery) cause diastolic arrest by inhibiting L-type Ca channels.
Abstract 1559: Increased Length Of Hospitalization And Weight Gain In Diabetic Patients Are Associated With induction of HIF1α expression and Higher serum Levels Of Permeability-inducing Growth Factors: Vegf, And Hgf
Authors: Emani Sirisha , Ramlawi Basel , Sodha Neel , Bianchi Cesario , Sellke Frank
Published: July 2021

Background-
Inflammatory mediators such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) play a critical role in the regulation of vascular permeability, and angiogenesis. We studied the serum levels of several growth factors including VEGF, FGF, and HGF as well as gene expression profiles of genes involved in growth factor signaling in the peripheral blood of patients with diabetes mellitus (DM) and without diabetes mellitus (ND) following cardiopulmonary bypass (CPB) and cardioplegic arrest (C).

Methods-
Serum for evaluation of growth factors and total RNA for microarray analysis were obtained from the blood samples collected from DM patients (n=8) and matched ND patients (n=8) who underwent coronary artery bypass graft (CABG) or valve procedures; before (pre), 6 hours (6h), and 4 days (4d) after CPB/C. The cytokine panel consisting of growth factors such as VEGF, HGF, FGF, and EGF were quantified in DM and ND patients; pre, 6h, and 4d post-CPB/C using a multiplex cytokine quantification system. cDNA microarray analysis was performed using Affymetrix Genechip U133 plus 2.0 software to assess gene expression of 47,000 genes. Further validation of gene expression was performed by quantitative real-time PCR.

Results-
Length of hospitalization (9 vs. 6 days post-surgery; p=0.04) and weight gain (6 lbs vs. 2.4 lbs 4d post-surgery; p<0.01) were significantly greater for DM patients when compared to ND patients. VEGF, and HGF were elevated in DM and ND patients; 6h post-CBP/C. The serum levels of these cytokines were elevated significantly in DM patients when compared to ND patients; pre vs. 6h post-CPB/C. In correlation with VEGF protein expression, microarray analysis showed significantly elevated levels of HIF1α mRNA expression (> 4 fold), a critical regulator of hypoxia signaling, 4d after CPB/C exclusively in DM patients. Other transcription factors such as CREB and P300 that directly affect HIF1α expression were also significantly elevated only in DM patients (p<0.01).

Conclusion-
The unique pattern of gene and protein expression profile of growth factors and their related genes in DM vs. ND patients could be associated with increased edema and weight gain in DM patients after CPB/C.
Abstract 1571: Hibernating Myocardium has Reduced High Energy Phosphate Levels and a Preconditioning-Like Effect with Slower ATP Depletion in Response to Acute Ischemia
Authors: Hu Qingsong , Suzuk Gen , Canty John M , Fallavollita James A
Published: July 2021

Background.
Pigs with a chronic LAD stenosis develop hibernating myocardium with contractile dysfunction and reduced resting flow. We hypothesized that this reduced energy utilization preserves ATP and protects the heart from irreversible injury during acute ischemia.

Methods.
Pigs with hibernating myocardium were studied 3-months after instrumentation with a 1.5 mm proximal LAD stenosis (n=7). Hibernating myocardium was confirmed by reduced LAD wall thickening (2.4±0.2 vs.6.1±0.6 mm in remote, p<0.05) and reduced resting flow (0.95±0.15 vs. 1.66±0.29 ml/min/g in remote, p<0.05) without infarction. Subendocardial samples were rapidly excised from propofol anesthetized pigs and serial depletion of high energy phosphates quantified by HPLC (in μmol/g dry weight) during simulated total ischemia in vitro (37°C).

Results.
At Baseline, ATP and ADP were significantly reduced in the hibernating LAD region in comparison to controls (n=8, Table

), with preserved CP/ATP and ATP/ADP ratios. During simulated ischemia, hibernating myocardium displayed a markedly reduced rate of ATP depletion (ΔATP), with ATP levels at 20 min significantly higher than control (Table

). Higher ATP levels were maintained throughout 80 min of ischemia. Interestingly, identical preservation of high energy phosphates occurred in the remote normally perfused region of hearts with hibernating myocardium (Table

).

