bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19139: Impact of Medical Study Publication on Cholesterol Medication Prescriptions
Authors: Borden William B , Lin Haizhen , Bishop Tara F , Mushlin Alvin I , Simon Kosali
Published: July 2021

Introduction:
The challenges of translating research findings into practice have been well demonstrated, though some high impact studies do change care delivery. It is unknown whether such trials have spillover effects onto similar but unrelated medications.

Hypothesis:
Cholesterol trial findings change prescriptions for both trial drugs and statins in the direction of the results, even if statins were not directly studied.

Methods:
The Symphony Health Solutions’ PHAST Prescription Monthly database provided retail prescriptions from 2007 to 2013. We selected 5 cholesterol trials that were all published in the New England Journal of Medicine. The trials [main drug(s) studied, result] were: ENHANCE [simvastatin/ezetimibe, negative], JUPITER [rosuvastatin, positive], ARBITER 6 HALTS [niacin, positive; ezetimibe, negative], ACCORD LIPID [fenofibrate, negative], AIM HIGH [niacin, negative]. For each trial, we performed a difference-in-differences analysis for both the main drug(s) studied and statins using anti-hypertensive drugs as the control, comparing the 1 and 12 month prescription averages after to an average of the 12 months before the trial.

Results:
The 12-month average study drug monthly prescriptions changed in the direction expected from the trial results for all (p<0.01), except niacin post ARBITER trial. After ENHANCE, simvastatin/ezetimbe changed -533,490 (95% CI -655,008, -411,976); after JUPITER, rosuvastatin changed 337,328 (278,722, 395,934); after ARBITER, niacin changed 1,335 (-17,625, 20,294) and ezetimibe changed -185,587 (-222,697, -148,147); after ACCORD, fenofibrate changed -263,522 (-316,805, -210,238); after AIM HIGH, niacin changed -154,460 (-182,760, -126,160). Over 50% of the year change occurred in the first month after each trial, except niacin post ARBITER. The trend of increasing statin prescriptions was unperturbed by the trial results.

Conclusions:
Individual cholesterol trial drug prescriptions changed substantially and as expected after trial results, with the majority of the change occurring immediately after trial publication. There was no evidence for detrimental spillover effects on statin prescriptions. These results suggest that the uptake of these trial findings was appropriate.
Abstract 19299: PPARγ Plays a Novel, Pivotal Role in DNA Damage Sensing and Repair, That is Perturbed in Pulmonary Arterial Hypertension
Authors: Li Caiyun G , Sweeney Nathaly , Kantamani Vivek , Sa Silin , Hennigs Jan K , Diebold Isabel , Guignabert Christophe , Cimprich Karlene A , Rabinovitch Marlene
Published: July 2021

We previously observed that mice with deletion of peroxisome proliferator-activated receptor γ (PPARγ) in endothelial cells (EC) (EC-Pparγ-/-) do not reverse pulmonary hypertension (PH) during recovery in room air after three weeks of chronic hypoxia. Impaired PPARγ interaction with ß-catenin was linked to pulmonary arterial (PA) EC dysfunction in the pathogenesis of PH. To gain further insight into PPARγ function, important in reversing PH, we applied affinity purification-mass spectrometry in HEK293T cells to analyse the PPARγ interactome. Analyses revealed a network highly enriched in DNA damage response (DDR) proteins, including the MRE11, RAD50 and NBN (MRN) heterotrimeric complex. MRN senses damaged DNA and activates the ATM/ATR pathway essential for DNA repair. Using co-immmunoprecipitation in PAECs, we confirmed the PPARγ:MRN interaction via the PPARγ ligand binding domain. To determine the function of this novel interaction, we depleted PPARγ with siRNA and induced DNA damage with doxorubicin (DOX) or hydroxyurea (HU). PPARγ depletion impaired DDR activation after DOX/HU, with reduced levels of pATM and its substrates, pCHK1, pCHK2 and γH2AX. To test whether these abnormalities were related to reduced DNA repair, we assessed damaged DNA 24h after removal of DOX/HU using the COMET assay. PPARγ depleted PAECs showed longer comet tails reflective of unrepaired DNA. To investigate if persistent PH in EC-Pparγ-/- mice after chronic hypoxia correlated with impaired DDR, we evaluated both γH2AX (sensor) and Brca1 (repair) foci formation in the mouse lung tissues using confocal microscopy. Consistent with impaired DNA repair, Brca1 foci formation was significantly increased in ECs of EC-Pparγ-/- mice compared to the wildtype littermates. Moreover, reduced PPARγ previously described in PAECs from PH patients relative to controls was also associated with unrepaired DNA, judged by longer comet tails and by persistent γH2AX foci as assessed by confocal microscopy in tissue sections. In summary we report a novel interaction between PPARγ and the MRN that is necessary in DNA damage sensing and repair. We suggest that persistent DNA damage associated with PPARγ deficiency in PAECs could cause dysfunction or transformation related to the pathology of PH.
Abstract 19356: Sex-differences in Left Ventricular Mass Changes in Treated Hypertensive Outpatients: The Campania Salute Network
Authors: Mancusi Costantino , Gerdts Eva , Izzo Raffaele , Trimarco Valentina , De Marco Marina , Sforza Alfonso , Lønnebakken Mai Tone , De Luca Nicola , Trimarco Bruno , de Simone Giovanni
Published: July 2021

Introduction:
In clinical trials, women achieve less regression of hypertensive LV hypertrophy (LVH) than men. Whether this is evident also in less selective hypertensive patients is uncertain.

Hypothesis:
Find sex-differences in LV mass changes during hypertensive treatment.

Methods:
We evaluated 6969 hypertensive patients with follow-up>12 months (43% women, 53±11 years) from the Campania Salute Network Registry, during a 4-year median follow up. Clinical and echocardiographic data from baseline and last visit during follow-up were used.

