bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 1776: Peripheral Arterial Disease Determined by Screening Ankle Brachial Index Testing Predicts High Risk Findings On Stress Myocardial Perfusion SPECT Imaging
Authors: Ward R Parker , Taillon Linda A , Weiner Justin , Williams Kim A
Published: July 2021

Background:
Peripheral arterial disease (PAD) as determined by ankle brachial index (ABI) testing is a potent marker of adverse cardiovascular prognosis. Stress myocardial perfusion SPECT (MPS) testing allows diagnosis of coronary artery disease (CAD) and stratification of cardiovascular risk. The stress MPS findings in patients (pts) with occult PAD are unknown. Accordingly, our goal was to determine the prevalence high risk (HR) MPS findings in pts with occult PAD diagnosed by screening ABI who are referred for MPS testing.

Methods:
As part of a prospective data collection, 679 male pts referred for MPS were screened for PAD with ABI evaluation. Pts with non-diagnostic ABIs (>1.3) or prior known PAD were excluded. PAD was defined as an ABI ≤ 0.9. PAD severity (mild [ABI 0.8 – 0.9], moderate [ABI 0.4 – 0.8], severe [<0.4]) and symptoms of PAD were also noted. CAD was defined as mild (summed stress score (SSS) ≥ 4) or severe (SSS>8), and the composite of any HR finding (SSS>8, left ventricular ejection fraction [LVEF] < 40%, or TID) was recorded.

Results:
PAD was present in 28%. Of pts found to have PAD, 65% reported no lower extremity symptoms. Compared to no PAD, pts with PAD were found to have significantly more mild or greater CAD (51% vs. 36%, p<0.01), severe CAD (35% vs. 19%, p<0.01), LV dysfunction [LVEF < 40%] (14% vs 7%, p < 0.01), and composite HR MPS findings (40% vs. 22%, p<0.01). On multivariate logistic regression analysis considering age, HTN, diabetes, tobacco use, hypercholesterolemia, and prior coronary artery disease, PAD was found to be an independent predictor of mild or greater CAD (OR 1.6, 95% CI 1.1–2.4, p<0.01), severe CAD (OR 1.9 95% CI 1.3–3.0, p<0.01), and any HR MPS finding (OR 2.0 95% CI 1.3–3.0, p<0.01).

Conclusions:
Among men referred for stress testing, occult PAD is common, and is an independent predictor of significant CAD and HR findings on MPS testing. Further study is needed to determine if PAD in pts without an indication for stress testing may benefit from screening MPS.
Abstract 1785: Renal Artery Angioplasty Improves Diastolic Cardiac Function In Patients With heart failure Possessing Renal Artery Stenosis.
Authors: Yamamoto Eisei , Takano Hitoshi , Tajima Hiroyuki , Tanabe Jun , Kawanaka Hidekazu , Tara Shuhei , Takahashi Yasuhiro , Fujita Nobuhiko , Takagi Gen , Aoki Satoshi , Asai Kuniya , Yasutake Masahiro , Takayama Morimasa , Mizuno Kyoichi
Published: July 2021

Background:

Renal artery stenosis (RAS) often plays an important role not only in malignant hypertension but also in sudden development of heart failure (HF) so called ‘flash pulmonary edema’ or chronic HF refractory to medical treatment. One of the possible mechanisms whereby RAS affects these unique conditions of HF is suppression of LV compliance through the complex interaction between neurohormonal systems originating from the reduction of renal blood flow. Renal artery angioplasty is expected to be an effective treatment for restoring renal blood flow in patients with RAS. The aim of the present study was whether the angioplasty can improve the impaired neurohormonal systems and diastolic cardiac function in patients with RAS.

Methods:

A prospective analysis was performed in 18 HF patients with RAS (age: 72±6, 3 females, NYHA I/II/III: 5/9/4) who underwent renal artery angioplasty between 2005 and 2007. Four patients with significant bilateral RAS and 3 patients with unilateral RAS in the vessel supplying a functional solitary kidney were included. We monitored the changes of biochemical and neurohormonal markers and blood pressure. Cardiac function was evaluated by tissue Doppler echocardiogram before and 3 months after the procedure.

Results:

Technical success was achieved in all interventions. The results are shown in table

. Systolic arterial blood pressure significantly decreased by renal angioplasty. B-type natriuretic peptide (BNP) was significantly reduced 3 months after the angioplasty, whereas the change of sCr or angiotensinII was not statistically significant. Myocardial early diastolic velocity (Em), a parameter of diastolic LV function, was significantly improved compared with that measured before the procedure.

Conclusions:

In patients with either overt or latent HF possessing RAS, renal artery angioplasty not only decreases arterial blood pressure but also improves diastolic cardiac function in parallel with the reduction of BNP level.
Abstract 1798: B-type Natriuretic Peptide and the Effect of Ranolazine in Patients with Non-ST Elevation Acute Coronary Syndromes in the MERLIN-TIMI 36 Trial
Authors: Morrow David A , Scirica Benjamin M , Sabatine Marc S , de Lemos James A , Murphy Sabina A , Jarolim Petr , Theroux Pierre , Bode Christophe , Braunwald Eugene
Published: July 2021

Ranolazine is believed to exert anti-ischemic effects by reducing myocardial cellular Na
+
& Ca
2+
overload and consequently LV wall stress. B-type natriuretic peptide (BNP) rises in response to increased wall stress and is a potent indicator of risk in ACS. Thus, we designed a prospective evaluation of the interaction between BNP and the effect of ranolazine as part of a randomized, blinded, placebo-controlled trial.

METHODS
: We measured plasma BNP (ADVIA BNP) at baseline (N = 4543) in pts with non-ST elevation ACS randomized to ranolazine or placebo in the MERLIN-TIMI 36 trial. Pts were stratified using BNP >80 pg/ml based on prior work. The 1
o
endpoint was a composite of cardiovascular death, myocardial infarction, or recurrent ischemia (CVD/MI/RI).

