bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5422Long-term performance of vagus nerve stimulation lead: low rate of complications and failures
Authors: Libbus I , Stubbs S , Mindrebo S , Kenknight B , Dicarlo L 
Published: October 2019

Abstract

Background
Autonomic Regulation Therapy (ART) is a novel therapy for heart failure (HF) that has been shown in a pilot study to be associated with improvement in left ventricular function, 6-minute walk distance, NYHA class, and quality of life. ART is provided using chronic stimulation through a self-sizing lead that is placed on the cervical vagus nerve without any need for response-mapping. The lead is functionally identical in its design and manufacture to a commercially available lead that has been implanted since February 2009 for the treatment of refractory epilepsy and treatment-resistant depression.

Purpose
A survival analysis was performed to evaluate long-term lead performance.

Methods
Lead survival was calculated for those patients whose survival status was obtainable from public records. All devices registered as implanted in the United States for any indication were included for the analysis. All available data on device explants, device replacements, returned product analyses, and customer complaints were collected and used to identify failures and out-of-specification conditions. Device survival probability was defined as the likelihood of the implanted device remaining implanted and performing as intended.

Results
As of the time of this analysis, there have been 26467 registered system implantations and a total of 53200 device-years of lead use. Survival status was obtainable for 9700 patients from public records. After 1 year, 99.5% of implanted leads have remained implanted and performing as intended. At 7 years, 95.8% of leads have remained implanted and performing as intended. The most common causes of lead failure have been infection (0.87%), vocal cord dysfunction (0.68%), lead protrusion (0.36%), and lead extrusion (0.27%).
At implant 1 year 2 year 3 year 5 year 7 year Cumulative Survival Probability (%) 100 99.5 (99.4–99.6) 99.1 (98.8–99.2) 98.6 (98.4–98.9) 97.4 (96.9–97.7) 95.8 (94.9–96.5) Number of Patients 9700 8500 7200 6000 3300 700

Conclusions
Lead performance during chronic vagus nerve stimulation has included over 5ehz746.0379 device-years of use in over 25000 patients. A low rate of long term complications and failures have been reported, and the cumulative survival probability of the lead appears to be high.

Acknowledgement/Funding
LivaNova PLC
P5424Anxiety and all-cause mortality in patients with congestive heart failure and implanted cardiac devices
Authors: Pushkarev G S , Kuznetsov V A , Fisher Y A , Enina T N 
Published: October 2019

Abstract

Background
Several studies suggest that psychological factors including anxiety are associated with negative outcomes and in particular higher mortality rates among congestive heart failure (CHF) patients. However, the impact of anxiety on mortality in patients with implanted cardiac devices has not been fully appreciated.

Purpose
To estimate the influence of anxiety on all-cause mortality in patients with CHF after implantation of cardiac electronic devices.

Methods
The study enrolled 268 patients (mean age 57.1±10.1 years, 218 men and 50 women) with CHF and implanted cardiac devices (170 patients with implanted cardiac devices for resynchronization therapy, 98 patients - with implantable cardioverter defibrillators). We measured symptoms of anxiety with the Spielberger State-Trait Anxiety Inventory (STAI) scale. Cox proportional hazards regression model was used to estimate hazard ratios (HR) with 95% confidence interval (95% CI) for impact of anxiety symptoms on all-cause mortality. HR was calculated after adjustment for the following confounders: age, gender, smoking status, hypertension, diabetes mellitus, body mass index, hypercholesterolemia, atrial fibrillation, left ventricular ejection fraction, number of hemodynamically significant lesions of the coronary arteries and the type of the implanted cardiac devices.

Results
According to State-A scale 119 (44.4%) patients had light symptoms of state anxiety (SA), 115 (42.9%) – mild SA symptoms and 34 (12.7%) – expressed SA symptoms. According to Trait-A scale 10 (3.7%) patients had light trait anxiety (TA) symptoms, 99 (40.0%) – mild TA symptoms and 159 (59.3%) – expressed TA symptoms. During prospective observation period, 46 (17.2%) patients died of all-causes. Multivariant analysis in patients with the expressed SA symptoms resulted in mortality HR which complied 5.26, 95% CI 1.99–13.90; patients with the expressed TA symptoms – 3.5, 95% CI 1.48–6.29.

