bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sacubitril/valsartan in real-life European patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis
Authors: Giovinazzo S , Carmisciano L , Toma M , Sormani M.P , Canepa M , Senni M , Porto I , Ameri P 
Published: November 2020

Abstract

Background
Real-world data are needed to gauge how a therapy is implemented in clinical practice.

Methods
We systematically reviewed the abstracts presented at international congresses and the peer-reviewed original research articles, which described the use of sacubitril/valsartan in European patients with HFrEF from Sep 2014 until Nov 30, 2019. Meta-analysis estimates were combined using a random effects model with inverse variance weights.

Results
15 abstracts and 11 articles, including 14,179 patients, were selected. Except for a study that evaluated 12,082 (85,2%) subjects, the sample size was 28 (0.2%) to 1,120 (7.9%) patients.
Taking as reference PARADIGM-HF, few baseline characteristic were reported for &gt;80% of the pooled population (Table), while all other ones were available for 12% of subjects or less (Figure). Underreporting was less common for articles than for abstracts (OR 0.42, 95% CI: 0.20–0.91).
Compared with the patients enrolled in PARADIGM-HF, those in real-life were older and more likely to being previously treated with ARB, MRA and diuretics (Table). NYHA class III-IV (OR 2.39, 95% CI: 1.58–3.59; I2=92%), ICD (OR 4.21, 95% CI: 2.31–7.69; I2=93%) and CRT (OR 4.53, 95% CI: 3.89–5.27; I2=0%) were also more likely, while a history of hypertension was less frequent (OR 0.61, 95% CI: 0.42–0.87; I2=82%).
The monthly achievement rate of the full dose of sacubitril/valsartan was 6%. When follow-up was ≥6 months, the percentage of subjects reaching the full dose was about 40% and very homogenous. Age and full dose attainment were inversely related (β −2.71, 95% CI: −5.3 to −0.1).
All cause-mortality and hospitalization rates were 6/100 person-year (9 studies, 1046 patients) and 25/100 person-year (5 studies, 775 patients), respectively.

Conclusions
With the limitation of being heterogeneous and of overall low quality, the literature suggests that, in Europe, sacubitril/valsartan is prescribed to patients with somehow more severe HFrEF than in the pivotal trial, who most often do not reach the full dose.

Funding Acknowledgement
Type of funding source: None
Guideline-based and personalized treatment approach to reduce hospitalizations and mortality for high risk advanced chronic systolic heart failure
Authors: Sisakian H , Hovhanisyan M , Lopatin Y.U , Martirosyan G.E , Minasyan A.M , Pepoyan S , Melik-Stepanyan S , Magakelyan A.A , Chopikyan A , Shahnazaryan S , Sahakyan L 
Published: November 2020

Abstract

The aim of our research was to evaluate mortality and rehospitalizations rates in patients with high risk subtype of heart failure (advanced HF) during 12 months of intensive monitoring after discharge on the basis of guidelines recommendations and personalized approach in treatment with frequent outpatient monitoring to reveal subcompensation/worsening of HF.

Methods
High risk advanced subtype of systolic HF was determined based on at least two hospitalizations during last year, severely reduced EF&lt;30%, right and left atria hypertension echo patterns, pseudonormal/restrictive diastolic dysfunction, frequent outpatient deterioration of euvolemic state.
Patients were randomized into two groups: 143 patients who underwent personalized intensive outpatient monitoring with care and 71 patients who underwent standard monitoring with regular guideline based treatment
Intensive monitoring in ambulatory settings included frequent attending protocol of clinical evaluation (from OPTIMIZE -HF multicenter study), body mass, heart rate, GFR controls and additional echo evaluation of pressures in right and left atria at every outpatient visit, lung ultrasound with detection of B-lines.

Results
Cumulative number of CV and HF deaths was 11% (16 out of 143 in intensive monitoring group) and 36% (26 out of 71 patients) in standard monitoring group.
Kaplan-Meier curve showed survival benefit in patients with personalized monitoring and treatment compared to those who were on standard care (Picture 1).

