bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17614: Multidimensional Post-Ectopic Response Pattern Predicts Mortality of Post-Infarction Patients
Authors: Sinnecker Daniel , Barthel Petra , Müller Alexander , Laugwitz Karl-Ludwig , Schmidt Georg
Published: July 2021

Background:
The integrity of the cardiovascular system is maintained by regulatory mechanisms at multiple levels. Distortions introduced by ventricular premature contractions (VPCs) result in typical response patterns that contain information about the integrity of these regulatory mechanisms and may inform risk stratification of cardiac patients. For example, heart rate turbulence (HRT, the post-ectopic heart rate response), or post-extrasystolic potentiation (PESP, the post-ectopic blood pressure response) are strong mortality predictors. The frequently observed post-extrasystolic T-wave change (PEST) might also have potential for risk stratification.

Study Aim:
To investigate whether HRT, PESP, and PEST provide independent risk stratification information in post-infarction patients.

Methods:
941 patients with acute myocardial infarction and sinus rhythm were prospectively enrolled and followed up for five-year all-cause mortality. Simultaneous 30-minute recordings of ECG and continuous blood pressure were obtained. HRT and PESP were calculated and dichotomized as described previously. Post-ectopic and normal T waves were compared in the three-dimensional vectorcardiogram space. PEST was quantified both as the change in T wave area (PEST
area
) and the angle between T wave main vectors (PEST
angle
). Dichotomies for PEST
area
and PEST
angle
were optimized by log rank statistics.

Results:
In multivariable Cox analysis, HRT, PESP, and PEST were independent mortality predictors with hazard ratios (HR) of 2.8, 4.7, and 3.0, respectively. A combined parameter termed M-PERP (multidimensional post-ectopic response pattern) was a particularly strong mortality predictor (see Figure). M-PERP was significantly associated with mortality in a multivariable Cox model considering also LVEF, VPC count, and GRACE score (HR 7.8, p<0.0001).

Conclusions:
M-PERP is a strong and independent mortality predictor in post-infarction patients.
Abstract 17617: History of Bleeding and Outcomes with Apixaban versus Warfarin in Patients with Atrial Fibrillation in the ARISTOTLE Trial
Authors: De Caterina Raffaele , Andersson Ulrika , Alexander John H , Bahit M.Cecilia , Commerford Patrick J , Goto Shinya , Granger Christopher B , Hanna Michael , Held Claes , Hohnloser Stefan H , Hylek Elaine M , Lanas Fernando , Lopes Renato D , Lopez-Sendon José L , Wallentin Lars
Published: July 2021

Background:
History of bleeding is important in decisions for anticoagulation. We analyzed outcomes in relation to history of bleeding and randomized treatments in patients with atrial fibrillation (AF) in the ARISTOTLE trial.

Methods:
The on-treatment safety population included 18,140 patients receiving ≥1 dose of study drug, apixaban 5 mg bd (2.5 mg bd if 2 of the following: age >80 yrs; body weight <60 kg; or creatinine >133 μmol/L) or warfarin aiming for INR 2.0-3.0 (median TTR 66%), for a median of 1.8 yrs. Adjudicated outcomes in relation to randomization and history of bleeding were analyzed using a Cox proportional hazards model. Efficacy endpoints were analyzed in the intention-to-treat population.

Results:
A history of bleeding was reported in 3033 patients (16.7%), who more often were male (68% vs 64%, p <0.0005); with a history of prior stroke/TIA/systemic embolism (23% vs 19%, p <0.0001); diabetes (27% vs 24%, p=0.0010); higher CHADS2 score (CHADS2 >3: 35% vs 29%), age (mean [SD] 71 [9] vs 69 [10], p <0001) and body weight (86 [21] vs 84 [21], p <0.0001); lower creatinine clearance (77 [33] vs 80 [33], p=0.0007) and mean systolic blood pressure (131 [17] vs 132 [16], p=0.0027). Calcium channel blockers, statins, non-steroidal anti-inflammatory drugs and proton pump inhibitors were used more often in patients with vs without a history of bleeding. Major bleeding was the only outcome event occurring more frequently in patients with vs without a history of bleeding, HR 1.7 (95% CI 1.4-2.3) with apixaban and 1.5 (1.2-1.0) with warfarin. Primary efficacy and safety outcomes in relation to randomization, see Table.

Conclusions:
In patients with AF, a history of bleeding was associated with several risk factors for stroke and bleeding and, accordingly, a higher bleeding risk during anticoagulation. Benefits with apixaban vs warfarin as to stroke, mortality and major bleeding, are however consistent irrespective of bleeding history.
Abstract 17698: Will Access to Timely Primary Care Influence the Success of the American Heart Association’s 2020 Strategic Impact Goals? A Report From the 2012 National Health Interview Survey
Authors: Venkitachalam Lakshmi , Gerkovich Mary M , Allsworth Jenifer E , Ross Janet N , Hoffman Mark , Williams Karen B
Published: July 2021

Background:
The AHA’s 2020 Strategic Impact Goals are to improve cardiovascular (CV) health and reduce related deaths by 20% by 2020. Our objective is to examine the association between perceived barriers to timely primary care and CV metrics relevant to these goals for the US population.

Methods:
We examined data on key CV metrics (aspirin, blood pressure, cholesterol and smoking) from 34,525 respondents (estimated 234.9 million adults) to the 2012 National Health Interview Survey. Barriers to primary care included: unable to get through on telephone, unable to obtain appointment soon enough, long wait in the physician’s office, limited clinic hours, and lack of transportation. National estimates were obtained using appropriate sampling weights. Odd ratios for CV metrics for adults with ≥ 1 vs. no barriers were obtained from logistic regression models.

