bluuebunny/crossref_metadata_2025 huggingface dataset:
P4448Profile of cardiovascular involvement and its relationship with disease activity in systemic lupus erythematosus
Authors: Niari J , Jena M R , Parida M , Tripathy S R , Tripathy R , Das B K
Published: October 2019

Introduction

The cardiovascular system is affected in systemic lupus erythematosus (SLE) by the disease itself, the state of chronic inflammation and also by the side effects of the treatment given.

Purpose

To find the burden of cardiovascular involvement in SLE, to correlate cardiovascular manifestation with SLE disease activity (SLEDAI-2K) and damage [SLICC/ACR Damage Index (SDI)].

Methods

Seventy-five consecutive SLE patients fulfilling SLICC criteria, aged between 15–55 years, with disease duration of <5 years, admitted to rheumatology ward, were included. Overlap syndromes, past history of cardiac disease, end stage renal disease, chronic liver disease and type 2 diabetes mellitus were excluded. Clinical examination, fasting serum lipid profile, electrocardiogram, 2D-Echocardiography, carotid intima media thickness (CIMT) and serum Troponin-I were used to assess the cardiovascular status of patients.

Results

In this cross-sectional study exploring cardiovascular disease burden in a cohort of SLE patients within 5 years of disease, we found the mean age of patients was 28.5±7.9 years with a male: female ratio of 1:14. Cardiovascular involvement was detected in 52% of patients. Raised systolic BP was detected in 42% and raised diastolic BP in 28% patients. ECG revealed sinus tachycardia in 32%. 2D-echocardiography revealed pericardial effusion in 14.66%, mitral valve involvement in 10.66% (7 had mitral regurgitation and one had mitral sclerosis). PAH and TR were observed in 5.33% and 6.66% of cases respectively. One case showed evidence of aortic sclerosis. Dilated cardiomyopathy was present in 2.66% of cases. In 2.66% of cases systolic dysfunction and diastolic dysfunction each was evident. No patient showed evidence of vegetations. Anti SS-A and anti nucleosome (30.7% each) were the most common antibodies found in SLE patients with cardiovascular involvement. Increased serum LDL, hypertriglyceridemia and low serum HDL was found in 29%, 47% and 51% of patients respectively. Sub clinical myocardial injury was absent in all our patients as evidenced by negative serum Troponin-I. The CIMT was within normal limits and comparable between patients with and without cardiovascular involvement. The mean SLEDAI-2K was 7.3±4.9 and mean SDI was 0.8±1.2. SLEDAI-2K and SDI were significantly higher in patients with cardiovascular involvement versus patients without cardiovascular involvement (p=0.002 and p=0.01 respectively).

SLEDAI-2K and SDI vs cardiac involvement

Conclusion

Cardiovascular involvement is associated with high SLEDAI-2K and SDI. Presence of anti-SSA and anti-nucleosome antibodies may predispose to cardiovascular involvement. Pericardial effusion was the most common echocardiographic abnormality. Low HDL was the most common dyslipidemia. However,atherosclerosis is not evident in patients with SLE with disease duration less than 5 years.
P4451Screening for Coronary Artery Disease USing Primary Evaluation with Cardiac CT (SUSPECT) in Aviation Medicine in the Royal Netherlands Air Force
Authors: Grobben R B , Frijters E , Velthuis B K , Beekmann R T A , Rienks R , Nathoe H M
Published: October 2019

Background

Military aircrew are subjected to both stress and excessive G-forces, which may be associated with an increased risk of coronary artery disease (CAD) and sudden cardiac death. Annual cardiac screening has therefore been implicated using exercise testing, which suffers from both false-positive and false-negative results. In this study, we have evaluated the prevalence of CAD in military aircrew using cardiac computed tomography (CT), and assessed whether cardiac CT would be a useful screening tool within this population.

Methods

Prospective, single-center, cohort study in 250 asymptomatic aircrew >40 years old in the Royal Netherlands Air Force. Included subjects underwent cardiac CT, in addition to the routine annual check-up that included an electrocardiogram, exercise test and laboratory analysis. Primary endpoint was obstructive CAD, defined as a coronary stenosis ≥50%. Secondary endpoints were non-obstructive CAD (<50% stenosis) and coronary artery calcium score (CACS) >100.

Results

Of the first 108 inclusions, mean age was 49 years (range 40–57), 99% were male and mean body mass index was 25.8 (SD 2.6). The prevalence of hypertension was 8%, hypercholesterolemia 9% and familial heart disease was noted in 22%. 16% were active smokers and none had diabetes. Obstructive CAD was observed in 2% of patients, non-obstructive CAD in 40% and CACS >100 in 11%. All subjects with obstructive CAD on cardiac CT underwent coronary artery angiography, which confirmed a stenosis >70% that required revascularization.

Conclusion

In asymptomatic military aviation aircrew >40 years old currently active in the Royal Netherlands Air Force, the prevalence of obstructive and non-obstructive CAD was 2% and 40%, respectively

Acknowledgement/Funding

Royal Netherlands Air Force
P4453Predictors of sustained ventricular arrhythmias during late phase in patients with reduced left ventricular ejection fraction after myocardial infarction
Authors: Saito K , Kondo Y , Kitahara H , Nakayama T , Fujimoto Y , Kobayashi Y
Published: October 2019

Background

Sustained ventricular arrhythmias (VAs) and death are feared events post myocardial infarction (post-MI). Patients with heart failure post-MI have higher risk of VAs, compared to those without heart failure. Although the risk of sudden cardiac arrest and death post-MI isn't small, previous clinical trials have failed to demonstrate the benefit of early use of implantable cardioverter defibrillators. Moreover, little is known about the relationship between the acute phase and the late phase VAs in patients with heart failure post-MI.

Purpose

The aim of this study was to determine the predictors of the late phase VAs in patients with heart failure post MI.

