bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4446Cardiopulmonary exercise test in young patients with in early stages of sarcoidosis
Authors: Bartosh-Zelenaya S Y U , Evsikova I A , Naiden T V , Mamaeva O P , Shcherbak S G 
Published: October 2019

Abstract

Purpose
To assess CPET data in young patients with pulmonary sarcoidosis (grade I-II) respectively corresponding parameters in healthy individuals.

Methods
99 people aged 25–44 years were examined: 66 people with pulmonary sarcoidosis (PS) I-II grade formed the main group. The control group included 33 healthy, non-smoking people. In both groups the CPET was performed for assessment functional status of cardiorespiratory system.

Results
Vital capacity and FEV1 didn't differ in both groups (p=0.6 and 0.19). However, Tiffno's index was significantly higher in the control group (p=0.0002). There were no differences in RVOT1, RVOT2, RA volume index in both groups. A comparative analysis of the RV wall thickness revealed that the values in both groups did not exceed the normal limits, but in the main group it was significantly larger (p=0.01). The basal RV diameter at rest were also larger in patients with sarcoidosis (p=0.007). LV contractility at rest was within normal values in both groups, however, in patients with sarcoidosis EF were statistically less than in the control group. At the peak of exercise EF increased more significantly in the control group (p<0.0001). The EF-2D increase was higher in healthy young's (15% vs 10%). GLS LV both at rest and at the peak of exercise in both groups had no statistically significant differences. RV GLS in patients with sarcoidosis at the peak of exercise didn't increase (p=0.18) in contrast to healthy individuals (p=0.002). PAP at rest in patients with sarcoidosis was slightly higher than in healthy individuals (p=0.03), but didn't exceed the standard values. At the peak of exercise, in the main group PAP increased more than in the control group (p=0.ehz745.084701). In the control group the upper quartile of PAP was 29 mm Hg, at the peak of exercise-38 mm Hg. In the main group these values were much higher: 35 and 62 mm Hg. In control group, the maximum OC was higher (27.07±3.53 ml/min/kg, p=0.014). The duration of exercise was longer in healthy individuals (p=0.04).
Thus, at the early stages of pulmonary sarcoidosis in young people there are no significant contractility abnormalities both at rest and at the peak of exercise, whereas the EF increase was lower than in healthy individuals. It is necessary to determine GLS RV, which may indicate RV dysfunction preceding the development of LV dysfunction. In patients with sarcoidosis, it's necessary to determine PAP at the peak of exercise, which increased in 79% of cases more than in healthy individuals. This may be due to secondary heart lesion at presence of pulmonary hypertension. The maximum oxygen consumption at the peak of exercise is higher in healthy individuals than in patients with sarcoidosis. So functional reserve was higher in the control group.
Thus, the CPET today is an informative diagnostic tool which should be included in the diagnostic algorithms for patients with sarcoidosis.
P4473Brain renin-angiotensin system blockade with firibastat, an orally active, central acting aminopeptidase A inhibitor prodrug prevents cardiac dysfunction after myocardial infarction in mice
Authors: Boitard-Joanne S , Marc Y , Keck M , Mougenot N , Agbulut O , Balavoine F , Llorens-Cortes C 
Published: October 2019

Abstract

Introduction
Brain renin-angiotensin system (RAS) hyperactivity has been implicated in sympathetic hyperactivity and progressive left ventricular (LV) dysfunction after myocardial infarction (MI). Brain angiotensin III, generated by aminopeptidase A (APA), is one of the main effector peptides of the brain RAS in the control of cardiac function.

Purpose
We hypothesized that orally administered firibastat (previously named RB150), an orally central acting APA inhibitor prodrug, would attenuate heart failure (HF) development after MI in mice, by blocking brain RAS hyperactivity.

Methods
Two days after MI induced by the left anterior descending artery ligation, adult male CD1 mice were randomized to three groups, for four to eight weeks of oral treatment with vehicle (MI+vehicle), firibastat (150 mg/kg; MI+firibastat) or the angiotensin I converting enzyme inhibitor enalapril (1 mg/kg; MI+enalapril) as a positive control.