Results:
The majority of respondents were 18-64 years of age (82%), non-Hispanic white (66%) and currently employed (62%); 52% were female and 16% reported no insurance. An estimated 24.7 million (10.7%) adults reported ≥ 1 barriers in the past year. Of the 46.3 million (32%) who were advised to take aspirin, 17% reported no aspirin use. Of the 60 million (26%) with documented hypertension, 85% had high BP in the last year. Of the 62 million (26%) with high cholesterol, 70% reported high rates in the last year. Of the 42 million (18%) who were current smokers, only 46% attempted to quit in the last year. Compared to those without barriers, adults with ≥ 1 barriers were more likely to be advised to take aspirin but less likely to follow the recommendation, were more likely to report diagnoses of CV risk factors and attempts to quit smoking (table).

Conclusion:
Barriers to timely primary care are likely markers of CV burden and are associated with key metrics that impact CV health and mortality among adults. These patient-centered factors merit further exploration when designing strategies to achieve the AHA’s 2020 Strategic Impact goals.
Abstract 177: Testing of a Novel Pelvic Hemostasis Belt to Control Lethal Pelvic Arterial Hemorrhage
Authors: Tiba Mohamad H , Draucker Gerard T , McCracken Brendan M , Alam Hasan B , Eliason Jonathan L , Ward Kevin R
Published: July 2021

Objectives:
Hemorrhage is the leading cause of death for both battlefield and injuries civilian. Hemorrhage caused by pelvic vascular injuries is of particular concern since it is challenging to manage or control prior to surgical intervention. Recently, there has been renewed interest in developing pre-surgical endovascular interventions to control such hemorrhage. However, other short-term techniques may be needed as a conduit to such endovascular approaches. Attempts at external tamponade of these complex injuries as a bridge to definitive surgical care of such injuries is not new. We tested a prototype device called the Pelvic Hemostasis Belt (PHB) for its ability to reduce or stop blood flow in a lethal model of pelvic arterial injury.

Methods:
Twelve male swine, 43(5.6) kg were utilized in this study. Animals were anesthetized, instrumented then randomized into two groups, Military Anti Shock Trousers group (MAST) and Pelvic Hemostasis Belt group (PHB). Through laparotomy, a stainless-steel monofilament suture was placed through the right iliac artery, the abdomen was closed and the suture was exteriorized. Hemorrhage was produced by pulling the suture through the iliac artery. In both groups, the hemostasis devices (MAST or BHP) were applied over the pelvis and lower abdomen for 60 minutes followed by release and monitoring for 30 minutes or until the animal expired. An infusion of 500 mL of hetastarch was started immediately after initiation of hemorrhage.

Results:
All animals in the PHB group and only two from the MAST group survived for 60 minutes. Average survival time for the rest of the MAST group was 44(17.9) minutes. The log-rank (Mantel-Cox) survival analysis demonstrated a significant difference in survival time between PHB and MAST group (p = 0.018). Significant differences were noted between the two groups in mean arterial pressure, lactate and central venous hemoglobin oxygen saturation levels.

Conclusion:
The PHB was successful in improving survival for 60 minutes after a lethal vascular injury. The Pelvic Hemostasis Belt might be helpful to bridge endovascular methods of hemorrhage control.
Abstract 17709: Framingham Risk Score and Coronary Plaque Characteristics as Assessed by Three-Vessel Optical Coherence Tomography Imaging
Authors: Vergallo Rocco , Jia Haibo , Soeda Tsunenari , Minami Yoshiyasu , Hu Sining , Tian Jinwei , Lee Hang , Biasucci Luigi M , Crea Filippo , Jang Ik-Kyung
Published: July 2021

Introduction:
Clinical prediction models, such as the Framingham Risk Score (FRS), are useful to identify patients at high risk for future events. However, their association with coronary plaque features is largely unknown.

Aim:
This study aimed at evaluating the relationship between FRS and coronary plaque features by optical coherence tomography (OCT).

Methods:
FRS was assessed in 176 patients with coronary artery disease [72 with acute coronary syndrome (ACS), and 104 with stable angina] who underwent 3-vessel OCT imaging. Based on the FRS values, patients were divided into 3 groups: lower FRS (FRS<5%, n=26), intermediate FRS (5%≤FRS<10%, n=105), and higher FRS (FRS≥10%, n=45). Nonculprit coronary plaque features were compared among the 3 groups.

Results:
A total of 448 nonculprit plaques were identified (lower FRS, n=61; intermediate FRS, n=267; higher FRS, n=120). Compared to the patients with lower and intermediated FRS, those with higher FRS were older (p<0.001), and more likely to have male gender (p<0.001), diabetes (p=0.023), lower HDL-cholesterol (p<0.001) and higher creatinine levels (p=0.023). Compared to the patients with lower FRS, those with higher FRS had greater lipid index (mean lipid arc x lipid length), and tended to have higher prevalence of thin-cap fibroatheroma (TCFA). Patients with higher FRS showed greater prevalence of calcifications compared to those with lower and intermediate FRS. Prevalence of cholesterol crystals was progressively higher across the 3 groups. At multivariate analysis, presentation with ACS (OR, 2.37; 95% CI, 1.27–4.39; p=0.006), and FRS (OR, 1.57 per 5% risk increase; 95% CI, 1.01–2.42, p=0.043) were independent predictors of TCFA.

Conclusions:
Nonculprit plaques of patients with higher FRS showed greater lipid content, and higher prevalence of calcifications and cholesterol crystals compared to those of patients with lower and intermediate FRS. ACS presentation and FRS were independent predictors of TCFA.
Abstract 17726: Comprehensive Evaluation of QT Interval During Abrupt Changes in Heart Rate and Associated Neurohormonal and Inflammatory Markers
Authors: Kolek Matthew J , Parvez Babar , Song Yanna , Abraham Robert L , Roden Dan M , Darbar Dawood
Published: July 2021

Background:
QT interval prolongation and risk of torsades de pointes have been associated with abrupt heart rate (HR) slowing after cardioversion from atrial fibrillation (AF) or AV nodal ablation. The degree to which the QT interval prolongs with abrupt changes in HR, and the underlying mechanisms, are poorly understood. We quantified ΔQT interval during cessation of rapid pacing and examined the relationship between QT and circulating neurohormonal and inflammatory markers.