Methods

We retrospectively analyzed our database of MI patients from January 2012 to September 2016.

Results

A total of consecutive 460 post-MI patients were included in this study (age, 67±12 year-old; male, 336 (73%); STEMI, 281 (61%)). All the patients underwent primary percutaneous coronary intervention. Of those, 90 patients (20%) had depressed left ventricular ejection fraction (LVEF) ≤35%. After a mean follow up period of 30±16 months, 45 patients (50%) had VAs after MI. Among them, 35 patients (78%) had VAs within 48 hours after MI onset, 8 patients (18%) within 7 days 48 hours later, and 21 patients (47%) more than 7 days. Cox-regression analysis showed that VAs within 7 days 48 hours later after MI onset was significantly related to sustained VAs more than 7 days after MI onset (Hazard Ratio, 4.97; 95% Confidence Interval, 1.31–18.9; p=0.019).

Conclusions

VAs in the sub-acute phase after MI predicted sustained VAs in the late phase in this population. Prompt initiation of aggressive antiarrhythmic therapies, including catheter ablation, after MI should be considered to reduce the mortality.
P4464Significative role of edoxaban on endotelial cell functions
Authors: Mosquera-Garrote N , Almenglo C , Gonzalez-Peteiro M , Gonzalez-Juanatey J R , Alvarez Castro E
Published: October 2019

Background

Edoxaban is a new oral anticoagulant with factor X activated (FXa) inhibition properties. It is approved for the prevention of ictus and embolism in patients with atrial fibrillation and for the treatment of venous thrombosis and lung embolism. However, little is known about its effects on endothelial cell functions.

Objectives

To study the edoxaban effects on key endothelial functions as proliferation, wound-healing, angiogenesis and peripheral blood mononuclear cells (PBMCs) adhesion.

Methods

Human umbilical endothelial cells (HUVECs) were obtained from donated umbilical cords after signed informed consent of the mothers. Cell proliferation and viability were measured by a real-time cell analyzer by noninvasive electrical impedance monitoring. Migration was study in wound-healing assays. Angiogenesis was measured after 16 hours of HUVECs' seeding in a three dimensional matrix and PBMCs adhesion to HUVECs' monolayers was assessed in the presence or in the absence of edoxaban and/or FXa. Measurements on each assay was compared between control conditions and edoxaban's or FXa's treatments and between treatments with FXa and the combination of FXa and edoxaban.

Results

Edoxaban (1 Nm – 1 μm) was a safe, non-toxic molecule for HUVECs. It significantly promoted HUVECs' growth at concentrations between 10–500 Nm, been the maximal response at 100 nM. The proliferative effect of edoxaban 100 nM was also observed in the presence of FXa 9 nM, which also induced proliferation by itself. In spite of this proliferative effect, edoxaban (50–100 nM) did not increased healing (cells' migration) after a wound, but counteracted the healing effects of FXa 9 nM. Edoxaban (100–500 nM) alone did not influence angiogenesis, but partially restore the anti-angiogenic effect of FXa on HUVECs. Finally, and very interestingly, edoxaban (50–500 nM) significantly inhibited PBMCs adhesion to endothelial cells' monolayers, and even blocked the FXa (50 nM)- and tumor necrosis factor (TNF; 10μg/ml)-induced adhesion.

PBMCs adhesion to endothelial cells

Conclusions

Edoxaban is a safe and proliferative-inducer drug in endothelial cells in vitro. It counteracts the anti-angiogenic and pro-migratory effects of FXa on HUVECs, but more importantly, edoxaban significantly reduced PBMCs adhesion to endothelial cells monolayers in comparison to control experiments and compared to stimulated cells, independently of the pro-inflammatory drug used.

Acknowledgement/Funding

Daiichi-Sankyo España S.A.U.
P4465Acute Cardio-Selective Functional Modulation via a Small-Molecule Direct Myosin-Attenuator (MYK-581) Preserves Diaphragmatic Function in vivo: Comparison versus Disopyramide
Authors: Del Rio C L , Roof S , Anto A R , Anderson R L
Published: October 2019

Background

Hypertrophic cardiomyopathy (HCM) is a heritable cardiac disease characterized by hyper-contractility, hindered relaxation, and impaired exercise capacity. Conventional negative inotropes can alleviate enhanced inotropy in HCM, but do not improve ventricular filling and have the potential to further decrease exercise capacity due to their off/on-target systemic effects. Recently, a novel small molecule cardiac-myosin attenuator, Mavacamten, has been shown to normalize hyper-contractility in the setting of HCM. This study evaluated and compared the in vivo functional selectivity of MYK-581, a mavacamten analog, with those of disopyramide (DISO), a commonly-used negative inotrope.

Methods

In vivo, the acute cardiac (left ventricular pressures) and neuro-muscular (force of diaphragmatic and skeletal muscle contractions) responses to MYK-581 (up to 0.5 mg/kg IV) and DISO (up to 10 mg/kg IV) were simultaneously evaluated using anesthetized and mechanically-ventilated Sprague-Dawley rats; diaphragmatic (both intrinsic and phrenic nerve stimulated) and skeletal contractions (stimulated quadriceps) were measured via strain gauges.

Results

MYK-581 decreased indices of systolic function (dP/dtmax: −32±2% and vmax: −14±2%, P<0.05 vs. pre-dose) and increased LV EDV (+9±2%, P<0.05), while preserving EDP (6±1 to 6±1 mmHg), suggesting improved ventricular distensibility. Despite these marked cardiac effects, MYK-581 preserved both diaphragmatic (23.7±2.0 to 23.3±2.2 g) and skeletal in situ function (14.9±1.4 to 13.9±0.8 g). In contrast, DISO at matched levels of negative inotropy (dP/dtmax: −25±2% and vmax: −19±2%, P<0.05 vs. pre-dose) depressed diaphragmatic force (−16±3%, 23.8±1.9 to 19.8±1.2 g, P<0.05). Finally, the cardiac selectivity of MYK-581 was confirmed in kinetic experiments evaluating the Ca2+-activated ATPase activity of both cardiac and diaphragmatic myofibrils.