Results:
At baseline, women were older, had higher systolic blood pressure (BP) and heart rate, lower diastolic BP, Framingham Risk Score and renal function, and included more patients with obesity and LVH (all p<0.001 vs. men). Despite optimal BP control in 62% of patients, LV mass increased over time in the total population, similarly in males and females, whereas relative wall thickness increased only in females (all p<0.0001). Percent change in LVM was positively related to follow-up duration and change in systolic BP, diastolic BP and body mass index (BMI) in both sexes (all p<0.0001).

During follow-up, women, but not men, exhibited significant increase in BMI (both p<0.0001). After adjusting for age, follow-up duration, changes in BP and BMI, LV mass increased in the presence of both controlled and uncontrolled BP, but in men the change was less evident when BP was controlled (all p<0.001). In subgroups with baseline LVH (by sex-specific LVM normalized by height2.7), LV mass decreased over time in men, but increased in women (p<0.001).

Conclusions:
In hypertensive, Caucasian outpatients participating in the Campania Salute Network registry, lack of reduction in LV mass was particularly evident in women, independently of confounders including age, duration of follow-up, changes in BP and BMI, with negligible benefit of BP control on LVH.
Abstract 19359: A Novel Parameter to Predict Long-term Cardiac Mortality in Mitral Stenosis
Authors: Nunes Maria Carmo P , Tan Timothy , Elmariah Sammy , Lodi-Junqueira Lucas , Nascimento Bruno R , Athayde Guilherme S , Zeng Xin , Lago Rodrigo d , Leon Leilane , Palacios Igor F , Hung Judy , Levine Robert A
Published: July 2021

The prognosis of patients with mitral stenosis (MS) depends on the severity of obstruction and hemodynamic burden affecting the pulmonary vasculature. Net atrioventricular compliance (C
n
) reflects the overall adverse hemodynamic consequence of MS and may be useful in predicting mortality.

Methods:
A total of 402 MS patients (mean age 51 ± 16 years, valve area of 1.04 ± 0.24 cm
2
, 84% female) undergoing percutaneous mitral valvuloplasty (PMV) between 2000 and 2013 at 2 centers were enrolled. Invasive hemodynamic and echocardiographic measures (pre and 24 hours post PMV) were examined and patients were followed for a median of 28 months post PMV. Endpoints were cardiovascular death (primary), and a composite of death from any cause, mitral valve replacement (MVR) or repeat PMV (secondary).

Results:
At baseline, 138 (34%) were in atrial fibrillation and 48% were NYHA functional class III or IV. PMV resulted in significant increase in valve area, decrease in transmitral pressure gradients, pulmonary pressures and an improvement in right ventricular (RV) function. A total of 47 (12%) died (39 cardiovascular deaths). In addition, 48 patients underwent MVR, and 12 required repeat PMV with an overall incidence of adverse events of 11.4 events per 100 patient-years. Baseline C
n
was a strong predictor of both cardiac death (adjusted hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.49 - 0.86, p = 0.008), and composite endpoint (adjusted HR 0.81, 95% CI 0.67 - 0.91, p = 0.016). Cardiac mortality was significantly higher in patients with C
n
≤ 4 ml/mmHg than in patients with C
n
> 4 ml/mmHg (adjusted HR 0.35, 95% CI 0.16 - 0.75, p=0.007), after adjusting for clinical factors, pulmonary artery pressure, tricuspid regurgitation (TR) severity, RV function and immediate procedural results. Survival rate at 1-, 3- and 5-years follow-up was 96%, 94% and 87% in patients with C
n
> 4 ml/mmHg compared to 89%, 79% and 75% in patients with C
n
≤ 4 ml/mmHg.

Conclusions:
Baseline C
n
is a strong predictor of cardiovascular-related mortality in patients with significant MS, after adjustment for other prognostic factors including postprocedural pulmonary artery pressure. C
n
assessment therefore has potential value in evaluation of mortality risk in the setting of MS.
Abstract 19365: The Novel Biomarker Osteopontin Predicts Adverse Outcome in Patients Undergoing Treatment of Severe Aortic Stenosis by TAVI
Authors: Lutz Matthias , Ingersleben Nora , Rosenberg Mark , Freitag-Wolf Sandra , Brehm Doreen , Frey Norbert , Frank Derk
Published: July 2021

Background:
Osteopontin (OPN) is an extracellular matrix protein that plays an integral role in myocardial remodeling and was previously shown as an important emerging biomarker in risk evaluation of cardiovascular disease. However, its prognostic value in patients with pressure overload of the left ventricular, caused by symptomatic severe aortic valve stenosis, undergoing transcatheter aortic valve implantation (TAVI) remains unclear.

Methods:
N=217 patients undergoing TAVI (using balloon-expandable Edwards Sapien XT prostheses) were included prospectively over a continuous period from Feb. 2011 until Dec. 2013. For all patients a complete clinical data set including biomarkers (OPN and NTproBNP), basic clinical assessment and echocardiography before and 7 days after TAVI was obtained. The primary endpoint was survival time.

During median follow-up of 349d (Q1, Q3: 106-659.5d), a total of 66 deaths occurred, 30d mortality was 6.9%. Mean age was 81.8 years (± 6.03 y) and 55.8 % of the patients were female. Mean log. Euroscore was 25.4% (± 17.2%) and mean STS Score was 6.2% (± 3.8%).

Results:
Median preprocedurale OPN values were significantly elevated in patients with severe aortic valve stenosis compared to healthy controls (675 ng/ml, Q1,Q3: 488.5-990.5 ng/ml vs. 386 ng/ml, Q1, Q3: 324.5 - 458.0, p<0.001). Increased OPN levels before TAVI (upper quartile compared to lower three quartiles) revealed a HR of 2.151 (CI 1.31-3.531, p=0.002) for reduced survival.

