bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2504Chronotropic incompetence and exercise capacity in patients treated with beta-blockers
Authors: Smarz K , Jaxa-Chamiec T , Zaborska B , Budaj A 
Published: October 2019

Abstract

Background
Chronotropic incompetence (CI) in patients treated with beta-blockers correlates with worse prognosis but influence of CI on exercise capacity (EC) is unclear.

Aim
To assess relationship between CI and EC in patients treated with beta-blockers.

Methods
We have analysed retrospectively data from consecutive cardiopulmonary exercise tests performed between 2008 and 2016 in our department. The inclusion criteria were: treatment with beta-blockers started at least 4 weeks before and continued on the day of the test, sinus rhythm during the test, respiratory exchange ratio ≥1.05 at peak exercise, absence of haemodynamically important valve dysfunction, pulmonary hypertension, exercise induced ischemia, pulmonary or peripheral limitations of exercise. CI was defined as chronotropic index ≤62%. Beta-blocker dose was calculated as bisoprolol equivalent dose. Included patients were divided, according to CI, in two groups: with CI and without CI. EC was assessed as percent of maximal predicted oxygen uptake achieved at peak exercise (%peakVO2).

Results
One hundred forty two patients (age 61±10 years, 73% males, hypertension 63%, ischemic heart disease 79%, chronic heart failure 12%, diabetes mellitus 20%, paroxysmal atrial fibrillation 10%) fulfilled the inclusion criteria. The group with CI comprised 115 and the group without CI 27 patients. Diabetes mellitus was more frequent and beta-blockers daily dose was higher in the CI group. There were no differences in other clinical parameters between groups. The group with CI had worse EC than the group without CI (69±18% vs 89±18%, p=0.ehz748.083301). In multivariate regression analysis, chronotropic index was independently related to EC (Table).
Table 1. Relationship of variables to exercise capacity in multivariate regression analysis Variable Coefficient β 95% Confidence interval p Age (years) 0.242 −0.049 to 0.533 NS Sex (male vs female) 5.260 −1.344 to 11.865 NS Body mass index (kg/m2) −0.786 −1.476 to −0.095 0.05 Left ventricular ejection fraction (%) 0.353 0.116 to 0.590 0.01 Beta-blocker daily dose (mg) 0.150 −0.962 to 1.262 NS Diabetes mellitus 0.070 −7.103 to 7.243 NS Heart rate at rest (bpm) −0.238 −0.440 to −0.035 0.05 Chronotropic index 0.496 0.327 to 0.665 0.ehz748.083301

Conclusions
In patients treated with beta-blockers CI was revealed as an independent factor related to worse EC.
P2508Physical exercise improves diastolic function and attenuates type III collagen myocardial accumulation in aged rats
Authors: Guirado G N , Cezar M D M , Pagan L U , Lima A R R , Damatto R L , Campos D H S , Bonomo C , Rosa C M , Gimenes C , Okoshi K , Okoshi M P 
Published: October 2019

Abstract

Background
Interstitial collagen matrix increase and left ventricular (LV) diastolic dysfunction are the most frequent cardiac alterations during aging. Whether changes are part of the aging process or induced by a sedentary life style is not clear.

Purpose
To evaluate the effects of aerobic exercise on functional capacity, cardiac and myocardial function, and interstitial collagen matrix of aging rats.

Methods
Male Wistar rats were assigned into three groups: 1) sedentary six-month-old rats (W6, n=24); 2) sedentary 21-month-old rats (W21-Sed, n=25); and 3) exercised 21-month-old rats (W21-Ex, n=20). Physical exercise was by treadmill for 12 weeks. In vivo cardiac evaluation was performed by Doppler echocardiography. Myocardial function was assessed in LV papillary muscle preparation. Total and soluble myocardial collagen concentrations were evaluated by spectrophotometry. Protein expression was analyzed by Western blot. Statistical analysis: ANOVA and Bonferroni or Kruskal-Wallis and Dunn.