Conclusions

Direct myosin modulation with MYK-581, a mavacamten analog, is characterized in vivo by reductions in systolic function with preserved filling pressures and improved LV compliance. Moreover, this cardiovascular profile was devoid in vivo of diaphragmatic/skeletal off-target effects that could further hinder exercise capacity in patients with HCM.
P4493Microvesicles from patients with pulmonary arterial hypertension modulate bFGF from endothelial cells
Authors: Aberg M , Khandagale A , Wikstrom G , Siegbahn A , Christersson C
Published: October 2019

Background

Pulmonary Arterial Hypertension (PAH) is a progressive condition with remodeling of precapillary arteries. Cytokines involved in angiogenesis have been found elevated in PAH but the role of proangiogenic factors and their regulation is far from fully understood. Microvesicles (MVs) can act as intercellular messengers and modify cell production of proteins.

Purpose

To evaluate whether MVs from patients with PAH modulate proangiogenic factors in plasma and endothelial cells.

Methods

62 patients with PAH and 20 healthy controls were enrolled in the study. The number of MVs were determined in whole blood by flow cytometry. For in vitro studies, MVs were isolated from plasma and a primary endothelial cell line of human pulmonary artery endothelial cells between passages 3 to 7 were used. Protein levels in plasma and conditioned media were analyzed by electrochemiluminescence whereas protein levels in cell lysates were analyzed by western blot (WB).

Results

The majority of the MVs in whole blood were derived from platelets and patients with PAH had higher concentrations compared to healthy controls (p<0.0001). In plasma both basic Fibroblast Growth Factor (bFGF) and vascular endothelial growth factor receptor 1 (Flt-1) were increased in the patients as compared to healthy controls (median in pg/ml (IQR) Pat. vs Ctrl: bFGF 4.2 (2.5–9.2) vs 1.2 (0.9–2.1); Flt-1 143.0 (88.5–234.5) vs 53.9 (47.7–59.67); p<0.001 for both).

Endothelial cells were incubated with or without MVs for 18 hours and effects were monitored by analyzing eNOS and ICAM-1 levels by WB. Both markers were significantly altered, i.e. an about 50% decrease of eNOS and a 50% increase of ICAM-1, by patient MVs but not by the control MVs. The endothelial cells were then incubated with MVs for 6h, 12h, 24h, and 48h and bFGF and Flt-1 were measured in the conditioned media. The presence in media of both proteins were increased over time, but only bFGF was significantly regulated by MVs from PAH patient as compared to MVs from the control group at 24h (2.8 fold increase) and at 48h (12.7 fold increase).

Conclusions

An increase of two important proangiogenic proteins were found in PAH patients. The MVs from these patients modulate the endothelial response and contribute to a release of bFGF, whereas the Flt-1 levels are regulated by other currently unknown mechanisms. Further studies of the MVs from PAH patients are needed to elucidate how they are involved in the angiogenic process.

Acknowledgement/Funding

Swedish Research Council, Science For Life Laboratory Sweden
P4512Impact of pulmonary artery catheter on all-cause death of patients with acute heart failure with preserved ejection fraction: Short-term results from the PURSUIT-HFpEF registry
Authors: Matsusaki N , Sotomi Y , Kobayashi T , Hayashi T , Takeda Y , Yasumura Y , Yamada T , Uematsu M , Tamaki S , Abe H , Hikoso S , Nakatani D , Hirayama A , Higuchi Y , Sakata Y
Published: October 2019

Background

Appropriate pulmonary artery catheter (PAC) use may effectively decrease mortality in acute heart failure patients. The concept that the pulmonary artery catheter (PAC) is a valuable tool for hemodynamic monitoring when used in appropriately selected patients and by physicians trained well to interpret and apply the data correctly provided has not been evaluated adequately yet in acute heart failure patients with preserved ejection fraction (HFpEF).

Methods

The PERSUIT-HFpEF Registry is a prospective, observational, multicenter cohort study on prognosis of HFpEF in Japan. Patients hospitalized for heart failure (diagnosed by using Framingham criteria) who met both of the following criteria were enrolled: 1) a left ventricular ejection fraction of 50% or more as measured at the local site by echocardiography; 2) an elevated level of N terminal pro brain natriuretic peptide (NT proBNP) (400 pg per milliliter or more) or brain natriuretic peptide (BNP) (100 pg per milliliter or more). In the present study, we evaluated the impact of PAC on all-cause death of the patients with HFpEF. PAC use was left at the discretion of attending physicians.

Results

The PERSUIT-HFpEF Registry enrolled 486 patients (81±9 years, 259 females, mean follow-up duration 198±195 days). Of these, data of PAC usage was available in 434 patients. Patients were further stratified according to use of a PAC: PAC 153 patients vs. non-PAC 281 patients. Length of hospitalization was numerically shorter in the PAC group than in the non-PAC group [20.3±14.7 vs. 22.5±17.4 days, p=0.182]. Kaplan-Meier estimated 1-year all-cause death rate was significantly lower in the PAC group than in the non-PAC group (9.5% vs. 19.1%, p=0.019). PAC use was associated with significant risk reduction of all-cause death [hazard ratio (HR) 0.425, 95% confidence interval (CI), 0.203–0.890, p=0.023] in the crude analysis. The significant risk reduction still existed after multivariate adjustment including potential confounders [HR 0.427, 95% CI, 0.185–0.984, p=0.046]

Kaplan Meier analysis

Conclusions

In the real-world Asian registry data, PAC use was associated with the improved all-cause death rate, suggesting that the PAC might be a useful guidance tool for treatment of the patients with HFpEF.