Conclusion.
These data indicate that there is a balanced reduction in high energy phosphate levels in hibernating myocardium with chronic protection from ischemia manifested by a slower rate of ATP depletion during acute ischemia. This preconditioning-like effect is global suggesting that it arises from stimuli that are not directly related to ischemia. This raises the possibility that stretch from cyclical elevations in LV filling pressure or a circulating factor released from the heart in response to ischemia can protect the heart in chronic coronary artery disease.
Abstract 1616: Intermediate Dose of Pentaglobin Eradicates Effectively Inflammation in Parvo B19 and Adenovirus Positive Myocarditis
Authors: Maisch Bernhard , Haake Hendrik , Schlotmann Nadine , Pankuweit Sabine
Published: July 2021

152 consecutive patients with myocarditis according to the quantitative World Heart Federation Criteria (> 14 infiltrating cells/mm
2
by endomyocardial biopsy(EMB)) were analysed for cardiotropic agents. In 90 pts parvoviruses B19 (59,5%) and in 36 pts adenoviruses (23,8%) were assessd by PCR as causative viral pathogens. All virus positive patients were treated with 10 g/day Pentaglobin® i. v.(enriched IgG, IgA and IgM preparation, Biotest) at day 1 and 3. After six months all patients were reevalutated clinically, 73 patients (48%) in addition by EMB.

Methods: We compared the following parameters before and after therapy: left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), shortening fraction (SF) by transthoracic echocardiography and LVEF or the left ventricular end-diastolic volume index (LVEDVI) using angiography. For exercise capacity we evaluated exercise ECG by treadmill test and clinical parameters according to the NYHA classification, before and after therapy.

Results: After Pentaglobin therapy, all patients demonstrated a significant clinical improvement of the NYHA class, of exercise capacity and of LVEF (from 54,4 to 60,0%, p<0,005) independent from the respective virus. In 52 of 73 (71%) rebiopsied pts inflammation had resolved. In 17 of the 19 rebiopsied patients (90%) with a positive PCR for ADV before therapy no more virus DNA was recovered after treatment, inflammation had resolved completely. In Parvo B 19 myocarditis inflammation had resolved in 31 of the 44 pts (70%), whereas Parvo B19 DNA was eradicated in only in 18 out of 44 pts(40%). In patients in whom both virus and inflammation were eliminated enddiastolic LV dimension decreased and EF increased significantly (p<0,001).

Conclusion: Treatment with an intermediate dose of Pentaglobin is highly effective in resolving myocardial inflammation independent of the underlying viral etiology, but it eradicates adenoviral much better than Parvo B19 infection.
Abstract 270: Insulin-Like Growth Factor-1 Promotes Vascular Smooth Muscle Survival By 26S Proteasome-Mediated Degradation of Wilms’ Tumor 1-Associating Protein
Authors: Small Theodore W , Pickering J. Geoffrey
Published: July 2021

Apoptosis of vascular smooth muscle cells (SMC) is a culprit event in atherosclerotic plaque destabilization. We recently discovered that Wilms’ tumor 1-associating protein (WTAP) is a dynamically expressed transcriptional regulator that can be pro-apoptotic for human SMCs (Circ Res, 2006). To identify upstream regulators of this nuclear protein, we screened growth factors for their capacity to impact WTAP expression and found that insulin-like growth factor-1 (IGF-1), a potent survival factor for SMCs, stimulated a striking decline in WTAP protein abundance, to 10% at 12 h. We further determined that this decline in WTAP was due specifically to WTAP protein degradation, established by pulse-chase analysis of
35
S-labeled WTAP and the absence of an acute effect of IGF-1 on WTAP mRNA abundance. IGF-1-mediated WTAP degradation was blocked by two mechanistically distinct IGF-1 receptor inhibitors (picropodophyllin and PQ401) and by inhibition of phosphatidylinositol 3 (PI3)-kinase but not by MEK inhibition. In addition, IGF-1 induced the association of WTAP with ubiquitin, established by coimmunoprecipitation, and the downregulation of WTAP by IGF-1 was abrogated by inhibiting 26S proteasome activity with lactacystin or MG132. Interestingly, IGF-1 also stimulated phosphorylation of WTAP, that preceded the association of WTAP with ubiquitin, and hyperphosphorylation of WTAP through phosphatase-inhibition further accelerated WTAP degradation. Finally, to determine if WTAP downregulation was necessary for IGF-1-mediated SMC survival, surface expression of phosphatidylserine was quantified by flow cytometry of SMCs infected with retrovirus containing WTAP cDNA. Whereas IGF-1 enhanced the survival of vector-infected SMCs this was completely abrogated in WTAP-overexpressing SMCs.

Conclusions:
IGF-1-mediated SMC survival is dependent on the rapid depletion of WTAP from the nucleus, a degradation cascade that is heralded by WTAP phosphorylation. This WTAP phosphorylation and clearance response represents a novel consequence of PI3-kinase activation and highlights WTAP as a key negative regulator of SMC survival during vascular remodeling.
Abstract 1630: Uric Acid Revisited: Interrelationships with Low-Grade Inflammation, Adiponectin and Arterial Stiffness in Essential Hypertension
Authors: Tsioufis Costas , Dimitriadis Kyriakos , Chatzis Dimitris , Tsiachris Dimitris , Vasiliadou Karmen , Tousoulis Dimitris , Stefanadis Christodoulos , Kallikazaros Ioannis
Published: July 2021

Introduction:
Increased uric acid (UA) levels are associated with high cardiovascular risk, while subclinical inflammation, arterial stiffening and hypoadiponectinemia contribute to atherosclerosis progression.

