bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14021: Angiographic and Hemodynamic Features of Symptomatic Vertebrobasilar Disease: Baseline Data from the VERiTAS Study
Authors: Amin-Hanjani Sepideh , Du Xinjian , Rose-Finnell Linda , Pandey Dilip , Richardson DeJuran , Xie Hui , Thulborn Keith R , Elkind Mitchell S , Zipfel Gregory J , Liebeskind David S , Silver Frank L , Kramer Jeffrey , Kasner Scott E , Caplan Louis R , Derdeyn Colin P , Gorelick Philip B , Charbel Fady T ,   VERiTAS Study Group
Published: July 2021

Introduction:
Atherosclerotic vertebrobasilar disease (VBD) is a significant etiology of posterior circulation stroke. In addition to thromboembolism, regional hypoperfusion is considered an important potential contributor to stroke risk. To examine the role of hemodynamic compromise in VBD, a prospective observational multi-center study, Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS), has recently been conducted. Here we report baseline features and vessel flow measurements from the study cohort.

Methods:
Baseline demographic and clinical data was collected in patients with recent vertebrobasilar TIA or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative MRA (QMRA).

Results:
The cohort (n=75, 56% male) had a mean age of 65.5 (range 40 to 90) years; two thirds presented with ischemic stroke. Hypertension (93%) and hyperlipidemia (79%) were the most prevalent vascular risk factors. Vertebral and basilar artery flows correlated negatively with degree of stenosis in the affected vessel, and positively to the minimal diameter at the site of stenosis (p<0.01). A threshold effect was evident, with affected vessel flows dropping significantly in patients with ≥70% stenosis or occlusion (p<0.05). Tandem disease involving the basilar and either or both the vertebrals had the greatest impact on immediate downstream flow in the basilar artery (38 ml/min vs. 74 ml/min, p<0.01). Assessment of distal flow status, incorporating collateral flow, however correlated neither with multifocality of disease nor severity of the maximal stenosis.

Conclusions:
Flow in stenotic posterior circulation vessels correlate with residual diameter and stenosis and drop significantly in the setting of tandem disease. However, distal flow status, incorporating collateral capacity, is not well predicted by the severity or location of the disease. Final clinical outcome results from the ongoing VERiTAS study will further clarify the relevance of anatomic stenosis and hemodynamic assessment to predicting stroke risk in patients with vertebrobasilar disease.
Abstract 14038: Multiple Infective Coronary Arteritis Complicated with Bacterial Pericarditis
Authors: Funabashi Nobusada , Takaoka Hiroyuki , Takano Hiroyuki , Kishimoto Takashi , Sano Masanori , Yamaoka Tomoki , Ozawa Koya , Kobayashi Yoshio
Published: July 2021

A 69 year old male was referred to our institute because of dyspnea, chest compression, and fever (39.1
o
C). He had had Sjögren’s syndrome, diabetes mellitus, and hypertension and had been taking a low dose of steroid orally for Sjögren’s syndrome. Serum white blood cell count and C-reactive protein were 22100/μL and 37.7mg/dl respectively. Transthoracic echocardiography revealed massive pericardial effusion and on pericardiocentesis, 200ml of purulent pericardial effusion was obtained. Pneumococcus was detected from blood culture and intravenous injection of antibiotics was started. Open-heart surgery was performed with maintenance of pericardial effusion and 300ml of purulent pericardial effusion was extracted. Inflammatory cells including neutrophils and lymphocytes were observed in the extract. On transesophageal echocardiography, presence of an abscess around the left coronary cusp was suspected and cardiac CT was performed. On CT, pericardial effusion and aneurysm with thickened wall, but without luminal stenosis in right coronary artery (RCA), aneurysm with thickened wall in left main (LM) trunk; and luminal stenosis with thickened wall in left anterior descending artery (LAD) were observed. From those findings, presence of coronary arteritis complicated with pericarditis was suspected. The patient had bloody bowel diarrhea, and colonoscopy revealed presence of colon cancer. As infection was not controlled, he died 31 days after admission. Subsequent autopsy showed macro-level findings of aneurysm with thickened wall complicated with hemorrhage in RCA and with thrombus in LM trunk. Thickened and hardened epicardium was also observed, which was in accordance with the clinical diagnosis of pericarditis. On hematoxylin and eosin staining, remarkable fibrous thickening of the intima and inflammatory cell invasion into vessel wall, mainly media, was observed. The epicardium was thickened and inflamed with fibrinous deposition.
Abstract 14210: Standardized Protocol to Optimize Management of Patients with Post-operative Atrial Fibrillation Reduces Length of Stay and Hospital Costs
Authors: Porten Brandon R , Strauss Craig E , Garberich Ross F , Wahl Sharon K , Sun Benjamin C , Abdelhadi Raed H , Henry Timothy D
Published: July 2021

BACKGROUND:
Post-operative atrial fibrillation (POAF) develops in approximately 30-40% of patients undergoing cardiovascular (CV) surgery and increases major adverse events, length of stay (LOS) and hospitalization costs. A standardized protocol may optimize POAF management and decrease LOS, hospital costs and adverse events including post-operative stroke.

METHODS:
In March 2013, an AF inpatient protocol was implemented in our CV surgery center’s post-operative care units. The protocol incorporates a consensus driven decision support algorithm based on blood pressure, heart rate and duration of AF to guide beta-blocker, antiarrhythmic and anticoagulation therapy recommendations in real-time. Using a shared electronic medical record we reviewed all coronary artery bypass graft (CABG) and valve surgery cases from March 1, 2013 to April 30, 2014 and compared LOS, intensive care unit (ICU) duration and post-operative stroke in POAF patients with and without the protocol. Based on actual CV surgery volume and average total variable cost per hospital day, we estimated the protocol’s impact post-implementation and at 50% annual use.