Acknowledgement/Funding

Roche diagnostics FUJIFILM Toyama Chemical
P4516Incremental prognostic values of cognitive impairment diagnosed by mini-mental state examination and mini-cog in older hospitalized patients with heart failure
Authors: Saito H , Yamashita M , Endo Y , Mizukami A , Yoshioka K , Hashimoto T , Koseki S , Shimode Y , Kitai T , Maekawa E , Kamiya K , Matsue Y
Published: October 2019

Introduction

Cognitive impairment (CI) is associated with worse prognosis in patients with heart failure, especially in the elderly; however, its incremental prognostic ability in pre-existing prognostic models has not been well elucidated. Moreover, although some tools have been proposed for evaluating cognitive function, their difference in prognostic prediction has not been explicitly compared.

Methods

A total of 352 heart failure patients aged ≥75 years admitted to three hospitals were evaluated for their cognitive function using the Mini-Mental State Examination (MMSE) and Mini-cog during index hospitalization. We diagnosed CI if MMSE and Mini-cog were ≤23 and ≤2, respectively. The primary endpoint was all-cause death.

Results

The median age of the entire cohort was 85 (IQR: 80–88) years, and 47.7% of the subjects were male. Based on the MMSE and Mini-cog, the CI was diagnosed in 167 (47.4%) and 159 (45.2%) patients, respectively. The two diagnostic tools showed poor to moderate agreement (Cohen's kappa coefficient: 0.37, 95% CI: 0.27–0.47). During the follow-up period of median 346 (IQR: 195–489) days, 53 patients (15.1%) died. Although the Kaplan-Meier analysis showed that CI diagnosed using Mini-cog (CI-MC) was associated with significantly higher mortality (P=0.001), this association was not significant for CI diagnosed using MMSE (CI-MMSE) (P=0.059). On multivariate Cox regression analysis, CI-MMSE and CI-MC were individually associated with worse prognosis in older heart failure patients even after adjustment for Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk model and log B-type natriuretic peptide levels (CI-MMSE, HR: 2.05 [95% CI: 1.16–3.61]; and CI-MC, HR: 2.57 [95% CI: 1.46–4.53]). The receiver operating characteristic curve analysis for Mini-cog showed significantly higher area under the curve (AUC) than that for MMSE (0.61 vs. 0.52, p=0.045). To test the incremental prognostic capability, models were constructed by individually adding each score to the MAGGIC risk model, and the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were evaluated. CI-MMSE did not show incremental prognostic predictability (NRI: 0.28, p=0.069; IDI: 0.01, p=0.090), whereas CI-MC (NRI: 0.45, p=0.001; IDI: 0.03, p=0.001) did. Adding CI-MC instead of CI-MMSE to the MAGGIC risk model showed significant reclassification improvement (NRI: 0.45, p=0.002, IDI: 0.02, p=0.041).

Conclusion

In older patients with heart failure, CI defined by Mini-Cog is superior in providing additive prognostic value than that defined by CI based on MMSE.

Acknowledgement/Funding

This study is partially funded by Japan Heart Foundation Research Grant and Novartis Research Grants.
P4521C-reactive protein as a predictor for diastolic dysfunction in patients with sleep-disordered breathing
Authors: Lebek S , Tafelmeier M , Schach C , Schopka S , Holzamer A , Schmid C , Maier L S , Arzt M , Wagner S
Published: October 2019

Background

Sleep-disordered breathing (SDB) is often associated with left ventricular diastolic dysfunction, but the mechanisms are poorly understood. SDB may increase systemic inflammation that could induce myocardial fibrosis leading to diastolic dysfunction.

Purpose

Systemic inflammation and diastolic dysfunction were analysed in patients with SDB.

Methods

295 patients undergoing coronary artery bypass grafting were included in the prospective observational trial CONSIDER-AF (NCT02877745). They were screened for SDB in the preoperative night and an apnoea-hypopnea index (AHI) of ≥15/h defined SDB. Preoperative echocardiography was used to measure the ratio of early (E) and late (A) diastolic transmitral flows (E/A), early diastolic mitral annular velocity (E'), the ratio E/E', LA volume index, and tricuspid regurgitation velocity. Left ventricular diastolic dysfunction was graded I-IV according to current guidelines. Patients with ventricular ejection fraction of less than 45% were excluded. We used serum C-reactive protein (CRP) as a marker for systemic inflammation, resulting in a full data set for 170 patients.

Results

In patients with SDB, serum CRP levels were 3.036 mg/L higher than in control patients (95% confidence interval: −0.393–6.466, P=0.082). Intriguingly, the severity of SDB (AHI) correlated significantly with the CRP levels (coefficient B: 0.13±0.06, P=0.021). CRP also correlated with the severity of diastolic dysfunction (coefficient B: 0.010±0.004, P=0.009). Importantly, multivariable linear regression analysis accounting for the potential confounders age, sex, body-mass index, existing atrial fibrillation, diabetes, AHI, and creatinine indicated that CRP was an independent predictor for the severity of diastolic dysfunction (coefficient B: 0.009±0.004, P=0.016). Interestingly, the latter effect was still present considering just patients with SDB (coefficient B: 0.013±0.005, P=0.015, N=72), but was completely abolished in patients without SDB (coefficient B: 0.001±0.007, P=0.912, N=98), indicating a potential SDB-dependence.

Conclusion

Systemic inflammation (CRP) is associated with the severity of SDB (AHI). Interestingly, only in SDB patients CRP predicts significantly and independently the severity of diastolic dysfunction. Consequently, anti-inflammatory therapeutic strategies could be beneficial for patients with SDB and diastolic dysfunction.