Results
Body weight was greater in W21-Sed and W21-Ex than W6. Before exercise, functional capacity did not differ between aged groups. After training, W21-Ex group ran farther and longer in treadmill than W21-Sed e W6, and W21-Sed presented worse physical capacity than W6. LV diastolic posterior wall, interventricular septum, and relative wall thicknesses were greater in W21-Sed and W21-Ex than W6, and did not differ between aged groups. E wave was lower in both aged groups than W6. E/E' ratio was lower in W21-Ex than W21-Sed. Isolated papillary muscle developed tension was higher in W21-Sed than W6; W21-Ex values did not differ from both W6 and W21-Sed groups. Time to peak tension was higher in W21-Sed and W21-Ex than W6 and did not differ between aged groups. The same results were observed after positive inotropic stimulation. Total collagen concentration was higher in W21-Sed and W21-Ex than W6 and did not differ between aged groups. Soluble collagen did not differ between groups. Type III collagen expression was higher in W21-Sed than W6; the W21-Ex group presented intermediary values that did not differ from W21-Sed or W6 groups. Type I collagen was similar between groups.

Conclusion
Regular physical aerobic training improves functional capacity and left ventricular diastolic function and attenuates type III collagen myocardial accumulation in aged rats.

Acknowledgement/Funding
Fapesp, CNPq, Capes, and UNESP
P2510Cardiorespiratory optimal point as a predictor of outcomes in patients enrolled in a cardiac rehabilitation program
Authors: Castelo A , Rio P , Silva A S , Alves S , Bras P , Mano T , Ferreira V , Ferreira R 
Published: October 2019

Abstract

Introduction
The cardiopulmonary exercise test (CEPT) allows the evaluation of peak and sub-maximal tolerance to the effort, giving us relevant information for clinical decisions. Evidence has emerged that Cardiorespiratory Optimal Point (COP)>30, calculated as the minimum ratio between ventilation and oxygen (VE/VO2) may be a good predictor of events.

Purpose
The aim was to characterize the population of the cardiac rehabilitation (CR) appointment that performed CEPT, evaluate COP as a predictor of events and determine the best cut off for our population.

Methods
Retrospective analysis of CR appointment patients who performed CEPT between 2014 and 2017 in a single center. We compared the mortality and hospitalizations according to COP and COP>30. We established the appropriate Cut Off for our population and compared the same with the occurrence of events.

Results
207Patients (P) (83.6% men) were included, with a mean age of 57 years. The mean COP was 23.6±5.8 (IC [24.06–25.66]). 15.9% P had COP >30 and 33.8% had COP<22. The majority (96.6%) had a cardiovascular disease or risk factors and 99% were medicated. The majority (87.9%) was referred for CR with isquemic cardiopathy (AMI or stable or unstable coronary disease), 9.2% with heart failure (HF) and 9.2% with valvulopathy. 6.9% P died from any cause, 33.8% had an hospitalization (78.6% from a cardiovascular reason). Higher COP values correlated with higher number of all causes hospitalizations (H) (CC = 0.123, p=0.032), cardiovascular H (CC = 0.123, p=0.032), heart failure H (CC = 0.189, p=0.001) and device placement H (CC = 0.173, p=0.003). COP did not correlate with mortality (p=0.453). The cut off of 30 only correlated with HF hospitalization in this population (OR = 5, IC [1.429–17.494] p=0.006). In our population, COP was a good predictor for all cause H and heart failure H (AUC = 0.8 in both). A cut off of 25 had a sensitivity (S) of 78% with a specificity (E) of 70% for all cause hospitalization and S 73% and E 68% for heart failure H. Values above this cut off correlate with more all cause H (OR = 1,928, IC [1.06–3.507], p=0.031) and heart failure H (OR = 5.63, IC [1,44–21.94]), p=0.006). COP was an independent predictor of all-cause H (p=0.018) and heart failure H (p<0.0001). Other independent predictors of HF hospitalization are BNP (p=0.0011) and ejection fraction (p<0.0001).