Hypothesis:
Serum UA levels may be related to high-sensitivity C-reactive protein (hs-CRP), adiponectin and arterial stiffness in essential hypertensives.

Methods:
In our population of 292 newly diagnosed untreated non-diabetic patients with stage I to II essential hypertension [190 men, aged 50 years, office blood pressure (BP)=148/95 mmHg], the distribution of UA was split by the median (5.3 mg/dl) and accordingly subjects were classified into those with high and low values. In all participants, arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV), by means of a computerized method (Complior SP).

Results:
Patients with high UA (n=143) compared to those with low UA (n=149) exhibited higher 24-h systolic BP (139±12 vs 132±11 mmHg, p<0.0001), while did not differ regarding age, body mass index and lipid profile (p=NS). Those with high UA compared to those with low UA had increased levels of hs-CRP (3.1±1.4 vs 2.3±1.2 mg/l, p<0.05) and PWV (8.7±1.2 vs 7.9±1.2 m/sec, p<0.05), whereas exhibited lower adiponectin (8.1±2.4 vs 9.7±2.8 μg/ml, p<0.05). In the entire population, UA was positively associated with 24-h systolic BP (r=0.297, p<0.0001), hs-CRP (r=0.204, p<0.001) and PWV (r=0.165, p=0.009), while it was negatively related to adiponectin (r=−0.218, p<0.0001). In multiple regression analysis, 24-h systolic BP (b=0.246, p<0.001), hs-CRP (b=0.142, p<0.05) and adiponectin (b=−0.154, p≥0.05) were independent predictors of UA. Analysis of covariance revealed that hs-CRP, PWV and adiponectin values were significantly different between groups after adjustment for confounders (p<0.05).

Conclusions:
Increased UA levels in essential hypertension are paralleled by a state of pronounced inflammatory activation, hypoadiponectinemia and accelerated arterial stiffening. These findings suggest that UA is interrelated with diverse mediators of vascular dysfunction, underscoring its pluripotent nature in the progression of the hypertensive atherosclerotic disease.
Abstract 1726: Genome-Wide Cell-Specific Gene Expression Analysis Identifies the Involvement of the Adipocytokine Signalling Pathway in Atherosclerotic Plaque Rupture
Authors: Lee Kelvin , Polvikoski Tuomo , Birchall Daniel , Santibanez-Koref Mauro , Mendelow Alexander D , Keavney Bernard D
Published: July 2021

The molecular mechanisms leading to plaque rupture are poorly understood. Genome-wide gene expression studies may reveal novel causal molecular pathways.

METHODS: Snap-frozen human atherosclerotic plaques removed at carotid endarterectomy were designated as stable or ruptured using stringent clinical, radiological and histopathological criteria. Accurate gene expression profiling of macrophages in 5 ruptured and 6 stable plaques was conducted by employing Laser Micro-Dissection to specifically isolate this cell type from the plaques. High quality RNA was amplified and hybridised to the genome-wide Affymetrix U133plus2 microarray.

RESULTS: Exploratory clustering by Principal Components Analysis showed the data to cluster into 2 distinct groups- stable and ruptured. We identified 889 statistically significant differentially expressed genes between the two groups (Fig.1

). Genes involved in lipid processing, signalling, apoptosis, immune response and extracellular matrix were found to play a role in plaque rupture. Pathway analysis identified the Adipocytokine Signalling Pathway to be the most significantly represented cell signalling pathway (p<0.0006). The microarray findings were technically validated by real-time qPCR (Pearson Correlation R=0.94) and biologically cross-validated on a larger number of samples successfully (n=25). Immunocytochemical staining confirmed the differential Leptin expression in macrophages of ruptured and stable plaques.

CONCLUSION: The involvement of Leptin and the Adipocytokine Signalling Pathway in macrophages in plaque rupture has been implicated here for the first time and may be a potential therapeutic target.

Figure 1.

Heatmap of 889 statistically significant differentially expressed genes (red for high expression, green for low expression) with the top 20 most highly expressed genes in ruptured and stable groups listed.
Abstract 1729: Objectively Measured, but Not Self-Reported, Medication Adherence Independently Predicts Event-Free Survival in Patients with Heart Failure
Authors: Wu Jia-Rong , Moser Debra K , Chung Misook , Lennie Terry A
Published: July 2021

Background: Medication nonadherence is presumed to be related to poor clinical outcomes including emergency department (ED) visits, rehospitalization and mortality, yet this relationship has not been tested using objective adherence measures in patients with heart failure (HF). Therefore, it is unknown which objective indicators of medication adherence predict clinical outcomes and how self-reported adherence measures compare to objective measures in predicting clinical outcomes. Objective: The purpose of this study was to determine which indicators of medication adherence are predictors of event-free survival in patients with HF.