Multivariate Cox regression analysis including NTproBNP, postprocedural aortic regurgitation, atrial fibrillation, clinical risk scores and preprocedural left ventricular function (EF) demonstrates that OPN is even superior to NTproBNP and preprocedural EF in predicting adverse prognosis, showing a HR of 1.826 (CI 1.096-3.044, p=0.021).

Conclusions:
Elevated OPN levels predict adverse outcome in patients with severe aortic stenosis undergoing TAVI. OPN is superior to the established biomarker NTproBNP in risk stratification of patients undergoing TAVI.
Abstract 19639: Infective Endocarditis Following Transcatheter Valve Implantation: A Systematic Review
Authors: Amat-Santos Ignacio J , Ribeiro Henrique B , Urena Marina , Allende Ricardo , Houde Cristine , Bedard Elisabeth , DeLarrochellière Robert , Paradis Jean-Michel , Dumont Eric , Doyle Daniel , Mohammadi Siamak , Côté Mélanie , Rodés-Cabau Josep
Published: July 2021

Objectives:
To describe the incidence, features, predisposing factors and outcomes of infective endocarditis (IE) following transcatheter valve implantation (TVI).

Background:
Very few data exist on IE following TVI.

Methods:
Studies published between 2000 and 2013 regarding IE in patients with aortic (TAVI) or pulmonary (TPVI) transcatheter valves were identified through systematic electronic search.

Result:
A total of 28 publications describing 60 patients (32 TAVI, 28 TPVI) were identified. Most TAVI patients (66% males, 80±7 years) had a very high-risk profile (LogEuroSCORE: 30.4±14.0%, p<0.001 compared to previous TAVI registries). In TPVI patients (90% males, 19±6 years), IE was more frequent in stenotic conduit/valve (61%) (p <0.001 vs. previous TPVI series). Median time between TVI and IE was 5.5 (2-12) months. Typical microorganisms were mostly found with a higher incidence of enterococci after TAVI (34.4% vs. 0%, p =0.009), and S.aureus after TPVI (29.4% vs. 6.2%, p =0.041). Up to 60% of the TAVI-IE patients were managed medically despite related complications such as local extension, embolism and/or heart failure in >50% of patients. Valve explantation rate was 57% and 23% in balloon- and self-expandable valves, respectively (p=0.07). In-hospital mortality for TAVI-IE was 34.4%. Most TPVI-IE patients (75%) were managed surgically, and in-hospital mortality was 7.1%.

Conclusions:
Most cases of IE post-TVI were males, with a very high-risk profile (TAVI) or underlying stenotic conduit/valve (TPVI). Typical -but different- microorganisms of IE were involved in half of the TAVI and TPVI cases. Most TPVI-IE patients were managed surgically as opposed to TAVI patients, and mortality rate was high in both cohorts.
Abstract 19684: Abnormal Aortic Wall Properties in Children with Isolated Bicuspid Aortic Valve
Authors: Natarajan Shobha S , Glatz Andrew C , Goldmuntz Elizabeth , Cohen Meryl S
Published: July 2021

Introduction:
Abnormal aortic wall properties have been reported in patients with isolated bicuspid aortic valve (IBAV) even in the absence of significant aortic stenosis or regurgitation.

Hypothesis:
We sought to assess aortic distensibility (DIS) and stiffness index (SI) in children with IBAV compared to age group-matched subjects with normal tricuspid aortic valves (TAV) and to determine whether these abnormalities in the aortic wall properties correlate with bicuspid valve morphology or left ventricular systolic or diastolic function.

Methods:
Children ages 8-18 years with an IBAV and age group-matched controls with a TAV were prospectively enrolled. Subjects with greater than mild stenosis or mild regurgitation were excluded. Using echo, aortic valve morphology, aortic root (AoR) and ascending aorta (AAo) diameters and z-scores were determined. Left ventricular shortening fraction (LVSF), DIS and SI were measured using M-mode echo. Diastolic function was determined using mitral valve septal E/Ea. Blood pressure (BP) was measured at the time of echo.

Results:
Nineteen had IBAV and 17 had TAV. There were no significant differences in age, weight, height or BP between the two groups. In the IBAV group, 11 had right-left type (R/L) and 8 had right-non type (R/N). There was no significant difference in AoR z-scores between groups. The IBAV group had larger AAo z-scores (2.48±1.9 vs. -0.02±0.98, p<0.0001), decreased DIS (9.6±4 vs. 12.3±3.1 cm2 dynes-1 x 10-6, p<0.05) and increased SI (21.4±9.2 vs. 14.4±3.8, p=0.007) compared to the TAV group. There were no differences in these variables between the R/L or R/N subgroups. No correlation was seen between aortic wall properties and ventricular function in the IBAV group. By multivariate regression, presence of an IBAV (coefficient = -2.4, p=0.03), LVSF (coefficient = -0.35, p=0.01) and age-adjusted systolic BP (coefficient = -0.13, p=0.03) were independently associated with DIS. Similarly, presence of an IBAV (coefficient = 6.7, p=0.005) and age (coefficient=0.85, p=0.02) were independently associated with SI.

Conclusions:
Children with IBAV have decreased DIS and SI even without hemodynamic abnormalities. Long-term studies to determine the impact of these findings on cardiovascular risk are needed.
Abstract 19827: Vascular Risk Levels Affect the Predictive Value of Platelet Reactivity for the Occurrence of Major Adverse Cardiovascular Events in Patients on Clopidogrel: Systematic Review and Collaborative Meta-analysis of Individual Patient Data
Authors: Reny Jean-Luc , Fontana Pierre , Hochholzer Willibald , Neumann Franz-Josef , ten Berg Jurren , Janssen Paul , Geisler Tobias , Gawaz Meinrad , Marcucci Rossella , Gori Ana-Maria , Cuisset Thomas , Alessi Marie-Christine , Gurbel Paul , Berdagué Philippe , Yong Gerald , Angiolillo Dominick , Aradi Daniel , Beigel Roy , Campo Gianluca , Campo Gianluca , Combescure Christophe
Published: July 2021

Introduction:
Prior studies have shown an association between high on-clopidogrel platelet reactivity (PR) and the risk of major adverse cardiovascular events (MACE). However, large intervention trials on PR-tailored treatments have been neutral.