RESULTS
: Pts with an elevated BNP (N = 1935) were at significantly higher risk of CVD/MI/RI (26.4% vs. 20.4%, p < 0.0001), CVD/MI (16.2% vs. 7.5%, p<0.0001) and CVD alone (9.0% vs. 2.4%, p<0.0001). In pts with BNP>80 pg/ml, ranolazine reduced the primary endpoint (HR 0.79; 95%CI 0.66 – 0.94, p=0.009) contrasting with the lack of detectable effect in those with a negative BNP result (

Figure

, p-interaction = 0.05). The apparent effect of ranolazine in pts with BNP>80 pg/ml was directionally similar when considering both recurrent ischemia (HR 0.78; 0.62–0.98; p = 0.04) and CVD/MI (HR 0.83; 0.66–1.05, p= 0.12, p-interaction 0.07).

CONCLUSIONS
: Elevated BNP is associated with worse outcomes in ACS. The results of this planned exploratory analysis suggest that ranolazine may have enhanced efficacy in pts with elevated BNP. The potential interaction of biomarkers of hemodynamic stress and the effects of ranolazine warrants additional study.
Abstract 1800: Unfractionated Heparin Dosing and Major Bleeding in Non-ST-Segment Elevation Acute Coronary Syndromes
Authors: Melloni Chiara , Alexander Karen P , Chen Anita Y , Roe Matthew T , Newby L. Kristin , Ohman E. Magnus , Gibler W. Brian , Smith Sidney C , Pollak Charles V , Peterson Eric D
Published: July 2021

Background
: Unfractionated heparin (UFH) is a mainstay in the treatment of ACS, but failure to adjust UFH dosing based on pt weight is common.

Methods
: We used data from 31,445 high-risk ACS pts in 420 CRUSADE hospitals to assess initial UFH bolus and infusion doses relative to guidelines recommendations (60–70 U/Kg bolus and 12–15 U/Kg/h infusion). We evaluated the following: UFH excess dosing (>70 U/kg bolus or >15 U/kg/min infusion) vs. no excess dosing; excess dosing and major bleeding, overall and in subgroups; and factors associated with excess dosing.

Results
: An excess dose of UFH was given 35% of the time (8.9% excess infusion, 9.0% excess bolus, 17.1% both); more often to women, elderly, and those with low body weight (Figure). There was a digit preference for bolus doses of 5000 U (37%), and infusion doses of 1000 U/h (45%). The factors most associated with excess dosing were older age (OR 1.11, 95% CI 1.08–1.15) and female sex (OR 1.45, 95% CI 1.33–1.59). Although individually excess bolus (OR 1.03, 95% CI 1.00–1.06) and excess infusion (OR 1.16, 95% CI 1.05–1.28) each contribute to bleeding, considered together only excess infusion remained significantly associated with bleeding (OR 1.13, 95% CI 1.01–1.26). Although women and elderly bleed more, the relationship between UFH dose (bolus and infusion individually) and major bleeding did not vary across sex and age.

Conclusion
: In high-risk NSTE ACS pts, both UFH bolus and infusion dosing is often outside the recommended range. Excess dosing is common among elderly and women and is related to increased bleeding. Attention to dosing by weight rather than one-size-fits-all bolus and infusion dosing should improve safety in the use of UFH.
Abstract 1803: Catheterization without In-hospital Revascularization is Associated with Increased Long-term Mortality in Patients with Non-ST Elevation Myocardial Infarction and Significant Coronary Artery Disease
Authors: Chan Mark Y , Mahaffey Kenneth W , Sun Jie-Lena , Pieper Karen S , White Harvey D , Aylward Philip E , Ferguson James J , Califf Robert M , Roe Matthew T
Published: July 2021

Background:
Despite guidelines recommendations for early invasive management in non-ST-elevation myocardial infarction (NSTEMI), some patients (pts) with significant coronary artery disease (CAD) found on early angiography do not undergo revascularization. The prevalence, clinical features, and long-term prognosis of this population have not been well-characterized.

Methods:
We evaluated 8225 NSTEMI pts from the SYNERGY trial (2002–2004) with >50% stenosis in at least 1 epicardial artery who received in-hospital percutaneous coronary intervention (PCI), in-hospital coronary artery bypass grafting (CABG), or no revascularization before discharge (medical management). A propensity-adjusted Cox proportional hazards model was used to compare death/MI rates at 6 months and mortality rates at 1 year among the 3 subgroups starting from the time of hospital discharge.

Results:
A total of 2633 of 8255 pts (32%) were medically managed, 4294 (52%) underwent PCI, and 1298 (16%) underwent CABG. Clinical features and unadjusted outcomes are shown below. Guidelines-recommended discharge medications were used in a large proportion of patients, but those undergoing PCI most commonly received evidence-based therapies. The adjusted risk of 6-month death or MI was 2.19 (95% CI: 1.79–2.67) for medical management compared with PCI, and 3.07 (95% CI: 2.18 – 4.34) for medical management compared with CABG. The adjusted risks of 1-year mortality for medical management were 1.52 (95% CI: 1.07–2.17) and 1.70 (95% CI: 0.96–3.03), respectively.

Conclusion:
A substantial proportion of NSTEMI pts with significant CAD are managed medically without in-hospital revascularization. These pts have higher-risk clinical characteristics and worse outcomes compared with those who undergo PCI or CABG, despite fairly good use of evidence-based medications. Therefore, innovative treatment strategies are needed to mitigate the increased risk of adverse outcomes in this population.

Baseline Characteristics, Discharge Medications, and Unadjusted Clinical Outcomes for the 3 Groups
Abstract 1804: Is CPR Quality Improving? A Retrospective Study Of Out-of-hospital Cardiac Arrest
Authors: Olasveengen Theresa M , Wik Lars , Kramer-Johansen Jo , Sunde Kjetil , Pytte Morten , Steen Petter Andreas
Published: July 2021

Aim of the study:
To evaluate quality of cardiopulmonary resuscitation (CPR) performed by a physician-manned ambulance, and assess whether it changed with time influenced by developing scientific evidence and guideline changes.

