bluuebunny/crossref_metadata_2025_split huggingface dataset:
P743The efficacy and the safety of the action of the complex drug of fibrin-specific streptokinase in arterial thrombosis in vivo
Authors: Adzerikho I E , Lutsik I L , Vladimirskaya T E , Cherniavsky E A 
Published: October 2019

Abstract

Introduction
The use of streptokinase (SK) in the clinic is limited by the absence of fibrin-specificity, low degree of recovery of the vessel lumen and hemorrhagic manifestations. We have developed a system of local delivery of SK based on fibrin-specific liposomes, which is a complex drug of streptokinase (SKf), containing “free” SK and SK “associated” with liposomes conjugated with monoclonal antibodies FnI-3C (IgG2 class) to fibrin in a ratio of 40%/60% respectively.
The purpose of this study was to evaluate the efficacy and the safety of the action of the SKf in different methods of its administration in arterial thrombosis in vivo.

Methods
Experiments were performed with 60 outbred male dogs weighing 15–18 kg on a 2-hour model thrombus of the femoral arteries. Experimental group (n=30) received SKf, control group (n=30) - native SK. The drugs were administered intravenously (IV) and intraarterially (IA) in the dose of SK 75000 ME. The observation time was 180 minutes. The pharmacokinetic parameters of the SKf and native SK were studied. Ultrasound, morphological and morphometrical methods of the arteries investigations were used. P<0.05 was taken as statistically significant.

Results
The SKf had better pharmacokinetic parameters than native SK. The duration of the half-life of SKf was significantly longer than that of native SK 24,1 [21,76; 27,53] min vs. 1,83 [1,64; 1,93] min, (p<0.001). The elimination constant of SKf was lower than that of native SK 0,0291 [0,0175; 0,0407] 1/min vs. 0,3867 [0,1679; 0,5135] 1/min, (p<0.001). Differences between pharmacokinetic parameters of SKf and the native SK, and the presence of fibrin-specificity of SKf contributed to increase of its thrombolytic effect. According to the data of the morphological analysis, the lysis of the central part of the thrombus was noted during the action of native SK. At the same time, the release of SKf initially caused the lysis of the central part of the thrombus with the further dissolution of the thrombus at the periphery. The morphometric evaluation of the artery samples showed that SKf leads to a significant increase in the degree of free vascular lumen compared to the native SK in different methods of its administration: IV - 65,25 [62,67; 68,53]% vs. 52,82 [50,60; 55,71]% respectively, p<0.001; IA - (74,27 [70,39; 77,39]% vs. 68,56 [67,36; 70,87]% respectively, p<0.001. The hemorrhagic complications were not revealed for different methods of SKf administration during the observation period.

Conclusions
The use of SKf with different methods of administration leads to highly efficient and safe fibrinolyc action in arterial thrombosis in vivo.
P746Protective role of the longevity associated variant of BPIFB4 in chronic ischemia
Authors: Veneziano C , Cervellin C , Caragnano A , Bulfoni M , Villa F , Sponga S , Livi U , Finato N , Cesselli D , Madeddu P , Puca A A , Beltrami A P 
Published: October 2019

Abstract

Background
A rare Longevity Associated Variant (LAV) of the gene BPIFB4, whose protein product can be secreted, is recessively associated with extreme longevity, positively impacting the cardiovascular system and promoting therapeutic angiogenesis in an hindlimb ischemia model.

Aim
Aim of this work is to verify if LAV-BPIFB4 may temper the phenotype of chronic ischemia in humans, thus suggesting its therapeutic potential.