Methods: A total of 134 patients with HF (70% male, 61 ±12, 61% NYHA III/IV) were enrolled in this 6-month longitudinal predictive study. Medication adherence was measured using an objective measure, the Medication Event Monitoring System (MEMS) and self-reported adherence from the Medical Outcomes Studies Specific Adherence Scale. Four indicators of adherence were assessed by the MEMS:

dose-count, percentage of prescribed doses taken;

dose-days, percentage of days the correct number of doses taken;

dose-time, percentage of doses taken on schedule; and

therapeutic coverage, percentage of time therapeutic drug action maintained.

Events (ED visits, rehospitalization, and mortality) were obtained by patient/family interview and hospital databases.

Results: In Cox regression, three of the four MEMS indicators, dose-count, dose-day, and therapeutic coverage, predicted time to first event before and after controlling age, gender, ejection fraction, NYHA, angiotensin-converting enzyme inhibitor use, and beta-blocker use (
p
= .004, .008, and < .001, respectively). Self-report medication adherence did not predict outcomes (
p
= .402).

Conclusions: The percentage of prescribed doses taken, percentage of days the correct number of doses taken, and overall therapeutic coverage predicted event-free survival. Neither the percentage of doses taken on schedule nor self-reported adherence predicted outcomes. Healthcare providers should assess specific behaviors related to medication taking rather than a global patient self-assessment of patient adherence.
Abstract 1731: Social Support, Personal Control, and Psychological Functioning Among Individuals with Heart Failure
Authors: Taylor Melissa V , Bohachick Patricia , Sereika Susan M , Schlenk Elizabeth A , Brown Charlotte , Burke Lora E
Published: July 2021

Heart failure places a large psychosocial burden on patients and their families. Although psychological functioning generally improves for most cardiac patients, impairment persists for a significant minority, posing a serious impediment to well-being. It has been proposed that personal resources, such as social support and coping style, facilitate adaptation to such threatening events as chronic illness, and thus impact psychological outcomes.

Purpose: The primary aim of this study was to develop and test two mediating models, drawn on an integrative stress coping framework. The models considered the complex relationships between
social support
and
personal control
and two key psychological outcomes,
depressive symptoms
and
anxiety,
in individuals coping with heart failure. Social support was hypothesized to have a direct effect on depressive symptoms (Model 1) and anxiety (Model 2),
and
an indirect effect, mediated by personal control, on these psychological outcomes.

Methods: We conducted a secondary analysis of data collected from a cross-sectional survey of patients (N = 242) between 21 and 82 years of age being treated primarily for idiopathic (55.8%) or ischemic (39.7%) cardiomyopathy. Structural equation modeling was used to test the hypotheses.

Results: Both models demonstrated good data model fit, with 52% of the variance explained for Model 1 and 38% of the variance explained for Model 2. Statistically significant estimates indicated that social support plays a key role in reducing depressive symptoms and anxiety. Notably, for each model, the mechanism whereby social support reduces psychological distress is entirely through the indirect effect, i.e., through patients’ perceived control.

Conclusions: The results provide support for existing theories that emphasize important roles of social support and personal control in improving psychological functioning among the chronically ill. This study raises the possibility that strategies designed to improve social support can be useful in reducing heart failure patients’ depressive symptomatology and anxiety. Such strategies would operate primarily through improving one’s sense of personal control. #
Abstract 1740: Risk of Proarrhythmia Following Alcohol Septal Ablation in Patients with Hypertrophic Obstructive Cardiomyopathy
Authors: Das Saumya , Palacios Igor , Vlahakes Gus J , Picard Michael H , Sanborn Danita Y , Lowry Patricia A , Ruskin Jeremy N , Fifer Michael A , Mela Theofanie
Published: July 2021

Background: Alcohol septal ablation (ASA) is a promising treatment option for patients with hypertrophic obstructive cardiomyopathy (HOCM), but the creation of myocardial infarct during the procedure has raised concern about the proarrhythmic risk of ASA. We analyzed the incidence of clinically significant ventricular tachycardia (VT) and sudden cardiac death (SCD) following ASA at our center.

Methods: A total of 97 ASAs in 88 patients were performed between 1998 and 2007 at MGH. 34 of these patients had an implantable cardiac defibrillator (ICD) or pacemaker (PPM) implanted prior to or immediately following ASA. 8 of 34 patients had prior ICD implants for either secondary (n=4) or primary (n=4) prevention for SCD. 8 patients had prior PPMs. 3 patients had implantation of ICD post-ASA and 15 patients had PPM implanted following ASA due to atrioventricular block (AVB). Clinical records as well as device data were analyzed to determine incidence of VT or SCD following ASA.