Hypothesis:
The clinical relevance of PR in predicting MACE varies according to patients’ cardiovascular risk levels.

Methods:
We undertook a systematic review and meta-analysis of individual patient data on MACE outcomes (acute coronary syndromes (ACS), ischemic strokes, and vascular deaths) in relation to PR and its interaction with cardiovascular risk levels. PR was determined using ADP-induced light transmission aggregometry with a primary concentration of 20μM ADP.

Results:
Thirteen prospective cohort studies totalled 6,478 clopidogrel-treated patients who experienced 421 MACE (6.5%) during a median follow-up of 12 months. The risk of MACE associated with PR increased differentially according to the number of risk factors present (age>75 years, ACS at inclusion, diabetes, and hypertension; interaction p=0.04): no association to PR in low-risk patients (no risk factor) (p=0.48); 3.2 times greater risk of MACE in high PR (> 60%) intermediate-risk patients (one risk factor) (p=0.001); 2.9 and 3.7 times greater risk of MACE in medium PR (41%-60%) and high PR (>60%) high-risk patients (≥2 risk factors) (p=0.0004 and 0.0003, respectively). These interactions followed the same trends in studies using 5μM ADP.

Conclusions:
The magnitude of the association between PR and MACE risk is strongly dependant on the level of cardiovascular risk faced by patients on clopidogrel suggesting that PR-tailored strategies may be most effective in higher-risk patients.
Abstract 20526: Computational Fluid Dynamics in Partial Mechanical Circulatory Support: Implications for Patient Care
Authors: Partovi Sasan , Karmonik Christoph , Rengier Fabian , Mueller-Eschner Matthias , Meredig Hagen , Kauczor Hans-Ulrich , Arif Rawa , Schmack Bastian , Karck Matthias , Ruhparwar Arjang
Published: July 2021

Introduction:
Partial mechanical circulatory support (pMCS) is used for the therapy of heart failure. The CircuLite® Pump has been introduced clinically with its inflow cannula connected to the left atrium and the outflow cannula to the right subclavian artery. Aim of our study was to visualize and quantify flow patterns using computational fluid dynamics (CFD) in CT angiography (CTA).

Methods:
Two heart failure patients with pMCS were imaged with ECG-gated CTA and echocardiography. CFD was performed in 3D derived from CTA using flow boundary conditions measured with ultrasound. Flow was visualized using velocity vectors of blood flow. Average velocity was calculated at 10 time points during cardiac cycle in the aorta and the innominate. Wall shear stress (WSS) was visualized on the wall of the digital model.

Results:
Flow reversal was observed in mid-systole for both cases distal from the origin of the innominate artery in both cases due to asynchrony of the constant flow of the device with the pulsatile flow of the heart (fig.). Maximum velocity of this back flow was 0.39 m/s in case 1 and 0.2 m/s in case 2. Therefore, further distal in the innominate artery, a region of slow and stagnant flow with low WSS at the artery wall was observed which changed during cardiac cycle.

Conclusions:
CFD analysis revealed an asynchronous behavior in the inducted flow patterns during systole. Further design should allow for synchronization with the native heart function.

Figure: On top flow during systole for both cases (case 1 on left), below flow during diastole. WSS is shown in pseudo-color representation with red indicating high values. Flow is visualized by arrows. During systole, a region of low WSS (blue) exists in the innominate artery which is absent during systole indicating flow reversal at this location.

Bottom panel: Velocity in inferior-superior direction during cardiac cycle for both cases. Red lines demonstrates change of direction of flow in the innominate during systole.
Abstract 20669: Urocortin-2 Improves Right Ventricular Function in Pulmonary Arterial Hypertension
Authors: Santos-Ribeiro Diana , Adão Rui , Maia-Rocha Carolina , Alves Bárbara , Mendes-Ferreira Pedro , Leite-Moreira Adelino F , Brás-Silva Carmen
Published: July 2021

Introduction:
Urocortin (UCN)-2 is a peptide highly expressed in the cardiovascular system and it has shown promising therapeutic effects in several studies in both humans and animal models of heart failure (HF). However, the role of UCN-2 in right ventricular (RV) failure is still unknown.

Hypothesis:
This study analyzed the effects of UCN-2 treatment in an animal model of RV HF, secondary to pulmonary arterial hypertension (PAH).

Methods:
Male Wistar rats (180-200g) randomly received monocrotaline (MCT, 60mg/Kg, s.c.) or vehicle. After 14 days, animals from these groups were randomly assigned to receive treatment with either UCN-2 (2.5μg/Kg/day, i.p.) or vehicle. The study resulted in 4 groups: control (CTRL) (n=12); CTRL+UCN-2 (n=10); MCT (n=9); MCT+UCN-2 (n=8). RV Pressure-Volume measurements were performed 24-25 days after MCT administration. Only significant results (mean±SEM, p<0.05) are given.

Results:
MCT group developed PAH, as shown by: increased RV end-systolic pressure (MCT vs CTRL: 59±3 vs 26±1 mmHg) and end-diastolic pressure (MCT vs CTRL: 6.7±0.9 vs 3.5±0.7 mmHg), RV dilatation (MCT vs CTRL: 270±17 vs 215±12 μL), and decreased cardiac output (MCT vs CTRL: 29±3 vs 63±3 mL/min) and ejection fraction (MCT vs CTRL: 37±6 vs 72±2%). UCN-2 treatment resulted in attenuation of RV pressure increase (RVESP: 42±2 mmHg; RVEDP: 4.7±0.6 mmHg), dilatation (RVEDV: 212±4 μL), and in improved cardiac function (CO: 48±2 mL/min; EF: 58±2%).

