bluuebunny/crossref_metadata_2025_split huggingface dataset:
5197Correlates and prognostic significance of nuisance bleeding after acute myocardial infarction. The FAST-MI programme
Authors: Danchin N , Puymirat E , Isaaz K , Druelles P , Dibon O , Lefevre T , Bernasconi F , Drouet E , Ferrieres J , Schiele F , Simon T 
Published: October 2019

Abstract

Background
Following acute myocardial infarction (AMI), most patients receive potent antithrombotic medications, which may promote nuisance bleedings (ecchymoses, minor nose or dental bleeds etc.). Little information is available on the factors related to nuisance bleedings, nor on their prognostic significance in post-AMI patients.

Aims and methods
A health status questionnaire was sent to all patients participating in the nationwide French FAST-MI cohorts (2010 and 2015) one year after the acute episode, with a specific question on the presence of nuisance bleedings. Overall, 3968 patients answered the question on the presence nuisance bleedings. In the 2010 cohorts, we also analysed whether the presence of nuisance bleedings at one year was an independent correlate of 5-year mortality.

Results
54% of the patients reported the presence of nuisance bleedings (59% in 2010 and 51% in 2015). In univariate analyses, nuisance bleedings were more frequently found in younger patients, women, patients with STEMI, current smokers, patients treated with PCI, those receiving newer P2Y12 inhibitors or ACE-inhibitors but less frequent in patients with diabetes, hypertension, or those receiving ARBs or direct oral anticoagulants. Using logistic regression analysis, however, the only independent correlates of nuisance bleedings were: female gender (OR 1.45, 1.25–1.68), age ≤60 years (OR 1.22, 1.06–1.41), VKAs (OR 1.72, 1.28–2.31), clopidogrel (OR 1.62, 1.29–2.03), prasugrel (OR 3.16, 2.43–4.09), ticagrelor (OR 2.61, 2.04–3.35) at discharge, diabetes (OR 0.74, 0.63–0.88) and year 2015 vs 2010 (OR 0.62, 0.53–0.73).
In the 2010 cohort, the presence of nuisance bleeding at one year was not a predictor of mortality at 5 years (90% survival in both patients with or without nuisance bleedings; adjusted HR 0.96, 95% CI 0.69–1.33) (Figure).
Figure 1. 5-yr survival by nuisance bleed

Conclusion
Nuisance bleedings one year after AMI are extremely frequent. They are more common in women, younger patients, in patients receiving P2Y12 inhibitors, especially newer P2Y12-i, and in those receiving VKAs; in contrast, diabetic patients report less nuisance bleedings. The presence of nuisance bleeding at one year does not appear to impact 5-year mortality.

Acknowledgement/Funding
Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Eli-Lilly, GSK, MSD, Novartis, Pfizer, Sanofi, Servier
5208Use of renal denervation in the electrical storm management
Authors: Gorev M , Nardaya S H , Petelko S , Rzaev F , Vasilieva E , Shpektor A 
Published: October 2019

Abstract

Background/Introduction
Electrical storm (ES) is a potentially lethal state developing in 4–28% of ICD patients. Neuroaxial modulation (beta-blockers, deep sedation, epidural anesthesia, stellate ganglion blockade etc) is used to decrease arrhythmogenic predisposition of ventricular myocardium to trigger and maintain ventricular arrhythmias. Catheter renal arterial denervation (RDN) is recently described to prevent atrial fibrillation recurrence after pulmonary vein isolation. We used this procedure in addition to standard care to improve the results of ES treatment.

Purpose
This retrospective single-center case-series is aimed to analyze ES patient population and to describe the effect of RDN on the in-hospital number of ventricular tachycardia (VT) episodes and ICD shocks and on the mid-term survival.

Methods
Pts admitted to the CCU for more than 3 sustained VT episodes or more than 3 appropriate ICD shocks during the 24h period in 2017–18 were enrolled into study. Demographic, echocardiographic, ICD check up, renal arteries anatomy and mid-term mortality/transplant data were retrospectively analysed.