Methods and results
39 hearts explanted from patients affected by end-stage ischemic heart disease were studied. Of these, 7 were homozygous for BPIFB4-LAV. Homozygous and non-homozygous patients did not differ in sex, age and in the prevalence of comorbidities or risk factors. However, the time elapsed from myocardial infarction to transplantation was significantly longer for LAV homozygous with respect to LAV heterozygous patients (159±95 vs 58±27 months, p=0.045). Histologically, while BPIFB4 levels did not differ in accordance with the genotype, the fraction of Tunel+and 53BP1+apoptotic and senescent myocytes was significantly lower in homozygous patients (1.2±0.4% vs 23.8±21.7%, p=0.026 and 31.5±6.7% vs 44.4±6.1%, p=0.031, respectively). Significantly lower levels of lipoperoxides and higher levels of Parkin were observed in homozygous hearts too. Next, we directly tested the role of BPIFB4 on PDGFRb+ NG2+Tbx18+cardiac pericytes/mural cells (PM) cultured from normal atria (PMnorm, n=10) and from ischemic failing hearts (PMfail, n=7). BPIFB4 gene transcript was significantly more expressed in PMnorm than PMfail. Silencing BPIFB4 expression in PMnorm significantly increased the proportion of senescent gH2AX+Ki67-cells (3.6±2.9% vs 13.6±9.5%, p=0.049). Conversely, addition of recombinant LAV BPIFB4 protein to PMfail cultures significantly reduced the rate of senescent cells (21.1±9.4% vs 6.0±4.8%, p=0.03), an effect that was not observed with the administration of WT BPIFB4. PMfail cultures exposed to LAV BPIFB4 significantly reversed alterations observed with pathology, such as the accumulation of both lipofuscins and of very elongated and interconnected mitochondria in the cell cytoplasm, as well as elevated mitochondrial superoxide anion levels. Finally, a larger fraction of PMnorm cells showed, with respect to PMfail, the nuclear translocation of vitamin D receptor (74.6±6.1% vs 50.1±14.4, p=0.04), coupled with a significant upregulation of its, longevity associated, target gene Klotho. Importantly, LAV BPIFB4 significantly increased the fraction of PMfail with vitamin D receptor nuclear localization (55.8±17.6% vs 85.1±8.2%, p=0.005).

Conclusion
LAV BPIFB4 could attenuate the progression of ischemic heart disease to heart failure. Part of its protective effect may be due to its ability to reduce mitochondrial oxidative stress and to revert the senescent phenotype of cardiac derived cells.

Acknowledgement/Funding
CARIPLO foundation
P767Survey of palliative sedation at the end-of-life in terminally ill heart failure patients - a five year experience in national cardiovascular center
Authors: Nakai E , Hamatani Y , Miyata M , Nakamura E , Kawano Y , Takada Y , Anchi Y , Funabashi S , Hirayama A , Kuroda K , Amano M , Sugano Y , Anzai T , Izumi C 
Published: October 2019

Abstract

Background
Palliative sedation is a therapeutic option when symptom relief is difficult to achieve at the end-of-life. However, little is known regarding palliative sedation in terminally ill heart failure (HF) patients.

Purpose
To survey the practice of palliative sedation in terminally ill HF patients at a tertiary referral cardiovascular center, and to investigate the efficacy and safety of sedative agents in HF patients.

Methods
We retrospectively reviewed consecutive patients who were referred to palliative care team at our institution between September 2013 and August 2018. Patients who were hospitalized for HF and died during hospitalization despite optimal medical therapy were selected and defined as terminally ill HF. We investigated the practice of palliative sedation in terminally ill HF patients and analysed the vital signs and sedation scale before starting sedative agents and about 1 hour afterward.