RESULTS:
Among 492 CABG and valve surgery cases, 176 (35.8%) developed POAF. Among patients with POAF, 55 (31.3%) used the AF protocol and 121 (68.7%) did not. In patients with POAF, median LOS was significantly shorter in cases with the protocol (6.9 [6.0, 9.1] days vs. 8.2 [6.1, 11.9] days; p=0.016). There was no difference in ICU duration or post-operative stroke (Table). Among 151 annual cases of POAF, average total variable cost was $2,374 per hospital day. Post-implementation, 71.5 hospital days and $169,741 have been saved. Achieving 50% protocol use, we estimate 98.0 hospital days and $232,652 could be saved annually.

CONCLUSIONS:
A standardized decision support protocol for POAF patients is associated with shorter LOS and provides a significant reduction in hospital days and total variable cost.
Abstract 14644: Impact of Time to Return of Spontaneous Circulation on Neuro-protective Effect of Target Temperature Management at 33 and 36 Degrees in Comatose Survivors of Out of Hospital Cardiac Arrest
Authors: Kjaergaard Jesper , Winther-Jensen Matilde , Nielsen Niklas , åneman Anders , Matt Wise P , Wetterslev Jørn , Wanscher Michael , Pascal Stammet , Pellis Thomas , Kuiper Michael , Hovdenes Jan , Horn Janneke , Gasche Yvan , Friberg Hans , Erlinge David , Cronberg Tobias , Hassager Christian
Published: July 2021

Introduction:
Prolonged time to Return of Spontaneous Circulation (ttROSC) after Out of Hospital Cardiac Arrest (OHCA) has consistently been associated with adverse outcome by a plausible direct relation to severity of anoxic injury.

Hypothesis:
Target temperature management (TTM) is assumed effective against anoxic brain injury and we hypothesized that TTM at 33 degrees would be more beneficial with prolonged time to ROSC compared to 36 degrees.

Methods:
In a post hoc analysis of the TTM trial, which showed no overall benefit of targeting 33 °C over 36 in 939 patients (NEJM 2013), we investigated the relation of time to ROSC and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) and Modified Ranking Scale (mRS) after 180 days.

Results:
Prolonged ttROSC was significantly and independently associated with increased mortality, p<0.001 (figure), with Hazard Ratio (HR) of 1.02 (95% CI 1.01-1.02, p<0.001) per minute increase and level of TTM did not modify this association, p
interaction
=0.85. In survivors prolonged ttROSC was associated with increased odds of surviving with an unfavorable neurological outcome for CPC (p=0.008 for CPC 3-4) and a similar trend, albeit not statistically significant was observed for mRS (p=0.17, mRS 4-5). Odds for unfavorable neurological outcome (CPC>2, mRS>3) was not modified by levels of TTM overall.

Conclusion:
Time to ROSC remains a significant prognostic factor in comatose patients resuscitated from OHCA with regards to risk of death and risk of adverse neurological outcome in survivors. TTM at 33 degrees offers no advantage over targeting 36 degrees with regards to mortality or neurological outcome in patients with prolonged time to ROSC.

Figure: Mortality rates stratified by quartiles of tome to ROSC and by TTM level. Differences tested by log rank test in between TTM in strata
Abstract 14658: Comparative Effectiveness of Torsemide versus Furosemide in Acute Heart Failure Patients: Insights from ASCEND-HF
Authors: Mentz Robert J , Hasselblad Vic , DeVore Adam D , Armstrong Paul W , Ezekowitz Justin A , Tang W.H. Wilson , Voors Adriaan A , Metra Marco , Hernandez Adrian F , Califf Robert M , Anstrom Kevin J , Velazquez Eric J , O’Connor Christopher M
Published: July 2021

Introduction:
Furosemide is the most commonly used loop diuretic in heart failure (HF) patients despite potential pharmacologic and anti-fibrotic benefits with torsemide.

Hypothesis:
We hypothesized that the comparative benefits of post-discharge use of torsemide would be superior to furosemide in a large acute HF trial.

Methods:
We investigated HF patients in ASCEND-HF who were discharged on either torsemide or furosemide. Given regional variation in torsemide use, we restricted analyses to the 6 countries with at least 20 patients on one of the diuretics and patients on torsemide. Using inverse probability weighting (IPW) to account for selection of diuretic, we assessed the relationship between diuretic at discharge with 30-day mortality or HF hospitalization, and 30- and 180-day mortality.

Results:
Of 7,141 patients in the trial, 3,282 patients were included in this analysis, of which, 88% (n=2,893) received furosemide and 12% (n=389) received torsemide. Torsemide-treated patients had lower blood pressure, and higher creatinine and BUN at baseline compared with furosemide-treated patients. On adjusted analysis, torsemide use was associated with a trend toward lower 30-day mortality or HF hospitalization (OR 0.62, 95% CI: 0.37-1.04; P=0.067). Torsemide was associated with similar 30-day mortality (OR 0.77, 95% CI: 0.28-2.09; P=0.60), and significantly reduced 180-day mortality (HR 0.56, 95% CI: 0.36-0.87; P=0.038) compared with furosemide (Figure).