Conclusions
A strong trend towards decline in mortality and rehospitalizations, when personalized outpatient monitoring was implemented was observed (P&lt;0,001) at 12 months in patients with advanced systolic heart failure.
Kaplan-Meier survival curves groups

Funding Acknowledgement
Type of funding source: None
Improving atrioventricular coupling in heart failure patients with PR prolongation, the ReachPR Trial
Authors: Salden F , Luermans J.G , Van Stipdonk A.M.W , Allaart C.P , Meine M , Prinzen F.W , Vernooy K 
Published: November 2020

Abstract

Background
PR prolongation is associated with poor hemodynamic performance and may contribute to heart failure (HF). There is some evidence that in HF patients, normalization of atrioventricular (AV) coupling can attenuate HF.

Purpose
To investigate acute hemodynamic effects of restoration of AV coupling by atrio-biventricular (BiV) pacing in patients with HF and PR prolongation, but without evident ventricular dyssynchrony.

Methods
Nineteen patients underwent BiV pacemaker implantation. An invasive hemodynamic pacing protocol was performed during BiV and right ventricular (RV) pacing with four paced AV delays (100, 75, 50 and 25% of patient's PR interval during baseline AAI pacing). All patients had symptomatic HF, left ventricular ejection fraction (LVEF) &lt;35% and PR interval ≥230 ms, without evident prolonged QRS duration &gt;150 ms or left bundle branch block. Acute hemodynamic response was assessed by invasive left ventricular (LV) stroke work measurements (conductance catheter technique).

Results
At baseline, PR interval was 255±22 ms, QRS duration 122±19 ms and LVEF 29±6%. Reducing AV delay to 50% of patient's intrinsic PR interval by BiV pacing resulted in a median 25% increase (p&lt;0.05) in LV stroke work relative to baseline (figure, left panel). This increase in LV stroke work was mainly determined by an increase in LV stroke volume (figure, right panel). In contrast to BiV pacing, reducing AV delay by RV pacing did not improve LV stroke work (figure, left panel).

Conclusion
In patients with HF and PR prolongation, BiV pacing can be used to improve AV coupling that leads to hemodynamic improvement. These results suggest that BiV pacing may also be beneficial in this subset of HF patients that are currently not indicated for CRT.
ReachPR Trial

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Abbott funded a part of this study.
Glucagon-like peptide-1 receptor agonists (GLP-1 RA) as adjunct to standard treatment in diabetic patients with chronic heart failure: a systematic review & meta-analysis
Authors: Afaga D.N , Esguerra J.C.A , Europa M.L.R , Cabaluna I.T.G 
Published: November 2020

Abstract

Background
Glucagon-like peptide 1 receptor agonists' (GLP-1 RA) effect on secondary prevention of MACE has yet to be investigated in diabetic patients with chronic heart failure.

Purpose
We aimed to determine the effectiveness of GLP-1 RA as adjunct to standard treatment among diabetic patients with chronic heart failure (LVEF &lt;50%), in preventing major adverse cardiovascular events (MACE): cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

Methods
We searched for eligible trials reporting MACE, all-cause mortality, hospitalization for heart failure, improvement of LVEF and functional capacity (6-minute walk test). Fixed-effects model was used to estimate overall risk ratio for MACE, all-cause mortality and hospitalization for heart failure, while mean difference was used for estimation of improvement of LVEF and functional capacity. Review Manager 5.3 was used for analysis.

Results
Ten studies (56,597 patients) were included: LIVE, FIGHT, ZHANG, LEADER, ELIXA, SUSTAIN-6, PIONEER-6, EXSCEL, HARMONY, and REWIND. Addition of GLP-1 RA and Liraglutide did not significantly reduce MACE (RR 0.90, CI 95% [0.78–1.03]), (RR 0.91, CI 95% [0.69–1.20]). Moreover, Liraglutide did not significantly reduce cardiovascular death (RR 0.99, CI 95% [0.14–7.15]). No significant effect on LVEF and functional capacity was demonstrated in this study.