Results
From one to four weeks post-MI, brain APA hyperactivity occurred, contributing to brain RAS hyperactivity. Firibastat treatment during four weeks after MI normalized brain APA hyperactivity, with a return to the control values measured in the sham group. Four and six weeks after MI, MI+firibastat mice had a significant lower LV end-diastolic pressure, LV end-systolic diameter and volume, and a higher LV ejection fraction than MI+vehicle mice. Moreover, the mRNA levels of biomarkers of HF (Myh7, Bnp and Anf) were significantly lower following firibastat treatment. For a similar infarct size, the peri-infarct area of MI+firibastat mice displayed lower levels of mRNA for markers of fibrosis such Ctgf and collagen types I and III than MI+vehicle mice.

Conclusions
Chronic oral firibastat administration after MI in mice normalizes brain APA hyperactivity, thereby normalizing brain RAS hyperactivity, whilst preventing cardiac dysfunction and attenuating cardiac hypertrophy and fibrosis.

Acknowledgement/Funding
INSERM, College de France, ANR LabCom, and Quantum Genomics
P4495Dimethylguanidino valerate a lifestyle related metabolite associated with future coronary artery disease and cardiovascular mortality
Authors: Ottosson F , Ericson U , Almgren P , Smith E , Brunkwall L , Hellstrand S , Nilsson P M , Orho-Melander M , Melander O 
Published: October 2019

Abstract

Background
Identification of lifestyle modifiable metabolic pathways related to cardiometabolic disease risk is essential for improvement of primary prevention in susceptible individuals. It was recently shown that plasma dimethylguanidino valerate (DMGV) levels are associated with incident type 2 diabetes (T2DM). Our aims were to investigate if plasma DMGV is related to risk of future coronary artery disease (CAD) and with cardiovascular mortality and to replicate the association with T2DM and to pinpoint candidate lifestyle interventions susceptible to modulate DMGV levels.

Methods
Plasma DMGV levels were measured using liquid chromatography-mass spectrometry (LC-MS) in a total of 5768 participants from the Malmö Diet and Cancer Study – Cardiovascular Cohort (MDC), the Malmö Preventive Project (MPP) and the Malmö Offspring Study (MOS). Dietary intake assessment was performed in MOS.

Results
Baseline levels of DMGV associated with incident CAD in both MDC (HR=1.29, C.I= 1.16–1.43, P=3.3e-6) and MPP (OR=1.25, C.I=1.08–1.44, P=2.4e-3). In MDC, DMGV was associated with cardiovascular mortality and incident CAD, independently of traditional risk factors. Furthermore, the association between DMGV and incident T2DM was replicated in both MDC (HR=1.83, C.I=1.63–2.05, P=8.7e-25) and MPP (OR=1.65, C.I=1.38–1.98, P=8.7e-8). Intake of sugar-sweetened beverages (SSB) associated with increased levels of DMGV, while intake of vegetables and level of physical activity associated with lower DMGV.

Conclusions
We discovered novel independent associations between plasma DMGV and incident CAD and cardiovascular mortality, while replicating the previously reported association with incident T2DM. Additionally, strong associations with SSB, vegetable intake and physical activity suggest the potential to modify DMGV levels using lifestyle interventions.

Acknowledgement/Funding
Knut and Alice Wallenberg Foundation, Göran Gustafsson Foundation, the Swedish Heart- and Lung Foundation, the Swedish Research Council
P4502Noninvasively assessed mitochondrial function estimated by skin fluorescence is abnormal in coronary artery disease
Authors: Rechcinski T , Cieslik-Guerra U , Siedlecki P , Trzos E , Wierzbowska-Drabik K , Szymczyk E , Wejner-Mik P , Kurpesa M , Lipiec P , Kasprzak J D 
Published: October 2019

Abstract

Mitochondrial NADH undergoes oxygenation to NAD+ and NADH molecules, activated by ultraviolet light, start to emit fluorescence at a wavelength 460nm. This phenomenon can be measured to non-invasively assess mitochondrial function in the forearm epidermis at rest, during transient ischaemia, and afterward reperfusion assuming that it reflects abnormal microvascular circulation. We hypothesized that flow-dependent skin fluorescence (FDSF) is abnormal in patients with coronary atherosclerosis.