Results: There were no deaths attributable to SCD in our cohort of 88 patients (mean follow-up 35 +/− 21 months, range 4 to 70 months). 1 patient with a previous ICD for primary prevention had VT storm 6 days following ASA. 1 patient who had a cardiac arrest 11 days following the ASA (thought to be a bradycardic arrest, since he had intermittent high grade AVB post-ASA) received an ICD. Neither of these patients had subsequent detections or therapies for VT. 1 patient was upgraded to an ICD following ASA due to NSVT, and 2 patients had ICD implants for NSVT or high risk of SCD. The former had subsequent detection of NSVT 24 months after implant, and therapy for VT 3 years later. 2 patients had upgrades of their PPM to an ICD > 12 months after ASA (for positive electrophysiology studies at other centers), but had no detection or therapies during the follow-up period. No other patients had therapies for tachyrrhythmias.

Conclusion: In our experience of 97 procedures, we observed 1 episode of VT storm in the first week following ASA, 1 cardiac arrest, likely bradycardic, in the first 2 weeks after ASA, and only 1 patient with clinically significant VT years after ASA. Our data suggest that close follow-up is warranted in the 2 weeks after ASA, but that ASA does not seem to have a long-term proarrhythmic effect in patients with HOCM.
Abstract 1752: Age-Related Differences in Left Ventricular Structure and Function: The Multi-Ethnic Study of Atherosclerosis
Authors: Cheng Susan , Fernandes Veronica R , Bluemke David A , Lima Joao A
Published: July 2021

Background:
Age-related alterations in LV structure and function that may predispose to myocardial dysfunction are not completely understood. We examined the association between older age and indices of LV remodeling in asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis.

Methods:
We used cardiac MRI to measure LV indices in 5004 participants free of CV disease (ages 45–84) and representing 4 racial/ethnic groups (non-Hispanic white, black, Hispanic, and Chinese); 1099 participants received additional strain analyses. We used linear regression to assess the association between age and LV indices while adjusting for multiple variables, including traditional CV risk factors.

Results:
Absolute LV mass decreased with age, but this effect was attenuated when mass was indexed to body size (

Table

). However, age was associated with markedly increased mass-to-volume (M/V) ratio (50 mg/mL per decade, p<0.001); this was driven by a substantial reduction in LV end-diastolic volume with older age, a trend that remained significant after indexing volume to body size and adjusting for CV risk factors. Older age was also independently associated with increased ejection fraction but decreased stroke volume and, importantly, with reduced peak systolic strain and strain rate as well as decreased diastolic strain rate.

Conclusion:
Older age is associated with increased M/V ratio, driven not by increased LV mass but by decreased LV volumes. This age-related remodeling is independently associated with asymptomatic systolic and diastolic myocardial dysfunction and progressively reduced stroke volume in the face of maintained chamber systolic performance indexed by ejection fraction. These data indicate that aging itself confers alterations in LV structure and function that predispose to reduced cardiac output and limited circulatory reserve in the presence of preserved ejection fraction.

Relation Between Age and Alterations in LV Structure and Function
Abstract 1753: Transcriptomic based Biomarkers Contain Diagnostic and Prognostic Information about Patients with new onset Heart Failure
Authors: Heidecker Bettina , Baughman Kenneth L , Kasper Edward K , Wittstein Ilan S , Breton Elayne , Hare Joshua M
Published: July 2021

INTRODUCTION: One of the clinical dilemmas in cardiology is to accurately diagnose the etiology of patients with new onset heart failure such as to differentiate between potentially reversible myocarditis from idiopathic dilated cardiomyopathy (IDCM). Furthermore, it is difficult to predict the clinical trajectory of patients with IDCM. We hypothesized that the transcriptomic signatures generated from endomyocardial biopsies, obtained from patients at first presentation of heart failure, could serve as novel biomarkers to distinguish between myocarditis and IDCM as well as to predict the prognosis of patients classified as having IDCM.

METHODS AND RESULTS: Endomyocardial biopsy samples were collected from 68 patients with new onset heart failure due to IDCM (n=49) and myocarditis (n=19). The average follow-up was 5 years and included information on mortality, need for left ventricular assist device (LVAD), or heart transplant. We used the U133 Plus 2.0 microarray (Affymetrix) and data analysis was performed with Significance Analysis of Microarrays (SAM) and Prediction Analysis of Microarrays (PAM). First, we identified a molecular signature of 39 genes in our training cohort (n=25 IDCM and n=8 myocarditis). When tested in independent patients (myocarditis: n=11; IDCM: n=11), this signature performed with 97% accuracy. Next, we identified a transcriptomic signature of 45 genes in a group of patients with IDCM that delineated between patients classified as having a good prognosis (event free survival > 5 years; n=18) vs a bad prognosis (death or requirement for insertion of LVAD or tx within 2 years of presentation; n=12). We tested this biomarker in independent samples and were able to predict prognosis with 87% accuracy. The transcriptomic biomarker was substantially more accurate in assigning prognosis than the Seattle Heart Failure Score (p=0.011).

