bluuebunny/crossref_metadata_2025_split huggingface dataset:
P3492Carvedilol and its analogue VK-II-86 attenuate stretch-induced manifestations of mechanoelectric feedback
Authors: Del Canto Serrano I , Santamaria L , Genoves P , Such-Miquel L , Zarzoso M , Parra G , Arias-Mutis O , Such L , Alberola A M , Soler C , Chorro F J 
Published: October 2019

Abstract

Background
Mechanical stretch modifies Ca2+ handling and myocardial electrophysiology, favoring arrhythmogenesis. The store-overload-induced Ca2+ release (SOICR) through the ryanodine receptor (RyR2) seems to be implicated in this deleterious effect. Carvedilol and its analogue VK-II-86 (which does not have significant beta-blocking effects) suppress SOCIR by directly reducing the open duration of the cardiac RyR2, and could modulate calcium-related changes produced by myocardial stretch.

Purpose
The aim of this study was to investigate, by the ventricular fibrillation (VF) spectral analysis, whether carvedilol and VK-II-86 prevents stretch-induced arrhythmogenic effects.

Methods
The VF modifications induced by acute stretch were studied in Langendorff-perfused rabbit hearts using epicardial multiple electrodes under control conditions (n=10), during carvedilol infusion (0.1 and 1 μM) (n=10) and during VK-II-86 infusion (0.1 and 1 μM) (n=10). Spectral techniques were used to establish the baseline and stretch characteristics in the three series above mentioned: VF dominant frequency (DF) and VF spectral concentration (SpC) were determined. A two-factor ANOVA test was used and significance was reached when p<0.05.

Results
Myocardial stretch significantly increased DF with respect to pre-stretch values in control conditions (13.3±1.2 vs. 16.1±3.0 Hz, p<0.05) and during the perfusion of 0.1μM carvedilol (11.6±1.5 vs. 13.6±2.9 Hz, p<0.05) and 0.1μM VK-II-86 (13.2±2.2 vs. 16.2±4.1 Hz, p<0.05). However, the maximum concentration of both drugs (1μM) abolished this stretch-induced VF acceleration (carvedilol: 6.9±2.2 vs. 7.3±2.6 Hz, ns; VK-II-86: 7.0±1.4 vs. 7.1±0.6 Hz, ns). The significant stretch-induced decrease in SpC in control conditions (31.4±8.6 vs. 23.2±6.4%, p<0.01) was attenuated under 0.1μM carvedilol (0.1μM: 27.6±8.4 vs. 23.5±6.1%, ns) and 0.1μM VK-II-86 (24.7±5.4 vs. 21.2±3.9%, ns), but not under 1μM of both drugs (carvedilol: 41.3±11.3 vs. 30.3±5.7%, p<0.05; VK-II-86: 34.7±7.2 vs. 28.3±3.9%, p<0.01). Nevertheless, during stretch, arrhythmia regularity and organization was greater (higher SpC) under the highest concentration of carvedilol (p<0.01) and VK-II-86 (p<0.05) than in control conditions (control: 23.2±6.4%, carvedilol 1μM: 30.3±5.7%, VK-II-86 1μM: 28.3±3.9%).

Conclusion
Carvedilol and its analogue VK-II-86 abolished the changes in VF activation frequency produced by myocardial stretch at the highest studied concentration, and also attenuated the stretch-induced activation heterogeneity at the lowest concentration. The similarity in the effects of both drugs on the stretch-induced alterations would imply that its protective effect is due to its ability to inhibit store-overload-induced calcium release.
P3499Myocardial extracellular matrix during post-infarction remodeling: The role of C3-complement system
Authors: Garcia-Arguinzonis M , Vilahur G , Juan-Babot O , Diaz-Riera E , Badimon L , Padro T 
Published: October 2019

Abstract

Background
Healing of the myocardium or progression to heart failure following myocardial infarction (MI) seems directly related to dynamic changes in protein composition of the extracellular matrix (ECM). The myocardial matrisome, fraction of functional non-structural ECM-associated proteins (ECMm), may regulate myocardial remodeling post-MI but the mechanisms involved remain unknown. We identified the C3-complement system (C3-CS), a central effector pathway of the innate immune system, and cleavage products by proteomic analysis of porcine myocardial tissue post-MI. Here we investigated the C3-CS dynamic changes in the myocardial ECMm of reperfused hearts in relation to the ischemic zone and time of evolution post-MI.