Results
Among 95 terminally ill HF patients, 37 were prescribed palliative sedation at the end-of-life (Picture). Of 37 patients (mean age: 70 years, median B-type natriuretic peptide: 1018 pg/ml, median creatinine: 3.0 mg/dl, intravenous inotrope: 81%), 25 were prescribed dexmedetomidine, and 12 were prescribed midazolam as first agent for sedation. Patient's backgrounds were comparable between the two groups. Richmond Agitation-Sedation Scale was significantly reduced (P<0.01), whereas blood pressure and heart rate were not altered after treatments in both groups. In midazolam group, significant decreases were noted regarding respiratory rate (P=0.01) and oxygen saturation (P=0.02); however, these parameters were not changed in dexmedetomidine group (Table).
Table 1. Vital signs and sedation scale Dexmedetomidine group (n=25) Midazolam group (n=12) Baseline After P value Baseline After P value Richmond Agitation-Sedation Scale 1 (0, 1) −1 (−2, 0) <0.01 1 (0, 1) −2 (−3, −1) <0.01 Vital signs   Systolic blood pressure (mmHg) 90±15 89±16 0.51 89±21 84±23 0.33   Diastolic blood pressure (mmHg) 52±13 54±11 0.34 60±14 56±23 0.48   Heart rate (beats per minute) 95±20 91±22 0.17 90±21 90±19 0.70   Respiratory rate (breaths per minute) 22±5 20±5 0.24 21±5 17±2 0.01   Oxygen saturation (%) 97±3 96±6 0.59 96±5 94±5 0.02
Picture. Study flowchart

Conclusions
Dexmedetomidine and midazolam were commonly used in real-word practice for HF patients at the end-of-life. Although impact on respiratory system differed by treatments, both agents could be prescribed effectively and safely in terminally ill HF patients.
P785Unplanned readmissions after discharge increases risk of death in acute dyspnoea patients: non-cardiac is as severe as cardiac causes
Authors: Cerlinskaite K , Mebazaa A , Cinotti R , Wussler D N , Gayat E , Juknevicius V , Muller C , Kavoliuniene A , Celutkiene J 
Published: October 2019

Abstract

Introduction
Acute dyspnoea is a major reason for admission to the emergency department and has been associated with high rates of readmission and mortality. However, the association of readmission with mortality risk has not been widely studied in patients with acute dyspnoea.

Purpose
To determine whether unplanned readmission during first 6 months after discharge is associated with greater risk of death within 1 year in patients with acute dyspnoea.

Methods
Derivation cohort consisted of 1371 patients from the prospective observational study, which enrolled acute dyspnoea patients admitted to emergency departments of two university centres from 2015 to 2017 and discharged alive from the hospital. Cox regression analysis compared 1-year risk of death between readmitted vs. non-readmitted patients in the first 6 months after discharge. In addition, we studied this association in 1986 patients from a multicentre validation cohort, which included acute dyspnoea patients from 2006 to 2014. Sensitivity analysis was done in the subgroups divided by cause of index admission (acute heart failure [AHF] and non-AHF) and cause of the first readmission (cardiovascular [CV] or non-CV). The statistical analyses were performed using R statistical software. P value of <0.05 was considered statistically significant.

Results
In the derivation cohort 666 (49%) of patients were readmitted at 6 months and 282 (21%) died in 1 year. Readmitted patients died more frequently than non-readmitted patients (211 [32%] vs. 71 [10%], respectively, p<0.001). All-cause 6-month readmission was associated with an increased 1-year risk of death in a multivariate analysis in both the derivation cohort (adjusted hazard ratio (aHR) 3 [95% confidence interval (CI) 2.2–4], p<0.001) and the validation cohort (aHR 1.8 [95% CI 1.4–2.2], p<0.001). Moreover, deleterious effect of readmission on 1-year survival was equally observed in AHF and non-AHF patients, independent of whether the reason of first readmission was cardiovascular or non-CV, in both study cohorts. The results are displayed in Figure 1.
Figure 1. Main results of the study

Conclusions
Our data demonstrates that readmission is associated with a markedly increased risk of death within 1 year in patients presenting to the emergency department with acute dyspnoea. Furthermore, the detrimental relationship between outcomes is similar in non-cardiac and cardiac causes.