Conclusion
COP was a good independent predictor of all-cause hospitalizations and HF hospitalization. In our population the cut off 25 for COP had the greatest S and E for predicting events. In our population this factor was not a good predictor of mortality.
P2525Relationship of Charlson Comorbidity Index with adverse events in elderly patients with Acute Coronary Syndromes: an analysis from LONGEVO-SCA Registry
Authors: Esteve Pastor M A , Martin E , Alegre O , Castillo Dominguez J C , Formiga F , Martinez-Selles M , Diez-Villanueva P , Sanchis J , Ariza-Sole A , Marin F 
Published: October 2019

Abstract

Background
Elderly patients with Acute Coronary Syndromes (ACS) are under-represented in clinical trials and they have higher risk of new due their comorbidities. Charlson Comorbidity Index (CCI) is an established tool for evaluating the burden of comorbidity status and a high score of CCI is related with an increased risk of death.

Purpose
The aim of this study was to analyze the relationship of CCI in adverse outcomes at short-term follow-up in elderly patients admitted by an ACS.

Methods
The prospective multicenter LONGEVO-SCA included unselected elderly patients (≥80 years old) hospitalized after non-STACS. In this substudy, we analyze the influence of comorbidities, comparing the relationship between quartiles of CCI and adverse events at 6 months follow-up of CCI.

Results
We analyzed 520 patients (mean age 84.4±3.6 years; 320 (61.5%) male). 196 (37.6%) were classified into Q1, 105 (20.2%) into Q2, 93 (17.9%) into Q3 and 126 (24.2%) into Q4. No differences were observed in treatment at discharge across different quartiles for aspirin (p=0.648), beta-blockers (p=0.908) or statins (p=0.756). We observed a significant increase for all-cause mortality [9 (4.8%) vs 10 (10.2%) vs 11 (12.0%) vs 32 (26.0%); p<0.001] and readmissions [36 (18.4%) vs 21 (20%) vs 33 (35.5%) vs 48 (38.1%); p<0.001] respectively from Q1 to Q4. After Cox multivariate regression analysis, CCI was independently associated with mortality or readmissions [HR 1.15, 95% CI (1.06–1.26); p=0.001] and patients into high quartile had 6-fold risk of mortality [HR 6.19, 95% CI (2.95–12.99); p<0.001]. Kaplan Meier analysis showed that patients in the highest quartiles had significantly worse prognosis during the follow-up with high risk of all-cause mortality and readmissions (both p<0.001).
Event Free Survival according Charlson

Conclusions
In LONGEVO-SCA registry, we validated for the first time CCI as an independent factor related with adverse events. Patients into high quartiles of CCI had significantly worse prognosis during the follow-up and elderly patients into Q4 had 6-fold risk of mortality compared to Q1 patients.
P2529Efficacy and safety of oral anticoagulation in nonagenarian patients with atrial fibrillation
Authors: Dominguez Rodriguez L , Raposeiras Roubin S , Alonso Rodriguez D , Camacho Freire S J , Abuassi E , Cubelos Fernandez N , Lopez-Masjuan Rios A , Rodriguez Albarran A , Muniz Pousa I , Cespon Fernandez M , Dominguez Erquicia P , Diaz Fernandez J F , Fernandez Vazquez F , Iniguez Romo A 
Published: October 2019

Abstract

Introduction
Embolic prevention with oral anticoagulation is the cornerstone for the management of patients with atrial fibrillation (AF). However, data about the efficacy and safety of oral anticoagulation in nonagenarian patients are limited. We aimed to analyze the impact of oral anticoagulation in mortality, embolic and hemorrhagic events, in patients ≥90 years with non-valvular AF.

Methods
We used data from a multicentric registry of 1,750 consecutive nonagenarian patients diagnosed of AF between 2013 and 2018. A propensity-matched analysis was performed to match the baseline characteristics of patients treated or not with oral anticoagulants, and for those treated with vitamin K antagonists (VKAs) vs direct oral anticoagulants (DOACs). The impact of oral anticoagulation in the embolic and hemorrhagic risk was assessed by a competitive risk analysis, using a Fine and Gray regression model, with death being the competitive event. For embolic risk, we have considered a stroke, pulmonary or peripheral embolism. For bleeding risk, we have considered any bleeding requiring hospital admission.