Methods
Prototype device manufactured by Angionica (Poland) was used to quantify FDSF recorded in forearm before, during and after 100 s of brachial artery occlusion in 63 individuals (26 with coronary artery disease (CAD) and 37 healthy volunteers. The absolute value of baseline FDSF (BASE), maximum FDSF (MAX), minimal FDSF (MIN), percentage ischemic response (IR) and hyperemic response (HR) were measured. Age, lipid profile, fasting glucose, HbA1c, C-reactive protein (CRP), systolic and diastolic blood pressure, pulse wave velocity (PWV), augmentation index, time domain heart rate variability parameters (SDNN, rMSSD) and estimated apnea/hypopnea index -eAHI (Holter ECG based), BMI, intima-media thickness (IMT), left ventricle systolic and diastolic function were determined in all study participants to search for potential correlations with FDSF.

Results
Measurements were feasible in all study subjects and examination duration was 9±1min. Hyperemic response (HR) was significantly lower in patients with CAD vs controls: 10,4 vs. 14,36 vs 14,73 – p=0,025. Other parameters: BASE, MAX, MIN, and IR were not significantly different between groups (p>0,05).
In the entire group, HR was correlated with age (r=−0,23 p=0,037), and with total or LDL cholesterol (r=0,37 p=0,001 and r=0,36 p=0,001). Interestingly, HR was also positively correlated with SDNN (r=0,26 p=0,044) and rMSSD (r=0,29 p=0,026).
Mode of FDSF examination

Conclusion
Abnormal mitochondrial function probably secondary to microcirculatory disorder is detectable by noninvasive skin fluorescence test as decreased hyperemic response in patients with coronary disease. Age and cholesterol concentration as well as autonomic balance Holter indices are correlated with hyperemic response.

Acknowledgement/Funding
POIR.01.01.01.0540/15-00
P4503A multi-site coronary vein sampling study on cardiac troponin T degradation in non-ST-elevation myocardial infarction
Authors: Cramer G E , Damen S A J , Vroemen W H M , Mezger S T P , Suryapranata H , Van Royen N , Bekers O , Meex S J R , Wodzig W K W H , Verheugt F W A , De Boer D , Brouwer M A , Mingels A M A 
Published: October 2019

Abstract

Background
High-sensitivity cardiac troponin (hs-cTn) assays have reduced specificity for myocardial infarction (MI). In conditions other than MI, cardiac troponin T (cTnT) elevations have been attributed to small cTnT fragments. In search of improved cTnT assay specificity for MI, determination of the in-vivo molecular appearance of cTnT during MI is pivotal.

Purpose
To determine cTnT composition close to its site of release and during the course of MI by multi-site coronary venous system (CVS) and peripheral sampling.

Methods
Lithium-heparinized (LH) plasma and serum samples were obtained from multiple CVS locations in NSTEMI patients. Additionally, samples were drawn from a peripheral artery and vein followed by collections at 6- and 12 hours post-catheterization. cTnT concentrations were measured using the hs-cTnT immunoassay (Roche). The molecular cTnT composition was determined by gel filtration chromatography and Western blotting in an early and late presenting patient.