Conclusion
SA and TA have significant and independent influence on all-cause mortality in patients with CHF after implantation of cardiac electronic devices.
P5442The non-steroidal mineralocorticoid receptor antagonist finerenone prevents structural cardiac remodeling
Authors: Lavall D , Jacobs N , Mahfoud F , Kolkhof P , Boehm M , Laufs U 
Published: October 2019

Abstract

Background
Mineralocorticoid receptor (MR) signaling mediates cardiac fibrosis. We studied the ability of the non-steroidal MR antagonist finerenone to prevent fibrotic remodeling.

Methods and results
In neonatal rat cardiac fibroblasts, finerenone prevented aldosterone-induced nuclear MR translocation. Treatment with finerenone decreased the expression of connective tissue growth factor (CTGF) (74±15% of control, p=0.005) and prevented aldosterone-induced upregulation of CTGF and lysyl oxidase (LOX) completely. Transforming growth factor β (TGF-β) upregulation induced through the Rac1 GTPase activator L-buthionine sulfoximine was attenuated by finerenone.
Transgenic mice with cardiac-specific overexpression of Rac1 (RacET) showed increased left ventricular (LV) end-diastolic (63.7±8.0 vs. 93.8±25.6μl, p=0.027) and end-systolic (28.0±4.0 vs. 49.5±16.7μl, p=0.014) volumes compared to wild-type FVBN control mice. Treatment of RacET mice with 100ppm finerenone over 5 months prevented LV dilatation. Systolic and diastolic LV function was similarly preserved in the three groups. RacET mice exhibited overactivation of MR and 11β hydroxysteroid dehydrogenase type 2. Both effects were reduced by finerenone (reduction about 36%, p=0.030, and 40%, p=0.032, respectively). RacET mice demonstrated overexpression of TGF-β, CTGF, LOX as well as collagen and myocardial fibrosis in the left ventricle. In contrast, expression of these parameters did not differ between finerenone-treated RacET and control mice. Finerenone prevented left atrial dilatation (6.4±1.5 vs. 4.7±1.4mg, p=0.004) and left atrial fibrosis (17.8±3.1 vs. 12.8±3.1%, p=0.046) compared to vehicle-treated RacET mice. The prevalence of atrial arrhythmias at 5 months did not differ between finerenone- and vehicle-treated RacET mice.

Conclusion
Finerenone prevented from MR-mediated structural remodeling in cardiac fibroblasts and in RacET mice. These data demonstrate anti-fibrotic myocardial properties of finerenone.
P5454PCSK9 as a predictor of cardiovascular events in atrial fibrillation: role of platelet activation
Authors: Carnevale R , Cammisotto V , Nocella C , Bartimoccia S , Pastori D , Violi F , Pignatelli P 
Published: October 2019

Abstract

Background
High circulating levels of proprotein convertase subtilisin/kexin 9 (PCSK9) were shown to be predictive of cardiovascular events (CVEs) in patients with atrial fibrillation (AF). Because high PCSK9 plasma levels were significantly correlated with 11-dehydro-thromboxane B2 (11-dh-TxB2), a marker of platelet activation, it is conceivable to hypothesize a direct effect of PCSK9 on platelet activation but the mechanism is still unclear.

Purpose
We evaluated the association between PCSK9 and platelet activation in FA patients and investigate the possible molecular mechanism involved.

Methods
According to our previous prospective study, we conducted a post-hoc analysis including 50 patients with baseline PCSK9 below and 50 above the median value of 1200pg/ml. The two groups were balanced for age and sex. In vivo platelet activation was assessed by aggregation (PA), recruitment, plasma thromboxane B2 (TxB2) formation and sPselectin levels. As markers of oxidative stress we used sNox2-dp, H2O2 production, urinary isoprostanes and oxLDL. To asses the role of PCSK9 in platelet activation, we performed an in vitro study with platelets from healthy subjects (n=5) added with PCSK9 concentrations achievable in human circulation (1000pg/ml and 2000pg/ml) measuring PA, TxB2, isoprostanes production, Nox2 activation, H2O2 production, oxLDL, p38, p47 and PLA2 phosphorylation.

Results
We observed an increased of platelet activation and oxidative stress in patients with PCSK9 levels above median (1200pg/ml) compared to those below (p<0.05). A significant correlation between plasma levels of PCSK9 and markers of platelet activation and markers of oxidative stress were found. In vitro study demonstrated that PCSK9, at the concentration similar to that of patients with CVEs, was able to increase platelet activation act by binding oxLDL receptor. PCSK9 dependent platelet activation is mediated by p47 phosphorylation, a key step in Nox2 activation and is mediated by the PLA2 phosporylation.