Conclusions:
UCN-2 chronic treatment significantly reduced the worsening of RV function in PAH. These findings suggest that the UCN-2 pathway has a relevant role on the pathophysiology of PAH and RV failure, representing a potential therapeutic target.
Abstract 211: Delayed Cell Death in CA1 Region in a Cardiac Arrest Rat Model: Continuing After 2 Weeks of Survival?
Authors: Högler Sandra , Teubenbacher Ursula , Weihs Wolfgang , Sterz Fritz , Magnet Ingrid A M , Ettl Florian , Warenits Alexandra-Maria , Schober Andreas , Testori Christoph , Holzer Michael , Grassman Daniel , Wagner Michael , Kodajova Petra , Janata Andreas
Published: July 2021

Background:
Evolution of histological lesions in selectively vulnerable brain regions in animal models of cardiac arrest (CA)give evidence of potential therapeutic windows. Delayed cell death is of special interest in this regard.

Methods:
In male Sprague-Dawley rats (350g) ventricular fibrillation (VF) CA was induced for 6 min followed by chest compressions, ventilation and drugs for 2 min. To achieve return of spontaneous circulation animals were defibrillated every 2 min. Animals were sacrificed after one week (n=5) or two weeks (n=7) of survival and compared to four sham animals. Brains were fixed in formalin, embedded in paraffin wax and cut into 3 μm thick coronary sections for histological examination. Viable neurons with nucleolus were counted in Hematoxylin-Eosin (HE)-stained sections in a 250 μm sector of the medial CA1 region. FluoroJade B staining was applied to count dying neurons in the same sector.

Results:
In HE-staining sham animals had 31±4 viable neurons. In one week survivors 11±9 viable neurons (p=0.003) and in two week survivors 7±7 viable neurons (p=0.001 vs sham, p=0.49 vs one week survivors) were counted. Furthermore, a lot of degenerated hypereosinophilic neurons were present in HE-staining in both CA-groups. FluoroJade B-staining was negative in sham animals. In one week survivors 29±8 dying neurons (p=0.006) and in two week survivors 33±13 dying neurons (p= 0.016 vs sham, p=0.343 vs one week survivors) were detectable.

Conclusions:
Consistent damage in the medial CA1 region was present after 6 min VFCA in both survival time groups. Lesions seemed to be constant, with no significant differences between time points. Contrary to expectations, FluoroJade B-staining was still positive after two weeks of survival, suggesting that delayed cell death might go on for a longer time period than assumed so far.
Abstract 312: "Stand Clear" Belongs to the Past: A Solution for Safe Hands-on Defibrillation
Authors: Thomsen Jakob E , Petley Graham W , Løfgren Bo , Deakin Charles D
Published: July 2021

Introduction:
Interruptions to chest compressions during defibrillation reduce the chances of subsequent ROSC and successful defibrillation. Safe hands-on defibrillation (HOD) will allow uninterrupted chest compression during defibrillation and may improve resuscitation success. We tested the safety of rescuer contact with the patient (at the waist) whilst additionally wearing electrical insulating gloves during clinical defibrillation; a worst case scenario.

Materials and Method:
Leakage current flowing from the patient to the ‘rescuer’ during defibrillation of patients undergoing elective defibrillation was measured. The ‘rescuer’ remained in contact with the patient during defibrillation, wearing Class 1 electrical insulating gloves while simulating an inadvertent contact with the patient, through an additional wired contact between rescuer’s waist and patient. The results were compared with an international safety threshold of 1 mA.

Results:
Data from 67 shocks of variable biphasic energy from a total of 50 patients was recorded. The median leakage current from all defibrillations was 30 μA, (range: 7 - 164). Of the 34 of the shocks delivered at 360J the median leakage current was 62 μA (range: 13 - 164), all below the safety threshold of 1 mA.

Conclusion:
This study demonstrates that leakage current through the rescuer is within a safe threshold to allow hands-on defibrillation when using electrically insulated gloves and in the presence of an additional point of contact with the patient
Abstract 9395: The Clinical Role of Atrial Fibrillation in Patients with Arrhythmogenic Right Ventricular Dysplasia
Authors: Saguner Ardan M , Baldinger Samuel , Medeiros-Domingo Argelia , Ganahl Sabrina , Tanner Felix C , Brunckhorst Corinna , Duru Firat
Published: July 2021

Introduction:
Atrial fibrillation/flutter (Afib/Aflu) in general, and clinical variables predicting Afib/Aflu in particular, are not well defined in patients with arrhythmogenic right ventricular dysplasia (ARVD).

Hypothesis:
We hypothesized that transthoracic echocardiography (TTE) and ECG could be helpful to predict Afib/Aflu in these patients.

Methods and Results:
12-lead ECGs and TTEs of 90 patients from three tertiary-care centers diagnosed with definite or borderline ARVD according to the 2010 Task Force Criteria were analyzed. Data were compared in two patient groups: (1) patients with Afib/Aflu and (2) all other patients. Eighteen (20%) patients experienced Afib/Aflu during a follow-up period of 5.8 years (interquartile range 2.0-10.4 years). Kaplan-Meier analysis (Figure) revealed reduced times to Afib/Aflu among patients with echocardiographic RV fractional area change <27% (p<0.001), left atrial diameter ≥24.4 mm/m2 (p=0.001), and right atrial short axis diameter ≥22.1 mm/m2 (p=0.05). From all ECG variables, P sinistroatriale conferred the highest hazard ratio (3.37, 95% CI 0.92-12.36, p=0.067). Five patients with Afib/Aflu experienced inappropriate ICD shocks compared to four patients without Afib/Aflu (36% vs. 9%, p=0.03). Presence of Afib/Aflu was more prevalent in heart transplanted patients and in those who succumbed to cardiac death compared to the remaining patients (56% vs. 16%, p=0.014).