Methods
ECMm proteins were investigated in the ischemic (ISCH) and non-ischemic (NISCH) zones in the porcine myocardium Post-MI. MI was induced by closed-chest balloon occlusion of the LAD for 90 minutes. Myocardial tissue was obtained after 2.5h, 1d, 3d and 30d after MI ((n=7/time-point). ECMm was extracted and C3-CS protein signature analyzed by western blot with specific antibodies. Myocardial tissue from the same areas was characterized by immunohistochemistry (IH).

Results
C3-cleavage products derived from activated C3-CS and its regulatory proteins (CFD, CFH, and CFHR5) were consistently detected in post-MI myocardium with a differential protein-signature between ISCH and NISCH zones and changed dynamically with elapsed time post-MI. The major changes were detected in the ISCH zone that was enriched with innate immunity cells (neutrophils and macrophages) as seen at day 3 by IH, suggesting local rather than systemic induction of C3-activation. Thus, CFD (C3-activating factor) and CFHR5 (C5-convertase inhibitor) were significantly increased in ISCH (>2fold vs. NISCH) at day 1, resulting in a high generation of the chemotactic and inflammatory C3a-product. At day 3, there was a high content of macrophages (>5fold higher than 24h) in the ISCH zone with enrichment of iC3b-products (p<0.05 vs. NISCH zone) derived from CFI/CFH-induced cleavage of C3b. In contrast, at day 30, there was enrichment in fibroblasts and collagen fibers in the ISCH zone and an increased C5-activation pattern compared to all the earlier times (2.5–24 h) and the NISCH zone. Thus, C5b, main source of the called “membrane attack complex” was significantly elevated and CFHR5 reduced compared to values at day 3.

Conclusion
Our results evidenced a time-dependant coordinated response of the C3-System in the ECMm of the ischemic myocardium, starting shortly after reperfusion and maintained up to 30 days that parallels changes in the cell pattern present in the ISCH zone. Our results show that C3-CS is associated to key cell functions for tissue remodeling and repair.

Acknowledgement/Funding
FIS PI16/01915 - Institute of Health Carlos III-ISCIII
P3511Gender differences in electrocardiographic risk markers of heart failure
Authors: Haukilahti M A E , Kentta T V , Tikkanen J , Anttonen O , Aro A , Kerola T , Rissanen H , Knekt P , Junttila M J , Huikuri H V 
Published: October 2019

Abstract

Background
Heart failure (HF) is one the leading causes of hospitalization in the Western world. Women have a lower rate of HF hospitalization and mortality compared to men. Role of 12-lead electrocardiography (ECG) as a risk marker of future HF in women is not well known.

Purpose
We studied the association of standard 12-lead ECG and clinical risk factors to HF hospitalization in women and in men separately from a large middle aged general population sample with a long-term follow-up.

Methods
Standard 12-lead ECG markers were analyzed from 10,864 subjects (48.8% women, N=5,215) of the prospective Mobile Clinic Study, and their predictive value for HF hospitalization was analyzed.