Materials and methods:
Retrospective, observational study of all cardiac arrest patients (except trauma) older than 18 years treated between May 2003 and December 2006 by the physician-manned ambulance in Oslo. CPR quality was assessed from continuous electronic recordings from the defibrillators (LIFEPAK 12, Physio-Control or a modified Heartstart 4000, Philips Medical Systems). Ventilations were assessed from changes in transthoracic impedance, chest compressions from transthoracic impedance for LIFEPAK 12 and from an accelerometer for Heartstart 4000 (nine patients). Values are given as mean ± SD and differences analysed with ANOVA and unpaired Student’s t-test with Bonferroni correction.

Results:
Forty-eight of 169 consecutive cases were excluded from CPR quality analysis, 47 due to missing defibrillator data and one due to short arrest time (<1 min). Hands-off intervals (fraction of time without spontaneous circulation where no chest compressions are given) were reduced from 0.18±0.11 in 2003 to 0.10±0.06 in 2006 (p=0.03). Compression and ventilation rates were significantly reduced from 122±12 and 16±3 per minute respectively in 2003 to 111±10 and 12±3 in 2006 (p<0.0001 and p=0.001). In 2003–4 10% were discharged alive vs. 16 % in 2005–6 (p=0.3, Chi square test).

Conclusion:
High quality CPR is achievable out-of-hospital, and the improvement with time could reflect developing scientific evidence focusing on reducing hands-off intervals and hyperventilation.

Quality of CPR from May 2003 to 2006.
Abstract 1806: End-tidal Carbon Dioxide as a Measure of Cardiopulmonary Resuscitation Efficacy during Human Cardiac Arrest
Authors: Wallbrecht Joshua L , Edelson Dana P , Litzinger Barbara , Walsh Deborah , Hoek Terry L Vanden , Becker Lance B , Abella Benjamin S
Published: July 2021

Background: End-tidal carbon dioxide (EtCO
2
) is a physiologic measure that has potential to serve as an indicator of chest compression efficacy, with higher EtCO
2
values during CPR correlating with improved hemodynamics during prior laboratory studies. EtCO
2
measurement could therefore guide resuscitation efforts and help optimize CPR performance.

Objective: To test the hypothesis that EtCO
2
levels positively correlate with improved chest compression rate and depth during human cardiac arrest.

Methods: A prospective, observational study was conducted using a commercially available monitor/defibrillator with CPR quality and EtCO
2
sensing capabilities (MRx-QCPR, Philips Medical Systems) during in-hospital cardiac arrests at one hospital from 4/2006 until 8/2006. Resuscitation transcripts were divided into 30-second segments and mean values of chest compression rate and depth and EtCO
2
were derived for each segment. Regression analysis, with cluster-adjustment for individual patients, was used to correlate compression rate and depth with EtCO
2
.

Results: Data were collected and analyzed from 281 30-second segments with a median of 12 (interquartile range: 8–33) segments per arrest from 13 consecutive patients for whom EtCO
2
and chest compression data were simultaneously available. Mean EtCO
2
was 19±7 mmHg. After adjusting for compression rate and clustering, there was a positive correlation between compression depth and EtCO
2
(regression coefficient 0.20; 95%CI [−0.01 – 0.42]). There was no significant correlation between compression rate and EtCO
2
after adjusting for compression depth and cluster, nor between survival and EtCO
2
levels.

Conclusion: We found that deeper chest compressions correlated with higher EtCO
2
levels. Based on this relationship, changes in EtCO
2
during the actual resuscitation event may be reflective of the CPR quality being delivered. This work also suggests the feasibility of continuous monitoring of physiology during CPR to ensure resuscitation quality.
Abstract 1807: Low-volume Resuscitation From Traumatic Hemorrhagic Shock With Na+/H+ Exchanger Inhibitor
Authors: Wu Dongmei , Dai Hui , Arias Jaqueline , Latta Loren
Published: July 2021

Background:
Severe hemorrhage from traumatic injury is a major causative factor in almost half of these deaths on the battlefield, especially during the early period (<2h) after injury. Intervention with low-volume fluid resuscitation is increasingly preferred than more aggressive fluid replacement. We evaluated the use of a Na+/H+ exchanger (NHE) inhibitor, as a cardioprotective adjunct therapy to low-volume resuscitation in a rat model of traumatic hemorrhagic shock.

Methods:
Femur fracture with soft tissue injury was induced in 28 anesthetized male rats. The animals were then bled via the carotid artery to maintain a mean arterial pressure of 40 mmHg for 20 minutes. Groups:

no therapy;

15 ml/kg Hextend infusion over 40 minutes;

3 mg/kg BIIB513 (NHE-1 inhibitor) + 15 ml/kg Hextend infusion over 40 minutes.

After 4 hours, the animals who survived received a second infusion of Hextend. The experiment was terminated at 6 hours after initial resuscitation. Data are reported as mean ± SD.

Results:
All animals in the no therapy group died within 2 hours. Compared to Hextend infusion alone, the addition of NHE-1 inhibition with BIIB513, improved the hemodynamic response to fluid resuscitation (Fig 1

), increased blood oxygen content, prevented metabolic acidosis, and improved 6 hour survival (42% in Hextend group vs 80% in BIIB513 + Hextend group). NHE-1 inhibition also resulted in reduced plasma levels of TNF-α, ICAM-1 and C-reactive protein, and attenuated neutrophil infiltration in the liver.

Conclusion
: NHE-1 inhibition with BIIB513 improved the hemodynamic response to fluid resuscitation, attenuated tissue inflammatory mediators, and most importantly improved survival.
Abstract 1809: Survival And Neurologic Recovery In Patients With ST-Elevation Myocardial Infarction Resuscitated From Cardiac Arrest
Authors: Reddy Vivek , Hosmane Vinay R , Mustafa Nowwar , Reese Charles , DiSabatino Angela , Kolm Paul , Weintraub William S , Rahman Ehsanur
Published: July 2021

Methods:
We examined records of 2290 consecutive patients at our institution suspected of having ST-Elevation myocardial infarction (STEMI) from 1/1/02 to 12/31/06. Our study group comprised 99 STEMI patients resuscitated from cardiac arrest who were taken for emergent catheterization. Percutaneous coronary intervention was performed in 66, bypass surgery in 12, and 21 have neither. Endpoints were in-hospital death and neurologic recovery. Logistic regression was used for analysis.