Results
Eleven pts (all male, age 69±9 years) were included. Seven pts (73%) had CAD, 3 pts (27%) – DCM. Echocardiography revealed LVEF 28±8%, and LV EDV - 226±91 ml. Time from ICD implantation to ES onset was from 4 mos to 13 yrs. In 5 pts RDN was performed without VT ablation, in 3 pts – prior to VT ablation, in 2 – after VT ablation and in 1 pt – both RDN and VT ablation were performed during the same procedure. Mean number of renal arteries was 2,5 per pt. Mean number of ablations was 4,8 per artery. The power was 2 to 11 Wt and lesion duration was 90 sec. Dramatic decrease in the number of VT episodes (49±52 vs. 6±2) was found in 6/11 pts directly after RDN procedure. In-hospital rhythm control was accessed in 10/11 pts, 1 pt with DCM was transferred for heart transplant due to recurrence of VT after VT ablation and RAD (excluded from survival analysis). There were no RDN procedure related complications in this group of pts. In mean 6 mos of follow-up 9/10 pts are free from ES recurrence, 1/10 was lost for the follow up.

Conclusion(s)
Catheter renal artery denervation is effective and safe additional procedure to treat ES patients. It allows to decrease the number of ICD shocks and stabilize arrhythmogenicity of ventricular myocardium. Larger multi-center randomized trials are warranted.
5949Interleukin-6 and growth differentiation factor-15 in hypertensive heart failure
Authors: Fernandez C , Rysa J , Nilsson J , Engstrom G , Orho-Melander M , Ruskoaho H , Melander O 
Published: October 2019

Abstract

Background
Hypertension is the leading cause for the development of heart failure (HF). Increased hemodynamic load, including mechanical stretch and neurohumoral factors, is able to trigger hypertrophic growth of cardiac myocytes. Although hypertensive HF is prevalent, there is no useful biomarker to identify HF due to chronic hypertension.

Aims
To identify plasma markers associated with incidence of hypertensive HF.

Methods
Circulating levels of 149 proteins were measured by proximity extension assay at baseline examination in 4469 individuals from the Malmö Diet and Cancer study. Protein levels were compared to stretch-activated gene expression changes in cultured neonatal rat ventricular myocytes (NRVM) in response to 1, 4, 12, 24 or 48 hours of cyclic mechanical stretch. Association between plasma proteins level and HF incidence and hypertension was studied using respectively Cox proportional hazards model and binary logistic regressions.

Results
After Bonferroni correction, 44 circulating proteins were significantly differentially expressed in individuals who developed HF during follow-up versus controls (P<3.4E-4). Out of these, 5 proteins (Interleukin-6 (IL-6), Growth Differentiation Factor-15 (GDF15), Interleukin-1 Receptor-Like-1 (ST2), Plasminogen Activator Urokinase Receptor (U-PAR), Transforming Growth Factor-α (TGF-α)), corresponding mRNA levels were upregulated by mechanical stretch in NRVM at all time points (P<0.05). Similar upregulation for the 5 proteins was shown in hypertensive versus normotensive individuals (P≤8.05E-4). In a model with all 5 proteins entered simultaneously, GDF15 and IL-6 were predictive of incident HF after adjustment for age, sex and NT-BNP levels (205 events; hazard ratio [HR] per SD increment of protein: HR=1.29, CI=1.05–1.58, P=0.013 and HR=1.16, CI=1.02–1.33, P=0.028). Using the same model, IL-6 but not GDF15 associated with hypertension (Odds ratio [OR] per SD increment of IL-6: OR=1.18, CI=1.09–1.27, P=3.3E-5). In hypertensive individuals GDF15 and IL-6 were individually predictive of future HF after adjustment for age, sex, NT-BNP levels, smoking, BMI and diabetes (183 events; HR=1.36, CI=1.16–1.60, P=1.64E-4 and HR=1.21, CI=1.05–1.40, P=0.008). Furthermore, in these hypertensive individuals, GDF15 and IL-6 were predictive of HF in a model with IL-6, GDF15, ST2 and TGF-α entered simultaneously after adjustment for age, sex and NT-BNP levels (176 events; HR=1.36, CI=1.13–1.64, P=0.001 and HR=1.16, CI=1.01–1.34, P=0.041).