Conclusions:
Afib/Aflu are associated with inappropriate ICD shocks, heart transplantation, and cardiac death in patients with ARVD. Echocardiographic evidence of reduced RV function and atrial dilation helps to identify those ARVD patients being at increased risk for Afib/Aflu, which may help to guide individual patient management.
Abstract 23: Divergent Temporal Trends in the Incidence of Heart Failure with Preserved and Reduced Ejection Fraction
Authors: Tsao Connie W , Lyass Asya , Larson Martin G , Vasan Ramachandran S
Published: July 2021

Background:
The past two decades have witnessed divergent trends in the prevalence of major cardiovascular disease risk factors and advances in medical therapy for coronary disease. Over this time period (1990-2009), we hypothesized that the incidence of heart failure with preserved ejection fraction (HFPEF) may have decreased with improved blood pressure control, whereas the incidence of heart failure with reduced ejection fraction (HFREF) may have increased due to improved treatment of coronary disease with myocardial salvage.

Methods:
We studied Framingham Heart Study Original and Offspring Cohort participants at least 40 years of age and free of HF (n=6648, 56% women, 21285 five-year epochs, 769 HF, 97829 person-years). We estimated age- and sex-adjusted rates of HF, HFPEF, and HFREF (cumulative incidence at 5 years) for 5-year time windows between 1990 and 2009 and for 10-year intervals, 1990-1999 and 2000-2009. We used proportional hazards models to estimate cumulative incidence and test time trends in hazards ratios, for the overall sample and for each sex separately.

Results:
HF incidence varied modestly across the time windows but differences were not statistically significant overall, in men, or in women (
TABLE
). Across the two decades, there was a 40% increase in the incidence of HFPEF (p=0.003), but a 20% decrease in the incidence of HFREF (p<0.0001). The incidence of HFPEF between decades did not change significantly in men but increased 56% in women (p=0.014). Between decades, the incidence of HFREF declined by 13% in men and by 29% in women (p=0.01 and 0.003, respectively).

Conclusions:
Whereas the overall incidence of HF has not changed significantly in the past two decades, the incidence of HFPEF has risen and that of HFREF has declined reciprocally, opposite to what we hypothesized. Future investigation into the potential factors underlying these intriguing trends is warranted.
Abstract P143: Circulating Level of Hepatocyte Growth Factor and Incidence of Diabetes Mellitus: The Multi-Ethnic Study of Atherosclerosis
Authors: Bancks Michael P , Bielinski Suzette J , Decker Paul A , Hanson Naomi Q , Larson Nicholas B , Sicotte Hugues , Wassel Christina L , Pankow James S
Published: July 2021

Introduction:
Increased levels of hepatocyte growth factor (HGF), active in cell growth, motility, and morphogenesis, are associated with the presence of obesity, poor metabolic health, and cardiovascular disease.

Hypothesis:
We assessed the hypothesis that higher baseline levels of HGF will be associated with increased risk of diabetes.

Methods:
We examined the association between HGF and incident diabetes in MESA, including 5395 men and women 45-84 years of age at enrollment (2000-02). Fasting serum HGF was measured at baseline and on a subsample of participants at exam 2 (n = 1915). From 2000-11, incidence of diabetes was ascertained over 4 follow-up examinations, determined by new use of insulin or oral hypoglycemic medication or fasting glucose ≥ 126 mg/dL. Cox regression was used to estimate hazard ratios (HR) for incident diabetes according to 1 standard deviation unit (SDU) of HGF (1 SDU =256 pg/mL), before and after adjustment for age, sex, race/ethnicity, education, study center, smoking status, alcohol consumption, BMI, WC, fasting glucose and insulin, CRP, and IL-6 levels. Similarly, hazard ratios for incident diabetes were estimated according to change in HGF levels from exam 1 to exam 2 in the subsample.

Results:
At baseline, older age, male sex, current smoking, and higher body mass index (BMI), waist circumference (WC), fasting glucose and insulin, C-reactive protein (CRP) and interleukin-6 (IL-6) levels were all associated with higher levels of HGF, while greater education and physical activity were associated with lower serum HGF. Incidence of diabetes in this analytic sample was 12% (n cases = 670). Per 1 SDU increase in baseline HGF level, unadjusted risk for diabetes increased 1.46 fold (95% CI=1.37, 1.56). After adjustment, diabetes risk per 1 SDU increase in HGF was attenuated but remained significantly increased (HR=1.22; 95% CI=1.12, 1.32). No association was found between change in HGF level between exam 1 and exam 2 and incidence of diabetes. There was no evidence of effect modification by race/ethnicity for either analysis.

Conclusion:
In conclusion, in this ethnically diverse U.S. adult population, higher levels of serum HGF were independently associated with increased incidence of diabetes.
Abstract P191: Carotid Intima-Media Thickness is Associated with Systolic Blood Pressure, Body-Mass Index and LDL Cholesterol in Low-Risk Individuals. A Cross-Sectional Analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).
Authors: Santos Itamar S , Bittencourt Márcio S , Oliveira Ilka R , Souza Angelita G , Meireles Danilo P , Rundek Tatjana , Foppa Murilo , Bezerra Daniel C , Roelke Leonard H , Benseñor Isabela M , Lotufo Paulo A
Published: July 2021

Introduction:
Carotid intima-media thickness (cIMT) is a noninvasive measurement of early atherosclerosis by ultrasound. Determinants of cIMT in individuals without classical cardiovascular (CV) risk factors are poorly studied.

Hypothesis:
We assessed the hypothesis that systolic blood pressure (SBP), body-mass index (BMI), serum glucose and LDL cholesterol (LDL-c) are associated with maximal cIMT values in low-risk individuals (no hypertension, diabetes, dyslipidemia or prior CV disease, no CV medications, no current or past smoking and a BMI < 30 kg/m
2
).

