bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5427Mid-term comparison of clinical outcomes between continuous-flow left ventricular assist devices
Authors: Itzhaki Ben Zadok O , Ben-Avraham B , Shaul A , Hammer Y , Rubachevski V , Baruch I , Aravot D , Kornowski R , Ben Gal T 
Published: October 2019

Abstract

Background
Continuous-flow left ventricular assist devices (cf-LVADs) are increasingly applied in patients with advanced heart failure (HF). Comparative data regarding cf-LVADs are lacking. We aim to determine the outcomes of patients supported with HeartMate 2 (HM2), HeartWare (HW) and HeartMate 3 (HM3).

Methods
A retrospective analysis of patients who underwent cf-LVAD implantation at our institution between 2008–2017. Follow-up duration was 18 months post implantation.

Results
Included were 105 cf-LVAD-supported patients of whom 51% (n=54), 24% (25) and 25% (26) underwent implantation of HM2, HW and HM3, respectively. Patients supported with HM3 versus HM2 had lower risk of thrombosis (0% vs. 37%, p=0<0.001), while patients supported with HM3 versus HW had lower risk of non-GI bleeding (15% vs. 46%, HR 0.28, CI 0.095, 0.85, p=0.024) and reduced unplanned hospitalizations (median 1 (interquartile range 0, 3) vs. 3 (interquartile range 2, 11), p=0.001). Patients supported with HM3 had a reduced risk of stroke compared with either HM2 or HW (0% vs. 26%, p=0.033 and 0% vs. 42%, p=0.005, respectively). Importantly, survival free from stroke or device exchange was higher in patients with HM3 compared to patients supported with either HM2 or HW (100% vs. 72%, p=0.029 and 100% vs. 56%, p=0.003, respectively) (Figure).
Mid-term event-free survival by VAD type

Conclusions
HM3 device presents the best currently available prognostic and adverse events profile when compared to HM2 and HW. We believe that HM3 should be offered as the device of choice for mechanically-supported advanced HF patients
P5438Cardiac abnormalities after induction of endoplasmic reticulum stress are associated with mitochondrial dysfunction and connexin43 expression
Authors: Liu T , He J , Gong M , Luo C , Zhao Y , Li G , Tse G 
Published: October 2019

Abstract

Background
The endoplasmic reticulum (ER) is responsible for protein synthesis and calcium storage. ER stress, reflected by protein unfolding and calcium handling abnormalities, has been studied as a pathogenetic factor in cardiovascular diseases.

Purpose
The aim of this study is to examine the effects of ER stress on mechanical and electrophysiological functions in the heart and explore the underlying molecular mechanisms.

Methods
A total of 30 rats were randomly divided into control, ER stress induction (tunicamycin) and ER stress inhibition (4-phenylbutyric acid, 4-PBA) groups.

Results
ER stress induction led to significantly systolic and diastolic dysfunction as reflected by maximal increasing/decreasing rate of left intraventricular pressure (±dp/dt), LV peak systolic pressure, LV development pressure and LV end-diastolic pressure. Epicardial electrical mapping performed in vivo revealed reduced conduction velocity, increased conduction heterogeneity and spontaneous ventricular tachycardia. Masson's trichrome staining revealed marked fibrosis in the myocardial interstitium and sub-pericardium and thickened epicardium. Western blot analysis revealed increased pro-fibrotic factor TGF-β1, decreased mitochondrial biogenesis protein PGC-1a, decreased mitochondrial fusion protein MFN2. These changes were associated with decreased mitochondrial membrane potential (MMP) and connexin 43 translocation to mitochondria. These abnormalities can be partially prevented by the ER stress inhibitor 4-PBA.

Conclusions
Our study shows that ER stress induction can produce cardiac electrical and mechanism dysfunction as well as structural remodeling. Mitochondrial function alterations are contributed by CX43 transposition to mitochondria. These abnormalities can be partially prevented by the ER stress inhibitor 4-PBA.

Acknowledgement/Funding
National Natural Science Foundation of China (No. 81570298 to T.L.)
P5439Protective effect of angiotensin-neprilysin inhibition compared to angiotensin inhibition on ventricular arrhythmias in spontaneous hypertensive rats
Authors: Lin T T L , Sung Y L S , Syu J Y S , Hsu H J H , Lin K Y L , Lin S F L 
Published: October 2019

Abstract

Background
Angiotensin-neprilysin inhibition compared to angiotensin inhibition decreased sudden cardiac death in patients with reduced ejection fraction heart failure. The protective effect from ventricular arrhythmia in diastolic heart failure (DHF) remains unknown.