Acknowledgement/Funding

This study was supported by Philips Respironics and the Medical Faculty of the University of Regensburg.
P4522Intravascular volume expansion mitigates the impact of impaired renal function and associated clinical outcomes in chronic heart failure
Authors: Miller W
Published: October 2019

Background/Introduction

Intravascular volume is regulated by the kidneys but the interconnection of the extent of volume expansion with renal function and outcomes in patients with chronic HF has not been assessed. Therefore, we evaluated how GFR-defined renal function and HF-related clinical outcomes are impacted by the relative extent of intravascular volume expansion. Our hypothesis was that greater rather than lesser volume expansion would be protective of worse renal function and contribute to better clinical outcomes than mild-moderate volume expansion.

Purpose

Assess the impact of quantitated intravascular volume expansion on heart failure (HF) outcomes in relation to renal function in post-hospital clinically determined “euvolemic” chronic HF patients.

Methods

Blood volume (BV) was prospectively measured in 87 HF patients considered clinically “euvolemic” post-diuresis at the time of hospital discharge using a standardized radiolabeled albumin indicator-dilution technique (Daxor Corp., NY, NY). A volume cut-point of ≥+25% above normal expected BV was used to define the greater degree of volume expansion from more mild-moderate expansion. These volume subgroups were then stratified by cohort median eGFR (46 mL/min/1.73m2) and analyzed for 1-year outcomes of HF-related mortality or 1st re-hospitalization using the Kaplan-Meier method.

Results

Volume expansion ≥+25% was demonstrated in 53% of the cohort at the time of hospital discharge despite hospital diuretic therapy. In this subgroup over 1.0 year of follow-up the risk for the composite outcome was significantly lower than in the group with mild-moderate volume expansion (Log-Rank p=0.017). Further, in the clinical setting of greater volume expansion, worse renal function with eGFR below the cohort median (<46 mL/min/1.73m2) was not associated with increased risk for the composite end-point (Figure). In contrast, low eGFR in the presence of mild-moderate volume expansion stratified risk and was associated with worse outcome relative to a higher eGFR above the median (Figure).

Figure 1

Conclusions

In post-hospital chronic HF patients significant intravascular volume expansion is common, and importantly the extent of BV expansion impacts outcomes including HF-related mortality. However, greater rather than lesser volume expansion appears to favorably mitigate the impact of worse renal function (low eGFR), while normal or mild-moderate expansion does not spare the impact of worse renal function on outcomes. Thus, a favorable degree of volume expansion appears to balance the risks of worse renal function. Volume-kidney interconnections are complex with volume status modulating the impact of impaired renal function on outcomes in chronic HF.

Acknowledgement/Funding

None
P4527Cardiac resynchronization therapy in patients with non-ischemic cardiomyopathy and severe heart failure may influence the development of unstable ventricular tachycardia
Authors: Lebedev D I , Mishkina A I , Lebedeva M V , Popov S V
Published: October 2019

Objective

The aim of the study was to determine the effect of cardiac resynchronization therapy (CRT) on the development of unstable ventricular tachycardia in patients with non-ischemic cardiomyopathy (CMP) and to analyze the potential of radionuclide methods in predicting life-threatening arrhythmias in the background of CRT.

Materials and methods

The study included 100 patients with non-ischemic cardiomyopathy aged from 32 to 75 years (55±12 years). Patients had III functional class of heart failure (HF); left ventricular ejection fraction (LV) (EF) 30.1±3.8%; 6 minutes walk at a distance of 290.5±64.3 m; and the final diastolic volume of the left ventricle (EDV) is 220.7±50.9 ml. Before implantation of the device with CRT and after 1 year, all patients underwent a 24-hour ECG monitoring. Patients were divided into two groups depending on the presence or absence of paroxysms of unstable ventricular tachycardia. The 1st group included 55 patients (55%) with registered paroxysms of unstable ventricular tachycardia with adequate doses of antiarrhythmic drugs. Group 2 consisted of 45 patients (45%) without reported episodes. Prior to CRT, myocardial metabolism defect (MMD) was evaluated in all patients using radionuclide methods.

Results

Control tests were performed 1 year after the onset of CRT and showed positive clinical dynamics: the left ventricular EF increased from 30.1±3.8% to 42.8±4.8% (p≤0.001); functional class decreased from III to II; The 6-minute walking distance increased from 290.5±64.3 m to 377.2±45.3 m (p≤0.001); and LV EDV decreased from 220.7±50.9 ml to 197.9±47.8 ml (p≤0.005). During 1 year of observation in the first group: 48 patients (80%) had no episodes of unstable ventricular tachycardia; In 7 patients (20%), episodes of unstable ventricular tachycardia were recorded. Evaluation of the effect of increasing EF and reducing EDV on the development of VT paroxysms was performed after the distribution of patients with CRT into subgroups based on the presence or absence of VT episodes. The data showed that in patients whose EF increased by 14%, and EDV decreased by 35 ml during 1 year of CRT, there were no VT episodes, even if VT paroxysms were recorded before CRT. Patients who had VT paroxysms showed an increase in EF of only 9% and a decrease in EDV of only 13 ml. Phase 2 of the study was to assess the impact of MMD changes. In the presence of CRT in patients with less than 15% MMD, there were no VT episodes. VT paroxysms were reported in patients whose MMD exceeded 15%.

Conclusions

(1) Effective CRT in patents with non-ischemic cardiomyopathy significantly reduces the number of VT episodes. (2) Improving fatty acid metabolism (LVD MMD less than 15%) in patients with non-ischemic cardiomyopathy reduces the incidence of VT episodes against the background of CRT.
P4539Android to gynoid fat ratio and its association with functional capacity in male patients with heart failure
Authors: Dos Santos M R , Fonseca G W P , Sherveninas L , Souza F R , Battaglia Filho A C , Pereira R M R , Negrao C E , Alves M J N N , Barretto A C P
Published: October 2019

Background

Obesity may have a protective role in patients with heart failure with reduced ejection fraction (HFrEF), a phenomenon known as obesity paradox. However, some patients can also present sarcopenic obesity with similar exercise intolerance as lean patients with muscle wasting. However, the impact of body fat distribution on exercise intolerance in HFrEF is unknown.