Methods:
We used data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline. ELSA-Brasil is a multicenter cohort of 15,105 civil servants aged 35-74 years in six Brazilian cities. Baseline assessment included cIMT measurements in both common carotid arteries. SBP, BMI, serum glucose and LDL-c values were standardized. We used multiple linear regression models to study the association of SBP, BMI, serum glucose and LDL-c with maximal cIMT (in mm).

Results:
We analyzed 1,569 ELSA-Brasil low-risk participants with complete cIMT data. There were 1,024 (65.3%) women and 924 (58.9%) of White race. Mean ± standard deviation (SD) for continuous variables were: age 46.1 ± 7.7 years; SBP 111.2 ± 10.8 mmHg; BMI 24.0 ± 2.9 kg/m
2
; serum glucose 99.7 ± 7.8 mg/dl; LDL-c 105.6 ± 17.1 mg/dl and maximal cIMT 0.700 ± 0.136 mm. The table shows the beta-coefficients associated to one standard deviation increase in SBP, BMI, serum glucose and LDL-c.

Conclusions:
Even in a low-risk subsample, excluding individuals with hypertension, dyslipidemia or obesity, SBP, BMI and LDL-c were positively associated with higher maximal cIMT. This probably reflects a continuum of risk for atherosclerotic disease mediated by these measurements that do not evanesce with the exclusion of subjects who fulfill current diagnostic criteria for these conditions.
Abstract P210: Lipoprotein Profiles in Patients With and Without Psoriasis
Authors: Lotufo Paulo A , Jones Steven , Blaha Michael , Sabbag Cid , Dias-Santos Raul , Toth Peter P , Bensenor Isabela M
Published: July 2021

Introduction:
Psoriasis is associated with chronically heightened systemic inflammatory tone and increased risk for cardiovascular disease. It remains to be established if the psoriatic state itself associates with dyslipidemia.

Hypothesis:
The lipid profile of patients with psoriasis is more atherogenic compared to disease-free control patients.

Methods:
The concentration and size of lipoprotein particles were measured using nuclear magnetic resonance spectroscopy in 221 patients with a diagnosis of psoriasis (53.6% men; mean age=56.6 years; mild cases=31%; moderate/severe only skin=27%; arthritis=27%)) and 689 disease-free persons matched by sex and age. We compared means of lipoprotein particle concentration and size using a univariate general linear model and adjusting for body-mass index, waist circumference, diabetes, use of lipid lowering-drugs, as well as duration/severity of psoriasis.

Results:
Patients with psoriasis were more overweight, had larger waist circumference, and a higher frequency of diabetes and use of lipid-lowering drugs. Total LDL particle means (nmol/L) for the psoriasis and control groups were 1436 (1378-1494) vs. 1420 (1388-1452) (P=0.4), respectively. The mean concentration of IDL was higher in patients with psoriasis compared to controls: 143.6 (130.7-156.5) vs. 106.1 (99.1-113.2), P<0.01. Large and small LDL particle concentrations were similar between groups. Large VLDL/chylomicron particle concentrations (nmol/L) were higher in psoriasis patients compared to controls 6.1 (5.2-7.0) vs. 4.0 (3.6-4.5) (P<0.01). Total HDL particle and subfractions were not statistically different between groups. The mean size (nm) of VLDL was higher in psoriasis patients: 50.2 (49.2-51.2) vs. 46.2 (45.6-46.7) (P<0.001) for psoriasis and controls, respectively. In contrast, mean sizes of LDL and HDL particles were similar (P=0.3). Adjustment for covariates above mentioned did not change these findings. The absence/presence of arthritis did not change the results.

Conclusion:
Patients with psoriasis have a more atherogenic lipid profile compared to controls with higher levels of IDL and VLDL of large and small size. In addition, the greater mean size of VLDL particles in psoriasis compared to controls suggests enhanced secretion of triglyceride loaded VLDL, impaired lipolysis and impaired clearance of remnant IDL.
Abstract 10036: Olmesartan Improves Not Only Vascular Endothelial Dysfunction but Cardiac Diastolic Dysfunction in Hypertensive Heart Failure With Preserved Ejection Fraction - ORION Study
Authors: Yamamoto Eiichiro , Ohba Keisuke , Hirata Yoshihiro , Tokitsu Takanori , Sugamura Koichi , Hokimoto Seiji , Sugiyama Seigo , Ogawa Hisao
Published: July 2021

Introduction:
The optimal treatment for heart failure (HF) with preserved left ventricular (LV) ejection fraction (EF) (HFpEF) has not been established. Using an experimental model of HFpEF, we previously reported a novel mechanism underlying reversal of endothelial dysfunction and HFpEF by AT1 receptor blocker (ARB). By performing this study (ORION: OlmesaRtan Improvement endothelial functiON with hypertension study), we examined the effects of ARB on hypertensive HFpEF patients, focusing on reactive oxygen species (ROS).

Methods and Results:
We examined prospectively 20 hypertensive HFpEF patients, taking any renin-angiotensin system inhibitors, switched to appreciable amounts of highly-selective ARB; olmesartan (average dosage amounts: 22.9 mg/day) for 3 months. Despite no additive hypotensive effects of olmesartan, endothelial dysfunction assessed by fingertrip digital reactive hyperemia (RH) peripheral arterial tonometry using Endo-PAT2000 was significantly reversed (RH-index; 1.57±0.34 to 1.87±0.50, P=0.034), accompanied by significant reduction of serum derivatives of reactive oxidative metabolites levels, novel biomarker of ROS (362.8±13.7 to 302.1±9.4 unit called the Carratelli unit [U.CARR], P=0.001). Olmesartan treatments significantly improved cardiac diastolic function evaluated by the ratio of early transmitral flow velocity to tissue doppler early diastolic mitral annular velocity (15.4 to 11.0, P<0.001) but not LVEF and LV anterior wall thickness in echocardiography, and decreased plasma B-type natriuretic peptide levels (214.9 to 191.4, P<0.05) in HFpEF patients. Additionaly, olmesartan significantly increased plasma superoxide dismutase activity (2.39±0.73 to 3.06±0.78 U/mL, P=0.02) and adiponectin levels (2.66±1.55 to 4.12±1.99 μg/mL, P<0.05), but not affect plasma nitrates and nitrites (NO3-/NO2-) levels (53.2±28.1 to 62.9±28.4 μmol/L).