Results:
Overall 64 (65%) survived and 35 (35%) died. Full neurologic recovery was seen in 59 (92%) of the survivors. On evaluation before catheterization: 25 were
alert
,
14 were
minimally responsive
to pain and stimuli, 60 were
unresponsive
. Patients in the latter two groups were intubated. In the
unresponsive
group (n=60), 27 survived (45%) and 33 died. Full neurologic recovery was seen in 23/27 survivors (85%). Predictors of death and neurologic recovery are shown in Table 1

and Table 2

.

Table 1:

Logistic Regression for Death For the Entire Group (c index = 0.894), N= 99

Table 2:

Logistic Regression for Death for the Unresponsive Group (c index = 0.898), N=60
Abstract 1812: More CPR with the New Guidelines. Does it Impact VF Termination by Defibrillation Shocks?
Authors: Hersan Olivier , Jost Daniel , Banville Isabelle L , Calamai Franck , Fontaine David , Lallement David , Chapman Fred W , Walker Rob G , Degrange Herve , Fuilla Claude
Published: July 2021

The 2005 resuscitation Guidelines emphasize reducing interruptions of cardiopulmonary resuscitation (CPR) and provide changes to the CPR and defibrillation protocols for automated external defibrillator (AED) use. We investigated whether the differences between Guidelines 2000 and 2005 resuscitation protocols influence the ventricular fibrillation (VF) termination rate of AED shocks during out-of-hospital cardiac arrest.

Methods: As part of a clinical trial, VF cardiac arrest patients treated by firefighters were prospectively randomized to treatment protocols consistent with Guidelines 2000 (CONTROL) or Guidelines 2005 (STUDY). The STUDY protocol removed stacked shocks and post-shock pulse checks. It featured 1 minute of CPR before the 1st shock, and CPR between rhythm analysis and shock delivery. All AEDs delivered escalating biphasic shocks beginning at 200J. We reviewed AED electronic records to evaluate VF termination for all shocks within the first 8 minutes of treatment. Successful defibrillation was defined per Guidelines 2005 as termination of VF for > 5seconds. A sample size of 400 shocks per group was prospectively chosen for statistical power to detect an 8% difference in VF termination rate.

Results: As expected, the STUDY protocol resulted in more prompted CPR time, more actual CPR delivered, and fewer shocks during the first 8 minutes of treatment. The VF termination rate did not differ between the two groups (85% CONTROL vs. 87% STUDY). The proportions of patients with ventricular complexes (24% vs. 27%), in asystole (61% vs. 60%), or remaining in a shockable rhythm (15% vs. 13%) at 5 seconds were also not different between the CONTROL and STUDY groups, respectively.

Conclusion: Despite a reduction in CPR hands-off time, VF termination effectiveness of biphasic shocks is similar for Guidelines 2000 and Guidelines 2005 cardiac arrest treatment protocols.
Abstract 1814: Perceived Cardiac Risk Underestimated Among Urban Diabetics
Authors: Allen Jerilyn K , Dennison Cheryl , Purcell Allison , Szanton Sarah , Hill Martha , Previte Rosemarie
Published: July 2021

Cardiovascular disease (CVD) is the leading cause of death in diabetics; however, understanding among diabetics of the importance of CVD as a major health threat is unknown. We studied perceived and actual risk of developing CVD and the factors associated with perceptions of CVD risk in a sample of 82 type II diabetic patients without diagnosed CVD. Data were collected during baseline evaluation for a randomized trial to reduce total CVD risk in urban community clinics. Perceived risk was determined by the patients’ estimation of their personal likelihood of developing heart disease and objective risk was calculated using the Framingham Index. Depressive symptoms were measured by the CES-D and overall perception of health by the EuroQuol. CVD risk factors were measured directly using standardized procedures. The sample was 73% female and 93% Black. Mean age was 54 ± 11 years, 32% had not graduated from high school and 55% had annual household incomes <$20,000. CVD risk factor burden was high: 70% were obese; 68% had BP≥130/80; 56% had high LDL-C; and 31% were current smokers. The Framingham 10 year CVD risk ranged from 1–33% with average risk of 11.4 ± 7.2%. In contrast, only 18% of patients perceived themselves at high risk for developing heart disease. Objective and perceived CVD risk were not significantly associated (β=−0.38; p<0.31). Increased levels of perceived risk were associated with younger age (β= −0.648; p=0.007), greater depressive symptoms (β=0.87; p<.000), poorer general health perception (β= −0.51; p<.000); and current smoking (β=14.27; p=0.02); but there was no association with HgA1c, LDL-C, or blood pressure levels. In a multivariate model, greater depressive symptoms, poorer general health perceptions, and current smoking were independently associated with perceived risk for CVD. Urban, disadvantaged diabetics in this study of predominately Black women had many CVD risk factors and increased objective risk for developing CVD. However, there was a gap between perceived and actual risk of CVD. Attempts to improve the cardiovascular health of underserved groups should include interventions to increase awareness and control of CVD risk factors among type II diabetics, particularly aimed at racial/ethnic minority women.
Abstract 1818: Beneficial Effects of Weight Loss Associated with a High Protein Diet on Cardiovascular Risk Profile, Functional Status and Quality of Life in Obese Heart Failure Patients: A Feasibility Study
Authors: Evangelista Lorraine S , Heber David , Li Zhaoping , Hamilton Michele , Fonarow Gregg C
Published: July 2021

OBJECTIVE: Clinical management of chronic heart failure (HF) related to adequate nutritional intake currently lacks a strong scientific basis. This study was conducted to evaluate the impact of 3 diet interventions on body weight and its potential to reduce cardiovascular risks and improve functional status.

METHOD: Fourteen obese HF patients (BMI > 27 kg/m2) were randomized to1 of 3 diets: high protein (HP); low fat (LF) or average diet/control group (CG). Body anthropometrics (weight, BMI, waist circumference), indices of cardiovascular risks including (% body fat, blood pressure, cholesterol, triglycerides), and measures of functional status (6-minute walk, max VO2) were obtained at baseline and after a 12-week nutritional support program. Statistics included two-way RMANOVA.