Purpose

To study the association between android to gynoid fat ratio and functional capacity (VO2 peak) in male patients with HFrEF.

Methods

We enrolled 118 male with HFrEF with left ventricular ejection fraction (LVEF) <40%, mean age of 56±7 years old. Body composition was measured with dual x-ray absorptiometry. Android and gynoid fat were measured and the ratio between them was calculated (A/G ratio). Appendicular lean mass (ALM) was calculated as the lean muscle mass of both arms and legs divided by the height squared. Sarcopenic obesity was defined according to Foundation for the National Institutes of Health criteria (ALM adjusted for body mass index <0.789 for men). Muscle strength was assessed using the handgrip dynamometer (cutoff point for sarcopenia was defined as proposed by European Working Group on Sarcopenia in Older People). Blood sample was used to measure metabolic and hormonal parameters.

Results

Of those 118 patients, 15 (12.7%) showed sarcopenic obesity. In our cohort, the median A/G ratio was 0.55. A/G ratio >0.55 was detected in 60 patients. Weight and BMI were higher in patients with A/G ratio >0.55 (P<0.001). Absolute peak VO2 was similar between patients with A/G ratio lower or higher than 0.55 (1.48±0.40 vs. 1.43±0.40 L/min, P=0.559), while relative peak VO2 was lower in patients with A/G ratio >0.55 (18.7±5.3 vs. 22.5±6.1 mL/kg/min, P<0.001). LVEF, total cholesterol, LDL, haemoglobin, and IGF-1 were similar between patients with A/G ratio lower or higher than 0.55 (P>0.05). On the other hand, HDL, total testosterone, free testosterone, and DHEA were lower in patients with A/G ratio >0.55 (P<0.05). Logistic regression analysis showed A/G Ratio >0.55 to be independently associated with reduced peak VO2 (L/min) adjusted for age, BMI, LVEF, presence of sarcopenia, anabolic hormones, and haemoglobin (odds ratio 3.895, 95% CI 1.030–14.730, p=0.045).

Conclusion

Our data suggest that body fat distribution, particularly android and gynoid fat composition, might have an important adverse role on functional capacity in male patients with HFrEF.

Acknowledgement/Funding

FAPESP #2016/24306-0 and 2016/24833-0
P4547Serum biochemical determinants of peripheral congestion assessed by bioimpedance vector analysis in acute heart failure
Authors: Scicchitano P , Massari F , Iacoviello M , Valle R , Sanasi M , Piscopo A , Sasanelli P , De Palo M , Guida P , Mastropasqua F , Caldarola P , Ciccone M M
Published: October 2019

Background

The pathophysiology of peripheral congestion is poorly investigated in patients with acute heart failure (AHF).

Purpose

This study evaluated the relative contribution of serum colloid osmotic pressure (COP), relative plasma volume status (PVS), biomarkers of renal function, electrolytes, haemoglobin, and brain natriuretic peptide (BNP) in peripheral fluid overload using bioimpedance vector analysis (BIVA).

Methods

We retrospectively analysed data from 485 patients with AHF. Hydration status was evaluated by semiquantitative and quantitative approach using BIVA (R/Xc graph) and Hydration Index (HI), respectively. COP was calculated from albumin and total protein concentration, while relative PVS was calculated from validated equations.

Results

Congestion assessed by BIVA was observed in 304 (63%) patients and classified as mild (30%), moderate (42%), and severe (28%). On univariate analysis, HI was inversely correlated with COP (P<0.01), glomerular filtration rate (P<0.01), and haemoglobin (P<0.01), while positive correlations were found for relative PVS (P<0.05), BNP (P<0.01), and blood urea nitrogen (BUN; P<0.01). On stepwise multivariate analysis, COP explained 12% of the total variability, while BUN, PVS, haemoglobin, and BNP added a further 6%, 4%, 2%, and 1%, respectively, to the final explanatory model.

Conclusions

COP was the major determinant of the presence and entity of peripheral congestion assessed by BIVA. BUN, PVS, haemoglobin, and BNP revealed reduced influence on congestion as compared with COP. Routine laboratory testing could be useful in peripheral fluid accumulation. Future studies should evaluate the relationship between COP and pharmacological target therapies for the fluid management of AHF patients.

Acknowledgement/Funding

None
P4548Early drop in systolic blood pressure and worsening renal function in the elderly acute heart failure: how does heart rate interact?
Authors: Takeuchi M , Nagai M , Dote K , Kato M , Oda N , Kunita E , Kagawa E , Yamane A , Higashihara T , Kobayashi Y , Shiota H
Published: October 2019

Background

Renal dysfunction is a frequent finding in patients hospitalized for acute heart failure (AHF). Worsening renal function (WRF) during hospitalization was found to be related with a poor outcome independently of baseline renal function. Early drop in systolic blood pressure (SBP) has shown to predict WRF in AHF. However, there have been few studies that reported the impact of on-admission heart rate (HR) on the relationship between early SBP drop and WRF in the elderly AHF.

Purpose

We assessed the hypothesis that early SBP drop predict WRF in the elderly patients with AHF, and investigated that on-admission HR might have an interaction with that relationship.

Methods

SBP and HR were measured on admission and 6 times during 48 hours in the 245 elderly AHF inpatients (82.9±6.0 years old, male 49.4%). WRF was defined as a serum creatinine increase of ≥0.3 mg/dL by Day 5. Early drop in SBP was calculated as the difference between admission and the lowest value measured during the first 48 hour of hospitalization.