Results
The mean of CHA2DS2-VASC and HASBLED scores was 4.5±1.3 and 2.8±1.0 points, respectively. Most of patients were anticoagulated (70.1%; n=1,256). DOACs were used in 709 patients, and VKAs in 517 patients. During a median follow-up of 25.2 months (IQR 12.2–44.3 months), 988 patients died (56.5%), 180 presented embolic events (10.3%), 186 had bleeding events (10.6%), and 29 had intracranial hemorrhage (ICH, 1.7%). After propensity-score matching, anticoagulation (versus non anticoagulation) was associated with lower mortality rate (HR 0.73, 95% CI 0.60–0.89; p=0.002), less mortality and embolic events (HR 0.77, 95% CI 0.64–0.92; p=0.005), but more bleeding events (HR 2.05, 95% CI 1.25–3.35; p=0.004). In comparison with VKAs, DOACs showed similar risk of mortality and embolic events (HR 1.14, 95% CI 0.88–1.47; p=0.337), and similar risk of bleeding events (HR 0.75, 95% CI 0.43–1.28; p=0.287), although a trend to lower risk of ICH was found (HR 0.17, 95% CI 0.02–1.39; p=0.097).

Conclusions
Among nonagenarian patients with AF, oral anticoagulation was associated with lower all-cause mortality. Although survival free of embolic events was significantly higher in patients with anticoagulation, the risk of major bleeding was twice than in non-anticoagulated patients. There was not differences between VKAs and DOACs in terms of embolic events and total major bleeding. However, compared with VKAs, DOACs were showed a trend to lower risk of ICH.
P2536Protective effects of ultra-low-dose menopausal hormonal therapy on endothelium function in postmenopausal women
Authors: Tolstov S N , Salov I A , Rebrov A P 
Published: October 2019

Abstract

Introduction
This is the first pilot study to assess the functional state of the vascular wall in postmenopausal women on the background of ultra low-dose menopausal hormone therapy (MHT).

Purpose
To evaluate the protective effects on endothelial function of ultra-low-dose MHT 0.5 mg of 17β-estradiol (E2) and 0.25 mg of drospirenone (DRSP) in postmenopausal women.

Methods
The study included 115 previously examined postmenopausal women. Group 1 (n=25) included patients who started receiving MGT with DRSP during the menopausal transition; in the 2nd group (n=31), women who started receiving MGT with DRSP in the early postmenopausal period. Women of the 1st and 2nd groups made the transition to a combination of 0.5 mg E2/0.25 mg DRSP. The control group (n=59) of women not taking MGT. The duration of therapy is 1.0 (0.9; 1.2) years. The age of women was 56.8±1.6 years, 57.1±2.8 years and 57.3±1.7 years (p>0.05). Endothelium-dependent vasodilation (EDV) of the brachial artery, levels of endothelin-1 (ET-1), metabolites of nitric oxide (NO), asymmetric dimethylarginine (ADMA), von Willebrand factor antigen (vWF: Ag) in plasma were evaluated.