Methods
The spontaneous hypertensive rat (SHR) has been well established as a suitable model for studies of DHF. A total of 18 10-week-old male SHR were divided into three groups: sacubitril/valsartan, valsartan and saline (0.9%) (n=6 in each group). Eighteen 10-week-old male Wistar-Kyoto rats (WKY) were served as the control group. After two weeks feeding with sacubitril/valsartan, valsartan and saline in SHR and WKY. Optical mapping was performed to measure the electrical dynamic of cardiac ventricle and the maximal slope of action potential duration restitution was calculated. An S1–S2 pacing protocol was applied at the right ventricle to determine inducibility of ventricular tachycardia and fibrillation (VT/VF).

Results
SHR revealed increased LV mass than those treated with sacubitril/valsartan, and valsartan. Compared with WKY, SHR had significantly higher max slope (1.32±0.12 vs. 0.28±0.08, p<0.001). SHR was less prone to arrhythmogenicity after treated with valsartan than saline (0.29±0.04 vs. 1.32±0.12, p<0.001). Furthermore, the max slope was even lower in SHR treated with sacubitril/valsartan than those with valsartan (0.10±0.03 vs. 0.29±0.04, p=0.005). The incidence of induced sustained VT/VF (duration >2 second) was significant higher in SHR compared with WKY (18±11.1% vs. 0%, p<0.001) and also higher in SHR treated with valsartan compared with those with sacubitril/valsartan (7±6.5% vs. 5±2.9%, p=0.036).

Conclusions
Angiotensin-neprilysin inhibition could provide better protection from ventricular arrhythmia than valsartan in SHR, warranting the further investigation of angiotensin-neprilysin inhibition in DHF patients.
P5440Systolic/diastolic effects of chronic treatment with omecamtiv mecarbil in minipigs with post-myocardial infarction Heart Failure with reduced Ejection Fraction (HFrEF)
Authors: Caillaud D , Baudot X , Gouraud L , Lucats L , Pruniaux M P , Janiak P 
Published: October 2019

Abstract

Background
Omecamtiv mecarbil (OM), a novel myosin ATPase activator, is currently developed for the treatment of Heart Failure with reduced Ejection Fraction (HFrEF). Phase I in healthy volunteers and patients showed that the positive inotropic effect of OM was associated with an impairment of diastolic function as assessed by change in E peak, e' wave and E/e' ratio.

Purpose
The diastolic impact of chronic treatment with OM has not been described yet. This study investigates the balance between positive inotropic effect and the diastolic impairment after chronic treatment with OM in a post-myocardial infarction (Post-MI) swine model of HFrEF.

Methods
HFrEF was induced in minipigs after myocardial infarction caused by a 150-min left anterior descending (LAD) artery occlusion performed under angiography. HFrEF minipigs were treated with OM at 3 mg/kg PO BID for 15 days (n=4), a dose known to increase systolic ejection time (SET) by ∼50 ms as achieved in healthy volunteers and patients at plasma levels between 200–300 ng/ml. Echocardiogram was performed before and after 15 days of treatment with OM. An additional echocardiogram was conducted 7 days after the last administration.

Results
One year after MI, minipigs displayed increased left ventricular end-diastolic volume index (LVEDVi 151±3.7ml/m2 vs 100±8.9ml/m2 before infarction) and decreased LVEF (42±2.5% vs 68±4.4% before infarction) associated with a pseudo-normal mitral pattern. A two-week treatment with OM increased SET by 64ms (p<0.0001 vs before treatment) and EF to 49±3.8% (p=0.07 vs before treatment) as well as it improved SVi by 13%. This inotropic effect was associated with a decrease of mitral E peak (p=0.01 vs before treatment) and e' waves, and with the prolongation of deceleration time (p<0.05 vs before treatment). OM treatment was associated with marked reduction of LVEDVi to 117±13.2ml/m2 (p<0.05 vs before treatment) concomitant with a ∼20% increase in diastolic septum and posterior wall thicknesses. None of these systolic or diastolic effects remained 7 days post OM treatment completion.

Conclusion
Similarly to clinical description, OM treatment increased LVEF and SVi principally through extension of SET. It provides positive inotropic effects associated with diastolic impairment resulting in impaired ventricular filling as assessed by LVEDVi decrease and the thickening of ventricular wall in diastole. Whether this profile will allow a beneficial reverse remodeling, needs to be investigated in a longer chronic study.