Results

Early SBP drop (51.3 vs 32.5mmHg, p<0.01) and on-admission HR (79.3 vs 89.6bpm, p<0.05) were significantly different between the group with WRF (n=36) and the group without WRF (n=209). In the multiple logistic regression analysis adjusted for the confounders including age, gender, hypertension, left ventricular ejection fraction, total cholesterol, BNP, baseline creatinine, beta-blockade use, intravenous loop diuretic, isosorbide dinitrate and carperitide use, early SBP drop (OR: 1.003, 95% CI: 1.003–1.03, p<0.04) and on-admission HR (OR: 0.98, 95% CI: 0.96–0.99, p<0.01) were significantly associated with WRF. The interaction term of early SBP drop by on-admission HR did not have a significant association with WRF (p=0.3).

Conclusions

In the elderly AHF patients, exaggerated early SBP drop and lower on-admission HR were shown as significant independent predictors of WRF. These two factors were additively associated with WRF. Too much reduction in SBP and that in HR might be harmful to renal circulation in AHF.
P4556Thrombin generation and platelet function in patients on RAAS inhibitors
Authors: Helten C , Dannenberg L , Mourikis P , Naguib D , Poehl M , M'pembele R , Ayhan A , Zako S , Knoop B , Hohlfeld T , Kelm M , Zeus T , Polzin A
Published: October 2019

Background

ACE inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are beneficial for patients with cardiovascular disease. However, little is known about whether one of these drugs is superior. First analyses show that the inhibition of the renin-angiotensin-aldosterone system (RAAS) affects platelet reactivity. Therefore we evaluated the effects of ACEI and ARB on platelet reactivity and thrombin generation.

Methods

In a time series analysis, samples of 24 patients before, 4h and 24h after initial intake of ACEI were analysed. Also we included 10 patients with permanent ACEI treatment and 4h, 24h and 3 months after switching to ARB. Platelet reactivity was measured via light transmission aggregometry (LTA). Thrombin generation was measured as endogenous thrombin potential (ETP) by calibrated automated thrombogram. Protease-activated receptor (PAR) expression was analysed by flow cytometry. Thrombin-antithrombin (TAT) complexes were measured with an enzyme-linked immunosorbent assay.

Results

TRAP-6 induced platelet reactivity increased during ACEI treatment (prior vs. 4h post ACEI: 41.9±16.2% vs. 55.2±16.7%; p=0.003, prior vs. 24h post ACEI: 52.3±12.7%; p=0.003). Switching from chronic ACEI to ARB treatment decreased platelet reactivity (permanent ACEI vs. 3 months after switching: 50.3±20.9% vs. 34.7±20.9%; p=0.033). ACEI reduced ETP from prior to 3 months post ACEI (1527±437 nM*min vs. 1088±631 nM*min; p=0.025). ARB did not affect ETP (1526±587 nM*min vs. 1369±516 nM*min; p=0.3). PAR1 levels rose from 37.38±10.97% before to 49.53±6.04% after ACEI treatment (p=0.036). ARB did not have an effect on PAR1 (33.16±11.73 vs. 32.86±8.99; p=0.89). ACEI slightly decreased plasma thrombin concentration. ARB treatment showed a minor but again not significant decrease in TAT complexes as well. (TAT complexes prior vs. 3 months post ACEI: 8.4±11.9 μg/l vs. 6.3±6.8 μg/l; p=0.99, permanent ACEI vs. 3 months after switching to ARB: 4.3±1.9 μg/l vs. 3.0±1.0 μg/l; p=0.3).

Conclusion

ACEI increased platelet reactivity. This can be reversed by switching to ARB. The mechanism behind RAAS influencing platelet function needs to be further investigated in larger trials.

Acknowledgement/Funding

Medical Faculty of the Heinrich-Heine-University Düsseldorf
P4569Differential prognostic impact of blood glucose levels at the acute stage of myocardial infarction according to HbA1c. The FAST-MI programme
Authors: Danchin N , Puymirat E , Ducrocq G , Henry P , Collet J P , Genee O , Joseph T , Belle L , Naccache N , Ferrieres J , Schiele F , Simon T
Published: October 2019

Background

Hyperglycemia is a well-known prognostic marker in patients with acute myocardial infarction (AMI), associated with higher mortality compared with normoglycemia. Whether the prognostic impact of glycemic status at the acute stage of AMI is similar in patients with chronic dysglycemia has not been extensively explored.

Aims and methods

Using data from the nationwide French FAST-MI cohorts (2005, 2010 and 2015), we analysed the association between glycemia at entry and 30-day death, according to HbA1c level. From the 13,130 patients included, 5,452 had both glycemia and HbA1c assessed at entry. Of those, 1173 (21.5%) had an HbA1c ≥7%.

Results

In patients with HbA1c <7%, LVEF was inversely correlated with glycemic levels (55±11% for glycemia <100, 52±11% for glycemia 100–140, 50±12% for glycemia 140–160 and 49±12% for glycemia >180 mg/dl); a graded association between admission glycemia and 30-day mortality was observed, ranging from 0.7% in normoglycemic patients to 6.3% in patients with admission glycemia >180 mg/dl. In contrast, in patients with HbA1c ≥7%, LVEF was not correlated with glycemia (<100 mg/dl: 49±14%, >180 mg/dl 49±12%), and mortality was the highest in patients with normoglycemia (9.2%) and the lowest in patients with glycemia between 140 and 180 mg/dl (3.1%) (Figure). In multivariate analyses adjusting for baseline characteristics and early management, normoglycemia was associated with a decreased risk of 30-day mortality in patients with HbA1c <7% (HR 0.27, 95% confidence interval 0.10–0.73, P=0.01), while it was associated with a two-fold increase in mortality in patients with HbA1c ≥7% (HR 2.49, 95% confidence interval 1.02–6.09, P=0.046).

Figure 1. 30-day death

Conclusion

In AMI patients with high HbA1c levels on admission, normoglycemia is associated with higher early mortality than hyperglycemia. In contrast, a graded correlation is observed between admission glycemia and early mortality in patients with HbA1c <7%. Management of glycemia at the acute stage of MI might require different measures according to the initial HbA1c level.