Conclusions
Circulating levels of IL-6 and GDF15 might be used as NT-BNP independent biomarkers for HF development in hypertensive patients.

Acknowledgement/Funding
Påhlsson, Crafoord, Lundström, Åke Wiberg, Royal Physiographic Society and the Swedish Foundation for Strategic Research for IRC15-0067
5952The involvement and interplay of HMGB1 with soluble MD-2 in dilated cardiomyopathy and its impact in immune cell recruitment
Authors: Kuemmel A , Feldtmann R , Stohbach A , Riad A , Chamling B , Felix S B 
Published: October 2019

Abstract

Objective
Dilated cardiomyopathy (DCM) is characterized by systolic dysfunction and simultaneous dilatation of the left or both ventricles. Besides other causes, the innate immune system plays a major role in the development and progression of the disease. To uncover links between molecular mechanisms and disease progression our group has focused on the toll like receptor 4 / myeloid differentiation factor-2 (MD-2) system.

Purpose
We already reported that soluble MD-2 (sMD-2) is a risk factor for survival in patients with DCM. High mobility group box protein 1 (HMGB1) is a potent intrinsic interaction partner of MD-2. In the current study, we quantified HMGB-1 in plasma from patients with DCM at baseline, upon first hospital admission. Furthermore, we studied the impact of different HMGB-1 isoforms on monocyte adhesion in vitro.

Methods
We included 77 DCM patients divided by median time point of death after first hospital admission into “early death”, “late death” and “alive” group. MD-2 was quantified by means of ELISA. MD-2 and HMGB1 was quantified by means of ELISA. Statistical analysis was performed using a linear regression model.
Human umbilical vein endothelial cells (HUVEC; n=6) were treated for 48h with two isoforms of HMGB1 (disulfide (ds) and fully reduced (fr)) alone and in combination with MD-2. Subsequently, those activated HUVEC were incubated with fresh isolated peripheral blood mononuclear cells (PBMCs) for 20 min. Finally, monocyte adhesion was quantified using multicolour FACS.

Results
At baseline, we found significantly increased sMD-2 level in the “early death” group (591.3±75.5 ng/ml) compared to the “later death” group (369.2±46.5 ng/ml; p=0.015) and the “alive” group (303.2±18.1 ng/ml; p<0.001). Likewise, we could demonstrate significantly increased levels of HMGB1 in the “early death” group (0.93±0.14 ng/ml) compared to the “later death” (0.57±0.17 ng/ml; p=0.04) and the “alive” group (0.49±0.06 ng/ml; p<0.001). In all patients who died during the observation period, sMD-2 and HMGB1 plasma levels showed a positive correlation.
In vitro, we could demonstrate a significantly increased monocyte adhesion on HUVECs in the dsHMGB1 and the frHMGB1 group compared to controls (p=0.001; p=0.004). In contrast, the dsHMGB1 MD-2 group showed a significantly decreased monocyte adhesion on HUVECs compared to dsHMGB1 treatment alone (p=0.049). In the frHMGB1 MD-2 group, however, the reduction of the monocyte adhesion was less pronounced and did not reach significance (Fig. 1).

Conclusion
Our findings give a first hint that the interplay between HMGB1 and MD-2 is particularly involved in the development and progression of DCM. Furthermore, the data suggest that soluble MD-2 is capable of reducing the pro-inflammatory effects of dsHMGB1 but not of frHMGB1
5962Incremental prognostic value of hybrid PET-CT assessed myocardial blood flow, coronary stenosis severity and adverse plaque characteristics
Authors: Bom M J , Driessen R S , Van Diemen P A , Everaars H , Schumacher S P , Van Rossum A C , Raijmakers P G , Lammertsma A A , Knuuti J , Ahmadi A , Min J K , Leipsic J A , Narula J , Danad I , Knaapen P 
Published: October 2019

Abstract

Background
Management of patients with suspected coronary artery disease (CAD) can be optimized with prognostic information derived from non-invasive imaging such as positron emission tomography (PET) perfusion imaging and coronary computed tomography angiography (CCTA). The aim of the present study was to determine the incremental prognostic value of combined functional testing using PET perfusion imaging and anatomical testing using CCTA-derived stenosis severity and morphological assessment of CCTA-derived plaque morphology.