Methods:
Eleven subjects with dual chamber pacemakers and intact AV conduction were atrially-paced at 90/min for 10 min, 60 min, and 1 week (Figure). Biomarkers were sampled during and after pacing. The relationships between QT, pacing stage, and biomarker levels were analyzed with a mixed effect model. QT intervals were compared for the 20 RR intervals before and 100 RR intervals after each pacing stage.

Results:
QT intervals prolonged after cessation of rapid pacing: 6.4 ms (95% confidence interval 4.9-7.8 ms) after 10 min (P<0.0001), 6.1ms (4.6-7.5 ms) after 60 min (P<0.0001), and 2.2ms (0.9-3.6 ms) after 1 week (P=0.002). QT interval was significantly associated with angiotensin II (P=0.002), epinephrine (P<0.0001), norepinephrine (P=0.03), dopamine (P<0.0001), C-reactive protein (P=0.0005), and interleukin-6 (P<0.0001), but not associated with atrial natriuretic peptide (P=0.26), B-type natriuretic peptide (P=0.08), renin (P=0.25), or aldosterone (P=0.42). There were no significant inter-individual differences in biomarker levels drawn before and after pacing (P>0.1 for all comparisons).

Conclusion:
Abrupt decreases in HR were associated with QT prolongation. QT interval changes correlated with several neuroendocrine and inflammatory biomarkers, though there were no inter-individual differences in biomarker levels before and after pacing. These findings may partially explain the increased risk of torsade de points after restoration of sinus rhythm from AF.
Abstract 17751: PCSK9 is Elevated in HIV+ Patients
Authors: Kohli Payal , Ganz Peter , Ma Yifei , Scherzer Rebecca , Deeks Steven G , Maka Kristinalisa , Wasserman Scott M , Scott Rob , Hsue Priscilla
Published: July 2021

Purpose:
Proprotein convertase subtilisin kexin 9 (PCSK9) is induced by inflammation and inhibits LDL receptor expression. Increased PCSK9 might explain the dyslipidemia observed in HIV patients, which has been previously attributed to HIV medication, HIV disease, and/or chronic inflammation. We aimed to compare PCSK9 levels in HIV patients and uninfected controls and identify predictors of elevated PCSK9 in HIV.

Methods:
We measured PCSK9 levels in 567 participants (495 HIV, 72 controls) from an outpatient cohort in San Francisco using a high affinity ELISA assay. Poisson regression models were used to determine factors associated with PCSK9.

Results:
The median age of all participants was 50 years (IQR 43-55) and 89% were male; 34% were smokers, 25% had hypertension, the median LDL was 103 mg/dL (IQR 80-127), and 21% were on statins. HIV patients and controls had similar rates of traditional risk factors except prior CAD was more common in HIV patients. Half of the HIV patients were treated and suppressed on HIV medication. Unadjusted PCSK9 levels were 11% higher in HIV patients vs. controls [mean 430 ng/ml (SD 166) vs. 386 ng/ml (SD134), p=0.015] with some HIV patients having extremely elevated levels >1000 ng/ml. After adjustment for demographics and statin use, HIV remained independently associated with 10% higher PCSK9 levels (p=0.03). In addition, older age, other race, statin use, Hepatitis C (HCV), higher triglycerides, current smoking and Lp(a)>90 nmol/L were all independently associated with higher PCSK9 levels in adjusted analysis. In contrast, neither inflammatory markers (IL-6, hs-CRP) nor CD4+ count or HIV viral load were associated with higher PCSK9.

Conclusion:
PCSK9 is increased in HIV-infected individuals. Traditional risk factors, HCV, and Lp(a)>90 nmol/L were also independently associated with PCSK9. Future studies should explore whether PCSK9 inhibition may be used to treat dyslipidemia and statin resistance in HIV+ patients.
Abstract 17756: Do Biventricular Mechanics in Transient Constrictive Pericarditis Improve After Medical Therapy?
Authors: Ayache Ayman I , Kusunose Kenya , Ismaeel Hussain A , Tariq Muhammad , Kwon Deborah H , Griffin Brian , Klein Allan L
Published: July 2021

Introduction:
Reversible constrictive pericarditis (CP) has been described with resolution of constriction after treatment with anti-inflammatory medications. In our study, we assessed the improvement of biventricular myocardial strain in CP patients treated medically compared to CP patients who underwent pericardiectomy.

Methods and Results:
We compared myocardial mechanics by 2-dimensional speckle tracking in 16 CP patients (age: 56±13; 75% males) who received anti-inflammatory medications to an age and sex matched CP group (age: 57±12; 75% males) who underwent pericardiectomy. At baseline, both treatment groups had depressed left ventricular (LV) anterolateral wall strain (LWS) and right ventricular (RV) free wall longitudinal systolic strain (FWS) but preserved LV septal wall systolic strain (SWS). In a median follow-up of 150 days the medically treated patients showed improvement of the depressed LVLWS/LVSWS (Pre: 0.61±0.17, Post: 0.89±0.21;P<0.001) and a trend in RVFWS/LVSWS (Pre:0.66±0.45, Post:0.89±0.38;P=0.12), that is similar to the improvement of the depressed LVLWS/LVSWS (Pre: 0.85±0.12, Post: 0.92±0.1;P<0.05) and trend in RVFWS/LVSWS (Pre: 0.77±0.32, Post: 0.86±0.18;P=0.09) of post pericardiectomy patients at a median follow-up of 74 days.