CONCLUSION: Together these findings illustrate the potential utility of using transcriptomic biomarkers generated from a single endomyocardial biopsy to improve the accuracy of diagnosis and prognosis in patients with new onset heart failure. This creates novel modalities to enhance management and identification of patients at highest risk for complications of heart failure in the short term.
Abstract 1794: Evaluation of Usefulness and Efficacy of a “Segmental Perfusion Abnormality Index”: A Novel Diagnostic Approach with Conventional Enhanced Computed Tomography for the Differentiation of Acute Coronary Syndrome in Patients with Acute Onset of Chest or Back Pain
Authors: Okamoto Nami , Morino Yoshihiro , Takeuchi Hiroki , Matsukage Takashi , Toda Eri , Iino Misako , Aizawa Toru , Tanabe Teruhisa , Ikari Yuji
Published: July 2021

Background:
Immediate and accurate differential diagnosis is critically important for the patients who present acute onset of chest and/or back pain. We have noticed that regions of decreased contrast enhancement existed within the myocardial wall of the patients with acute coronary syndrome (ACS) on conventional computed tomography (CT) images, performed to differentiate other acute thoracic diseases (e.g. aortic dissection, pulmonary embolism). This study was designed to utilize these features for the differential diagnosis of ACS.

Methods:
The study population consisted of 95 consecutive patients who required enhanced CT for the differential diagnosis of acute chest discomfort at the emergency room. Using the representative apical four-chamber view, the left ventricular (LV) wall was divided into the following 6 segments: 1) basal septum, 2) mid septum, 3) apex, 4) mid lateral, 5) basal lateral and 6) basal posterior. A CT number was measured at each segment, and was then fitted into either of the following formula to calculate a segmental perfusion abnormality (SPA) index based on the existence of visually-apparent low density segments (VALDS): 1) In case of VALDS presence: average CT numbers of VALDS/average CT number of the rest normal segments × 100 (%), 2) in case of VALDS absence: the minimum CT number/average CT number of the rest 5 segments × 100 (%). The SPA index was compared between the two groups, one with ACS and another without ACS, both confirmed by coronary angiography.

Results:
Forty-five patients (47.4%) were eventually diagnosed as ACS by coronary angiography. Importantly, the SPA index was significantly smaller in the ACS group compared to the non ACS group (48.7±17.2% vs 85.5 ± 7.1%, p<0.0001). The standard receiver operating characteristic curve indicated that an optimal threshold of the SPA index is estimated to be 65%, with an achievement of high diagnostic accuracy (sensitivity: 86.7%, specificity: 98.0%, positive predictive value: 97.5%, and negative predictive value: 89.0%).

Conclusions:
The SPA index, a novel CT-based diagnostic approach for the non-invasive visualization of the ischemic LV wall, is confirmed to be easy and accurate method to differentiate ACS among the various patients who present acute chest or back pain.
Abstract 1841: Left Atrial Volume From 3-dimensional CT Correlates With Atrial Fibrillation Recurrence Following Ablation
Authors: Helms Adam , Mangrum J. M , Mounsey J. P , DiMarco John P , Mahapatra Srijoy , Lake Douglas E , Moorman Randall , Ferguson John D
Published: July 2021

Objective:
Recurrence of atrial fibrillation (AF) following ablation is common, and further delineation of prognostic markers is needed. We investigated whether LA volume, which can be accurately obtained from 3-dimensional CT, correlates with AF recurrence.

Methods:
73 consecutive patients (52 paroxysmal, 21 persistent) undergoing AF ablation were studied. Follow-up was for a minimum of 9 months, and success was determined by 12-lead EKG and lack of symptoms (unless symptoms proven not AF by Holter). LA volume was calculated by summation of axial CT slices. The left atrial appendage was measured separately.

Results:
Overall procedure success was 66% including 11 (15%) who had repeat ablations and 9 (12%) who were on antiarrhythmics. Pulmonary vein isolation was performed in all, with additional linear ablation in 44 (60%). The mean (95% CI) LA volume for those with recurrent AF was 119 cc (104, 135) versus 98 cc (90, 106) for no recurrence (p=0.01, rank sum). Wide variation in LA volume was noted in both groups (see box plot). For those patients with a volume >135cc (n=11), 9 (82%) had recurrent AF. No correlation existed between recurrence and type of AF or ablation strategy. Patients who had received a linear ablation had a larger mean LA volume than those who had not (111 cc vs. 97 cc, p=0.03, rank sum). LA appendage volume was not associated with recurrence.