Results
CVS hs-cTnT concentrations were 28% higher than in the peripheral artery sample (n=71, p<0.001). In contrast to LH plasma, serum caused pre-analytical cTn T-I-C complex disintegration and cTnT degradation. CVS samples demonstrated presence of cTn T-I-C complex, free intact cTnT, and 29 kDa and 15–18 kDa cTnT fragments in higher absolute concentrations than measured peripherally. While the proportion of cTn T-I-C complex decreased and disappeared over time, 15–18 kDa cTnT fragments increased. Moreover, cTn T-I-C complex was more prominent in the early versus the late presenting patient.
Central illustration

Conclusions
In NSTEMI, cTnT is released as a combination of cTn T-I-C complex, free intact cTnT and multiple cTnT fragments. Over time, the composition of observed cTnT forms changes due to in-vivo degradation. These findings serve as a stepping stone to improve diagnostic accuracy of the hs-cTnT assay for MI.
P4508Uncoupling of right ventricular and arterial elastance in advanced HFrEF predicts poor survival
Authors: Melenovsky V , Tupy M , Solar N , Al-Hiti H , Reichenbach A , Havlenova T , Monzo L , Netuka I , Kautzner J 
Published: October 2019

Abstract

Background
Right ventricular dysfunction (RVD) in heart failure (HF) is poorely understood and difficult to recognize due to complex RV geometry and load-dependency. Pressure volume analysis using SPECT ventriculography combined with right heart catheterisation (RHC) ar rest and during load-altering maneuver (7 min 60° leg rise, LR) can improve detection of RVD.

Methods
Advanced HF patients underwent RHC with thermodilution CO measurement (Corodyne, Braun, Germany) followed by gated 3D equilibrium Tc-labeled blood pool SPECT ventriculography (D-SPECT, Israel). QBS software was used to calculate chamber volumes to derive contractility (EF, elastance: Ees) and afterload (Ea). Patients were followed for occurence of death without Tx, urgent Tx or VAD implant.

Results
From 157 patients (age 55±12 years, LV EF 22±12%, 86% males), 83% had PH (mPA>25 mmHg) and 58% had RVD (RV EF <35%). Despite afterload (PAm, Ea) correlated with RV function (RVEF, RV Ees), it explained <10% of its variance; at rest or during LR. Leg rise led to significant (p<0.01) increases of RVEDP, PAWP, mPA (+2, +3, +4 mmHg), to increases of RVEDV, RVESV (+18 and +9 ml), but to reductions of LVEDV and LVESV (−14 and −9 ml) and to no change of RV or LV EF, CO, HR. LR inreased RV afterload (Ea), had no change on RV contractility but it further reduced RV-PA coupling (Ees/Ea). With LR, 70% of patients had relative increase in RV diastolic volume compared to LV (REDV/LVEDV ratio), reflecting RV diastolic reserve. After median of 112 (IQR: 33–229) days, 73 pts (46%) had an event (urgent Tx, VAD or death). In Cox analysis, both RVD and PH were associated with adverse outcome. From all volume- and pressure-derived measures acquired at rest and during LR, low resting RV coupling ratio (Ees/Ea) had strongest association with events (Z-standartized RR 0.4, 95% CI: 0.2–0.6, p<0.0001). Patients with larger relative increase in RV volume during LR (larger RV diastolic reserve) had better outcome.

Conclusion
Pressure-volume analysis of RV function provides more precise characterization of RV-PA coupling and allows better event-free survival prediction than isolated volumetric or hemodynamic indexes. Low resting RV Ees/Ea ratio (< median 0.324) predicts particularly poor survival.

Acknowledgement/Funding
Ministry of Health of the Czech republic, grant AZV 17-28784A
P4518Cerebral blood flow is lower in heart failure patients with reduced ejection fraction
Authors: Babayigit E , Cavusoglu Y , Dural M , Mert K U , Ulus T , Gorenek B 
Published: October 2019

Abstract

Purpose
Heart and brain interaction is a well-known entity in heart failure (HF) and left ventricular systolic dysfunction poses an increased risk for stroke and cognitive impairment. Transcranial Doppler (TCD) provides valuable information on cerebral blood flow and detects microembolic signals that can be used to determine the risk of cerebrovascular events. However, less is known about cerebral blood flow in HF patients with reduced EF. So, we aimed to evaluate cerebral blood flow rates by means of TCD in HF patients with reduced ejection fraction (EF).