Conclusions:
Biventricular myocardial strain imaging is a robust technique for assessment of response to anti-inflammatory therapy in CP patients. Medical treatment of CP leads to systolic strain improvement that is more pronounced in the LV and RV free walls, hence having similar impact on the biventricular myocardial mechanics as pericardiectomy.
Abstract 17775: Foxo3a Regulates Response to Coxsackievirus B3 Myocarditis via microRNA-155 Triggered NK-cell Activity
Authors: Holzhauser Luise , Loebel Madlen , Jenke Alexander , Bauer Sandra , Demski Sonya , Wilk Sabrina , Pinkert Sandra , Fechner Henry , Poller Wolfgang , Schultheiss Heinz-Peter , Scheibenbogen Carmen , Skurk Carsten
Published: July 2021

Background:
FoxO3a is a transcription factor crucial in regulation of cell metabolism, stress resistance and immunity. Recently polymorphisms of FOXO3a have been associated with favorable outcome in inflammatory disease. However, mechanistic insight in FoxO3a effects is still limited. Here, we investigated the role of FoxO3a on NK-cell responses in viral myocarditis.

Methods:
A mouse model of Coxsackie Virus B3 (CVB3) myocarditis in wild-type and FoxO3a-/- mice was used to investigate the effects of FoxO3a on viral load and inflammation. Characterization of NK cells was performed by cytotoxic assay, surface marker- and interferon expression.

Results:
FoxO3a-/- mice showed significantly reduced myocardial inflammation, lower viral titers and attenuated expression of pro-inflammatory cytokines compared to wild-type mice 7 days post infection. Viral titers were significantly lower in FoxO3a-/- mice at day 3 while IFN γ and NKp46 expression were up-regulated within the heart suggesting early viral control by enhanced NK cell activity. There were no differences in expression of CAR (coxsackie-adenovirus receptor). Additionally NKp46+ splenic NK cells of FoxO3a-/- mice exhibited a superior functional status ex vivo determined by enhanced expression of CD69, higher frequencies of CD11b+CD27+ effector NK cells and increased cytotoxicity compared to NK cells of wild-type littermates. These effects were not due to different levels of apoptosis. MicroRNA-155 expression, recently reported to be essential in NK-cell activation, was significantly elevated in FoxO3a-/- NK cells while its inhibition led to diminished production of IFNγ in Foxo3a deficient animals. Moreover analysis of healthy human donors for the gain of function FoxO3a SNP rs9400239 revealed significantly reduced CD107a dependent degranulation activity in donors homozygous for the allelic variant.

Conclusion:
Our results implicate FoxO3a directly in regulation of NK-cell function and suggest an important role in innate immune responses to viral infection. While the anti-inflammatory effects of FoxO3a seem beneficial in chronic inflammation the suppression of innate immunity in acute viral myocarditis could have detrimental effects.
Abstract 17780: Pulmonary Arterial Aldosterone Levels Associate with Impaired Cardiac Reserve Capacity During Exercise in Left Ventricular Systolic Heart Failure Patients
Authors: Stephens Thomas E , Maron Bradley A , Farrell Laurie A , Loscalzo Joseph , Leopold Jane A , Lewis Gregory D
Published: July 2021

Elevated pulmonary arterial aldosterone levels (PA-ALDO) are associated with decreased exercise capacity in pulmonary hypertension patients despite normal left ventricular (LV) function. Pulmonary endothelial ALDO synthesis occurs in vitro under experimental conditions akin to LV systolic heart failure (HFrEF); however, the relevance of PA-ALDO to the clinical profile of HFrEF is not known. Therefore, we analyzed PA and radial arterial plasma in control and HFrEF patients to assess for transpulmonary ALDO release and determine if circulating ALDO is related to hemodynamic indices of cardiac reserve capacity during exercise. Data from 20 controls (51 ± 13 y, 13 females, LVEF=0.66 ± 0.9, volume of oxygen uptake at peak exercise [pVO2]=94.1 ± 11.5 % predicted) and 42 consecutive HFrEF patients (57 ± 13 y, 20 females, LVEF=0.36 ± 0.1, pVO2=47.1 ± 2.5 % predicted) undergoing invasive cardiopulmonary exercise testing were analyzed. At rest, HFrEF patients had increased PA-ALDO (714 ± 450 vs. 380 ± 187 ng/dl, P<0.001) and radial ALDO levels (796 ± 483 vs. 371 ± 175 ng/dl, P<0.001) compared to controls. Transpulmonary ALDO release (radial ALDO - PA-ALDO) was increased significantly in HFrEF at rest (+82 ± 20, P=0.02) and a trend was present with exercise (+62 ± 21, P=0.08). Although in controls, transpulmonary ALDO release levels were not significantly increased at rest (-9 ± 8, P=NS) or with exercise (+48 ± 13, P=NS), levels differed significantly between groups at rest and exercise (P<0.05 for both). By contrast, an incremental increase at peak exercise was present in PA-ALDO by 16.3% (P<0.01) and 9.2% (P<0.02) for controls and HFrEF patients, respectively, but there was no significant change in levels between groups. We next explored the relationship between ALDO and cardiovascular reserve capacity measures. After controlling for age and weight in the overall cohort, resting PA-ALDO levels correlated with pVO2 (Spearman coefficient -0.37, P<0.01), peak cardiac output (-0.36, P<0.01), and resting mean PA pressure (0.36, P<0.01). Collectively, these findings identify transpulmonary ALDO release as a novel characteristic of HFrEF and suggest that increased PA-ALDO in patients merits further investigation as a potential marker of impaired cardiac reserve capacity.
Abstract 17790: Can 3D Echocardiography Play a Role in Left Ventricular Assist Device Optimization?
Authors: Maffessanti Francesco , Addetia Karima , Sayer Gabriel , Kim Gene , Fedson Savitri , Collins Keith , Kruse Eric , Lang Roberto M , Uriel Nir
Published: July 2021

Introduction:
Left ventricular (LV) assist device (LVAD) has emerged as a valuable option for patients with severe congestive heart failure both as bridge to transplantation or destination therapy. Speed optimization of LVAD is currently based on the position of the inter-ventricular septum, mitral regurgitation severity and aortic valve opening.

Hypothesis:
We hypothesized that 3D transthoracic echocardiography (3DE) would provide additional information on left and right ventricular (RV) volumes and shape, which could be valuable in determining optimal LVAD speed. Our aim was to assess the feasibility of combined 3D LV and RV analysis during an incremental RAMP study.