Conclusion:
In this acute HF trial, a minority of patients received torsemide and commonly had indicators of higher risk. After risk-adjustment, torsemide was associated with lower risk of 180-day mortality. These data should be considered as hypothesis-generating and prospective, randomized comparative effectiveness trials are needed to investigate the optimal diuretic choice between torsemide vs. furosemide.
Abstract 14717: Endocrine Mechanisms against Ischemic Cardiomyocyte Calcification
Authors: Liu Shu , Zhang Brian , Wu Yu H
Published: July 2021

Myocardial infarction causes cardiomyocyte calcification or deposition of hydroxyapatite crystals, structures disrupting cardiomyocytes and intensifying myocardial injury. While cardiomyocyte calcification is well recognized, the underlying mechanisms remain elusive and few treatment strategies have been established. Here, we test the hypotheses that annexins (ANXs), intracellular Ca++ carriers associated with the plasma membrane, contribute to ischemic cardiomyocyte calcification and the endocrine protein trefoil factor 3 (TFF3) is upregulated and released from the liver in ischemic myocardial injury, protecting ischemic cardiomyocytes from annexin-dependent calcification. Myocardial ischemia/reperfusion injury in 129s1/sv Imj mice caused translocation of ANXs A2, A3, A4, A5, and A7 from the cardiomyocyte membrane to α actin filaments in association with hydroxyapatite deposition to α actin filaments prior to cardiomyocyte death from 1 to 10 days. siRNA-mediated silencing of the ANX A2, A3, A4, A5, and A7 genes reduced the fraction of calcified cardiomyocytes at day 5 from 6.3+/-1.8% (control siRNA) to 2.1+/-0.6% in reference to the infarct area (p<0.01), suggesting a pro-calcification role for these ANXs. Myocardial injury caused upregulation and release of TFF3 from the liver. TFF3-/- mice exhibited intensified ischemic cardiomyocyte calcification (17.8+/-5.2%) compared to wildtype mice (5.6+/-2.3%, p<0.001), suggesting an anti-calcification role for TFF3. TFF3 was able to bind to ANXs A2, A3, A4, A5, and A7, demonstrated by TFF3 crosslinking assay and mass spectroscopy. ANX A2, A3, A4, A5, or A7 was able to co-immunoprecipitate with TFF3 in ischemic cardiomyocytes. Computational molecular interaction analyses by using the Autodocking software system showed TFF3 interaction with the ANX C-terminus, a structure binding to actin filaments. Myocardial administration of recombinant TFF3 reduced ANX-dependent cardiomyocyte calcification. These observations suggest that ANXs cause ischemic cardiomyocyte calcification by binding to α actin filaments and TFF3 is upregulated and released from the liver in myocardial ischemia, mitigating cardiomyocyte calcification by blocking ANX binding to actin filaments.
Abstract 14732: The Prognostic Implications of Right Bundle Branch Block in Healthy Population: a Systematic Review and Meta-analysis
Authors: Sharma Sunita , Hazem Ahmad , Sharma Amit , Leitch Cameron , Sharadanant Roopalakshmi , Uriell Matthew , Henry Jason , Neutzling Kari , LeBlanc Annie , Barrionuevo Moreno Patricia , Wang Zhen , Sorita Atsushi , Vilenski Leonid , Prokop Larry , Makkuni Premraj , Ting Henry , Murad M Hassan
Published: July 2021

Objective:
Multiple large population based observational studies have evaluated the association of various ECG changes with long term adverse outcomes demonstrating conflicting results regarding the significance of right bundle branch block (RBBB). Therefore, we conducted a systematic review and meta-analysis to determine the prognostic significance of RBBB in healthy population.

Methods:
This systematic review follows an a priori established protocol and is reported following the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We systematically searched EMBASE, Web of Science and Scopus through January 2014. We also consulted with content experts to recommend studies for screening. Reviewers working independently and in duplicate screened all eligible abstracts, selecting randomized trials and prospective cohort studies that described all cause mortality or cardiovascular death in patients with RBBB. We excluded studies that reported unadjusted outcome or unadjusted event rates. For statistical analysis, hazard ratios were considered to approximate risk ratios. The main outcomes of the study are all-cause mortality and cardiovascular mortality.

Results:
Based on the eligibility, four large cohorts, with total patient count > 100,000 were included in the meta-analysis. Risk of bias was assessed using the Newcastle-Ottawa scale and included studies were deemed to be of high quality. As demonstrated in Figure 1, RBBB was not associated increase in all-cause mortality (RR 1.05; 95% CI 0.89-1.25) or cardiovascular mortality (RR 1.09; 95% CI 0.70-1.69).

Conclusion:
In asymptomatic healthy patients, RBBB is not associated with poor outcome.
Abstract 14753: A Novel Quadripolar Lead with a Narrow-Spaced Bipole Allows for Effective LV Pacing While Avoiding Phrenic Nerve Stimulation - Attain Performa LV Lead Study Primary Results
Authors: Crossley George H , Biffi Maurio , Johnson W. Ben , Lin Albert C , Gras Daniel , Hussin Azlan , Li Shelby , Smedberg Angela , Exner Derek V
Published: July 2021

Introduction:
The Medtronic Attain Performa™ Model 4298 Quadripolar left ventricular (LV) Lead has 4 electrodes, provides 16 different polarities & includes a short bipole (1.3 mm between 2nd & 3rd electrodes). A prospective clinical study was conducted to investigate the safety and effectiveness of this new lead in 20 countries worldwide.

Methods:
Cardiac resynchronization therapy defibrillator (CRT-D) patients were enrolled & implanted with the Model 4298 LV lead & a Quad CRT-D device. All implanted subjects(SUB) were followed at 1, 3, 6 and every 6 months (M) post-implant. Pacing capture thresholds (PCTs) were measured manually or with automated testing methods. Adverse events (AEs) were reported upon occurrence & reviewed by an independent committee. Events requiring invasive intervention or resulting loss of CRT were considered to be complications.

Results:
Of 499 SUB (68 + 11 yr, 71% male) who underwent an LV lead implant attempt, 487 (97.6%) had an LV lead implanted, Most (73%) had NYHA Class III or IV symptoms, average LV ejection fraction was 25 ± 7%, QRS duration was 155 ± 24ms & most (71%) had LBBB. There were 20 LV lead related complications in 19 SUB over 6M (LV lead related complication free survival rate = 96%). Phrenic nerve stimulation (PNS) occurred in 31 SUB (6.3%) & resolved with no treatment (N=1) or noninvasive reprogramming (N=29). The average PCT at 6M was 1.1 + 0.7 V at the programmed vector and 93.9% of SUB had a PCT≤ 2.5V. The vast majority (97.7%) of SUB had > 1 additional selectable pacing vector with a PCT ≤ 4V and no PNS. Non-standard pacing polarities (i.e., vectors other than LV1 [LV tip] to right ventricular coil [RVC], LV2 to RVC & LV1 to LV2) were utilized in 56% of SUB. LV1 was not used in the final vector in 46% of SUB. The LV1 to RVC was utilized in 19%, LV1 to LV2 in 18% & the short bipole (LV2 to LV3) in 12%.