RESULTS: There were no significant differences in age (59±10 years), gender (78% male), NYHA (43% class II; 57% class III), HF etiology (57% non-ischemic), or ejection fraction (0.26±0.07) between the groups. The HP diet resulted in moderate reductions in body weight (Figure

) and improvements in several health parameters (Table

).

CONCLUSION: The data show that in a small group of obese HF patients, a 12-week HP diet resulted in moderate weight loss that was associated with reduced cardiovascular risks and better functional status. However, the long-term effects of a HP diet remain uncertain.

Figure

Comparison of Weight Changes in the HP, LF and CG from Baseline to 12 Weeks

Mean changes in outcomes from baseline to 12 weeks, by diet group and time
Abstract 291: Association of Single Nucleotide Polymorphisms in Inflammatory Candidate Genes with Circulating Inflammatory Biomarker Concentrations: The Framingham Heart Study
Authors: Schnabel Renate , Lunetta Kathryn L , Larson Martin G , Dupuis Josée , Keaney John F , Lipinska Izabella , Govindaraju Diddahally R , Hirschhorn Joel N , Kathiresan Sekar , Meigs James B , Lee Douglas S , O’Donnell Christopher J , Newton-Cheh Christopher , Chen Ming-Huei , Zhao Zhenming , Rong Jian , Sutherland Patrice , Vasan Ramachandran S , Benjamin Emelia J
Published: July 2021

Background
: Chronic subclinical inflammation is a prominent feature of atherosclerotic disease. The genetic background for this pro-inflammatory state is not well-established. Circulating biomarker concentrations have become attractive candidates to measure disease activity and prognosis.

Methods
: We examined 2356 single-nucleotide polymorphisms (SNPs) in 235 inflammatory pathway genes in association with 11 circulating inflammatory biomarkers in about 1800 Framingham Offspring cohort participants [CD40 ligand, CRP, intercellular adhesion molecule-1, interleukin-6 (IL6), urinary isoprostanes, monocyte chemoattractant protein-1 (MCP1), myeloperoxidase, P-selectin, tumor necrosis factor alpha, tumor necrosis factor receptor-2, fibrinogen]. We created residuals of log transformed biomarker concentrations adjusting for 16 potential confounders. Only SNPs with call rate ≥0.98 and HWE p>0.01, which had at least 5 minor allele carriers entered analyses. False discovery rate (FDR) and q-value methods were applied.

Results
: We observed similar results with FDR and q-value methods. A total of 45 associations were significant at a cutoff q value of 0.25. The top SNPs were observed in the
SELP
gene in association with P-selectin concentrations (rs6136 [nonsynonymous], p= 5.17*10
−39
, rs3753305 [intronic], p= 6.17*10
−9
) and the
ICAM1
gene in relation to ICAM-1 concentrations (rs1799969 [coding-nonsynonymous], p= 1.32*10
−8
). Lowest p-values for trans-acting SNPs were observed for
APCS
(rs1374486 [function unknown], p= 1.01*10
−7
, and rs6695377 [function unknown], p= 1.85*10
−7
) with MCP-1 concentrations and for
IL6R
(rs8192284 [coding-nonsynonimous,intronic], p= 3.36*10
−5
) with IL6 concentrations. In addition, we could replicate reported findings for rs1799969, and rs5498 in the
ICAM-1
gene in relation to ICAM-1 concentrations as well as associations of SNPs rs2857654, rs1024611, and rs2857657 in the
CCL-2
gene with MCP-1 concentrations.

Conclusions
: The results of this candidate gene approach support the relevance of genetic variation for circulating inflammatory biomarker traits. Some former findings were confirmed and novel potential candidates are reported. Our findings merit replication in other cohorts.
Abstract 1837: Effects of the Gap Junction Modifier, GAP-134, on Conduction and Atrial Fibrillation/Flutter Inducibility in Dogs
Authors: Rossman Eric I , Liu Kun , Morgan Gwen A , Swillo Robert E , Butera John , Gruver Matthew , Kantrowitz Joel , Haugan Ketil , Petersen Jorgen S , Hennan James K
Published: July 2021

Atrial fibrillation (AF) and atrial flutter (AFL), the most common sustained cardiac arrhythmias, are major contributors to cardiovascular morbidity and mortality in the adult population. Current pharmacologic treatment of AF/AFL is only moderately successful and not well tolerated among patients, highlighting an unmet medical need for safer, effective agents. GAP-134 is the first small molecule gap junction modifier developed for the prevention of AF/AFL. In preliminary experiments, this modified antiarrhythmic dipeptide with similar activity to the antiarrhythmic hexapeptide rotigaptide, significantly prevented conduction velocity slowing in rat atrial strips subjected to metabolic stress at 10 nM (5.6±9.4%) and 100 nM (0.4±5.0%) compared to controls (−29.1±5.3%). In the canine sterile pericarditis model, conduction time (CT, n=5) and AF/AFL inducibility (n=9) were measured 2–3 days post-operatively in closed chest studies, using electrodes placed at the right atrial appendage (RAA), the Bachmann’s bundle (BB), and the posterior left atrium (LA). CT, measured between the BB and LA, was significantly faster after GAP-134 infusion (average plasma concentration was 73.1 ng/ml) at RAA pacing rates of 200 bpm (66.2±1.0 ms vs 62.0±1.0 ms; p=2.49E-08), 300 bpm (64.4±0.9 ms vs 61.0±1.3 ms; p=2.67E-03), and 400 bpm (67.2±1.6 ms vs 65.0±1.9 ms; p=0.041). Induction of AF/AFL was attempted using a burst pacing protocol, at all three atrial sites, starting at 500 bpm and increasing at increments of 20 bpm until 800 bpm. The average number of successful AF/AFL inductions per animal was significantly decreased after GAP-134 infusion (2.7±0.6 vs 1.6±0.8; p=0.021), with the total number of inductions being decreased from 24 to 14. Mean AF/AFL duration per induction (603±119 s vs 260±116 s; p=0.021) and mean AF/AFL duration per animal (1364±419 s vs 705±483 s; p=0.049) were also significantly decreased after GAP-134 infusion, with total AF/AFL burden being decreased from 12280 s to 6348 s. In conclusion, GAP-134 shows consistent efficacy on measures of conduction and AF/AFL inducibility in the canine sterile pericarditis model. These findings, along with its oral bioavailability, underscore its potential as a highly effective atrial antiarrhythmic compound.
Abstract 1842: Inflammatory Activation In Patients With Lone Atrial Fibrillation: New Insights By Coronary Sinus Thermography.
Authors: Toutouzas Konstantinos , Drakopoulou Maria , Vaina Sophia , Dilaveris Polychronis , Gatzoulis Kostas , Karabelas John , Riga Maria , Stefanadi Elli , Tousoulis Dimitrios , Stefanadis Christodoulos
Published: July 2021