Acknowledgement/Funding
Sanofi sponsored study
P5441Ventricular dysfunction and fibrosis precedes atrial conduction defects in JDP2 overexpression mice
Authors: Parahuleva M , Bornbaum J , Heger J , Kockskaemper J , Schieffer B , Schulz R , Euler G 
Published: October 2019

Abstract

Introduction
JDP2 (Jun Dimerization Protein 2) was recently characterized as potential prognostic marker for progression of heart failure after myocardial infarction. Furthermore, persistent cardiac-specific JDP2 overexpression provokes ventricular dysfunction, atrial dilatation and atrial fibrillation.

Purpose
In this study we investigated, if ventricular dysfunction is predisposed to atrial fibrillation. Therefore, we analyzed ventricular function in mice with 1 and 5 weeks of JDP2 overexpression and compared gene expression in ventricular and atrial tissues at these time points.

Methods
JDP2 expression was under control of a Tet-off system. Therefore, JDP2 overexpression was started by withdrawal of doxycycline diet in 4-week-old mice. After 1 or 5 weeks, cardiac function was determined by echocardiography and ECG. mRNA expression was analyzed by real-time RT-PCR and protein expression in western blots.

Results
After 1 or 5 weeks, JDP2 mRNA levels were increased in ventricular and atrial tissues of JDP2 mice. Already after 1 week ventricular dysfunction emerged in JDP2 mice: Ejection fraction decreased from 64.6±10.4% in WT to 58.8±9.3% in JDP2 mice, fractional shortening from 38.3±7.9% in WT to 27.4±4.8% in JDP -mice, and cardiac output from 23.0±4.7 ml/min in WT to 19.4±3.3 ml/min in JDP2 mice (n=11–16, p<0.05). In ventricular tissues, elastin mRNA expression increased, and the calcium handling protein SERCA decreased within one week of JDP2 overexpression (n=6, p<0.05 vs. WT). After 5 weeks of JDP2 overexpression ventricular dysfunction became even stronger with a cardiac output of 13.6±2.5 ml/min (n=11, p<0.05 vs. WT). Still reduction in SERCA protein was observed, and increased mRNA levels of fibrotic marker genes were detected, as well as contractile function of isolated cardiomyocytes of JDP2 mice continued to decline. In atrial tissue, besides the 3.6 times increase of JDP2 mRNA, no changes could be detected within one week. In addition, ECG recordings over 30 minutes on awake mice did not show any abnormalities after one week of JDP2-overexpression. Atrial dilatation became evident only after 5 weeks of JDP2 overexpression. ECG-recordings revealed prolonged PR-intervals (34.6±3.9 ms in JDP2-mice vs. 30.2±7.0 ms in WT) and broadened QRS-complexes (15.8±2.8 ms in JDP2 mice vs. 13.9±1.7 ms in WT, n=10–12, p<0.05). At the same time point, mRNA of the calcium-handling proteins PLB, NCX and SERCA, and of the fibrotic marker genes collagen I, fibronectin and elastin were dramatically reduced in atrial tissue of JDP2 compared to WT mice (n=6, p<0.05), and may be functionally involved in atrial conduction defects.

Conclusion
Enhanced expression of JDP2 provokes ventricular dysfunction and fibrosis within one week, whereas changes in the atrial tissue and conduction defects occur later and seem to be a secondary effect that is provoked by the pre-existing ventricular dysfunction.
P5453Cardiorenal biomarker N-acteyl-beta-D-glucosaminidase (NAG) potentially predicts mortality in chronic heart failure - A 10 year follow up
Authors: Schober A D , Strack C , Bauer S , Hubauer U , Schober A L , Uecer E , Maier L S , Luchner A , Jungbauer C G 
Published: October 2019

Abstract

Background
The strong relation between chronic heart failure (CHF) and chronic kidney disease (CKD) is well known as cardiorenal syndrome (CRS). The current study focused on the impact of novel markers of kidney injury next to the established cardiac marker NT-proBNP as predictors for mortality in patients with CHF in a long term follow up.

Methods
We conducted a prospective longitudinal study. The novel renal biomarkers kidney injury molecule-1 (KIM-1), N-acteyl-β-D-glucosaminidase (NAG) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) were assessed from urine samples. Additionally, blood levels of NT-proBNP were determined. The primary endpoint all-cause mortality was evaluated after a median follow-up of 104 months (interquartile range 42–117 months).