Acknowledgement/Funding

Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Eli-Lilly, GSK, MSD, Novartis, Pfizer, Sanofi, Servier
P4579Prediction of CABG indication in patients admitted for NSTEMI with the new CABG DAPE2S score
Authors: Faria Da Mota T , Azevedo P , Fernandes R , S J , Guedes J , Bento D , Marques N , Santos W , Mimoso J , Jesus I
Published: October 2019

Introduction

A significant number of patients admitted for Non-ST Elevation Myocardial Infarction (NSTEMI) have multivessel complex coronary artery disease (CAD) and benefit from Coronary Artery Bypass Graft surgery (CABG). These patients frequently present high-risk surgical profiles, constituting a challenging group when it comes to balancing ischemic and haemorrhagic risk.

Objective

To develop a simple predictive risk model of referral to CABG in patients admitted for NSTEMI.

Methods

The authors present a retrospective, descriptive and correlational study including all patients admitted for NSTEMI in a Cardiology department between the 1st of October 2010 and the 1st of October 2018. Demographic profile, clinical characteristics, risk factors and hospitalization data of NSTEMI patients referred to CABG were studied, and a correlational analysis was performed with Chi-square test for categorical variables and t-Student test for continuous variables (confidence level of 95%). Independent predictors of CABG in patients with NSTEMI were identified through Binary logistic regression analysis, using a significance level of 0,05. A discriminatory function was subsequently applied, and the Wilks lambda test was used to determine the discriminant score for the studied groups. The authors used SPSS 24,0 for statistical analysis.

Results

A total of 2476 patients were included, 668 (27%) of which were female, with a mean age of 68,5±13,4 years. In the studied sample, 273 patients (11%) were proposed to CABG. The authors found a significant association between CABG and multiple clinical, laboratorial and therapeutical variables, but after multivariate analysis only male sex, previous Diabetes Mellitus, previous angina, previous Percutaneous coronary intervention, absence of a normal EKG, ST segment depression at admission, sinus rythm and brain natriuretic peptide (BNP) >100pg/mL proved to be independent predictors of referral. Using these variables, the authors developed a risk model to predict CABG referral in NSTEMI patients: −0,614 − (0,756 x female sex) + (0,305 x diabetes) + (0,631 x angina) − (1,513 x previous PCI) + (1,216 x sinus rythm) + (0,672 x ST depression) − (0,806 x normal EKG) + (0,562 x BNP>100). In this function, variables should be substituted by 1 or 0, depending on wheter the condition they specify is present or absent. The optimal discrimination cutoff was 0,23, with a 64% sensibility and 59% specificity, and a discriminant power of 60%.

Conclusion

Being able to predict referral to surgical revascularization in NSTEMI may help physicians to optimize a specific approach in each patient, in particular with regard to anti-thrombotic strategies. The authors developed a risk predicting model for CABG in NSTEMI patients based on simple clinical and laboratory variables, which will require validation in a larger cohort, before it can be applied in a clinical context.
P4591Impact of extent of non-culprit lesions on one-year outcomes in patients with acute myocardial infarction
Authors: Tanaka T , Akahori H , Imanaka T , Miki K , Yoshihara N , Yanaka K , Ishihara M
Published: October 2019

Background

Presence of severe stenosis in non-infarct related arteries, i.e. multi-vessel disease (MVD), is associated with poor outcomes after acute myocardial infarction (AMI). However, impact of mild to moderate stenosis in non-culprit lesions remains unclear.Gensini score is an angiographic application grading the extent of coronary artery lesions including mild to moderate stenosis.

Purpose

To evaluate whether the extent of non-culprit lesion is related to one-year outcomes after AMI.

Methods

This study consisted of consecutive 168 patients who underwent primary percutaneous coronary intervention (PPCI) for AMI between 2015 and 2017. Patients with coronary bypass grafts were excluded from the analysis. To assess the extent of non-culprit lesions, we used “non-culprit Gensini score”, which is calculated by excluding score of the culprit lesion from the original Gensini score. Patients were divided into 2 groups by the median ofnon-culprit Gensini score: low score (0–14, n=84) and high score (>15, n=84). Major adverse cardiac events (MACE) included all cause of deaths, non-fatal MI, stroke and ischemia driven coronary revascularization during one-year follow-up period.

Results

MVDwas more frequent in patients with high score than those in those with low score (90% vs 25%, P<0.05). Kaplan-Mayer curves of patients with and without MVD are shown in left figure, and curves of patients with low score and those with high score are shown in right figure. Multivariable analysis showed that high score was an independent predictor of one-year MACE (HR 5.28, 95% CI 1.93–14.9, P<0.05), but MVD was not (HR 0.56, 95% CI 0.23–1.54, P=0.25) (Table).

Multivariable analyses Univariable analyses Multivariable analyses HR (95% CI) P-value HR (95% CI) P-value Age 1.03 (1.01, 1.06) <0.05 1.15 (0.99, 1.05) 0.31 eGFR (<45ml/min/1.73m2) 2.95 (1.59, 5.38) <0.05 2.35 (1.26, 4.35) <0.05 Multi-vessel disease 1.84 (1.01, 3.55) <0.05 0.56 (0.23, 1.54) 0.25 Non-culprit-Gensini score (>15) 3.37 (1.79, 6.78) <0.05 5.28 (1.93, 14.9) <0.05 HR = hazard ratio; CI = confidence interval; eGFR = estimated glomerular filtration rate.

Kaplan-Meier curves

Conclusion

These findings suggested that extent of mild to moderate stenosis in non-culprit lesions might affect the prognosis after AMI in patients undergoing PPCI. Non-culprit Gensini score may be useful to predict outcomes of patients with AMI.

Acknowledgement/Funding

None