Conclusions:
These data suggested that strong AT1 receptor blockade by olmesartan restored not only endothelial dysfunction but cardiac diastolic dysfunction in HFpEF beyond hypotensive effects. Increased in SOD activities and adiponectin levels, but not nitric oxide levels, might contribute to these beneficial effects of olmesartan.
Abstract 10905: Pulse Amplitude Changes During the Valsalva Maneuver Measured Using Finger Photoplethysmography Identify Elevated Pulmonary Capillary Wedge Pressure in Heart Failure Patients
Authors: Gilotra Nisha A , Wanamaker Brett L , Rahim Hussein , Kunkel Katherine , Rizvi Saadia , Yenokyan Gayane , Wittstein Ilan S , Tedford Ryan J , Russell Stuart D , Silber Harry A
Published: July 2021

Introduction:
Pulse amplitude ratio (PAR) (ratio of pulse pressure at end of Valsalva maneuver (VM) to before onset) correlates with filling pressure. We developed a noninvasive device to measure PAR using finger photoplethysmography (PPG).

Hypothesis:
PAR reflects PCWP in heart failure (HF) patients and can detect a change in volume status.

Methods:
Patients referred for right heart catheterization (RHC) or admitted for HF performed three 10-second trials of a standardized VM (at 20 mmH measured via a pressure transducer) while PPG waveforms were recorded.

Results:
Amongst 60 patients undergoing RHC (Table 1), PAR correlated with PCWP (Pearson correlation coefficient = 0.53, p<0.0001; Fig 1A), particularly in the 25 patients with systolic HF (Pearson correlation coefficient = 0.60, p=0.002; Fig 1B). A multivariable linear model for PCWP including PAR, age, BMI, blood pressure and heart rate improved ability to predict PCWP (r2=0.54). Difference in mean PAR for patients with a PCWP < 15 mmHg versus ≥ 15 mmHg was statistically significant (p=0.0001; Fig 1C). PAR ≥ 0.515 predicted PCWP ≥ 15 mmHg with 83% sensitivity and 80% specificity (85% PPV). Presence of a positive Kussmaul’s sign did not alter the correlation between PAR and PCWP (p=0.897 for interaction). In 8 patients admitted with HF, PAR decreased by a mean of 0.10 from admission to discharge (p=0.023, effect size=0.85).

Conclusions:
We demonstrate that the response of a finger PPG waveform to a standardized VM in HF patients can estimate PCWP and also detect changes after diuresis. The ability to detect elevated filling pressures noninvasively prior to development of symptomatic congestion could reduce HF hospitalizations.
Abstract 11691: Atorvastatin Reverses Impaired Voltage-gated K
+
Channels-mediated Coronary Vasodilation By Upregulating PPARγ In Diabetes
(Best of Basic Science Abstract)
Authors: Su Wen , Li Wei-Ping , Chen Miao , Chen Hui , Li Hong-Wei
Published: July 2021

Aims:
Voltage-gated K
+
(K
v
) channels in vascular smooth muscle cells (VSMCs) play an important role in the regulation of coronary microcirculation. Atorvastatin (ATV) has shown some beneficial effects on vascular function, but the effect of ATV on K
v
channels-mediated coronary vasodilation remains unknown. The present study was designed to investigate the role of ATV in improving K
v
channels-mediated coronary dilator function in diabetes and the underlying mechanisms.

Methods:
Isolated VSMCs were incubated in normal or high glucose medium plus a different dose of ATV for 24 h at 37
o
C. Patch-clamp recording and molecular biological techniques were used to assess the function and expression of K
v
channels. Control or type 2 diabetic rats were treated with ATV (50 mg/kg daily) by oral gavage for 10 weeks. Vasodilation of isolated rat coronary arteries was measured using a pressurized myograph. GW9662, the peroxisome proliferator-activated receptor gamma (PPARγ) antagonist, was used to determine whether the mechanism of ATV-improved K
v
channel function can be explained by upregulation of PPARγ pathway.

Results:
Patch-clamp analysis revealed that high glucose reduced K
v
current density by 58.7 ± 4.6%, which was accompanied by a downregulation of K
v
1.2 and K
v
1.5 expression. Treatment with ATV reversed the inhibitory effect of high glucose on K
v
current density in a dose-dependent manner (1 μmol/L, 15.0 ± 2.6%; 10 μmol/L, 49.1 ± 3.8%; 100 μmol/L, 69.9 ± 4.8%;
P
< 0.05). In addition, ATV restored high glucose-induced downregulation of K
v
channel protein expression, and the difference was significant in both 10 μmol/L and 100 μmol/L groups. For
in vivo
study, K
v
channels-mediated coronary vasodilation was decreased in diabetic rats, compared with controls (9.1 ± 1.3
vs.
36.7 ± 1.4%,
P
< 0.05), whereas this decrease was partly corrected by ATV (25.0 ± 2.8
vs.
9.1 ± 1.3%,
P
< 0.05). Treatment with ATV prominently increased protein expression of PPARγ both
in vitro
and
in vivo
. The effect of ATV in regulating K
v
channels and K
v
channels-mediated vasodilation was markedly blunted by GW9662.

Conclusions:
In conclusion, treatment with ATV activates PPARγ pathway and preserves K
v
channel activity in VSMCs, thus providing improvement of coronary dilator function in diabetic rats.