Conclusions:
This large multicenter study demonstrated that implantation of the Model 4298 LV quadripolar lead is associated with a low complication rate and no unanticipated complications. PNS can be readily resolved with reprogramming & that PCT values are low & stable over time. Moreover, At least 1 back-up LV pacing vector was available in the vast majority of SUB. Non-standard vectors, including the short bipole (LV2-LV3) were used in 56% of subjects.
Abstract 14782: Incidence and Characteristics of Pulmonary Vein Stenosis Following Catheter Ablation of Atrial Fibrillation: Insights From the Contemporary Multicenter ADVICE Trial
Authors: Gomes Sophie , Khairy Paul , Andrade Jason , Nattel Stanley , Talajic Mario , Guerra Peter G , RIvard Lena , Dubuc Marc , Dyrda Katia , Thibault Bernard , Montdesert Blandine , Levesque Sylvie , Tadros Rafik , Malliet Nicolas , Venier Sandrine , Millette Catherine , Roy Denis , Macle Laurent
Published: July 2021

Introduction:
Pulmonary vein (PV) stenosis is a well-described complication of atrial fibrillation (AF) ablation. Available data regarding the incidence of pulmonary vein (PV) stenosis associated with radiofrequency catheter ablation of AF are limited to surveys, single-center studies, and small trials. We prospectively assessed the incidence of PV stenosis after catheter ablation of AF in the context of a large randomized multicenter international study (ADVICE).

Methods:
Patients undergoing a first PV isolation procedure for the treatment of symptomatic paroxysmal AF were enrolled from 13 centers. PV isolation was performed by encircling all PVs using an irrigated-tip radiofrequency ablation catheter guided by a circular mapping catheter with the endpoint of electrical PV isolation. Systematic imaging of the left atrium and PVs using computed tomography-scan (CT-Scan) or magnetic resonance (MRI) was performed at 90 days post ablation to assess the incidence of PV stenosis. Significant PV stenosis was defined by a narrowing of PV luminal diameter greater than 70% as per Heart Rhythm Society guidelines. The incidence of moderate PV stenosis defined by a narrowing between 50% and 70% was also analyzed. Predictors of PV stenosis were explored by logistic regression analyses.

Results:
A total of 197 patients (mean age 59±9 yrs, 71% male) were included in this study. Electrical PV isolation was achieved in all patients. On the post ablation imaging study (performed at a mean of 103±33 days post ablation), a significant PV stenosis was observed in 1.52% [95% confidence interval (0.00%-3.23%)] of patients. In addition, a moderate PV stenosis was seen in 3.55% [95% confidence interval (0.97%-6.14%)] of patients. The affected PVs included 8 left inferior PVs, 1 right inferior and 1 right middle PV. None of the patients were symptomatic or required an intervention related to the PV stenosis. The presence of PV stenosis could not be predicted by clinical, hemodynamic, or procedural parameters.

Conclusions:
Our systematic evaluation of the incidence of PV stenosis in the context of a prospective multinational trial confirms previously reported low rates of significant PV stenosis following radiofrequency catheter ablation of AF.
Abstract 14806: Predictors of Survival and Favourable Functional Outcomes Following an Out of Hospital Cardiac Arrest in Patients Systematically Brought to a Dedicated Heart Attack Centre
Authors: Iqbal M Bilal , Al-Hussaini Abtehale , Rosser Gareth , Salehi Saleem , Phylactou Maria , Rajakulasingham Ramyah , Patel Jayna , Elliott Katharine , Mohan Poornima , Green Rebecca , Smith Robert , Ilsley Charles
Published: July 2021

BACKGROUND:
Despite advances in cardiopulmonary resuscitation, survival remains low after out of hospital cardiac arrest (OOHCA), with less than 20% of patients surviving to hospital discharge. Acute coronary ischaemia is the predominating cause and prompt delivery of patients to dedicated facilities may improve outcomes. Since 2011, all patients in London with OOHCA, in whom a cardiac aetiology is suspected, are brought to dedicated Heart Attack Centres (HACs).

OBJECTIVES:
We sought to determine the predictors for survival and favourable functional outcomes following OOHCA in this setting.

METHODS:
We analysed 182 consecutive OOHCA patients brought by the emergency services to Harefield Hospital - a designated HAC in London. Of these, 174 patients achieved return of spontaneous circulation. We analysed (a) all-cause mortality at 1 year; and (b) functional status at discharge using a modified Rankins score (mRS:0-6, where mRS0-3=favourable functional status). We used multivariate models to determine predictors of survival and favourable functional status.

RESULTS:
The overall survival rates were 66.7% at 30 days and 62.1% at 1 year. Of the 174 patients, 95 patients (54.5%) had favourable functional status at discharge. Patients with favourable functional status had significantly reduced mortality rates compared to those with poor functional status: 30 days (1.2% vs. 72.2%, p<0.001) and 1 year (5.3% vs. 77.2%, p<0.001). Multivariate analyses identified a shorter duration of resuscitation and absence of cardiogenic shock as consistent independent predictors of both favourable functional status and long-term survival (figure).