Methods
This study included 46 HF patients with an EF less than 35% (mean age 65.2±11 years, mean EF 20.1±3.8%) who underwent to TCD examination. In addition, 26 healthy individuals with sinus rhythm and EF >50% (mean age 64.4±9.0 years, mean EF 63.5±2.38%) were included in the study as a control group. Minimum, maximum and mean flow velocities of the both right middle cerebral artery (RMCA) and left middle cerebral artery (LMCA) determined by TCD were analyzed.

Results
The average of RMCA maximum and mean flow velocities were found to be significantly lower in HF patients than those in control group (76,06±23,7 cm/s and 48,49±16,4 cm/s in HF group vs 87,84±14,5 cm/s and 56,41±10,7 cm/s in control group, p=0,025 and p=0,016, respectively). The average of LMCA maximum and mean flow velocities were also significantly lower in HF patients than those in control group (75,1±22,3 cm/s and 47,57±14.8 cm/s in HF group vs 88,73±17,7 cm/s and 57,15±12,4 cm/s in control group, p=0,009 and p=0,007, respectively). However, there was no significant difference in minimum RMCA or LMCA flow velocities between HF group and control groups (33,5±10,6 cm/s and 32,86±9,58 cm/s in HF group vs 36,34±9,2 cm/s and 36,53±10,4 cm/s in control group, p=0,226 and p=0,157, respectively). No significant microembolic signals were detected in HF and control groups.

Conclusions
The results of this study showed that HF patients with reduced EF have lower cerebral blood flow velocities as compared to healthy controls, which might be one of the explanations of the adverse interaction between heart and brain in HF.
P4519Sleep Apnea screening in Heart Failure: an exploratory analysis
Authors: Gomes R M , Rocha M L , Cunha G J , Morais R M , Duarte J D , Araujo I , Fonseca M C 
Published: October 2019

Abstract

Background
Sleep Apnea (SA) is increasingly recognized in patients (pts) with Heart Failure (HF). Nocturnal polysomnography (PSG) is the gold-standard to diagnose SA. Currently, portable devices have been thoroughly validated in HF cohorts.

Purpose
To determine the correlation between clinical, laboratory and respiratory measurements with the presence of SA (defined as apnea-hypopnea index (AHI) >15/h) and desaturation time with SpO2 <90% (T90) ≥22 minutes, a strong mortality predictor in HF with reduced ejection fraction (HFrEF); and to compare the features of pts with HFrEF vs HF with preserved ejection fraction (HFpEF).

Methods
Our work is based on a single-center retrospective cohort of pts hospitalized for decompensated HF during 2013–2018. All pts were screened for SA with ApneaLinkTM after compensation the night preceding discharge. HF was defined as recommended by the European Society of Cardiology guidelines. A left ventricular ejection fraction ≤45% and >45% was used to define HFrEF and HFpEF, respectively, as per SERVE-HF trial.

Results
A total of 228 pts were included in the analysis (mean age 75.3±10.5 years, 48.9% male). SA was present in 135 (59.2%) pts and 41.2% had HFrEF. Mean AHI was 24.5±19.2/h, mean O2 desaturation index (ODI) was 24.4±21.0/h and mean T90 was 169.6±151.2 minutes. In multivariate models, ODI, gender and ischemic HF were predictors of AHI >15/h (R2 65.8%), with ODI being the strongest predictor (standardized coefficient 64.8%). Similarly, mean SpO2 was the only predictor of T90 ≥22minutes (R2 65.8%) (Figure 1). HFrEF pts had more often AHI>15/h (73.4% vs 48.5%, p<0.001), more total apneas (62±148 vs 16±79, p<0.001), obstructive apneas (28±76 vs 8±43, p<0.001) and central apneas (6±20 vs 0±5, p<0.001) than those with HFpEF. In multivariate models, ODI (OR 1.14, CI 1.03–1.26, p=0.013 for HFrEF; OR 1.21, CI 1.11–1.33, p<0.0001 for HFpEF) and mean SpO2 (OR 0.29, CI 0.14–0.60, p=0.001 for HFrEF; OR 0.23, CI 0.10–0.52, p<0.0001 for HFpEF) were the only predictors of AHI >15/h and T90 ≥22 minutes in both groups, respectively.