Results
149 adolescents (mean age 62±12 years) with CHF (mean ejection fraction 32±9%) were enrolled. 79 (53%) patients died. The secondary endpoint was reached by 104 patients (70%).
The renal marker NAG (HR 1.02, p=0.002) was a significant and independent predictor for all-cause mortality next to the established cardiac biomarker NTproBNP (HR 1.0, p<0,001) using Cox regression analysis, opposite to KIM-1 as well as NGAL (each p=n.s.). Similar results were obtained for the combined endpoint of all-cause mortality and hospitalization for heart failure.
In a multivariate analysis model with biomarkers and clinical parameters NAG (HR 1.02, p=0.036) remained a significant predictor for all-cause mortality next to NT-proBNP (HR 1.0, p=0.027, older age (HR 1.04, p=0.004), the lack of diabetes mellitus (HR 0.39, p<0.001), reduced EF (HR 0.97, p=0.034) and creatinine (HR 1.45, p=0.026). Again similar results were obtained for the secondary endpoint.
Patients were stratified into groups with markers above and below Youden Index to calculate Kaplan-Meier analysis. A combined analysis of NT-proBNP (< and ≥1906 pg/mL) and NAG (< and ≥10 U/gUCr) revealed an increase of the predictive value of each marker: patients with all three markers above Youden index had the highest mortality rate (79%) compared to patients with one (43%) or none (26%) marker above Youden Index.
All-cause Mortality

Conclusion
The current 10-years long-term follow-up suggests that the tubular biomarker NAG as cardiorenal biomarker in combination with NT-proBNP may allow to discriminate a high-risk collective of chronic heart failure patients. These findings emphasize the close relationship of kidney injury and renal function in patients with CHF.
P5460Prevalence of left atrial enlargement in patients undergoing an echocardiogram for cardiovascular risk stratification at an esh excellence centre in italy
Authors: Muiesan M L , Salvetti M , Paini A , Aggiusti C , Bertacchini F , Stassaldi D , Capellini S , Casella E , Arnoldi C , Agabiti Rosei E 
Published: October 2019

Abstract

Background
Left atrial (LA) enlargement (LAE) is associated to an increased risk of cardiovascular complications, and in particular of atrial fibrillation. The 2018 ESH/ESC Hypertension guidelines suggested the use of LA volume instead of linear dimensions, and for the first time proposed the indexation to height2 (h2)
The aim of our study was to assess the prevalence of left atrial dilatation in a large sample of patients undergoing an echocardiogram for cardiovascular risk stratification at an ESH excellence centre in Italy.
Design and methods 3872 subjects undergoing a diagnostic work-up for arterial hypertension (known or suspect) were analysed. The mean age was 56±15 years, BMI 26±5 kg/m, 44% normal weight, 39% overweight, 17% obese, 53% males. Left atrial volume was measured by the area-length method using the apical 4-chamber and 2-chamber views.

Results
The prevalence of left ventricular hypertrophy (LVH) was 11% when indexing for BSA and 12% when indexing for height2.7. LAE was observed in 30% of subjects when indexing for h2 and in 9% when indexing for BSA. In obese or overweight subjects the prevalence of LAE was 38% of subjects when indexing for h2 and in 11% when indexing for BSA. The different prevalence of LAE was particularly evident in extremely obese patients.
LAE was very common in patients with LVH: 62% and 26% when indexing for h2 and for BSA, respectively. Interestingly, it was frequent also in patients without LVH, in particular when the indexation for h2 was used (25% as compared to 7% when indexing for BSA).

Conclusions
In a large sample of subjects undergoing a diagnostic work-up for arterial hypertension LAE was frequently observed, particularly when the new indexation proposed by the 2018 ESH/ESC hypertension guidelines was used. Even in the absence of clear-cut LVH, LAE was observed in one quarter of subjects. The indexation to BSA leads to an under-recognition of LAE, in particular in patients with overweight and/or obesity
P5466Exaggerated exercise blood pressure response is accompanied by increased sympathetic activity and arterial stiffness in subjects with high normal blood pressure
Authors: Kalos T , Tsioufis C , Dimitriadis K , Vogiatzakis N , Kasiakogias A , Iliakis P , Konstantinidis D , Xanthopoulou M , Kakouri N , Laina A , Andrikou E , Tousoulis D 
Published: October 2019

Abstract

Background/Introduction
The clinical importance of a hypertensive response to exercise (HRE) in subjects with high normal blood pressure (BP) is not fully elucidated, while sympathetic overactivity and arterial stiffening are linked with adverse cardiovascular prognosis.