Results
During the follow-up (29.6±11.2 yrs.), a total of 1,743 subjects had HF hospitalization; out of these, 861 were women (49.4%). Several baseline characteristics, such as age, body mass index, blood pressure, and history of prior cardiac disease predicted the occurrence of HF both in women and men (P<0.001 for all). After adjusting for baseline variables, ECG sign of left ventricular hypertrophy (LVH) (P<0.001), and atrial fibrillation (P<0.001) were the only baseline ECG variables that predicted the future HF in women. In men, HF was predicted by fast heart rate (P=0.008), T wave inversions (P<0.001), abnormal Q waves (P=0.002), and atrial fibrillation (P<0.001). Statistically significant gender interactions in prediction of HF were observed in ECG sign of LVH (P<0.001), inferolateral T wave inversions (P=0.005), and heart rate (P=0.012).

Conclusions
ECG sign of LVH predicts future HF in middle-aged women independently, and T wave inversions and elevated heart rate are associated with HF hospitalization in men in.

Acknowledgement/Funding
Finnish Cultural Foundation, The University of Oulu Scholarship Foundation, Juho Vainio Foundation
P3515Gender differences in plasma levels and prognostic value of NT-proBNP in chronic heart failure
Authors: Aimo A , Januzzi J , Vergaro G , Latini R , Anand I S , Cohn J N , Gravning J , Brunner-La Rocca H P , Bayes-Genis A , De Boer R A , Takeishi Y , Eggers K M , Huber K , Passino C , Emdin M 
Published: October 2019

Abstract

Background
Natriuretic peptides are established biomarkers of heart failure (HF). The existence of gender-related differences in circulating levels and prognostic value are still controversial.

Methods
Individual patient data from studies assessing cardiac biomarkers (N-terminal fraction of pro-B-type natriuretic peptide - NT-proBNP - and high-sensitivity troponin T) for risk prediction in stable chronic HF were analysed.

Results
Women (n=1964, 23%) had higher median [interquartile interval] NT-proBNP concentrations than men (1678 [659–4215] vs. 1294 [522–2973] ng/L, p<0.001). Female gender predicted higher NT-proBNP independently from age, body mass index, glomerular filtration rate, left ventricular ejection fraction (LVEF), and atrial fibrillation.
Over a 2.4-year follow-up (1.6–3.2), 2351 patients (27%) died, and cardiovascular death occurred in 1558/8271 (19%). HF hospitalization was recorded in 2088/7944 (26%) over 2.0 years (1.3–2.6). Women and men had similar areas under the curve for the 3 endpoints, with higher cut-offs among women: all-cause death, 2328 ng/L vs. 1319 ng/L; cardiovascular death, 2328 ng/L vs. 1413 ng/L; HF hospitalization, 1265 ng/L vs. 907 ng/L. In the prognostic model above, the risk of the three endpoints increased by 32%, 35%, and 17%, respectively, per doubling of NT-proBNP in women, and by 41%, 45%, and 30% in men.

Conclusions
Women with chronic HF display higher NT-proBNP levels than men in the whole population as well as across many patient subgroups. This difference is not entirely explained by heterogeneity in age, BMI, or renal function. NT-proBNP holds independent prognostic significance in both genders, although alternative prognostic cut-offs might be considered for women.
P3517Failure to achieve adequate heart rate control in women during therapy optimization
Authors: Kutyifa V , Erath J W , Burch A , Assmus B , Bondermann D , Russo A M 
Published: October 2019

Abstract

Background
Previous studies highlighted the importance of adequate heart rate control in heart failure patients, and suggested under-treatment with beta-blockers especially in women. However, data on women achieving effective heart rate control during beta-blocker therapy optimization are lacking.

Methods
The wearable cardioverter defibrillator (WCD) allows continuous monitoring of heart rate (HR) trends during WCD use. In the current study, we assessed resting HR trends (nighttime: midnight-7am) in women, both at the beginning of WCD use and at the end of WCD use to assess the adequacy of beta-blockade following a typical 3 months of therapy optimization with beta-blockers. An adequate heart rate control was defined as having a nighttime HR <70 bpm at the end of the 3 months.