CONCLUSIONS:
The strategic delivery of OOHCA patients to HACs is associated with improved functional status and survival. Those with favourable functional status at discharge have significantly improved survival. Our study supports the standardisation of care for such patients with the widespread adoption of dedicated facilities.
Abstract 14810: Sam68 Promotes Nf-kb Signaling and Inflammation and Impedes the Recovery of Arterial Injury
Authors: Han Shuling , Zhou Junlan , Qin Gangjian
Published: July 2021

Background:
The role of Src-associated in mitosis 68 kDa (Sam68) protein in cardiovascular biology has not been studied. A recent report suggests that Sam68 suppresses TNF-α-mediated NF-kB activation. Since NF-kB plays a critical role in vascular inflammation and injury via generation of inflammatory cytokines and recruitment of inflammatory cells, we sought to dissect the molecular mechanism by which Sam68 regulates NF-kB signaling and its functional significance during vascular injury.

Methods & Results:
The endothelial denudation injury was induced in the carotid arteries of Sam68-null (Sam68
-/-
) and WT mice. Sam68
-/-
mice displayed an accelerated re-endothelialization (
P
<0.05 at day 5 post-injury) and attenuated neointima formation (by 2.2 folds,
P
<0.05, at day 14), which was associated with a reduced number of macrophages and lowered expression of pro-inflammatory cytokines (i.e., TNF-alpha, MCP-1 and IL-6) in the injured vessels. In cultured Raw264.7 macrophages, knockdown of Sam68 resulted in a significant reduction in the TNF-α-induced expression of TNF-α, MCP-1, and IL-6 and in the level of nuclear phospho-p65, which indicates attenuated NF-kB activation. These results were confirmed in peritoneal macrophages and macrophages differentiated from bone-marrow mononuclear cells of Sam68
-/-
and WT mice. To identify molecular mechanisms, Raw264.7 cells were treated with TNF-α and Vehicle, followed by Sam68 co-immunoprecipitation and mass-spectrometric identification of the Sam68-interacting proteins. We found that TNF-α treatment results in altered interactions of Sam68 with 22 cytosolic, cytoskeletal, and nuclear proteins. Further experiments are under way to validate their involvement in the NF-kB signaling.

Conclusions:
Our results for the first time suggest that Sam68 promotes pro-inflammatory response in injured arteries and impedes recovery, and this effect may be partially attributable to the exaggerated NF-kB activity.
Abstract 14819: The Red Cell Distribution Width Predicts Mortality among Patients Free from Systemic Inflammation
Authors: Horne Benjamin D , Muhlestein Joseph B , Bennett Sterling T , Anderson Jeffrey L
Published: July 2021

Background:
The causal mechanism is unknown for why the red cell distribution width (RDW) predicts mortality and morbidity outcomes. One explanation is an inflammatory process: statistically significant, weak magnitude correlations (r<0.30) have been found between RDW and markers of inflammation. This study evaluated the association of RDW with mortality in patients with normal levels of inflammation, as indicated by normal high-sensitivity C-reactive protein (hsCRP) and white blood cell count (WBC).

Methods:
Intermountain Heart Collaborative Study patients undergoing coronary angiography (N=650) from 1994-2000 were evaluated if they never smoked, were free of acute myocardial infarction (MI), and had baseline hsCRP≤3 mg/L, WBC>4 K/μL, and WBC≤10.6 K/μL. RDW and WBC were tested clinically at index hospitalization via the complete blood count; hsCRP testing used stored research samples. Subjects were followed until December, 2013, and all-cause mortality was determined from hospital records, Utah death certificates, and US Social Security data.

Results:
Age averaged 66.7±11.6 years, 31.1% were female, and 62.9% died during a mean follow-up of 15.2±1.6 years (range:12.6-19.6 years). Continuous RDW predicted mortality after adjustment for demographics, risk factors, comorbidities, and baseline treatments (hazard ratio [HR]=1.15 per +1%, 95% CI=1.06, 1.26; p=0.002). In quartiles, this was significant for Q4 vs. Q1 (survival 23.6% vs. 43.4%, HR=1.56, CI=1.17, 2.08; p=0.003), but not Q2 (HR=1.18, p=0.29) or Q3 (HR=1.08, p=0.60) vs.Q1. In subjects with hsCRP<1 mg/L (n=259), RDW (adj. HR=1.13 per +1%, CI=0.99, 1.29, p=0.08) and RDW quartiles [Q2: adj. HR=1.70 (p=0.036), Q3: HR=1.88 (p=0.020), Q4: HR=1.97 (p=0.013) vs. Q1] predicted mortality. Among subjects free from heart failure (LVEF≥40%), diabetes, prior or current coronary disease, prior MI, stroke, renal failure, COPD, and depression (n=66), RDW had adjusted HR=1.70 per +1% (CI=1.06, 2.75; p=0.029).

Conclusions:
RDW predicted mortality in patients with normal hsCRP and WBC. This suggests that RDW marks the risk of a breadth of health concerns, likely including but not limited to inflammation. Further investigation is required to explain the causes of RDW elevation.
Abstract 14850: Independent Role of the Priming and Triggering of the NLRP3 Inflammasome in the Heart
Authors: Toldo Stefano , Mezzaroma Eleonora , McGeough Matthew D , Pena Carla A , Marchetti Carlo , Sonnino Chiara , Van Tassell Benjamin W , Mauro Adolfo G , Salloum Fadi N , Hoffman Hal M , Abbate Antonio
Published: July 2021

Introduction:
The NLRP3 inflammasome is activated in the heart following ischemic injury, and it promotes cardiac dysfunction. Ischemic injury establishes both a priming signal (leading to transcription of inflammasome components) and a trigger (NLRP3 activation). Whether activation of NLRP3 (in absence of priming) represents the limiting step in the formation of the inflammasome in the heart is unknown.

Hypothesis:
Both priming and the triggering signals in the heart are necessary for the formation of the inflammasome and ensuing cardiac dysfunction.