Conclusions
PCSK9, at concentration achievable in patients with CVEs, increased platelet aggregation via oxLDL receptor with a pathway involving Nox2 activation.
P5457Assessment of carotid cross sectional area in hypertensive patients: phenotyping and prognostic validation in the campania salute network
Authors: Mancusi C , Izzo R , Losi M A , Barbato E , Trimarco V , Morisco C , Canciello G , Manzi M V , Rozza F , De Luca N , De Simone G , Trimarco B 
Published: October 2019

Abstract

Background
Increased intima media thickness (IMT) of common carotid artery (CA) is considered the hallmark of vascular hypertension-mediated target organ damage, even though vessel remodeling due to mechanical stress can be accompanied also by changes in diameter.

Purpose
We developed a method computing both diameter and IMT of CA, and assessed correlates and prognostic impact of carotid cross sectional area (CCSA) in a large registry of treated hypertensive patients.

Methods
We selected 7049 hypertensive patients of the Campania Salute Network registry free of overt cardiovascular (CV) disease and with available CA ultrasound (54±11 yrs; 57% male). CCSA was computed as:
π × [((CA diameter + 2 × (mean IMT)) / 2)]2 − π × [((CA diameter) / 2)]2.

Results
CCSA was considered high if >90th percentile of the sex-specific distribution (>48 mm2 in men and >41 mm2 in women). Higher CCSA correlated with older age, male sex, higher pulse pressure (PP), higher total and LDL cholesterol and presence of diabetes (p<0.01 for all). During a median follow-up of 45 months (IQR 19–92), 324 incident composite major and minor CV events occurred. In Cox regression analysis high CCSA was associated with more than 100% increased risk of incident CV events (p<0.0001, figure), independently of the effect of older age, male sex, PP>60mmHg, presence of left ventricular hypertrophy (LVH), carotid plaque (CP), and less anti-RAS therapy (p<0.05 for all).

Conclusions
In treated hypertensive patients, increased CCSA is associated with worse metabolic and lipid profile and predict incident CV events, independently of high PP, presence of LVH and CP.
P5480Impact of Silent Myocardial Ischemia on One Year Mortality after Successful Coronary Intervention: Data from Japanese Multicenter (KICS) Registry
Authors: Motozato K , Sakamoto K , Nakao K , Fujimoto K , Miyao Y , Shimomura H , Tsunoda R , Sato R , Nagamatsu S , Yamashita T , Kaikita K , Tsujita K 
Published: October 2019

Abstract

Introduction
Under the awareness of appropriate use criteria, the significance of PCI for the patients with silent myocardial ischemia (SMI) decreases. On the other hand, the prognoses of SMI patients have been reported to be equivalent to those of symptomatic effort angina pectoris (EAP) patients. We aimed to clarify the prognosis of SMI after PCI and elucidate the factors influencing the mortality.

Methods
The Kumamoto Intervention Conference Study is multicenter registry enrolling consecutive patients undergoing PCI in 16 centers in Japan. Overall, 17,688 consecutive patients were enrolled during April 2008 to March 2017. To compare the clinical events between SMI and EAP, 8,278 subjects, excluding acute coronary syndrome, post successful PCI were enrolled with 1-year follow-up data.

Results
In this study, 2,071 patients were classified as SMI and 6,207 patients were EAP. Male, lower body mass index (BMI), diabetes, chronic kidney disease (CKD), smoking habits, prior myocardial infarction (MI), composite of cerebrovascular disease and composite of peripheral arterial disease were all significantly higher in the SMI group. Although nonfatal MI and stent thrombosisduring 12-monthswere comparable between the 2 groups, all-cause mortality and cardiac death during 12-months were significantly higher in the SMI group than in the EAP group (3.9% vs 1.8%, p<0.001, 1.4% vs 0.5%, p<0.001, respectively). On the other hand, Repeat Revascularization rate during 12-months was significantly lower in the SMI group than in the EAP group (15.7% vs 19.5%, p<0.001).Kaplan-Meier analysis for cardiac death showed a significant difference between the 2 groups (Figure). In a multiple logistic regression analysis, in addition to lower BMI and CKD, SMI was an independent predictor for cardiac death. Even after adjustment by propensity-score matching with predictive factors for cardiac event, SMI showed a higher cardiac death rate compared with EAP (1.4% vs 0.5%, p=0.004), and it remained as a significant predictor.