Background:
In the clinical setting there are conflicting results regarding the role of inflammatory activation in atrial fibrillation (AF). Coronary sinus (CS) thermography assesses myocardial heat production and is correlated with inflammatory states. The purpose of this study was to investigate in patients (pts) with AF whether

there is increased CS blood temperature and

the correlation of heat production with systemic inflammation.

Methods:
We included pts with AF and subjects with sinus rhythm (controls). C-reactive protein (CRP) levels were measured in all pts. CS and right atrium (RA) blood temperature measurements were performed by a dedicated 7F thermography catheter. ΔT was calculated by subtracting RA from CS blood temperature.

Results:
We included 70 pts: 47 with lone AF and 23 controls. We stratified pts with AF into two groups: normotensive (AFN; n=25) and hypertensive (AFH; n=22). Heart rate was similar between the three groups (AFH: 72.91±4.11/min, AFN: 72.84±4.50/min control:72.52±4.19/min, p=0.89). Mean blood temperature was lower in the RA compared with the CS in AFH (37.27±0.52°C vs 37.47±0.54°C, p<0.01), in AFN (37.13±0.53°C vs 37.34±0.54°C, p<0.01), and in controls (37.41±0.69°C vs 37.55±0.68°C, p<0.01). ΔT was greater in AFH, and AFN compared to controls (0.20±0.07°C, 0.20±0.08°C, vs 0.14±0.06°C, p<0.01 for both comparisons). ΔT was similar between AFH and AFN (p=0.95). CRP was higher in AFH and AFN compared to controls (1.72±0.85mg/Dl, 1.69±0.94mg/dL vs 0.98±0.71 mg/dL, p<0.01). CRP was similar between AFH and AFN (p=0.87). Pts with high ΔT (≥0.15°C) had significantly higher CRP compared to pts with low ΔT (1.73±0.95mg/dL vs 1.01±0.57 mg/dL, p=0.01). A correlation between CRP levels with ΔT was observed in AFH and AFN (R=0.58, p<0.01, R=0.44, p=0.02, respectively). Multiple linear regression analysis confirmed that pts with lone AF (b±SE: 0.07±0.02, p=0.01) and pts with hypertension and AF (b±SE: 0.07±0.03, p=0.03) had higher ΔT compared to the control group.

Conclusions:
Pts with AF have increased myocardial heat production, which is correlated to the systemic inflammation. CS blood temperature measurement may provide significant information for the pathogenesis of AF.
Abstract 1844: Increased Mortality And Perioperative Complications In Patients After Previous Elective Percutaneous Coronary Interventions Undergoing Coronary Artery Bypass Surgery
Authors: Bonaros Nikolaos , Hennerbichler Diana , Alber Hannes , Kocher Alfred , Pachinger Otmar , Laufer Guenther , Bonatti Johannes
Published: July 2021

Introduction. The number of patients with previous Percutaneous Coronary Interventions (PCI) referred to Coronary Artery Bypass Grafting (CABG) is continuously increasing. The relationship between previous elective PCI and the perioperative outcome after CABG remains undetermined. The aim of the study was to investigate whether patients referred to CABG after previous elective PCI have an increased perioperative risk.

Methods. Between January 2002 and May 2007, 4412 consecutive patients underwent first-time open heart surgery at our department. After excluding patients with a history of emergent PCI, we isolated 306 patients after previous elective PCI during the last 24 months before CABG (Group 1). Those patients were compared to 452 consecutive patients without history of previous PCI, who underwent CABG during the same period and who were matched for age, gender and preoperative risk factors (Group 2). Both groups were compared in terms of 30-day mortality, Major Adverse Cardiac Events (MACEs), and perioperative complications.

Results. Both groups were comparable concerning preoperative linear EuroSCORE (Group 1: 4.83±0.18, Group 2: 4.72±0.14, p=0.63). Patients with previous elective PCI before CABG had increased perioperative mortality (Group 1: 3.3% vs Group 2: 1.9%, p<0.001) and MACEs (Group 1: 7.9% vs 4.3%, p<0.001). This fact was associated with a worse logistic perioperative outcome (Group 1: 1.26±0.39, Group 2: 2.33, p=0.044). In addition, the incidence of bleeding complications (Group 1: 5.9% vs Group 2: 3.8%, p=0.017) and the number of blood products (Group 1: 1.70±0.31 vs 0.61±0.17, p<0.001) used were higher in patients of the Group 1. A higher incidence of acute renal failure (Group 1: 5.9% vs 2.7%, p=0.025) and renal replacement therapy (Group 1: 3.6% vs Group 2: 1.7%, p=0.03) was observed in patients of the same group.

Conclusions. Patients with previous elective PCI before referral to CABG have a worse perioperative outcome in terms of mortality, MACE and perioperative complications as compared to patients with no history of PCI.
Abstract 1867: Real-Time Three-Dimensional Echocardiographic Left Ventricular Mass to Volume Ratio Is Superior To Volumetric Indices For Arrhythmic Risk Prediction
Authors: Chukwu Ebere O , Toole Rena S , Mclaughlin Jeanette , Levine Joseph H , Greenberg Steven , Hoch David , Schecter Stuart O , Jayam Vinod , Reichek Nathaniel , Gopal Aasha
Published: July 2021

Background:
Left ventricular (LV) mass is an important prognostic factor for predicting cardiac morbidity and mortality. LV mass to volume ratio (M/V) by CMR has been shown to relate to adverse outcomes in several settings. However, the relevance of this M/V has not been established for post-MI arrhythmias. We evaluated the use of 3D echo (3D) LV M/V in predicting event free survival in post-MI patients meeting the MADIT II criteria, and compared it to EDV and ESV indexed to the body surface area (EDVi, ESVi).