Methods
In this retrospective study, 539 patients referred for hybrid [15O]H2O PET – CCTA imaging because of suspected CAD were investigated. PET perfusion imaging was used to determine hyperemic myocardial blood flow (MBF), whereas CCTA images were evaluated for obstructive stenosis and high-risk plaque morphology. Major adverse coronary events (MACE) included all-cause death, non-fatal myocardial infarction (MI), urgent revascularization and late non-urgent revascularization (i.e. not guided by initial diagnostic work-up with non-invasive imaging). Kaplan Meier analysis and Cox proportional hazard regression were used to evaluate the independent prognostic value of PET-derived MBF, CCTA-derived stenosis and CCTA-derived high-risk plaque.

Results
During a mean follow-up of 6.8 [4.8–7.9] years, 79 (14.7%) patients experienced MACE, including 23 (4.3%) deaths, 19 (3.5%) MIs, 8 (1.5%) urgent revascularizations and 29 (5.4%) late non-urgent revascularizations. Annualized event rates for normal vs. abnormal results of PET perfusion imaging, CCTA-derived stenosis and high-risk plaque morphology were 1.2% vs 4.1%, 0.6% vs 4.4%, and 1.7% vs 5.6%, respectively (p<0.001 for all). The combined use of these three imaging parameters resulted in excellent long-term risk prediction, with a MACE-free survival of 97% in patients with no positive imaging findings. In contrast, MACE-free survival was only 69% in patients in whom all imaging findings were positive (figure 1). Multivariate Cox proportional hazard regression demonstrated incremental prognostic value of PET perfusion imaging, CCTA-derived stenosis and CCTA-derived high-risk plaques for the occurrence of MACE (p<0.05 for all)
MACE-free survival stratified by PET-CT

Conclusion
PET-derived myocardial blood flow and CCTA-derived stenosis severity and high-risk plaque morphology are independent long-term predictors of adverse cardiac events and provide incremental prognostic value. Combined functional, anatomical and morphological assessment may allow for improved risk stratification in patients with suspected CAD.
5967A randomized trial of yoga therapy for reflex syncope
Authors: Sinam S I , Gangwar R S , Banavalikar B , Padmanabhan D , Gangwar V , Valappil S P , Ghadei M K , Ali M , Shenthar J 
Published: October 2019

Abstract

Background
Reflex syncope (RS), the most common cause of syncope is usually recurrent, associated with decreased quality of life, and frustrates both the clinicians and the patients with a paucity of effective treatment options.

Purpose
To assess the effectiveness of yoga therapy on the recurrence of reflex syncope.

Methods
Subjects with recurrent RS (>3 episodes) and positive head-up tilt test were enrolled prospectively, and randomized to conventional therapy with physical maneuvres (Group 1) and yoga therapy (Group 2). Group 1 patients were taught physical counter-pressure maneuvers as per guidelines. Group 2 patients were taught yoga for 7 sessions by a certified Yoga instructor/therapist, and then advised to perform yoga for 60 minutes at least five days/week for six months. The Yoga module consisted of Pranayama (breathing techniques), Asanas (Postures) and Dhyana (Meditation) for 60 minutes/session. Both groups were followed up monthly for 6 months in the syncope clinic noting down the recurrences and the quality of life using the syncope functional status questionnaire score.

Result
The study group consisted of 97 patients (group 1: 46 patients and group 2: 51 patients) enrolled prospectively between June 2015 to February 2017. The mean age was 33.1±16.6 years, with male: female ratio 1.1:1, and a mean of 6.4±6.06 syncope episodes (group 1: 6.8±8.0 vs. group 2: 6.0±4.0; p=0.551). The mean duration of symptoms was 17.1±20.71 months (group 1: 16.1±22.8 months vs. group 2: 17.8±19.1 months; p=0.694). There was a significant decrease in the recurrences of syncope in the yoga group compared to the conventional group at three months (group 1: 1.8±1.4 vs group 2: 0.8±0.9, P<0.001) as well as six months follow-up (group 1: 3.38±3.0 vs group 2: 0.98±1.23, P<0.001). The quality of life score at 6 months improved in 20 patients in group 1 and in 45 patients in group 2 (<0.001).