Methods:
Six consecutive patients undergoing a RAMP test were studied. Device speed was increased from 8000 to 12000 rpm in 400-rpm increments for axial-flow pumps (n=2) and from 2300 to 3200 rpm in 100 rpm increments for centrifugal-flow pumps (n=4). Transthoracic 3DE apical full-volume datasets of the LV and the RV were acquired (Philips) at every other step. RV and LV endocardial surfaces were reconstructed using commercial software (TomTec) and used to calculate ventricular volumes. Custom software was used to calculate LV shape indices of sphericity and conicity (a perfectly spherical/conical ventricle would result in 1.0 value).

Results:
Data acquisition and post-processing was feasible in 5/6 patients. In axial pumps (Figure), increments in LVAD speed were associated with gradually decreasing LV volume, while RV volume initially decreased to a minimum and then increased at higher speeds. These volumetric changes were associated with alterations in LV shape, with the LV becoming less spherical and more conical at higher speeds. With centrifugal pumps, increased speed was associated with similar changes in LV shape but with minimal changes in volumes.

Conclusions:
Acquisition of 3D datasets during RAMP studies is feasible and could become a valuable aid in optimizing LVAD pump speed.
Abstract 17805: Association of LpPLA2 with Lipoprotein Subclasses, Inflammation, Atherosclerosis & Endothelial Dysfunction in a Web-Based Lifestyle Intervention Study: Baptist Employee Healthy Heart Study (BEHHS)
Authors: Jamal Omar , Aneni Ehimen , Roberson Lara , Shaharyar Sameer , Younus Adnan , Ali Shozab S , Rosell Beatriz , Oni Ebenezer , Guzman Henry , Ye Chen , Ye Chen , Malik Rehan , Aziz Muhammad , Post Janisse , Cury Ricardo , Fialkow Jonathan , Ozner Michael , Feldman Theodore , Agatston Arthur , Veledar Emir , Nasir Khurram
Published: July 2021

INTRODUCTION:
A recent meta-analysis demonstrated that Lipoprotein-associated phospholipase A
2
(LpPLA
2
) activity is associated with CVD events. However, the mechanisms which mediate this risk are poorly established. This study aims to assess the cross-sectional association between LpPLA
2
and components of an advanced lipid panel, subclinical CVD and markers of inflammation.

METHODS:
The Baptist Employee Healthy Heart Study (BEHHS) is an ongoing study examining the effect of web-based interventions on reducing CVD risk in individuals with metabolic syndrome & type II diabetes mellitus. Cardio IQ™ Ion Mobility lipoprotein fractionation was utilized for advanced lipid subclass measurement resulting in direct quantification of particles in each lipoprotein sub-class fraction. Endothelial function was assessed using endoPAT2000 (Itamar, Israel) and individuals older than 35 years had CT scan for coronary artery calcium (CAC). LpPLA
2
was measured by Enzyme-linked Immunosorbent Assay (ELISA).

RESULTS:
The population consisted of 182 individuals, 74% female with a mean age of 51±10 years (range 25 - 72). Overall the median plasma LpPLA
2
level was 199 ng/mL. In univariate analyses, there was a significant association with several lipid subclasses and with hs-CRP. After adjusting for risk factors, LpPLA
2
was independently associated with LDL-c and LDL particle size, Large LDL subclass A, small IDL, small, medium and large VLDL, and with hs-CRP. On the other hand there was no association between LpPLA
2
mass and HOMA-IR, reactive hyperemia index or presence of CAC.

CONCLUSIONS:
LpPLA
2
is significantly associated with several lipoprotein sub-classes and with systemic inflammation without affecting vascular endothelial function or atherosclerosis. Further studies are required to determine if lifestyle interventions affect LpPLA2 and how this may translate to reduced systemic inflammation and an improvement in cardiometabolic profile.
Abstract 17810: Spectral Analysis-Based Risk Score to Early Predict Mortality and Cerebral Performance in Patients Undergoing Therapeutic Hypothermia for Ventricular Fibrillation and Comatose Status
Authors: Filgueiras-Rama David , J. Calvo Conrado , Salvador- Montañés Óscar , Cádenas Rosalía , Ruiz-Cantador Jose , Armada Eduardo , Rey Juan Ramón , Merino JL , Peinado Rafael , Pérez-Castellano Nicasio , Pérez-Villacastín Julián , G. Quintanilla Jorge , Jiménez Santiago , Castells Francisco , J. Chorro Francisco , López-Sendón JL , Berenfeld Omer , Jalife José , López de Sá Esteban , Millet José
Published: July 2021

Introduction:
Early reliable prognostication in comatose survivors after cardiac arrest due to ventricular fibrillation (VF) is very limited, especially in patients undergoing mild hypothermia.

Hypothesis:
Spectral analysis of VF before a DC shock will reflect the degree of acute cerebral injury as a consequence of time in VF and concomitant myocardial ischemia.

Methods:
We included consecutive patients undergoing mild hypothermia after cardiac arrest due to VF, eventually with return of spontaneous circulation (ROSC), and a comatose status on admission. Background clinical variables, VF time and frequency domain fundamental variables were considered in the analysis. The primary and secondary outcomes were a favorable neurological performance (FNP) during hospitalization and survival to hospital discharge, respectively. The predictive model was developed in a retrospective cohort (September 2006 to September 2011) and further validated in a prospective cohort (October 2011 to July 2013). The model was also tested at follow-up.

Results:
Sixty-one patients out of 239 who underwent mild hypothermia fulfilled the inclusion criteria. FNP was present in 16 (50.0%) and 21 patients (72.4%) in the retrospective and prospective cohorts, respectively. Seventeen (53.1%) and 21 patients (72.4%), respectively, survived to hospital discharge. Both outcomes were significantly associated (p<0.001). Multivariate analysis on the retrospective cohort

provided a prediction model (sensitivity=0.94, specificity=1) including dominant frequency, ratio between number of peaks in high and low frequency bands, power spectral density ratio between high and low frequency bands and the number of shocks delivered before ROSC. Validation on the prospective cohort showed sensitivity=0.88 and specificity=0.91 for both primary and secondary outcomes. A

model-derived risk score properly predicted 93% of FNP. The model showed cstatistic ≥0.89 after a median follow-up of 48.5±10.5 and 5±1.8 months in the retrospective and prospective cohorts, respectively.