Conclusion:
LA volume variation is large in both those with and without successful AF ablations. Mean LA volume is significantly larger in those with recurrent AF. Patients with LA volumes >135 cc are very likely to experience recurrent AF. More aggressive ablation strategies may be required in patients with large LA volumes.
Abstract 1861: Myocardial Assistance by Grafting a New Bioartificial Upgraded Myocardium (MAGNUM Clinical Trial): One Year Outcome
Authors: Chachques Juan , Trainini Jorge , Cortes-Morichetti Miguel , Schussler Olivier , Carpentier Alain
Published: July 2021

Objectives
Cell transplantation for myocardial regeneration is limited by poor graft viability and low cell retention. In addition, in ischemic cardiomyopathy the extracellular matrix is deeply altered. Therefore it could be important to associate a procedure aiming at regenerating myocardial cells and restoring the extracellular matrix function. We evaluated intrainfarct stem cell therapy associated with a cell-seeded collagen scaffold grafted onto infarcted ventricles.

Methods
In 15 patients (aged 54.2±3.8 years) presenting LV postischemic myocardial scars (age of the infarcts 8.2±3.5 months) and with indication for a single OP-CABG, bone marrow was collected by aspiration from the iliac crest. The cell suspension was loaded on Ficoll-Paque density gradient and 300 ± 28 million mononuclear bone marrow cells (BMC) were implanted during surgery in the scar. A type I collagen matrix seeded with the same number of BMC (300 ± 28 million cells) was added on top of the scarred area and fixed onto the epicardium by 6 single PDS sutures and covered by a second non-cellularized matrix.

Results
There was no mortality and any related adverse events (follow-up 15±4.2 months), no malignant cardiac arrhythmias were reported, no patient was lost to follow-up. NYHA FC improved from 2.3±0.5 to 1.4±0.3 (p=0.005). LV end-diastolic volume evolved from 142±24 to 117±21mL (p=0.03), LV filling deceleration time improved from 162±7ms to 196±8ms (p=0.01). Scar area thickness progress from 6±1.4 to 9±1.5mm (p=0.005). EF improved from 25±7 to 33±5% (p=0.04).

Conclusions
Simultaneous intramyocardial injection of BMC and fixation of a cell seeded matrix onto the epicardium is feasible and safe. The cell seeded collagen matrix seems to increase the thickness of the infarct scar with viable tissues and help to normalize cardiac wall stress in injured regions, thus limiting ventricular remodelling and improving diastolic function. Functional improvements can not be conclusively related to the cells and matrix due to the association of CABG. Cardiac tissue engineering seems to be a promising way for the creation of “bioartificial myocardium”. Efficacy and safety of this approach should be evaluated in a large randomized controlled trial.
Abstract 1908: Assessment of Coronary Segment Inflammation With Combined 18-Fluorodeoxyglucose Positron Emission Tomography and 64-slice Multidetector Computed Tomography.
Authors: Rogers Ian S , Figueroa Amparo L , Nasir Khurram , Vermylen David , Cury Ricardo C , Hoffmann Udo , Fischman Alan J , Brady Thomas J , Tawakol Ahmed
Published: July 2021

Background
: It has been well demonstrated that inflammation is strongly associated with ruptured plaques. Invasive angiographic studies have shown that vulnerable plaques tend to be clustered proximally in the coronary arteries. We tested the hypotheses that patients with ACS have a higher overall level of inflammation in their proximal coronary vessels compared to patients with stable coronary disease and that a gradient of inflammatory activity is seen within the coronary vasculature.

Methods
: Twenty-five patients (mean age 57.9 ± 9.8 years, 72% male) who underwent coronary angiography for chest pain were studied. Ten patients underwent PCI for ACS, 5 underwent PCI for chronic stable angina; and 10 with previously placed stents underwent diagnostic cath but did not require additional PCI. 64-slice MDCT angiography was performed (Siemens Sensation) followed by PET imaging (Siemens ECAT HR+) with 13mCi 18-FDG. PET imaging was done 3 hours after FDG injection. Myocardial uptake of FDG was minimized by a dietary intervention and beta blockade. Images were coregistered, SUVs were obtained at the locations of interest, and target to background ratios (T/B) were calculated.

Results
: Inflammation, measured as FDG activity (T/B), in the proximal coronary segments was significantly greater in patients presenting with ACS than with stable coronary disease (2.31 ± 0.62 vs. 1.84 ± 0.53, p = 0.0004). Similarly, aortic root inflammation was significantly greater in ACS patients presenting with ACS than in patients not presenting with ACS (3.61 ± 1.27 vs 2.52 ± 0.68, p = 0.028). A strong correlation was also observed between aortic root and proximal coronary inflammation in all patients (r = 0.76). Finally, a gradient of glycolytic activity (likely due to inflammation) was observed, as the left main T/B were significantly greater than the proximal vessels (2.38 ± 0.59 vs 1.77 ± 0.40, p < 0.001) in all patients.