Conclusion
Guided yoga therapy is superior to conventional measures in reducing the number of syncopal episodes and improves the quality of life in patients with reflex syncope. Yoga therapy should be considered as treatment strategy for patients with reflex syncope.
6108Efficacy of the PCSK9 inhibitor for lipid-rich coronary plaque reduction: a near-infrared spectroscopy analysis
Authors: Ota H , Omori H , Tanigaki T , Okamoto S , Hirata T , Kikuchi J , Sobue Y , Miyake T , Kawamura I , Kawase Y , Okubo M , Kamiya H , Tsuchiya K , Matsuo H 
Published: October 2019

Abstract

Background
Recently, some studies have highlighted proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors produce incremental low-density lipoprotein cholesterol (LDL-C) lowering effect. However, it is unknown whether the lipid composition of plaque changes is associated with serum LDL-C reduction due to PCSK9 inhibitors administration.

Purpose
The purpose of this study was to determine the effects of PCSK9 inhibitor (PCSK9i) on coronary plaque component in patients with a history of coronary artery disease (CAD) assessed by near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS).

Methods
A total of 67 non-culprit coronary segments were identified in 34 patients. These lesions were analyzed utilizing NIRS-IVUS at baseline and follow-up coronary angiography (CAG). The subjects were divided into two groups according to lipid-lowering treatment; administration of PCSK9i group (PCSK9i: 19 segments, 9 patients) and traditional statin treatment group (Control: 48 segments, 25 patients). The change of lipid-rich plaque distribution between baseline and follow-up NIRS-IVUS was defined as the change of maximal lipid core burden index (LCBI) score for each of the 4-mm longitudinal segments (maxLCBI4mm).

Results
Mean duration from baseline to follow-up CAG was 239.4±52.4 days in the PCSK9i group and 341.0±84.1 days in the Control group (p<0.001). Despite the higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the PCSK9i group at baseline (206.6±40.9 mg/dl vs. 168.5±37.1 mg/dl, 131.5±35.4 mg/dl vs. 100.0±29.5 mg/dl; respectively, p<0.001 for both), the PCSK9i group was significantly lower TC and LDL-C at the follow-up (111.5±23.5 mg/dl vs. 157.4±27.8 mg/dl, 40.8±15.7 mg/dl vs. 86.2±19.6 mg/dl; respectively, p<0.001 for both). Furthermore, the PCSK9i group induced greater regression of maxLCBI4mm than that of Control group (99.6±156.6 vs. 27.9±118.0, p=0.046) (Figure).
Figure 1

Conclusion
Compared with traditional statin therapy, PCSK9i treatment resulted in a greater decrease in lipid component in non-culprit coronary plaques. Therefore, PCSK9i may be useful option in preventing from adverse coronary events for the patients with CAD.
6121Phrenic nerve injury during pulmonary vein isolation using the second-generation cryoballoon: characteristics and follow-up - The YETI registry
Authors: Heeger C H , Pott A , Sohns C , Rillig A , Kuniss M , Cay S , Miyazaki S , Aryana A , Jedrzejczyk-Patej E , Aytemir K , Inaba O , Chun J K R , Sommer P , Dahme T , Tilz R R 
Published: October 2019

Abstract

Background
Second-generation cryoballoon (CB2) based pulmonary vein isolation (PVI) has emerged as a safe and effective treatment option for symptomatic atrial fibrillation (AF). Although published complication rates of CB2 based-PVI are relatively low and several safety algorithms have been implemented in the protocols the most frequent complication is right-sided phrenic nerve injury (PNI). The reported incidence of PNI varies from 2–5% of patients. However data on PNI characteristics as well as follow-up is sparse.

Purpose
We aimed to evaluate the incidence, characteristics and outcome of PNI during after CB2 based-PVI in a large patients population.