Conclusions:
A spectral analysis-based model reliably correlates time-dependent VF spectral changes with acute cerebral injury in comatose survivors after cardiac arrest undergoing mild hypothermia.
Abstract 17826: Age Difference in Plaque Characteristics of Culprit Lesions in Patients with Acute Coronary Syndrome: an Optical Coherence Tomography Study
Authors: Jia Haibo , Hu Sining , Soeda Tsunenari , Vergallo Rocco , Minami Yoshiyasu , Tian Jinwei , Zhang Shaosong , Yu Bo , Jang Ik-Kyung
Published: July 2021

Introduction:
The relationship between age and culprit plaque characteristics in patients with acute coronary syndrome (ACS) has not been reported.

Hypothesis:
The characteristics of the culprit plaques differ between younger population and older population with ACS.

Methods:
We studied 154 patients with ACS who underwent OCT imaging before intervention. The distribution and plaque morphology of the culprit lesion were compared according to the age: Group A (65 years, n=44).

Results:
There were more smokers in Group A than in Group B and C (58.3% vs. 36.5% vs. 15.9%, p<0.001). Plaque erosion was more frequently observed in the younger age group, whereas plaque rupture was more frequent in the older age group (Figure). The prevalence of calcified nodule was not different among the three groups (Figure). Other features of thin-cap fibroatheroma, thrombus, and macrophage infiltration showed no differences among the three groups.

Conclusions:
Plaque erosion was the primary cause for ACS in younger patients, whereas plaque rupture was more commonly observed in older patients.
Abstract 17851: Is Positive Psychological Well-being Associated with Physical Functioning in Older Adults? Results From the Chicago Healthy Aging Study (CHAS)
Authors: Hernandez Rosalba , Vu Thanh-Huyen T , Liu Kiang , Daviglus Martha L
Published: July 2021

Background:
There is mounting evidence linking positive psychological well-being to restorative health processes, i.e., positive health behaviors and biological functioning. However, very little is known about the relationship between positive affect and physical functioning or whether there is a potential mediational effect on this relationship (if any) via traditional cardiovascular risk factors.

Methods:
We analyzed in-person interview data collected from older adults ages 63-84 that participated in the Chicago Healthy Aging Study [CHAS] in 2007-10. Positive affect was captured using a subscale of the Center for Epidemiologic Studies Depression Scale that considered only positively worded items, with higher scores indicative of greater positive affect (see Table); tertiles were created with the following cutoffs <2 (low), ≥2 to <4 (medium), and ≥4 (high). Physical functioning for the upper and lower extremities considered the Short Physical Performance Battery and 2 levels of hand grip strength. Traditional risk factors consisted of blood pressure, serum cholesterol, body mass index, diabetes, and smoking status.

Results:
We analyzed data from 1,247 individuals. Mean age was 71 years; and 26% female. A significant positive correlation was found between positive affect and all measures of physical functioning (all P-values < 0.05). In multivariate adjusted models (see Table), a graded association was evident such that higher mean scores for physical functioning were observed with increasing levels of positive affect (i.e., Short Physical Performance Battery [
p
-trend = 0.004] and 2 kg hand grip strength [
p
-trend = 0.034]). Inclusion of traditional risk factors did not significantly attenuate observed association between positive affect and physical functioning.

Conclusion:
The current study offer preliminary evidence for an association between positive affect and physical functioning in older adults independent of cardiovascular risk factors.
Abstract 17912: Importance of Acute Hemodynamic Effects of Inhaled Nitric Oxide in Optimization of Heart Failure Treatment in Patients with Pulmonary Hypertension due to Left Heart Disease
Authors: Tatebe Shunsuke , Sugimura Koichiro , Nochioka Kotaro , Aoki Tatsuo , Miura Masanobu , Yamamoto Saori , Yaoita Nobuhiro , Sato Haruka , Satoh Kimio , Shimokawa Hiroaki
Published: July 2021

Background:
Pulmonary hypertension (PH) due to left heart disease (LHD) is a major category of the disorder. We have recently reported that elevated pulmonary vascular resistance (PVR) in patients with post-capillary PH (pc-PH: defined as mean pulmonary arterial pressure (mPAP)≥25mmHg and pulmonary capillary wedge pressure (PCWP)>15mmHg) is associated with poor prognosis compared with those with no PH or pc-PH without elevated PVR. Although new treatment is required for targeting pulmonary vascular disease (PVD), thereis a concern about raising PCWP. In this study, we thus examined acute hemodynamic effects of inhaled nitric oxide (iNO) in patients with PH due to LHD and whether optimal heart failure (HF) treatment ameliorates pc-PH.

Methods:
We examined 60 consecutive pc-PH patients with chronic heart failure (63±14[SD] years, M/F 38/22, NYHA≥2) who underwent acute vasoreactivity test by iNO (40 ppm for 10 min) under right heart catheterization at our hospital from June 2011 to May 2014. Among them, 25 had valvular heart disease (VHD) and 35 had non-VHD. PVD (defined as PVR> 240dynes/s/cm
-5
) was noted in 18. We also evaluated right ventricular systolic pressure (RVSP) by echocardiography after optimization of HF treatment such as medications and valvular surgery.