Results
There were a total of 21,453 women with at least 30 days of WCD use (>140 hours WCD use on the first and last week). The mean age was 67 years (IQR 58–75). The mean nighttime heart rate was 72 bpm (IQR 65–81) at the beginning of WCD use, that decreased to 68 bpm (IQR 61–76) at the end of WCD use with therapy optimization. Women had an insufficient heart rate control with resting heart rate ≥70 bpm in 59% at the beginning of WCD use that decreased to 44% at the end of WCD use, but still remained surprisingly high. Interestingly, there were 21% of the women starting with HR ≥70 bpm at the beginning of use (BOU) who achieved adequate heart rate control by the end of use (EOU). Interestingly, 6% of women with adequate heart rate control at the start of therapy optimization ended up having higher heart rates >70 bpm at the end of the therapy optimization time period (Figure).
Figure 1

Conclusions
A significant proportion of women with heart failure and low ejection fraction do not reach an adequate heart rate control during the time of beta blocker initiation/titration. The wearble cardioverter defibrillator is a monitoring device that has been demonstrated in this study to appropriately identify patients with inadequate heart rate control at the end of the therapy optimization period. The WCD could be utilized to improve management of beta-blocker therapy in women and improve the achievement of adequate heart rate control in women.
P3518Men with heart failure have higher readmission rates: a closer review of sex and gender based analyses
Authors: Hoang-Kim A , Parpia C , Freitas C , Austin P C , Ross H J , Wijeysundera H C , Tu K , Mak S , Farkouh M E , Schull M , Rochon P , Mason R , Lee D S 
Published: October 2019

Abstract

Background
There has been increased attention on reducing hospital readmission rates. However, little is known about any difference in readmission rates in heart failure by sex, although evidence exists demonstrating differences in the etiology of heart failure. As a result, strategies to optimize readmission reduction programs and care strategies for women and men remain unclear.

Purpose
(1) To identify studies examining readmission rates according to sex, and (2) to provide a qualitative overview of possible considerations for the impact of sex or gender.

Methods
A scoping protocol was developed using the Arksey and O'Malley framework and the Joanna Briggs Institute methodology. Our search strategy was reviewed according to the peer-review of electronic search strategy (PRESS) checklist. Full text articles published between 2002 and 2017 and drawn from multiple databases (i.e. MEDLINE, EMBASE), grey literature (i.e. National Technical Information, Duck Duck Go), and experts were consulted for additional articles. Screening criteria were established a priori. Once an acceptable inter-rater agreement was established at 80% by two independent reviewers, articles were screened for potential eligibility. A descriptive analytical method was employed to chart primary research articles. Articles were considered relevant if the cohort consisted of adult heart failure patients who were readmitted after an index hospitalization and a sex/gender-based analysis was performed.

Results
The literature search yielded 5887 articles, of which 746 underwent full text assessment for eligibility. Of 164 eligible articles, 34 studies addressed the primary outcome, 103 studies considered sex differences as a secondary outcome and 25 studies included disaggregated data for sex but no subsequent interaction was reported. Good inter-rater agreement was reached: 83% for title and abstract screening; 88% for full text review; kappa: 0.69 (95% CI: 0.526–0.851). Twelve of 34 studies included for the primary outcome reported higher readmission rates for men compared to five studies reporting higher readmission rates for women. However, there were differential readmission rates that were dependent on duration of follow-up. Women were more likely to experience higher readmission rates than men when time to event was less than one year. Readmission rates for men were higher when follow-up was longer than one year.

Conclusion
Sex differences in readmission rates were dependent on follow up time. Most studies used composite outcomes and had short times to event, which may mask underlying effects of sex on readmission.

Acknowledgement/Funding
Ontario SPOR Support Unit
P3534Optimal dosing of initial bolus of intravenous furosemide in acute heart failure: insights from REALITY-AHF
Authors: Matsue Y , Okumura T , Kida K , Oishi S , Akiyama E , Suzuki S , Yamamoto M , Kitai T 
Published: October 2019

Abstract

Background
Although intravenous diuretics are a cornerstone in the treatment of patients with acute heart failure (AHF), optimal dosing of initial bolus of IV diuretics has not been well elucidated.