Acknowledgement/Funding
The work was supported by the Research Council of Lithuania, grant Nr. MIP-049/2015 and approved by Lithuanian Bioethics Committee, Nr. L-15-01.
P792Cardiac myosin-binding protein C for the diagnosis and long-term prognosis of acute heart failure
Authors: Kozhuharov N , Wussler D , Kaier T , Walter J , Strebel I , Twerenbold R , Marber M , Breidthardt T , Mueller C 
Published: October 2019

Abstract

Background
Cardiac myosin-binding protein C (cMyC) is a novel biomarker quantifying cardiac injury. Its utility for the diagnosis, prognosis, and therapy guidance in acute heart failure (AHF) is unclear.

Methods
In a prospective diagnostic multicentre study, unselected patients presenting with acute dyspnoea to the emergency department were enrolled. cMyC, high-sensitive cardiac troponin T (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma concentrations were measured. Two independent cardiologists/internists centrally adjudicated the final diagnosis using all individual patient's information. Co-primary outcome measures were cMyC's: diagnostic safety and efficacy; prognostic accuracy.

Results
Among 1,330 recruited patients, 247 from an AHF substudy were not included in the diagnostic analysis. Accordingly, 548 patients (51%) in this analysis had an adjudicated diagnosis of AHF. For the rapid rule-out of AHF, the cMyC cut-off concentration at 16 ng/L achieved a sensitivity of 95% (95% CI, 93–97%), a negative predictive value of 88% (95% CI, 84–92%), and allowed to rule-out 21% of the patients. Correspondingly, cMyC's efficacy and safety in the triage of AHF were slightly lower than NT-proBNP's. Of the 790 AHF patients in the prognostic analysis, 222 (28%) died during the 360 days' follow-up. Patients with cMyC plasma concentrations above the median had significantly shorter mean time to death (274 versus 320 days, p=0.001). Compared to hs-cTnT and discharge NT-proBNP, cMyC showed non-inferior prognostic accuracy. No significant interactions between cMyC and cardiac medical therapies at discharge in predicting 360 days survival were present.

Conclusion
cMyC performs well in the rapid triage and prognosis of AHF.

Acknowledgement/Funding
European Union, Swiss National Science Foundation, Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University Hospital of Basel
P800Proposal of an algorithm for the diagnosis of hypertension by using out-of-office blood pressure measurements
Authors: Rhee M Y , Kim J H , Namgung J , Lee S Y , Cho D K , Choi T Y , Kim S Y 
Published: October 2019

Abstract

Background and purpose
Based on the data of patients who measured office BP (OBP) in controlled condition, home BP (HBP), and 24-hour ambulatory BP (24hABP) for diagnosis of hypertension, we developed and validated a diagnostic algorithm for hypertension.

Methods
Patients who have high BP (≥140/90 mmHg) at the outpatient clinic were referred to measure OBP in controlled condition, HBP and 24hABP. The OBP was measured three times at each visit for 3 days in controlled condition by using a validated oscillometric device. HBP was measured for 7 days in triplicates every morning and evening. The 24hABP was measured on the 8th day. Same study protocol was used for development and validation population.

Results
In the development of algorithm, 319 patients were recruited and data of 256 patients (51.8±9.7 years, 119 men) with valid HBP and 24hABP measurements were analyzed. In the validation of algorithm, 300 patients were recruited and data of 257 patients (52.4±9.8 years, 126 men) with valid HBP and 24hABP measurements were analyzed. In the development population, the prevalence of masked hypertension was 19.5% (n=50) and most of them (n=47, 94%) was in the range of 130–139/80–89 mmHg. The BP in the range of 130–144/80–94 mmHg was defined as the grey zone of OBP, because prevalence of white-coat hypertension was lowered to 1.6% from 4.3% with threshold of 145/95 mmHg. The diagnostic sensitivity, specificity, positive and negative predictive value of OBP was improved to 97.4%, 76.5, 96.5% and 81.3% after excluding the grey zone of OBP (n=125). The diagnostic agreement between 24hABP and HBP in the grey zone of OBP was 64%. The diagnostic sensitivity, specificity, positive and negative predictive value of HBP were 88.8%, 74.7, 93.5% and 61.5% after excluding the grey zone of HBP (130–134/80–84 mmHg, n=28). Based upon these results, we developed a diagnostic algorithm for hypertension by using on out-of-office BP measurements to improved diagnostic accuracy of hypertension (Figure). In the validation population, the developed algorithm showed similar diagnostic accuracy.
Diagnostic algorithm for hypertension