Conclusion
In this study, SMI itself was associated with higher mortality after PCI. Strict follow-up and assessment of residual ischemia should be necessary for SMI patients.
P5499Coronary angioplasty for octogenarian acute coronary syndrome patients? Is it worth it?
Authors: Vila Cha Vaz Saleiro C , Campos D , Teixeira R , Lopes J , Sousa J P , Puga L , Ribeiro J M , Lourenco C , Costa M , Goncalves L 
Published: October 2019

Abstract

Background
As the population ages, doctors are being challenged by the decision to offer intervention treatment in increasingly older and fragile patients. The comorbidity burden and performance status should be considered when making the decision.

Purpose
To assess the impact of optimal medical therapy (OMT) versus percutaneous coronary intervention (PCI) in non-ST elevation acute coronary syndrome (ACS) patients older than 80 years.

Methods
182 patients older than 80 years old admitted to a single coronary care unit with a diagnosis of non-ST elevation ACS, who survived hospital stay were included. Clinical, laboratorial and echocardiographic data were evaluated. Two groups were created: Group A (OMT group) N=83; Group B (PCI group) N=99. The primary endpoint was long-term all-cause mortality. Kaplan-Meyer curves and Cox regression were conducted to evaluate the impact of OMT versus PCI on the primary endpoint. The mean time of follow-up was 37±29 months.

Results
Groups were homogenous regarding gender, cardiovascular risk factors, heart failure diagnosis, left ventricular (LV) systolic function and peak troponin I. OMT group patients were older (85.1±3.7 vs 82.7±3.2 years old, P<0.01), had a higher prevalence of chronic kidney disease (CKD) (61.4% vs 46.5%, P<0.05), a lower haemoglobin (Hb) level (12.0±1.9 vs 12.6±1.7 g/dL, P<0.05) and were less likely to receive double antiplatelet therapy at discharge (80.8% vs 100%, P<0.001). 84 patients met the primary outcome. Kaplan-Meyer curves showed increased survival in the PCI group (36.5% vs 59.3%, Log Rank P<0.001 – Figure 1). Nevertheless, PCI was not associated with long-term mortality (HR 1.05, 95% CI 0.98–1.12) in a model adjusted for age, CKD, peak troponin, LV systolic function and Hb level. Only Hb (HR 0.81, 95% CI 0.73–0.93), peak troponin (HR 1.01, 95% CI 1.00–1.01) and LV function (slightly impaired [HR 1.89, 95% CI 1.03–3,48] and moderate/severely impaired [HR 1.96, 95% CI 1.14–3.36]) remained associated with the outcome.

Conclusion
Increased survival in older patients receiving PCI after a non-ST elevation ACS may be ascribed to the selection of patients with less comorbidities. This reinforces the idea it may be applied in well-fit patients regardless of age. In our elderly population, lower Hb level, peak troponin and impaired LV systolic function appear to be the main contributors to decreased survival, irrespective of intervention.
P5510High plasma sRAGE is associated with slower carotid intima media thickness progression and lower risk for first-time coronary events and mortality
Authors: Grauen Larsen H , Nilsson P M , Nilsson J , Engstrom G , Melander O , Orho-Melander M , Schiopu A 
Published: October 2019

Abstract

Background/Introduction
The receptor for advanced glycation end products (RAGE) and the extracellular matrix metalloproteinase inducer (EMMPRIN) are immune receptors for pro-inflammatory mediators. These receptors can also be found in a soluble form in the circulation. Soluble RAGE (sRAGE) has shown atheroprotective properties in animal studies, by acting as a decoy receptor for its ligands. Whether sEMMPRIN has similar roles is unknown.

Purpose
The purpose of our study was to investigate the associations between sRAGE and sEMMPRIN in plasma and the progression of vascular disease, incident coronary events and mortality in the general population.

Methods
We measured baseline sRAGE and sEMMPRIN in 4612 cardiovascular disease-free middle aged individuals from a population-based cohort. Measurements of intima media thickness (IMT) in the common carotid artery were performed at inclusion and after a median of 16.5 years. Incident major adverse coronary events (MACE) and mortality were recorded during a follow-up period of 21 years.

Results
sRAGE was negatively correlated with the progression of carotid IMT, independently of traditional cardiovascular risk factors, kidney function and hsCRP. Additionally, sRAGE was associated with decreased risk for MACE [HR=0.91 (0.83–0.99); p=0.031] and total mortality [HR=0.92 (0.87–0.99); p=0.017] in multivariate Cox regression analyses. We found no correlations between EMMPRIN, IMT progression or prognosis.

Conclusion
We show that individuals with high levels of circulating sRAGE have a slower rate of carotid artery disease progression, and a lower risk for coronary events and mortality. These findings support further research into the potential atheroprotective properties of sRAGE.