Methods:
Forty patients (35 males, mean age 69.6y) meeting the MADIT II criteria for implantable defibrillator (ICD) placement with an EF of ≤30% were imaged and followed up for a mean of 472 days for adverse events (ventricular fibrillation or sustained ventricular tachycardia, and appropriate ICD discharges). Patients had 3D within 24 hours of ICD implantation. EDVi, ESVi and LV mass were determined and M/V calculated. Receiver operator curves (ROC) were used to determine the associations between M/V, EDVi, ESVi and adverse events.

Results
: Mean indexed LV mass was 109.7 g. Mean EDVi, ESVi were 123.3 ml/m
2
and 93.4ml/m
2
. The adverse event rate was 25% (10/40 patients). ROC curve analysis showed that M/V was significantly associated with adverse events(p = 0.002) while EDVi (p=0.12) and ESVi (p=0.08) were not. Patients with higher M/V were more likely to have events than those with smaller M/V (area under the curve = 0.74, sensitivity 80%, specificity 67%).

Conclusion:

3D derived LV M/V is useful for determining risk of adverse events in high-risk post-MI patients who meet the MADIT II criteria.

M/V is superior to 3D EDV, ESV for prediction of arrhythmic events this high risk population.
Abstract 132: Endothelial Progenitor Cells Prevent Endothelial Barrier Injury by Cdc42-dependent Assembly of VE-cadherin
Authors: Ohkawra Hiroshi , Zhao Yidan D. , Malik Asrar B.
Published: July 2021

We investigated the use of bone-marrow derived endothelial progenitor cells (EPCs) for the treatment of microvascular endothelial injury caused by inflammatory diseases. As activation of the monomeric RhoGTPase Cdc42 signals annealing of adherens junctions (AJs) in the endothelial barrier, we examined the possibility that EPCs could restore endothelial barrier dysfunction by promoting Cdc42 activation in endothelial cells (ECs). We observed that co-culture of EPCs with ECs prevented the decrease in transendothelial electrical resistance (TER), a measure of AJ assembly, and the decrease in VE-cadherin expression induced by thrombin (4 U/mL). EPCs also significantly reduced the formation of inter-endothelial gaps mediated by RhoA activation as well as myosin light chain phosphorylation in response to thrombin. We showed that EPCs induced activation of Cdc42 in ECs and increased TER within 15 min after the addition EPCs to ECs, indicating the enhancement of endothelial barrier function. Addition of EPCs after thrombin-induced disruption of AJs also promoted rapid recovery of TER compared to controls. Based on siRNA knockdown data, the endothelial barrier protective effect of EPCs was mediated by Cdc42 activation in ECs. Thus, EPC-mediated activation of Cdc42 in ECs decreases basal endothelial permeability and prevents endothelial hyper-permeability induced by the mediator thrombin. EPC/EC cross-talk is a critical mechanism regulating endothelial barrier function suggesting the value of EPCs in the treatment of microvascular injury associated with vascular inflammation.
Abstract 133: Transplantation Of Neurosphere-forming Stem Cells Into Circulating Blood Attenuates Acute Inflammatory Activation Of Both Brain And Spleen After Cerebrovascular Ischemic Injury.
Authors: Lee Soon-Tae , Chu Kon , Jung Keun-Hwa , Park Hee-Kwon , Kim Jeong-Min , Lim Jae-Sung , Kim Se-Jeong , Choe Vit Nary , Kim Dong-Hyun , Kim Jin-Hee , Ban Jae-Joon , Lee Sang Kun , Kim Manho , Roh Jae-Kyu
Published: July 2021

Background and Objectives:
Transplantation of neural progenitor cells (NPCs) has been studied to achieve the regeneration of damaged brain in experimental stroke models. Tissue ischemia induces systemic inflammatory activation, especially in spleen. However, the interaction between NPCs and immune/inflammatory cells has not been studied in ischemia models. In this study, we investigated whether NPC can attenuate cerebral and systemic inflammatory activation in focal cerebral ischemia.

Methods:
Focal cerebral ischemia was induced by intraluminal thread occlusion of the middle cerebral artery for 60 minutes (c57/bl6 adult male mice), and mouse NPC from primary neurosphere (1 million cells) or vehicle (PBS, control group) was injected via tail veins with cerebral reperfusion. Inflammatory cytokines were evaluated with RealTime-PCR at 22 hrs, and the weights of each spleen and thymus were measured.

Results:
Cerebral ischemia induced progressive atrophies of spleen and thymus when measured at 22 hr and 96 hr after ischemia. Intravenous injection of NPC accelerated these lymphoid organ atrophies, and the weights of spleen and thymus were significantly lower in NPC-injected mice at 96 hr after the ischemia compared to the vehicle injected mice. RealTime-PCR analysis using ischemic hemispheres and spleens showed reduced expressions of inflammatory cytokines, including TNF-alpha, IL-6, MIP-2, IL-13, FoxP3, IL-1beta, and IP10 in NPC-injected brains and spleens at 22 hr after the ischemia. Transplanted NPCs were detected in systemic organs, and mostly in spleen. NPC-injected mice showed reduced infarct volume and neurologic deficits.