Conclusion
For accurate diagnosis of hypertension, OBP measurement according to guidelines and 24hABP measurement to grey zone of OBP is preferred. To improve diagnostic accuracy of HBP measurement, 24hABP measurement to grey zone of HBP is required.

Acknowledgement/Funding
Part of this study was supported by a grand from Dong-A ST Co. Ltd., Seoul, Korea.
P801Continuous cuff-less blood pressure monitoring using vascular elasticity model on photoplethysmogram
Authors: Lin T T L , Guo H W G , Lee H F L , Su P Y S 
Published: October 2019

Abstract

Background
Hypertension is a well-known risk factor for potentially cardiovascular diseases, which is underdiagnosis and treatment. Clinical evidence suggests that periodic and continuous monitoring of blood pressure (BP) is helpful for the early detection of hypertension to reduce the cardiovascular risk. Photoplethysmogram (PPG) is a simple and non-invasive technique to measure the instantaneous blood flow in capillaries. This study proposes a miniaturized PPG sensor, which is feasible to integrate into smartphone, to estimate cuff-less BP and heart rate (HR).

Methods
A miniaturized PPG sensor, provided by FocalTech Smart Sensors Co., Ltd., was used to collect reflective finger PPG signal. The methodology of BP estimation from PPG was using a vascular elasticity model which estimating the physiological parameters from PPG features Simultaneously, we utilized oscillometric blood pressure monitors to obtain automated BP readings as the validation standard.

Result
Seventy-one subjects were recruited in this validation study. By using our PPG algorithm, an accuracy of ± 11.9 mmHg for systolic BP and ± 8.0 mmHg for diastolicBP was observed at 71 subjects. There was a good linear correlation (CC) between PPG-estimating BP and automated BP (systolic BP, CC=0.4; diastolic BP, CC=0/.45).Likewise, slopes of the liner fit on the Bland Altman plots for both systolic BP (slope = −0.23) and diastolic BP (slope = −0.11) indicated there was no particular bias in predicting high or low BP.
Subjects characteristics Parameters Total number (subjects) 71 Entry BP range Normal 21 Prehypertension 27 Stage 1 hypertension 17 Stage 2 hypertension 6 Sex Male 37 Female 34 Age (years) Mean ± standard deviation 55±12 Range 27–77

Conclusion
In this study, the feasibility of mobile based cuff-less BP measurement using a vascular elasticity model on finger PPG signal was demonstrated with a level of acceptable accuracy. Based on mobile-based and easy-to-use features of our sensor/device, the incorporation this real-time measurement into the monitoring of BP could be helpful for the management of hypertension.
P808Characteristics of patients with reproducible masked hypertension
Authors: Smirnova M I , Gorbunov V M , Volkov D A , Koshelyaevskaya Y N , Deev A D , Furman N V , Dolotovskaya P V 
Published: October 2019

Abstract

Background
Masked hypertension (MH) is associated with cardiovascular complications and poor prognosis. Characteristics of untreated patients with reproducible MH are studied insufficiently.

Purpose
The aim of our study was to assess characteristics of ambulatory patients with reproducible MH in comparison to patients with non-reproducible MH in two visits.