Methods:
We induced systemic expression of a floxed mutant NLRP3-A350V, that is constitutively active, in 10 mice using a tamoxifen-inducible Cre recombinase, to create a condition in which NLRP3 is activated, in absence or presence of priming with low dose LPS (2 mg/kg). Molecular analyses were performed on the heart and the spleen (myeloid organ not dependent on priming) to measure caspase-1 activity using a fluorogenic assay, mRNA expression of the component of the inflammasome (caspase-1 and IL-1β), and echocardiography to measure left ventricular (LV) dimension and systolic function.

Results:
NLRP3-A350V mutant mice had increased caspase-1 activity in the spleen but not in the heart and had normal LV systolic function (Figure), showing that in NLRP3 activation without priming is insufficient to induce inflammasome formation in the heart nor LV systolic dysfunction. Priming with LPS induced the expression of the inflammasome components in the heart which in absence of NLRP3 activation (control mouse) had no effects on LV systolic function, whereas in the presence of NLRP3 activation (mutant mouse) led to reduced LV systolic function and premature death (Figure).

Conclusions:
The inflammasome formation in the heart requires a priming signal to be coupled with activation of NLRP3 in order to induce LV dysfunction.
Abstract 14958: Global Longitudinal Strain is a Superior Predictor of All-cause Mortality Compared to Left Ventricular Ejection Fraction in Male Patients with Heart Failure and Without Atrial Fibrillation
Authors: Sengeløv Morten , Biering-Sørensen Tor , Jørgensen Peter Godsk , Bruun Niels Eske , Fritz-Hansen Thomas , Bech Jan , Olsen Flemming Javier , Sivertsen Jacob , Jensen Jan Skov
Published: July 2021

Object:
Myocardial strain deformation analysis (global strain) may be superior to left ventricular ejection fraction (LVEF) in predicting all-cause mortality in patients with heart failure.

Methods:
In this retrospective study transthoracic echocardiographic examinations were retrieved from Gentofte Hospital heart failure clinic’s database in 1061 patients. The echocardiographic images were subsequently analyzed and conventional echocardiographic parameters and strain data were obtained.

Results:
During a median follow-up of 40 months 177 (16.7 %) patient died. Mean LVEF was 23.7 % and mean global strain was -8.12.884 (83.3%) were patients alive at follow-up and mean LVEF was 28.2 % while mean global strain was -9.86 %.

The risk of dying increased with decreasing tertile of global strain being approximately three times higher for the patients in the lower tertile compared to the highest tertile (1. tertile vs 3. tertile HR: 3.38 95% CI: 2.3 [[Unable to Display Character: –]] 5.1), p-value: 0.001.

Many of the conventional echocardiographic parameters proved to be predictors of mortality. Global strain remained an independent predictor of mortality in cox proportional-hazards models after adjusting for age, gender, BMI, total cholesterol, heart rate, atrial fibrillation, non-independent diabetes mellitus and conventional echocardiographic parameters (p-value: 0.014, 95% CI: 1.04 [[Unable to Display Character: –]] 1.37) while ejection fraction proved to be insignificant adjusted for aforementioned characteristics (p-value: 0.81, 95% CI: 0.96 [[Unable to Display Character: –]] 1.05

Atrial fibrillation modified the relationship between GLS and mortality (p for interaction = 0.023). HR 1.08 (CI 0.97 to 1.19, p=0.150) and HR 1.22 (CI 1.15 to 1.29, p<0.001) per 10 % decrease in GLS for patients with and without atrial fibrillation, respectively. Gender also modified the relationship between mean GLS and mortality (p for interaction = 0.047); HR 1.23 (CI 1.16 to 1.30, p<0.001) and HR 1.09 (CI 0.99 to 1.20, p=0.083) per 10 % decrease in GLS for men and women, respectively.

Conclusion:
In male patients with systolic heart failure and without atrial fibrillation global strain is an independent predictor of all-cause mortality. Furthermore, global strain proved to be a superior prognosticator when compared to left ventricular ejection fraction.
Abstract 14964: Sudden Cardiac Death in Current vs. Former Smokers
Authors: Reinier Kyndaron , Teodorescu Carmen , Uy-Evanado Audrey , Gunson Karen , Jui Jonathan , Chugh Sumeet S
Published: July 2021

Introduction:
Smoking is a well-established risk factor for cardiovascular disease, but its role in sudden cardiac death (SCD) specifically has not been as well investigated. We sought to describe smoking prevalence among cases that suffered SCD in the general population.

Hypothesis:
We hypothesized that smoking prevalence would be high among SCD cases.

Methods:
Cases of SCD from an ongoing multiple-source community-based study of SCD in the northwest US (pop. approx. 1 million) were included if they were age ≥18 with smoking history available from medical records. We describe the prevalence of smoking in the SCD population, as well as characteristics of smokers vs. non-smokers.

Results:
From 2002 -2012, 1833 (76%) of 2402 SCD cases had pre-SCD medical records available, and smoking history was available for 1241 (68%) of these. While 2007-8 community data (Behavioral Risk Factor Surveillance Study) indicated that 16% of Oregonian adults were current smokers, among the SCD cases, 40% were current smokers, 31% former smokers, and 29% non-smokers. Men were more likely than women to be current smokers (42% vs. 37%) or former smokers (35% vs. 23%); 40% of women and 24% of men were non-smokers (p<0.0001). Among SCD cases, current smokers were significantly younger at the time of their SCD (57.8 ± 13.2 yrs) than former smokers (70.0 ± 12.9 yrs) or non-smokers (66.6 ± 17.9 yrs; p<0.0001), despite a similar number of years smoked among the current and former smokers (33 vs 29 years, p=0.22). Former smokers were more likely to have a history of myocardial infarction and documented CAD than current smokers (p<0.0001).