Conclusion:
This preliminary investigation demonstrates that metabolic activity - a surrogate for inflammation - is higher in patients with ACS and that a gradient of inflammatory activity is seen within the coronary vasculature. With further advances in methodology and technology, coronary PET imaging may prove useful for assessment of risk and response to therapy.
Abstract 303: Arteriogenesis Requires Leukocytic Co-Signaling of TLR2 and TLR4
Authors: Hoefer Imo , Schoneveld Arjan , Grundmann Sebastian , van Keulen Karlijn , Bot Pieter , Timmers Leo , Pasterkamp Gerard , de Kleijn Dominique
Published: July 2021

Background:
Collateral artery growth (arteriogenesis) is promoted by the accumulation of leukocytes in the perivascular tissue. Ligand binding to Toll-Like Receptors (TLR), a family of 13 receptors which forms an important part of the innate immune system, leads to activation of inflammatory cells such as leukocytes. We therefore hypothesized that TLRs, in particular TLR expression on leukocytes, plays a prominent role in adaptive arteriogenesis.

Methods
: Localization of TLR expression in growing collateral arteries was assessed by immunohistochemistry. The role of TLR signaling during arteriogenesis was assessed in TLR2−/− mice on a C57BL/6J background, TLR4−/− mice on a BALB/c background and their respective controls after femoral artery occlusion. Furthermore, 6 weeks old mice underwent lethal irradiation and subsequent bone marrow (bm) transplantation before undergoing femoral artery occlusion 6 weeks later. Wild-type mice (WT) received either WT bm or TLR −/− bm, whereas TLR −/− mice received WT bm. On day 7, microsphere perfusion measurements were performed to assess collateral function.

Results
: Immunohistochemistry revealed that TLRs are mainly expressed by infiltrating leukocytes during arteriogenesis. In TLR2 and TLR4 deficient mice, collateral perfusion was significantly reduced compared to controls (perfusion occluded vs. unoccluded hind limb: TLR 2 −/−: 37.7 ± 1.8 %; C57BL6J: 54.9 ± 6.0%; TLR 4−/−: 15.8 ± 5.1%; Balb-C: 25.1± 5.1 %; p<0.01) After transplantation of WT bm into WT mice, collateral function was decreased to a minor, non significant degree compared to WT mice (C57BL/6J into C57BL/6J: 49.7 ± 2.6%; BALB/c bm into BALB/c: 23.1 ± 1.0%. After transplantation of TLR −/− bm into WT mice, arteriogenesis was significantly reduced (TLR2 −/− bm into C57BL/6J: 38.2 ± 3.5%; TLR4 −/− bm into BALB/c: 16.7 ± 1.5%), whereas WT bm transplantation into TLR −/− mice normalized the arteriogenic response (C57BL/6J bm into TLR2 −/−: 46.5 ± 5.5%; BALB/C bm into TLR4 −/−: 22.6 ± 3.3%).

Conclusion
: Arteriogenesis is impaired under conditions of TLR2 or TLR4 deficiency. Among the many different cell types that are able to express Toll-Like receptors, TLR signaling of circulating leukocytes seems to be of major importance for adaptive arteriogenesis.
Abstract 1956: Age-associated Changes In Left Ventricular Contractility And Ventricular-vascular Stiffness In Apolipoprotein E-deficient Mice
Authors: Van den Bergh An , Holvoet Paul , Herijgers Paul
Published: July 2021

Objectives
. To assess left ventricular contractile function and characteristics in the apolipoprotein E-deficient mouse model of severe atherosclerosis.

Methods
. We studied cardiac performance in 24- and 60-weeks-old ApoE−/− mice and age-matched wild type (WT) mice, using a miniature pressure-volume (PV) conductance catheter. Load-independent contractility was assessed using preload recruitable stroke work (PRSW) and preload-corrected dP/dt
max
(dP/dt
max
/V
ed
).

Results
(Table

). The two genotypes exhibited comparable contractile parameters at 24 weeks. Contracility (PRSW and dP/dt
max
/V
ed
) of WT mice at 60 weeks was lower than at 24 weeks, as was arterial (E
a
) and left ventricular end-systolic (E
es
) elastance. In 60-week-old ApoE−/− mice, E
a
and E
es
were less reduced than in WT. End-diastolic left ventricular stiffness (EDPVR) increased with age in ApoE−/− mice. This was accompanied by a higher heart to body weight ratio and a reduced end-diastolic volume (V
ed
) indicating the presence of concentric hypertrophy in these mice. Load-independent contractility parameters decreased less in ApoE−/− than in WT, which can be explained by the left ventricular hypertrophy.

Conclusions.
Our findings indicate that contractility is impaired at old age. In old ApoE−/− mice, exhibiting extensive atherosclerosis, ventricular-vascular stiffness is higher than in WT, end-diastolic left ventricular stiffness is increased, and concentric left ventricular hypertrophy develops.