Results:
iNO significantly decreased mPAP (-1.7±0.5 mmHg; P<0.01) and PVR (-66 ±14dyne/s/cm
-5
, P<0.01) without altering cardiac output. iNO significantly increased PCWP (1.3±0.5 mmHg, P=0.01) only in non-VHD patients, while it significantly increased mean arterial pressure and systemic vascular resistance in VHD patients than in non-VHD patients (both P<0.05). Pc-PH patients with PVD were re-classified as having pc-PH without PVD in 9 and no PH in 1. Eight patients remained pc-PH with PVD. After the optimal medical treatment for 7.6 months, RVSP was significantly decreased in both non-VHD and VHD patient (-8±3mmHg, P=0.04, -19±8mmHg, P=0.01, respectively). However, in non-VHD group, significant reduction in RVSP was noted only in pc-PH patients without PVD (-8±3mmHg, P=0.03).

Conclusions:
These results indicate that elevated PVR in patients with pc-PH and non-VHD could be a novel therapeutic indication for NO-related pulmonary vasodilators in the current practice of HF.
Abstract 17913: Inhibition of CETP by Dalcetrapib Results in a Modest Increase in Cholesterol Efflux Capacity Associated With an Increase in Large HDL Particles, but Does Not Impact Carotid Intima-Media Thickness in a dal-PLAQUE-2 Substudy
Authors: Rhainds David , Boule Marie , Alem Sonia , Brodeur Mathieu R , Charpentier Daniel , Gingras Olivier , Chabot-Blanchet Malorie , Guertin Marie-Claude , Lettre Guillaume , Rhéaume Eric , Tardif Jean-Claude
Published: July 2021

Inhibition of cholesteryl ester transfer protein (CETP) is an approach aiming at raising HDL-cholesterol levels and reducing cardiovascular risk. The dal-PLAQUE-2 phase III study recruited 988 subjects with stable coronary artery disease. Its primary objective was to evaluate the effect of dalcetrapib on the progression of carotid atherosclerotic disease measured by intima-media thickness after one year of therapy. As dalcetrapib showed a neutral effect on cardiovascular risk in the dal-OUTCOMES study, our objective was to evaluate its effect on cIMT and markers of HDL mass, lipoprotein subclass distribution and HDL function. All subjects from dal-PLAQUE-2 who had provided serum samples at baseline and one year were included in our substudy of 193 subjects on placebo and 186 subjects on dalcetrapib. Comparisons between groups at one year were made by ANCOVA after adjustment for baseline levels. No significant differences between groups for all variables considered were observed at baseline. Dalcetrapib reduced CETP activity as measured by a fluorescent method by 30% after 1 year (p<0.001), which resulted in increases in HDL-cholesterol and apoA-I levels by 32% and 11%, respectively (both p<0.001). Dalcetrapib markedly increased the concentration of large HDL particles measured by NMR profiling (+59%, p<0.001), at the expense of small HDL particles (-9.5%, p<0.001). Cholesterol efflux capacity of serum was measured from J774 macrophages under basal conditions and after cAMP stimulation. Dalcetrapib increased basal and stimulated efflux by 7.1% and 5.5% (both p<0.001), but was without effect on the ABCA1-dependent component (p=0.26). Despite these effects, dalcetrapib had no impact on mean and maximal cIMT (p=0.98 and p=0.85). While the change in cIMT was inversely correlated with basal cholesterol efflux in the placebo group (Spearman r=-0.163, p<0.05), such a relationship was not found in the dalcetrapib group. Moreover, the change in total HDL particles concentration was inversely correlated with change in cIMT (r=0.181, p<0.05) in the placebo arm only. In conclusion, dalcetrapib raised HDL-C and larger HDL, but this had minimal effects on cholesterol efflux capacity of patients’ serum and had a neutral effect on carotid artery plaque burden.
Abstract 17927: Bayesian Hierarchical Meta-Analysis Clarifies the Trade-Off Between Bleeding and Stent Thrombosis in Trials Comparing Bivalirudin with Heparin During Percutaneous Coronary Intervention
Authors: Bittl John A , Lang Christopher D
Published: July 2021

Introduction:
Calculating the net benefit between bleeding risks and ischemic complications of antithrombotic therapy remains challenging.

Hypothesis:
Hierarchical meta-analyses may allow inferences to be made about the parameter θ, which reflects the underlying hypothesis that one therapy is superior to another conditional on the types of risks associated with various end points in clinical trials.

Methods:
We employed Bayesian hierarchical meta-analyses of 10 randomized clinical trials randomizing 34,658 patients to either bivalirudin or heparin, with or without platelet glycoprotein inhibitors, during percutaneous coronary intervention (PCI).

Results:
No difference was seen in the rate of death 30 days after using bivalirudin or heparin (OR 1.01, 95% Bayesian credible interval [BCI] 0.79-1.28), but the risk of major bleeding was lower (OR 0.58, 95% BCI 0.38-0.84) and the risk of definite stent thrombosis (ST) was higher (OR 1.86, 95% BCI 1.19-2.94) after using bivalirudin than after using heparin. For every 100 patients, using bivalirudin in place of heparin prevented 4.1 episodes of major bleeding episodes but caused 0.8 episode of definite ST. (Figure Legend: Probability density functions normalized to 1 for risk of major bleeding, death and definite stent thrombosis at 30 days after treatment with bivalirudin or heparin, with or without platelet glycoprotein inhibitors.)

Conclusions:
Neither bivalirudin nor heparin emerges as a preferred strategy in an analysis that accounts for mortality differences. Because bivalirudin reduces major bleeding at the cost of increased stent thrombosis, decisions between bivalirudin and heparin based on baseline bleeding risk and ST risk are likely to maximize net clinical benefit.
Abstract 17934: Normal Doppler Hemodynamics of Pulmonary Valve Prostheses in Adults
Authors: Hoskoppal Arvind , Connolly Heidi , Miller Fletcher , Dearani Joseph , Schaff Hartzell , Blauwet Lori
Published: July 2021

Introduction:
Pulmonary valve (PV) replacement is rare, so data regarding normal hemodynamics are limited. We sought to determine the normal Doppler-derived hemodynamic profiles of various PV prostheses (PVPs) in adults.

Hypothesis:
Doppler-derived hemodynamic profiles of normal PVPs will vary according to prosthesis type in adult patients.