Conclusions:
In this community-based study of SCD, current and former smoking was a common finding; current smokers suffered SCD at a younger age than former smokers, despite less documented CAD and MI at the time of their arrest.
Abstract 14990: Sudden Death in Patients with Heart Failure and Preserved Ejection Fraction
Authors: Reinier Kyndaron , Uy-Evanado Audrey , Teodorescu Carmen , Marijon Eloi , Narayanan Kumar , Gunson Karen , Jui Jonathan , Chugh Sumeet S
Published: July 2021

Introduction:
Severely reduced left ventricular ejection fraction (EF) is an established risk factor for sudden cardiac death (SCD), but has limited sensitivity and specificity. We evaluated the contribution of heart failure (HF) with preserved ejection fraction toward risk of SCD in the general population.

Hypothesis:
We hypothesized that HF would predict risk of SCD, even among patients with preserved EF.

Methods:
Subjects from an ongoing community-based study of SCD in the northwest US (pop. approx. one million) were included if age ≥18 (2002 - 2012) with clinical history and assessment of EF. Clinical history of heart failure (HF) was determined by physician report. Ejection fraction (EF) was determined from echocardiogram, angiogram, or multigated acquisition scan, and categorized as EF <20%, 20-34%, 35-44%, 45-54%, and ≥55%. Laboratory values of brain natriuretic peptide (BNP) were obtained from routine clinical laboratory testing for a subset of patients.

Results:
Cases (n=628, mean age 69.9, 65% male) were more likely than controls (n = 580, mean age 66.8, 66% male) to have a history of clinically-recognized HF (58% vs. 24%, p<0.0001) and to have an EF ≤ 35% (27% vs. 12%, p<0.0001). At each EF level above 20%, HF was approximately twice as prevalent in cases compared to controls (Figure, p≤0.002). Median BNP levels were significantly higher for patients with HF vs. those without, across EF categories. Adjusting for age and sex, each category of decreasing EF was associated with an increased risk of SCD (OR 1.4, 95% CI 1.3 - 1.6, p<0.0001), but the association was diminished by adjustment for HF, and for BNP. Odds of SCD were 4-fold higher (p<0.0001) in the presence HF, adjusting for age and sex, across all categories of EF.

Conclusions:
In this population, the significant role of HF with preserved EF in SCD was confirmed by BNP level trends. Improvements in SCD prevention will require focused investigation of high risk SCD markers in patients with heart failure and preserved EF.
Abstract 15064: Control of Left Ventricular Load and Pulsatility by a Continuous-flow Left Ventricular Assist Device With a Native Heart Load Control System in Chronic Awake Phase
Authors: Date Kazuma , Nishimura Takashi , Kishimoto Satoru , Takewa Yoshiaki , Ono Minoru , Tatsumi Eisuke
Published: July 2021

Introduction:
We have previously developed a Native Heart Load Control System for a continuous-flow left ventricular assist device (EVAHEART) and demonstrated that the rotational speed (RS) in synchronization with the cardiac cycle can alter left ventricular (LV) load and pulsatility under general anesthesia. In this study, we assessed this system in chronic awake phase.

Methods:
We implanted EVAHEART in five goats (59.4±5.6kg) with a normal heart. Two weeks after the implantation, we examined the effects of the continuous mode (constant RS), counter-pulse mode (increase RS in diastolic phase) and co-pulse mode (increase RS in systolic phase) of this system on LV load and pulsatility in 100%, 75% and 50% bypass. We used two parameters to evaluate LV load, including stroke work (SW) and end-diastolic volume (LVEDV) determined from LV pressure-volume loops. About pulsatility, we used pulse pressure (PP) and mean dP/dt max of aortic pressure.

Results:
The co-pulse mode created greater LV load and pulsatility than the continuous mode in all bypass rates. In contrast, LV load and pulsatility in the counter-pulse mode were smaller than those in the continuous mode. There were statistically significant differences between values about LV load and pulsatility in counter-pulse and co-pulse mode; continuous/counter-pulse/co-pulse SW (ml·mmHg); 2601.71±2208.50/2127.88±1745.11/2845.54±2230.82 (100%): 2968.05±2265.75/2485.79±1714.07/3133.92±2203.64 (75%): 3134.42±2319.75/2927.76±2111.76/3313.13±2350.49 (50%), LVEDV (ml); 52.79±26.43/46.95±20.31/56.32±25.43 (100%): 57.22±28.19/51.38±21.83/59.06±26.63 (75%), 59.59±28.24/56.02±25.40/61.88±28.61 (50%), PP (mmHg); 30.09±10.01/22.63±8.09/36.79±9.32 (100%): 32.88±9.88/26.66±10.80/40.69±7.83 (75%): 37.30±10.86/32.76±12.43/41.97±9.59 (50%), mean dP/dt max of aortic pressure (mmHg/s); 979.89±369.20/687.98±230.12/1165.67±391.36 (100%): 1321.25±446.14/1047.78±393.29/1474.99±474.53 (75%): 1511.06±519.18/1332.6±471.91/1666.59±511.55 (50%).

Conclusions:
Our newly developed system could control LV load and pulsatility in the chronic awake phase. This system may provide the most favorable LV loading conditions for the recovery of the native heart.
Abstract 15094: Prevalence of Coronary Microvascular Dysfunction in Women With Angina and No Obstructive Coronary Artery Disease: Preliminary Results From the iPower Study
Authors: Mygind Naja D , Michelsen Marie M , Pena Adam A , Faber Rebekka , Kastrup Jens , Prescott Eva
Published: July 2021

Background:
Women are more often than men found to have no obstructive coronary artery disease (CAD) when evaluated with a coronary angiogram (CAG) due to angina pectoris and suspected ischemic heart disease. Coronary microvessel dysfunction (CMD) is a possible explanation, and can be assessed by transthoracic Doppler echocardiography (TTDE) with measurement of coronary flow reserve (CFR). Reduced CFR carries an adverse prognosis despite absence of obstructive CAD. The aim of the ongoing iPower study is to evaluate CFR in women with angina pectoris and no obstructive CAD.