Purpose
The aim of this study was to assess the relation of HRE with sympathetic drive as assessed by muscle sympathetic nerve activity (MSNA) and arterial stiffness in subjects with high normal BP.

Methods
42 subjects with high normal office BP [defined as office systolic BP=130–139 mmHg and office diastolic BP=85–89 mmHg (age: 53±9 years, 29 males, office BP: 134/84 mmHg, 24-hour BP: 114/72 mmHg)] with a negative treadmill exercise test (Bruce protocol) were divided into those with HRE (n=12) (peak exercise systolic BP ≥210mmHg in men and ≥190 mmHg in women) and those without HRE (n=30). Arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV) values. In all participants sympathetic drive was assessed by MSNA estimations based on established methodology (microneurography).

Results
Subjects with a HRE compared to those without exhibited higher waist circumference (108.2±5.3 vs 94.7±9.2 cm, p=0.001) and were characterized by greater levels of carotid to femoral PWV (8.5±0.8 vs 7.0±0.9 m/sec, p<0.001) and sympathetic nerve traffic as reflected by MSNA levels (41.1±1.5 vs 32.1±1.9 bursts per 100 heart beats, p<0.001), while did not differ regarding metabolic profile and left ventricular mass index (p=NS). In the total population, peak exercise systolic BP was related to 24-h systolic BP (r=0.229, p<0.05), PWV (r=0.218, p=0.002), and MSNA (r=0.214, p<0.05). Moreover, MSNA was related to waist circumference (r=0.33, p=0.004) and office systolic BP levels (r=0.31, p<0.05) but there was no association with PWV values (p=NS).

Conclusion
In subjects with high normal BP, a HRE identifies a state of arterial stiffening and sympathetic overdrive, as reflected by increased PWV and MSNA levels respectively. These finding suggest that exercise testing provides additional clinical information regarding the vascular status and modulation of sympathetic tone in this setting.
P5468Systolic versus diastolic blood pressure as predictors of cardiovascular events among treated hypertensive patients: a 6-year prospective study
Authors: Kasiakogias A , Tsioufis C , Konstantinidis D , Iliakis P , Leontsinis I , Konstantinou K , Koumelli A , Kakouri N , Dimitriadis K , Tousoulis D 
Published: October 2019

Abstract

Background/Introduction
There has been a long debate regarding the association of systolic versus diastolic blood pressure with cardiovascular outcome and data regarding hypertensive patients under treatment have been conflicting.

Purpose
To investigate the association of different patterns of uncontrolled blood pressure (BP) among treated hypertensive patients.

Methods
We prospectively studied 1507 treated hypertensive patients (age 59±11 years) that are followed in the setting of a single-center, clinic-based registry. During follow-up, patients underwent regular visits for hypertension and risk factor management. Based on the cut-off limits for uncontrolled hypertension of office systolic BP≥140mmHg and diastolic BP≥90mmHg, study participants were divided into four groups: those with controlled hypertension (796 patients, 53% of the population), uncontrolled systolic BP (257 patients, 17%), uncontrolled diastolic BP (135 patients, 9%) and uncontrolled systolic and diastolic BP (319 patients, 21%). The outcome studied was the composite of cardiovascular morbidity set as coronary artery disease and stroke, and the controlled hypertension group served as reference.

Results
The median follow-up period was 6.4±3.0 years and the composite endpoint (13 strokes and 41 cases of coronary artery disease) occurred in 54 patients (3.6%). Unadjusted Cox regression analysis showed that, compared to the reference group of controlled hypertensives, the risk for cardiovascular morbidity was similar in patients with uncontrolled diastolic BP (HR: 0.88, 95% CI: 0.26–2.97) but significantly higher in patients with uncontrolled systolic BP (HR: 2.17, 95% CI: 1.08–4.36), while patients with both uncontrolled systolic and diastolic BP showed the worse prognosis (HR: 2.35, 95% CI: 1.24–4.43). This pattern of risk was overall sustained after adjusting for different sets of confounders.

Conclusions
Among treated hypertensive patients, uncontrolled systolic BP is associated with a greater risk for cardiovascular events compared to uncontrolled diastolic BP while uncontrolled systolodiastolic hypertension presents with the worse prognosis.