Acknowledgement/Funding
This study was supported by grants from the Swedish Research Council, Marianne and Marcus Wallenberg Foundation, Swedish Heart and Lung Foundation
P5530The low expression of circulating microRNA-19a represents an additional mortality risk in stable patients with vascular disease
Authors: Mayer O , Seidlerova J , Bruthans J , Cerna V , Pesta M 
Published: October 2019

Abstract

Background
Secondary prevention of atherosclerotic vascular diseases represents a cascade of procedures to reduce the risk of future fatal and non-fatal cardiovascular events. We sought to determine whether the expression of selected microRNAs influenced mortality of stable chronic cardiovascular patients.

Methods
The plasma concentrations of five selected microRNAs (miR-1, miR-19, miR-126, miR-133 and miR-223) were quantified in 826 patients (mean age 65.2 years) with stable vascular disease (6–36 months after acute coronary syndrome, coronary revascularization or first-ever ischemic stroke). All-cause and cardiovascular mortality rates were followed during our prospective study.

Results
Low expression (bottom quartile) of all five miRNAs was associated with a significant increase in five-year all-cause death, even when adjusted for conventional risk factors, treatment, raised troponin I and brain natriuretic protein levels [hazard risk ratios (HRRs) were as follows: miR-1, 1.65 (95% CI: 1.16–2.35); miR-19a, 2.27 (95% CI: 1.59–3.23); miR-126, 1.64 (95% CI: 1.15–2.33); miR-133a, 1.46 (95% CI: 1.01–2.12) and miR-223, 2.05 (95% CI: 1.45–2.91)]. Nearly similar results were found if using five-year cardiovascular mortality as the outcome. However, if entering all five miRNAs (along with other covariates) into a single regression model, only low miR-19a remained a significant mortality predictor; and only in patients with coronary artery disease [3.00 (95% CI: 1.77–5.08)], but not in post-stroke patients [1.63 (95% CI: 0.94–2.86)].

Conclusions
In stable chronic coronary artery disease patients, low miR-19a expression was associated with a substantial increase in mortality risk independently of other conventional cardiovascular risk factors.

Acknowledgement/Funding
Health Development Agency of the Czech Ministry of Health [project 17-29520A], Charles University Research Fund (PROGRES, project Q39)
P5534Causes and predictors of short, intermediate and long-term mortality in patients after PCI
Authors: Zeitouni M , Procopi N , Kerneis M , Hammoudi N , Berman E , Barthelemy O , Choussat R , Guedeney P , Braik N , Silvain J , Le Feuvre C , Helft G 
Published: October 2019

Abstract

Background
Causes of death after percutaneous coronary intervention (PCI) along multiple time-periods are poorly described.

Objective
To describe causes and predictors of short-term, intermediate-term, and long-term mortality after PCI.

Methods
Consecutive men and women admitted for PCI from 2008 to 2011 were prospectively included and followed-up in this cohort study. A dedicated follow-up by independent reviewers was performed to collect the outcomes and adjudicate the causes of death. A log-rank analysis was used to compare the occurrence of cardiovascular and non-cardiovascular death at 30 days, one year and up to 8 years. Last detailed cardiovascular and vital status were collected in January 2019.

Results
A total of 3524 patients including 2720 men (77.2%) and 804 women (22.8%) were followed-up for a median time of 7.0 years (IQ1: 5.4; IQ 3: 7.2). The rate of complete follow-up was 97.6%. All-cause death occurred for 30.3% (n=1070) of patients in the cohort, in a median time of 2.5 years after PCI, with a rate of 5.3 deaths per 100 patient-years. Overall, mortality was mostly related to cardiovascular causes than non-cardiovascular causes (17.7% versus 12.6%, log-rank <0.001) (Figure). This trend was strong within 30 days (4.7% vs. 0.3%, p<0.0001) and the first year after PCI (3.1% vs. 2.2 p=0.01), but became non-significant beyond one year (9.9% vs. 10.2%, P=0.67). Of note, cancer was the major cause of non-cardiovascular death (5.6%; 1 per 100 patient-years). Diabetes (adHR = 1.48 95% [1.29–1.71], p<0.001), active smoking (adHR = 1.37, 95% [1.16–1.62]) and chronic kidney disease (adHR = 1.97, 95% [2.55–3.45], p<0.001) were the strongest risk factors for all-cause death.
Survival after PCI

Conclusions
In this long-term cohort study, cardiovascular death was more frequent than non-cardiovascular death in patients treated with PCI in the short and intermediate-term but not beyond one year. Cancer accounted for one fifth of the overall mortality.