Results
In the control group EDV 8.6±5.1% of the original and 7.4±4.5% by the end of the study (p=0.08); in women of the 1st group 12.5±3.8% and 12.2±4.4; in women of the 2nd group11.1±8.5% and 10.5±0.2% (p=0.07 between women of the 1st and 2nd groups by the end of the study).
The level of NO metabolites in women of the 1st group 43.4 (28.6; 45.9) at baseline and 40.7 (34.4; 41.5) μmol/l by the end of the study, in women of the 2nd group 38.8 (36.5; 44.9) and 35.2 (32.8; 38.9) μmol/l (p=0.04 between the women of the 1st and 2nd groups). In the control group 34.6 (30.4; 38.2) and 27.8 (24.5; 34.9) μmol/l (p<0.001 for women of the 1st and 2nd groups).
In women of the 1st group a significant increase in ET-1 was detected from 1.02±0.26 initially to 1.18±0.24 fMol/ml by the end of the study; levels of vWF:Ag with 0.839 (0.695; 0.940) and 0.900 (0.782; 0.925) U/ml. The level of ADMA did not change significantly 0.43±0.10 and 0.45±0.10 μmol/L.
In women of the 2nd group a significant increase ET-1 was detected from 1.08±0.42 to 1.29±0.59 fMol ml; vWF:Ag from 0.841 (0.718; 0.960) to 0.829 (0.811; 0.984) U/ml and ADMA from 0.43±0.10 to 0.48±0.15 μmol/l (p>0.05).
In the the control group a significant increase in the level of ET-1 was observed from 1.40±0.43 to 1.74±0.34 fMol/ml by the end of the study; vWF levels:Ag 0.860 (0.743; 0.941) and 0.960 (0.850; 1.025) U/ml, ADMA 0.48±0.16 and 0.60±0.18 μmol/l (p<0.01 compared with women of the 1st and 2nd groups).

Conclusions
Revealed protective effects on endothelial function of ultra low-dose MHT in postmenopausal women. Early and prolonged MHT has an additional positive effect on the functional state of the vascular wall.

Acknowledgement/Funding
None
P2538Arterial stiffness and remodeling from large to small arteries in patients with spontaneous coronary artery dissection: evidence for a systemic subclinical involvement
Authors: Bruno R M , Di Lascio N , Al Hussaini A , Vitali S , Rossi P , Caramella D , Regazzoli D , Cortese B , Lettieri C , Spontoni P , Emdin M , Faita F , Ghiadoni L , Taddei S , Adlam D 
Published: October 2019

Abstract

Background and aim
Spontaneous coronary artery dissection (SCAD) is a major cause of acute coronary syndrome in women aged 50 years or less (22–43%). Its etiology is still unknown, though an association with systemic diseases such as fibromuscular dysplasia and collagenopathies has been found. This study is aimed at investigating the presence of subclinical structural and functional alterations in extracoronary districts in SCAD patients.

Methods
The design was a case-control study. Carotid, radial and digital arteries were scanned by standard or ultrahigh frequency ultrasound; clips were analyzed by automated image analysis software for diameter, intima-media thickness (IMT) and local distensibility. Applanation tonometry was used to obtain carotid-femoral pulse wave velocity, a measure of regional, aortic stiffness, and carotid pressure waveform.

Results
30 patients previously diagnosed with SCAD (27 women, age 51±10 years, 8 treated hypertensives, 4 smokers, mean BP 83±11mmHg, BMI 25±5kg/mq) and 30 controls, matched for age, sex and CV risk factors by propensity score, were enrolled. 18 SCAD patients underwent PTCA and 6 had a diagnosis of extracoronary fibromuscular dysplasia. In the left radial artery, wall thickness, cross-sectional area (2.96±1.07 vs 1.79±1.41mm2, p=0.008), and wall inhomogeneity were increased, especially in the outer layer, whereas diameter, wall/lumen ratio and distensibility were comparable to controls. In the left common carotid artery, an increased carotid stiffness was shown in SCAD (5.99±0.89 m/s vs 5.6±0.85, 0.03), while IMT tended to be increased bilaterally (0.63±0.12 vs 0.59±0.10mm, p=0.08). Aortic stiffness was similar in the two groups (7.0±1.9 vs 6.7±1.7m/s, p=0.60). Carotid (20.4±14.2 vs 11.9±15.0%, p=0.03), but not aortic augmentation index, was increased bilaterally.