Methods:
We performed a retrospective review of comprehensive two dimensional and Doppler echocardiographic examinations of 327 patients (median age, 35; range 18 -83 years) with normal PVPs performed early after implantation. Data were analyzed to determine mean±SD.

Results:
Parasternal short axis was the most commonly used window (96%) for assessment of PVPs. For the 327 PVPs, peak instantaneous gradient was 25±11 mmHg, mean systolic gradient was 13.1±6.1 mmHg, and mean right ventricular outflow tract velocity was 0.8±0.6 m/s. Results for selected variables analyzed by prosthesis type are listed in the Table. Pericardial prostheses had significantly lower peak gradient (21±10.1 mmHg; P=0.002) compared with porcine (25±9.7 mmHg), mechanical (26±16.6 mmHg), bovine venous (34±15.5 mmHg) and homograft PVPs (35±8.4 mm Hg).

Conclusions:
This is the largest series reporting normal Doppler-derived hemodynamic profiles of PVPs. This study establishes normative values for Doppler-derived variables for normal PVPs implanted in adults. Pericardial prostheses had the optimal hemodynamic profile in this patient population.
Abstract 17979: Left Atrial Cross Sectional Area is a Novel Echocardiographic Measure Which Improves the Predictive Value of Chads2 Score in Risk Stratification of Cardioembolic Strokes
Authors: Tan Timothy C , Handschumacher Mark , Pontes-Neto Octavio M , Nunes Maria C , Park Yong H , O’Brien Cashel , Piro Victoria , Jiao Yuan , Zeng Xin , Kim Gyeong M , Helenius Johanna , Avery Ross , Furie Karen , Ay Hakan , Hung Judy
Published: July 2021

Background:
Cardioembolic (CE) stroke carries significant morbidity and mortality. Current risk stratification tools such as CHADS2 score do not include any imaging parameters and are based on clinical features, which have limitations. Left atrial (LA) enlargement and remodeling may be associated with CE risk due to predisposition for atrial arrhythmias and thrombus formation. Left atrial cross sectional area (LACSA), a novel echo measure which reflects both LA size and shape, may improve CE stroke risk assessment.

Aim:
This study examined the value of LACSA in predicting CE stroke risk and the improvement in risk prediction when added to CHADS2 score.

Methods:
Clinical and echo parameters were examined in a prospective cohort of 1275 consecutive patients with ischemic stroke. Strokes were classified using the Causative Classification of Strokes and 259 (20%) were classified as CE stroke. LACSA was calculated using the formula: π/4*largest measured LA diameter*smallest measured LA diameter where mid LA diameter was measured in the parasternal long axis, 4 chamber and 2 chamber views.

Results:
Patients with CE stroke had greater LACSA (8.6 ± 2.3 vs 6.4 ± 1.8 cm2/m2; p<0.001) and mean CHADS2 score (2.25 ± 1.28 vs 1.87 ± 1.40; p<0.0001) compared to non-CE stroke patients. LACSA was independently associated with CE strokes (OR 1.21; 95% CI 1.08-1.34; p=0.001) in a multivariable model adjusted for CHADS2, gender, score, BMI, atrial fibrillation, anti-platelet and anti-coagulant use, E/E’ and LVEF. The addition of LACSA to CHADS2 score improved the prediction of CE stroke (c-statistic for predicting CE stroke using CHADS2 alone was 0.59 (95% CI 0.55-0.63) vs CHADS2 and LACSA 0.78 (95% CI 0.72-0.80) (p<0.001).

Conclusion:
LACSA is a novel measure of LA remodeling and associated with CE stroke. LACSA, an imaging parameter, enhances the risk prediction of the CHADS2 score, a clinical measure of risk, improving risk stratification for CE stroke and impacting therapeutic strategies.
Abstract 18065: Combining Echo Doppler and CT Derived LVOT Measurements Improve Accuracy of Continuity Equation Based Aortic Valve Area Determination
Authors: Alnasser Sami , Cheema Asim , Kotha Vamshi , Deva Djeven , Edwards Jeremy , Buller Christopher E , Peterson Mark , Latter David , Benhomeid Osama , Finken Laura , Chisholm Robert J
Published: July 2021

Background:
Left ventricular outflow tract (LVOT) measurement by Echo falsely assumes circular LVOT with implications for aortic valve area (AVA) determined using continuity equation. In this study, we investigated the utility of combining Echo Doppler and computed tomography (CT) based LVOT area for precise AVA assessment.

Methods:
AVA-echo was calculated using continuity equation and standard echocardiography techniques. CT-LVOT area was measured by 3 independent readers. Blinded measurements were obtained in candidates for percutaneous aortic valve replacement. AVA-CT was calculated using CT-LVOT area and echo Doppler measurements. The inter-observer variability for CT-LVOT area and correlation between AVA-echo and AVA-CT was analyzed using intra-class (ICC) and Spearman correlation coefficient.

Results:
Complete data for 66 patients was analyzed. The ICC for CT derived LVOT measurement by three observers was 0.96 demonstrating excellent reliability. The LVOT area by echo was significantly smaller than that obtained by CT (3.43±0.8 vs. 4.45±1.2 cm2, p<0.0001) and showing moderate correlation (r=0.66, p=0.006). Similarly, the AVA-echo was significantly lower compared to AVA-CT (0.76±0.46 vs. 0.97±0.53 cm2, p<0.0001). The correlation coefficient for AVA-echo and AVA-CT was 0.7 (p < 0.0001), 0.4 (p=0.06) and 0.9 (p<0.0001) for AVA-echo of 0.8 cm2 respectively. The regression analysis showed that AVA-CT could be predicted by applying a correction factor to the AVA-echo as AVA-CT = AVA-echo x 1.1+0.14.

Conclusion:
CT provides accurate and reliable LVOT assessment. Combining CT-LVOT and echo Doppler measurements result in a larger AVA compared to AVA-echo representing a true anatomic measurement. These findings have important implications for grading of aortic stenosis and management of patients with moderate to severe aortic stenosis.