Methods
The initial IV bolus dose of furosemide and its association with outcomes were analyzed in 1290 AHF patients (median age, 81 years, 55% were male) derived from REALITY-AHF (Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure). The patients were divided into 3 groups; lower dose (lower than recommended dose, n=371), standard dose (same as recommended dose, n=807), and higher dose (higher than recommended dose, n=112) groups according to the recommended initial IV bolus furosemide dose derived from the maintenance loop diuretics dose (for those without taking oral loop diuretics or taking ≤40mg/day oral furosemide-equivalent loop diuretics, 20mg IV bolus furosemide; those on >40mg/day oral furosemide-equivalent loop diuretics, IV bolus furosemide at the same dose as oral loop diuretic dose). Outcomes were length of hospital stay, diuretic response (urine output achieved within 48 hours of admission per 40 mg furosemide-equivalent diuretics dose), and 60-day all-cause mortality.

Results
Median amount of first IV bolus furosemide dose were 10, 20, and 40 mg for lower, standard, and higher dose groups, respectively. After adjustment for other covariates, length of hospital stay was significantly longer by 2.6 days (p=0.018) in the lower dose group compared to the standard dose group, and there was no difference between the standard and high dose groups (p=0.221). Diuretic response within 48 hours of admission was significantly better in the lower dose group (beta coefficient: 244 mL, p=0.025) and significantly worse in the higher dose group (beta coefficient: - 1098 mL, p<0.001) compared to the standard dose group after adjustment for covariates. During 60 days of admission, 91 deaths were observed, and 60-day mortality was significantly higher in the higher dose group (HR: 2.80, 95% CI: 1.49–5.26, p=0.001), but not in the lower dose group (HR: 1.18, 95% CI: 0.67–2.08, p=0.571) compared to the standard dose group after adjustment for other prognostic factors.

Conclusion
Treatment with the recommended initial bolus of IV furosemide is associated with a shorter hospital stay compared to lower dose regimen and better diuretic response and better 60-day survival compared to higher dose regimen in patients with AHF.

Acknowledgement/Funding
This study was funded by The Cardiovascular Research Fund, Tokyo, Japan.
P3552Estimating left ventricular myocardial deformation during cardiopulmonary exercise testing in patients with dilated cardiomyopathy and reduced ejection fraction
Authors: Triantafyllidi H , Birba D , Ikonomidis I , Makavos G , Benas D , Cokkinos D V , Iliodromitis E 
Published: October 2019

Abstract

Background
Cardiopulmonary exercise testing (CPET) has been recognized as a valuable tool regarding the integrated estimation of exercise ability in patients with several cardiopulmonary diseases, dilated cardiomyopathy (DCM) included. Left ventricular (LV) abnormal myocardial deformation might be studied by newer echocardiography techniques. Aim of this study is to explore differences of LV myocardial deformation in DCM patients during a CPET session.

Methods
Forty-four DCM patients (mean age 53±13 years, 34 men) with an ejection fraction <50% (mean EF = 33±10%) and no history of previous pulmonary disease were subjected to maximum CPET. Simultaneously, we estimated LV myocardial deformation using speckle tracking imaging and we measured global longitudinal strain (GLS), longitudinal strain rate both at systole (GLSrS) and diastole (GLSrE) at baseline and at peak exercise. The difference between GLS at baseline-GLS at peak exercise was defined as GLS difference.