Conclusion:
Intravenous transplantation of primary neuro-sphere cells in cerebral ischemia attenuated systemic inflammatory activation, which suggests that the immunomodulating property of neural progenitor cells can be applicable for preventing harmful inflammations after the tissue ischemia.
Abstract 297: Caveolae and Mitochondria: a Subcellular Symbiotic Relationship that Facilitates Cardiac Myocyte Function
Authors: Patel Hemal H , Head Brian P , Lesnefsky Edward J , Jennings Michelle , Peart Jason N , Headrick John P , Rothstein Emily R , Niesman Ingrid R , Roth David M , Farquhar Marilyn G , Balaban Robert S , Insel Paul A
Published: July 2021

Caveolae, membrane microdomains composed of lipids and various proteins, including the protein caveolin (Cav), are involved in trafficking and compartmentation of signaling molecules. The possible relationship between caveolae and intracellular organelles is poorly defined. Here, we used whole hearts and cardiac myocytes (CM) and sought to determine whether caveolae and mitochondria associate and if this association has a functional consequence. Electron microscopy of CM revealed close apposition of subsarcolemmal mitochondria and caveolae. Subsarcolemmal mitochondria have greater expression of Cavs-1 and -3 relative to interfibrillar mitochondria and expression of Cav-3 in mitochondria was confirmed by immunoelectron microscopy. Immunoblotting of sucrose density gradient fractions prepared from CM, which facilitates the isolation of caveolae from other cellular membranes, detected enrichment of multiple enzymes that can serve as antioxidants (heme oxygenase-1, eNOS, cytochrome P450 reductase, and Cu-Zn and Mn superoxide dismutase) in caveolin-enriched buoyant fractions. Hearts of aged animals (24+ months), which have mitochondrial dysfunction, showed a 48% reduction in Cav-3 expression (p<0.01) relative to young animals (6 months). Adenoviral overexpression of Cav-3 in CM resulted in increased formation of caveolae and reduced generation of superoxide (as assessed by dihydroethidium staining) in response to hypoxia/reperfusion stress compared to control and LacZ- treated CM. Cav-3 overexpressing myocytes had endogenously elevated levels of phosphorylated Akt and glycogen synthase kinaseβ, two downstream mediators of cardiac protection. The close apposition of caveolae and mitochondria, the enrichment of redox-enzymes in caveolae, the ability of increased Cav expression to form caveolae and attenuate free radical generation and loss of Cav expression with age suggest that caveolae are microdomains that may serve as “antioxidant sinks” for free radicals produced by adjacent mitochondria in CM. The close association of caveolae and mitochondria may thus represent an important symbiotic subcellular organization that helps promote function and limit oxidative damage in the heart.
Abstract 1869: Real-Time Three-Dimensional Echocardiography of the Left Atrial Appendage: Initial Experience in Humans with Validation by 64-Slice Computed Tomography
Authors: Shah Sanjiv J , Bardo Dianna M , Weinert Lynn , Sugeng Lissa , Knight Bradley P , Lopez John J , Lang Roberto M
Published: July 2021

Background:
Real-time left atrial appendage (LAA) quantification is increasingly important with the advent of LAA occluder devices for stroke prevention. However, accurate quantification is difficult using 2D-TEE because measurements must be made in multiple views, and LAA orifice cannot be viewed directly. We aimed to determine the accuracy of LAA geometry measured by a new matrix-array (mTEE) probe which can provide unique real-time 3D (RT3D) views of the LAA.

Methods:
29 consecutive patients (age 53±18) referred for 2D-TEE underwent additional RT3D-mTEE (Philips ie33; frame rate 8–10/s). The LAA orifice diameter and LAA depth were measured from biplane 2D images, and 2D LAA orifice area was calculated as an ellipse. LAA orifice area and LAA depth were measured in 3D and correlated to 2D. In 8 patients who had cardiac CT available, 2D- and 3D-TEE LAA measurements were correlated with 64-slice CT. All LAA measurements were made at atrial end-diastole.

Results:
All 29 patients underwent RT3D-mTEE without complication. The LAA was well-visualized in 3D in 26/29 (90%). Because the shape of the LAA orifice in 3D was an ellipsoid with an irregular contour, 2D images resulted in underestimation of area vs. 3D (3.0±1.2 vs. 4.2±2.2 cm
2
). LAA depth by 2D and 3D correlated well (3.7±0.7 vs. 3.4±0.7; r=0.72, p=0.001). CT LAA orifice area correlated well with 3D-TEE (r=0.98, p<0.0001) but not with 2D-TEE (p=0.78).

Conclusions:
RT3D-TEE for analysis of LAA geometry is safe and feasible and appears to be more accurate than 2D-TEE. RT3D-TEE provides unique visualization of the LAA orifice in real-time, making it the ideal tool for intra-procedural sizing and placement of LAA occluder devices.
Abstract 1872: New Fusion Technique Significantly Improves Image Quality and Completeness of Datasets in Real Time 3 Dimensional Echocardiography
Authors: Szmigielski Cezary , Grau Vicente , Hoeschen Martin , Noble J. A , Kerber Richard , Becher Harald
Published: July 2021

Introduction: Real time 3 dimensional echocardiography (RT3DE) still presents a challenge for full volume acquisition in many patients because of incomplete datasets due to inadequate sector width and/or limited acoustic windows.

Hypothesis: We assessed the hypothesis that fusion of standard datasets from different transducer positions improves the completeness and image quality of RT3DE.

Methods: We studied 14 patients (mean age 47.0±22 yrs, 9 men, 5 women) referred for echocardiographic assessment of LV function. Standard full volume RT3DE was performed with an iE33 scanner with X3 probe (Philips Medical Systems, Andover, USA). We fused at least 2 standard RT3DE datasets from different transducer positions using a new, developed on site technique. All standard and fused datasets were processed with research software (Research Arena, TomTec, Germany). Readings were done by an experienced echocardiographer, who graded endocardial border definition and wall thickening: good quality: grade 2; intermediate: 1; poor or out of sector: 0. We studied separately segments in the short axis view (PSAX) and in apical views, yielding 32 segments per patient and total 896 cardiac segments for standard and fused datasets.

Results: Table 1

summarizes the segmental quality assessments using the 2 techniques, and the number of segments per patient (mean±SD). Quality gains from grade 0 to 1 and 1 to 2 in the fused images were similarly distributed among PSAX and apical segments.

Conclusions: The new fusion technique improved analysis of segmentation of the heart with RT3DE when compared with standard datasets. It increased the number of segments available for assessment and upgraded their image quality.

Table 1