Conclusions
SCAD patients showed a peculiar pattern of alterations in vascular remodeling and stiffness in extracoronary arterial segments such as the carotid and radial arteries, supporting the hypothesis that a systemic susceptibility is present even in the absence of systemic diseases.
P2552Triple vs. double antithrombotic therapy in patients needing oral anticoagulation undergoing percutaneous coronary intervention: a meta-analysis
Authors: Errigo D , Saglietto A , Angelini F , Lip G Y H , Lopes R D , Conrotto F , Omede P G , Montefusco A , Manzano-Fernandez S , Raposeiras-Rubin S , Varbella F , D'Amico M , D'Ascenzo F , Rinaldi M , Giustetto C 
Published: October 2019

Abstract

Background
The optimal antithrombotic therapy strategy in patients undergoing PCI who need OAC is currently debated.

Purpose
To determine the best regimen in terms of safety and efficacy.

Methods
We performed a meta-analysis of RCT and adjusted results reporting outcomes of patients who underwent PCI and were on TT or DAPT or DT. All-cause death was the primary end point, while MACE was the secondary outcome, along with its individual components, and major bleedings.

Results
15 studies encompassing 27070 patients were included. After a follow up of 12 (11–14) months, TT reduced all-cause death compared to DAPT (OR 0.52, 0.35–0.78), mainly driven by a lower incidence of MI (OR 0.81, 0.69–0.85) and stroke (OR 0.76, 0.56–1.03) despite higher rates of major bleedings (OR 2.81, 1.54–5.12). Comparing TT vs. DT with warfarin, all-cause death was non-significantly different (OR 1.23, 0.60–2.53), nor MI (OR 0.77, 0.23–2.59) and stroke (OR 4.01, 0.80–20.07), while major bleeding was increased with TT (OR 2.40, 1.34–4.38). When compared to DT with NOACs, TT did not reduce risk of MI (OR 0.96, 0.67–1.36) or stroke (OR 0.82, 0.55–1.24), but increased major bleedings (OR 1.98, 1.43–2.73). The non-randomized comparison between DT with warfarin and DT with NOACs showed a neutral effect on death and major bleedings, with similar rates also of MI (OR 0.47, 0.20–1.11, all CI 95%).

Conclusion
Double therapy with warfarin or with NOAC plus a single antiplatelet agent reduces the risk of major bleeding compared to triple therapy, with a neutral impact of subsequent ischemic events.
P2570Synergistic activation of the cardiac enhancer landscape during reprogramming
Authors: Hashimoto H , Wang Z , Garry G , Zhou H , Bassel-Duby R , Olson E N 
Published: October 2019

Abstract

Introduction
Cardiogenic transcription factors (TFs), Gata4, Mef2c, and Tbx5, can directly reprogram fibroblasts to a cardiac fate and their cardiogenic activity is enhanced by the Hand2 TF and the Akt1 kinase. Although these cardiac reprogramming factors are key regulators of heart development, their expression and biological functions are not limited to the heart, and the mechanism by which these cardiac factors orchestrate reprogramming remains unclear.

Purpose
We sought to study the molecular mechanisms by which cardiac reprogramming factors contribute to cell fate conversion using a genome-wide approach.

Methods
Here, we used chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) to explore the genomic binding sites of reprogramming TFs and the landscape of active enhancers, annotated by H3K27ac histone modification, during cardiac reprogramming.

Results
We found that reprogramming TFs rapidly silence fibroblast enhancers and synergistically activate cardiac enhancers which were predominantly enriched with Mef2 motifs. Addition of Hand2 and Akt1 to GMT expands TF co-occupancy and thereby activates additional cardiac enhancers, which further augments cardiac gene expression. Moreover, additional cardiac enhancers were sequentially activated during the reprogramming process, in accordance with the temporal acquisition of functional phenotypes in induced cardiac-like myocytes. We discovered that subsets of reprogramming enhancers are conserved among other cardiogenic processes, and a collection of reprogramming enhancers displayed unique spatial expression patterns in the developing heart in transgenic mouse embryos.

Conclusion
Our study describes the epigenomic dynamics that underlie cardiac reprogramming which is cooperatively orchestrated by reprogramming factors to convert fibroblasts toward a cardiac lineage.

Acknowledgement/Funding
NIH (AR-067294, HL-130253, HL-138426, HD-087351), Fondation Leducq Transatlantic Networks of Excellence in Cardiovascular Research