Methods
The patients from the ambulatory BP monitoring (ABPM) database (>2000 patients) were selected according to the following criteria: absence of any antihypertensive treatment (AHT), availability of clinical BP (CBP) and ABPM records at two visits with the 6 months interval, CBP<140 and 90 mmHg at both visits, availability of clinical, anthropometric data and history. MH criteria in each patients should be present at least at one of the visits. ABPM was performed by the oscillometric device equipped with software for arterial stiffness calculation. The standard statistical methods and analysis of variance (ANOVA) were used.

Results
We selected 295 patients (men 43%, mean age 49.0±7.6 years, CBP 128.4±9.4/80.5±7.2 mm Hg, body mass index 27.6±4.3 kg/m2, 24h pulse wave velocity in aorta [PWV] 10.7±1.7 m/s). MH only at one visit was found in 168 patients (56.9%). Respectively, MH at both visits was in 127 patients (43.1%). The patients with reproducible MH were characterized by the presence of: mother's (p=0.011) or father's hypertension (p=0.025), mother's ischemic heart disease (p=0.015), mother's myocardial infarction (p=0.020), father's stroke (p=0.030), higher arterial stiffness (PWV 11.0±1.7 m/s vs. 10.5±1.8 m/s, p=0.022), and systolic BP in aorta (120.0±7.5 mmHg vs. 117.8±9.4 mm Hg).

Conclusions
The patients with reproducible MH (without AHT) are characterized most of all by the family history of hypertension and its complications. The correlation of stable MH with arterial stiffness confirms the importance of PWV and central aortic pressure measurement in patients with CBP<140 and 90 mmHg.
P822Statin treatment in symptomatic patients with non-obstructive coronary artery disease reduces the risk of all-cause mortality
Authors: Kissel C K , Chen G , Fung M , Wilton S B , Anderson T J 
Published: October 2019

Abstract

Introduction
Symptomatic patients with non-obstructive coronary artery disease (NOCAD; stenosis >0% <50%) have a worse prognosis and an increased risk for all-cause mortality compared with age-matched controls. Currently, treatment of these patients is empiric, and secondary preventive measures are less often implemented. The goal of the study was to examine whether statin prescription has an impact on all-cause mortality in symptomatic NOCAD patients, and which factors influence statin prescription in patients with NOCAD.

Methods
We examined 4039 symptomatic patients who presented either with stable angina (SA) or an acute coronary syndrome (ACS) who underwent coronary angiography; 1582 had angiographically normal coronary arteries, 2457 had minimal disease (NOCAD). The comparison group consisted of 2998 patients with stable obstructive CAD (stenosis ≥50%). Patients had at least one lipid panel tested between April 1, 2010 to March 31, 2014. We examined the rate of statin prescription amongst the groups, as well as predictors of all-cause mortality and statin treatment.

Results
Symptomatic patients with NOCAD are less likely to receive statin therapy (60.4%) compared to patients with obstructive CAD (87.3%). After one, three and five year(s), LDL levels in NOCAD patients are higher than in CAD patients (2.21±0.88mmol/l vs. 1.84mmol/l±0.77mmol/l after 1 year). Statin treatment was associated with a significantly lower risk of all-cause mortality in NOCAD (HR 0.64 (0.44–0.95)), as well as in CAD (HR 0.44 (0.31–0.62)), but not in patients with normal coronaries HR 0.55 (0.27–1.15)). Sex, age and the presence of other cardiovascular risk factors influenced the prescription of statin therapy in the first 5 years after initial diagnosis of NOCAD- older patients with diabetes and hypertension were more likely to receive statin therapy. Women received statin therapy to a lower percentage than men in the NOCAD group (year 1: men 62.9% vs, women 56.9%; p=0.003). No effect of cardiovascular risk factors, age or sex on statin prescription was seen in the CAD group or patients with normal coronaries.

Conclusion
Statin therapy reduces the risk of all-cause mortality in symptomatic patients with NOCAD. In spite of this benefit, patients with NOCAD, and especially women, are less likely to receive secondary-preventive statin therapy.