Methods and results
From July 2012 to November 2018 a total of 13693 patients received CB2 or CB3 (third-generation) based-PVI in 23 EP centers (Germany: 12, China: 1, Turkey: 3, Japan: 3, USA: 1, Austria: 1, Poland: 1, Swizerland: 1). A total of 596 (4.4%) of patients experienced PNI during treatment of the right superior (84%) right inferior (15%) right middle (0.3%) (and left superior (0.3%) pulmonary veins. The mean time to PNI was 127±51 seconds and the mean temperature at the time of PNI was −49±7 °C. The target PV was isolated at time of PNI in 84% of cases. The applications were interrupted using double-stop technique in (71%). In 212/306 (52%) a CMAP was utilized.
At the end of the procedure PNI persistent in 45% of patients. Fluoroscopic or sonographic evaluation of PNI was performed 1–3 days after the procedure and revealed persistent PNI in 35% of patients. Dyspnea before discharge was reported in 18% of patients with persistent PNI. Patients follow up at 1–3, and 6–12 months included fluoroscopy and a visit in an outpatient clinic. After 1–3 months 18% of patients showed persistent PNI including 13% of patients complaining of dyspnea. After 6–12 months of follow-up including fluoroscopic evaluation PNI was persistent in 1.8% of patients while dyspnea was reported by 1.7% patients. Only 0.08% of the overall population of 13693 patients showed permanent and symptomatic PNI.

Conclusion
The incidence of PNI during CB2-based PVI is low. About 55% of PNI recovered until the end of the procedure. Most of PNI recovered within 12 months. Symptomatic permanent PNI is very rare in patients after CB2/CB3-based PVI.
P4981The reduction of coronary flow velocity reserve in heart failure with reduced, mid-range or preserved ejection fraction
Authors: Daros C , Cortigiani L , Ciampi Q , Gaibazzi N , Zagatina A , Wierzbowska-Drabik K , Pretto J L C S , Torres M A R , Djordjevic-Dikic A , D'Andrea A , Simova I , Amor M , Merlo P M , Lowenstein J , Picano E 
Published: October 2019

Abstract

Background
Coronary microvascular disease has been described in heart failure (HF) in presence of angiographically normal epicardial coronary arteries. The prevalence of a reduction of coronary flow velocity reserve (CFVR) in different types of HF and its link with left ventricular contractile reserve (LVCR) is unclear.

Aim
To assess CFVR and LVCR in HF.

Methods
In a prospective, observational, multicenter study, we recruited 380 patients (234 male, 61%, age 66±11 years): 143 (38%) with HF and reduced (<40%) ejection fraction (HFrEF); 98 (26%) with HF and mid-range (40–50%) ejection fraction (HFmrEF); 139 (36%) patients with HF and preserved (>50%) ejection fraction (HFpEF). A control group of 52 asymptomatic patients (23 male, 44%, age 61±14 years) referred to testing for screening was also selected (Controls). All patients underwent dipyridamole (0.84 mg/kg) stress echocardiography in 12 accredited laboratories of 3 countries (Argentina, Brazil and Italy). CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed-Doppler assessment of left anterior descending (LAD) artery flow. We assessed left ventricular contractile reserve (LVCR) based on global LV Force (systolic blood pressure/end-systolic volume).

Results
Reduced (≤2.0) CFVR was observed in 0/52 controls (0%); 25/139 HFpEF (18%); 28/98 HFmrEF (29%); 78/143 HFrEF (54%, p<0.001 vs all other groups). CFVR was highest in controls (2.80±0.57), lower in HFpEF (2.51±0.57) and HFmrEF (2.26±0.44), lowest in HFrEF (2.04±0.48, p<0.001 vs all other groups). The correlation with LVCR was absent in controls (r=0.098, p=0.491) and HFmrEF (r=0.032, p=0.756), present in HFrEF (r=0.375, p<0.001) and HFpEF (r=0.314, p<0.001).
LVCR vs CFVR

Conclusions
CFVR is frequently abnormal in all types of HF, although more frequently and more profoundly in HFrEF. CFVR mirrors contractile reserve in HFrEF and - less tightly - in HFpEF.