Methods:
Women with angina pectoris and a CAG without obstructive coronary artery disease (>50%) are systematically invited to participate. Assessment includes demographic and clinical data, blood samples and TTE during rest and high-dose dipyridamole stress (0.84mg/kg) with measurement of CFR by Doppler of the left anterior descending artery.

Results:
To date (May 21st 2014) 3500 women have been screened (flowchart), 793 women have been included (response rate 23%). Mean age was 62.4 (+/-9.6) and the burden of risk factors was relatively high (Table 1). CFR was successfully measured in 763 patients (96%). Median (IQR) CFR was 2.4 (2.0-2.8). Cut-off point for CMD of both 2 and 2.5 has been used previously. In this population, 214 (28%) had a CFR≤2 and 468 (61%) a CFR≤2.5.

Conclusions:
To our knowledge, iPower is the largest and most comprehensive study systematically assessing CMD in women with angina pectoris and no obstructive CAD. Non-invasive CFR assessment is feasible, and microvascular function impaired in a large proportion. Future follow-up will determine the prognostic value of CFR as a measure of CMD.
Abstract 15097: Altered TGFβ Signalling Effector Molecules Contribute to Bicuspid Aortic Valve-associated Thoracic Aortopathy
Authors: Dilworth Candice L , Sadnick Francesca , Padang Sari , Lu Yaxin , Robertson Elizabeth N , Maleki Sanaz , Kekic Murat , Bao Shisan , McLachlan Craig , Jeremy Richmond W , Hambly Brett D
Published: July 2021

Upregulated TGFβ signalling plays a key role in mediating congenital thoracic aortic aneurysms (TAA), and has been implicated in bicuspid aortic valve-associated TAA (BAV-TAA). TGFβ is normally stored within the extra-cellular matrix via sequestration proteins bound to the microfibrillar protein, fibrillin. TGFβ is released in response to changes in these sequestration proteins, allowing TGFβ to exert its signalling effects. We hypothesised that in BAV-TAA the upregulation of TGFβ signalling will pathologically alter effector molecule expression, causing matrix degradation and altered TGFβ sequestration. Immunohistochemistry was used to quantify protein expression in aortic tissue from 8 human BAV-TAA and 6 normal controls. In BAV-TAA, TGFβ expression was elevated in all layers (2.5:1; p<0.05), particularly in the adventitia (3.4:1; p<0.001). Microfibril-associated glycoprotein-1 (MAGP-1), which promotes TGFβ release, was elevated (2:1; p<0.03), while latent TGFβ binding protein-1 (LTBP-1), which promotes TGFβ sequestration, was decreased (0.3:1; p=0.03). Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression was elevated (2.6:1; p<0.005, 1.5:1; p<0.05, respectively), and MMP-3 expression was decreased (0.5:1; p<0.05). Fibrillin-1 expression was not altered. The observed changes in TGFβ sequestration proteins will increase unbound TGFβ, leading to upregulation of downstream signalling. The elevated levels of MMP-2 and MMP-9 mediate pathological matrix remodelling, leading to aortic dilatation. The paradoxical decrease in MMP-3 may represent a compensatory mechanism that attempts to reduce overall pathological MMP activity, in order to limit damage to the aortic wall. In conclusion, in BAV-TAA excessive TGFβ signalling is potentiated by reduced TGFβ sequestration, causing extra-cellular matrix degradation by MMPs. This supports the rationale for the use of angiotensin II receptor blockers in BAV-TAA.
Abstract 15100: Inhibition of P38 Mapk Improves Heart Function in Sustained Pressure-overload Induced Right Ventricular Hypertrophy and Failure
Authors: Kojonazarov Baktybek , Novoyatleva Tatyana , Sabiska Zaneta , Janssen Wiebke , Tian Xia , Luitel Himal , Kriechling Philipp , Newman Julia , Evans Steven , Grimminger Friedrich , Weissmann Norbert , Ghofrani Hossein Ardeschir , Seeger Werner , Schermuly Ralph Theo
Published: July 2021

Introduction:
The p38 mitogen-activated protein kinases (MAPK) considered as a key signaling pathway that responds to varied stresses, including those that contribute to heart failure. However, the role of p38 MAPK in pulmonary vascular and right ventricular remodeling is still need to be elucidated.

Methods:
The effects of p38 MAPK inhibitor PHA-00797804 (Pfizer, USA) investigated in mice subjected either to hypoxia-induced PH or to pulmonary artery banding (PAB). After 21 days, mice exposed to hypoxia were randomized and treated by vehicle or 5 mg/kg bw PHA-00797804 for 14 days. PAB mice were treated by vehicle or PHA-00797804 in a dose 5 mg/kg bw from day 7 to 21. The echocardiography, invasive hemodynamic measurement and hitomorphometry were performed. The myocardin-related transcription factor (MRTF) translocation and stress fibers formation were determined by immunofluorescence staining on isolated mouse cardiac fibroblasts.

Results:
The 38αMAPK inhibition significantly reversed pulmonary vascular remodeling and improved RV functions in hypoxia-induced PAH. However, to determine whether the effect in hypoxic mice was due to a direct impact of pharmacological interventions on RV or an indirect impact due to reduced pulmonary vascular resistance, we have investigated the effects of p38 MAPK inhibition in an established model of RVH and failure by PAB. The PHA-00797804 significantly increased cardiac output (p<0.001), tricuspid annular plane systolic excursion (p<0.001) and improved myocardial performance index (p<0.001) in PAB mice. Improvement in RV functions was associated with strong antifibrotic effect of PHA-00797804. The p38 MAPK inhibition reduced collagen synthesis and myofibroblast differentiation via MRTF A dependent mechanism.

Conclusion:
Inhibition of p38 MAPK improved RV remodeling and function in experimental models of RV hypertrophy and failure.