Conclusions
SA was highly prevalent in HFrEF and HFpEF. ODI and mean SpO2 were highly predictive of AHI >15/h and T90 ≥22minutes, respectively, both prognostic markers validated in a population with HFrEF, and equally so in HFrEF and HFpEF. These findings hypothesize a similar pathophysiology of SA in HF, regardless of left ventricular systolic function. Also, whether simple pulse oximetry can be routinely used for SA screening, since PSG and portable devices are often not widely available, is a finding worth being prospectively assessed.

Acknowledgement/Funding
None
P4525Differential effect of CRT in ischemic and non-ischemic cardiomyopathy: longterm follow-up data from a single center cohort study
Authors: Kahr P C , Kaufmann P , Kuster J , Tonko J , Breitenstein A , Flammer A , Ruschitzka F , Steffel J , Winnik S 
Published: October 2019

Abstract

Background
Cardiac-resynchronization therapy (CRT) reduces morbidity and mortality in selected symptomatic patients with reduced left ventricular ejection fraction (LVEF) and wide QRS complex. However, some patients fail to benefit from CRT. Data on the differential role of baseline and follow-up left ventricular ejection fraction (LVEF) on outcome in patients with ischemic compared to non-ischemic cardiomyopathy (ICM, N-ICM) is controversial.

Purpose
To test, whether ICM and N-ICM patients differ in outcome after CRT during long-term follow-up and whether predictors for survival after CRT differ between the two groups.

Methods
All patients undergoing CRT implantation at our institution between November 2000 and January 2015 were evaluated (n=418). All ICM/N-ICM patients with follow-up echocardiography within 1 year after CRT implantation (FU1) and a second echocardiography >1 year after FU1 (FU2) were included in the analysis (n=253). Primary post-hoc defined study endpoint was the composite of all-cause death, heart transplantation or implantation of a ventricular assist device.

Results
Compared to patients with N-ICM (n=160, median age 64 years [IQR 54–71], 71% male), ICM patients (n=93, median age 70 years [IQR 61–75], 84% male) were significantly older and had a higher prevalence of male gender, concomitant diabetes mellitus and arterial hypertension. There were no significant differences in pre-implantation echocardiographic features (LVEF, LVEDV, RV-FAC, severity of mitral regurgitation), QRS width and NT-proBNP levels between the groups. However, the hazard for reaching the primary endpoint was significantly higher in patients with ICM compared to N-ICM both on univariate analysis (HR 1.62 [95% CI 1.09–2.42], p=0.018) and after multivariate correction (aHR 2.13 [1.24–3.66], p=0.006). While higher NT-proBNP levels and greater right ventricular fractional area change were positively correlated with the hazard of death in both ICM and N-ICM (see Figure), lower LVEF at baseline was associated with an increased risk of death only in ICM but not in N-ICM (HR 0.95 [0.91–0.99], p=0.029 vs. HR 1.00 [0.96–1.04], p=0.945). Male gender, lower BMI and NYHA class ≥ III were positively correlated with the endpoint in N-ICM, but not in ICM. Importantly, LVEF at FU1 (median 4.7 months after implantation) and FU2 (median 47.1 months after implantation) were found to correlate signficantly with the endpoint in both ICM and N-ICM.

Conclusion
Our findings highlight important differences in ischemic and non-ischemic patient populations undergoing CRT. While overall survival of patients with N-ICM exceeds survival in ICM, several other factors (including LVEF) have differential effects on response to CRT in these two patient groups.