Results
All patients finished uneventfully CPET (peakVO2 = 20±7 ml/min/kg) and improved GLS at peak exercise (GLS difference = 1.5±2). We found that at peak exercise, systolic blood pressure (SBP) was increased (119±14 vs. 159±23 mmHg, p<0.001) while GLS (−12.5±4 vs. −14±5, p<0.001), GLSrS (−0.7±0.2 and −1.0±0.4, p<0.001) and GLSrE (0.7±0.4 and 1.0±0.6, p=0.001) were improved. A positive correlation between peakVO2 and GLS difference was found, independent of peak SBP (β=0.38, p=0.01).
Relationship between GLS dif and CPET

Conclusions
Patients with dilated cardiomyopathy and ejection fraction <50% present an increased exercise ability when they manage to improve LV GLS during maximum exercise. Consequently, LV GLS improvement during exercise characterizes beside patient's exercise ability the severity of heart failure as well.
P3576Histopathological validation of optical coherence tomography assessment for cholesterol crystals
Authors: Tanaka A , Taruya A , Katayama Y , Akasaka T , Kondo T 
Published: October 2019

Abstract

Background
Cholesterol crystals (CCs) are well recognized as one of important components of advanced atherosclerotic plaques. Whilethe consensus document for intravascular optical coherence tomography (OCT) has proposed that CCs are appeared as thin, linear regions of high-signal intensity within a plaque, no study has validated CCs assessment by OCT in comparison with histopathology.

Purpose
Thepurpose of this study was to validate OCT assessments of CCs with histopathology.

Methods
A total of 27 diseased coronary artery samples (10–20 mm length) were resected from 7 randomly selected cadavers. OCT imaging was performed for the samples. Then, arterial samples were fixed in 10% formalin for ≥48 hours, decalcified and processed for standard paraffin embedding. Sections 5μm thick were sliced at the ink-marked imaging sites and stained with hematoxylin and eosin, and Masson's Trichrome. An independent pathologist blinded to the OCT results diagnosed all of the plaques. Subsequently, the OCT images were interpreted by an observer blinded to the histological results. In the OCT assessment, CCs were defined as thin, linear regions of high-signal intensity within a plaque.

Results
We obtained 27 pairs of OCT/ histopathology. CCs were diagnosed by histology in 10 (37%) of the 27 pairs. The sensitivity and specificity of OCT for detecting CCs were 60% and 94%, respectively.

Conclusion
OCT has a high specificity but modest sensitivity for detection of CCs in comparison with histopathology. CCs diagnosed with OCT would help the identification of advanced atherosclerotic plaques.

Acknowledgement/Funding
JSPS KAKENHI 17K09557
P3577Predictors analysis of restenosis in calcified nodule with OCT-guided PCI
Authors: Shibata H , Kijima Y , Nagoshi R , Kozuki A , Fujiwara R , Suzuki A , Kakizaki S , Fujimoto D , Kyo S , Masuko E , Miyata T , Shite J 
Published: October 2019

Abstract

Background
Recent reports show that stenting for coronary calcified nodule (CN) resulted in frequent in-stent restenosis, however, its predictors are unclear.

Method
117 consecutive calcified nodule lesions which underwent optical coherence tomography (OCT)-guided PCI were analyzed between January 2013 and March 2018. We investigated baseline characteristics and OCT parameter in CN site (Arc of CN, Lumen area and Symmetry index before and after PCI).

Result
CN site in-stent restenosis was seen 35 lesions (29.9%). Baseline characteristics was significantly different between restenosis group and non-restenosis group (Age; 68.9y.o vs. 73.3y.o, p=0.01, diabetes mellitus; 80.0% vs. 57.3%, Chronic Kidney Disease (CKD); 74.3% vs. 36.6%, Hemodialysis; 54.3% vs. 12.2%). Arc of CN before PCI in restenosis group was larger than that in non-restenosis group (122.7 vs. 110.0 degrees, p=0.01). Post stent symmetry index in restenosis group was smaller than that in non-restenosis group (0.64 vs. 0.75, p<0.01).

Conclusion
Younger patients, diabetes mellitus, CKD, hemodialysis, arc of CN before PCI, post stent symmetry index may be predictors of CN site restenosis.