Conclusion
GLP-1 RA use in diabetic patients with chronic heart failure may have modest effect on functional capacity but did not significantly affect MACE, all-cause mortality, and LVEF.

Funding Acknowledgement
Type of funding source: Private hospital(s). Main funding source(s): Department of Internal Medicine, Manila Doctors Hospital
Sex differences in pharmacological therapy among heart failure patients: a systematic review and meta-analysis
Authors: Danielson C , Lileikyte G , Teng T.H.K , Ouwerkerk W , Lam C.S.P , Erlinge D 
Published: November 2020

Abstract

Background
Renin Angiotensin System Inhibitors (RASi) and Beta-Blockers (BB) have been proven effective in trials of heart failure with reduced ejection fraction (HFrEF) in which men were overrepresented. Recent studies have suggested sex differences in pharmacological therapy benefits in HF. We aimed to perform a systematic review and meta-analysis comparing treatment effect among women and men with HFrEF.

Method
Systematic search was performed on PubMed, Cochrane Library and Embase for RCTs published 1990–2019. Treatments included BB and RASi. Selected outcomes were all-cause mortality and combined outcome of all-cause mortality and/or hospitalisation for heart failure. Mean characteristics of articles included in data extraction were estimated by combined fixed-and random-effects meta-analysis. Z-scores for outcomes in sex were analysed using R software.

Results
Of 2188 articles identified through search, 26 articles and 103 746 patients [mean age 62±1.8 years, women 22.2%, mean LVEF 26.2±31.4%] were included in the meta-analysis. For all-cause mortality, there was a significant reduction in risk for men with HFrEF prescribed BB [HR 0.77 (0.69–0.86)] compared to no significant benefit in women [HR 0.87 (0.69–1.05)]; similarly there was a borderline significant reduction in risk for men with HFrEF prescribed RASi [HR 0.89 (0.78–1.00)] compared to no significant benefit in women [HR 0.80 (0.59–1.02)]. For the composite outcome of all-cause mortality and HF hospitalisation, there was significant reduction in risk in both women and men treated with BB (men [HR 0.73 (0.63–0.84)]; women [HR 0.74 (0.56–0.91)]); however significant risk reduction with RASi was observed in men [HR 0.82 (0.76–0.88)] but not women [HR 0.98 (0.86–1.09)]).

Conclusions
Our meta-analysis revealed potential sex differences in response to HFrEF therapies, where beneficial effects of RASi appeared more prominent in men compared to women. While mortality benefits with BB were also more prominent in men, reduction in the composite outcome of all-cause mortality and HF hospitalization with BB were evident in both men and women with HFrEF.
Effects of treatment on the outcomes

Funding Acknowledgement
Type of funding source: None
Safety of sacubitril/valsartan in heart failure outpatients with chronic heart failure in real life in Europe: results from ARIADNE registry
Authors: Zeymer U , Lund L.H , Barrios V , Fonseca C , Clark A.L , Damy T , Drozdz J , Kalus S , Koch C , Maggioni A 
Published: November 2020

Abstract

Background
Recently, the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan was introduced as novel therapeutic option into European guidelines for the management of heart failure. The ARIADNE registry provides information about its safety and tolerability profile in real life in outpatients with heart failure with reduced ejection fraction (HFrEF) in Europe.

Methods
ARIADNE was a prospective registry of patients with HFrEF treated by office-based cardiologists or selected primary care physicians (recognized as HF specialists) in a real world setting. In total, 9069 HFrEF patients in 687 centres from 17 European countries were included and prospectively followed over 12 months. Here we report the safety information from 4614 patients that received sacubitril/valsartan at baseline.

Results
The mean age of patients was 67.3 years at baseline. The majority of enrolled patients were in NYHA class II or III (49.7% and 48.2%, respectively). Mean LVEF was 32.7% in the S/V group. Patients with S/V had arterial hypertension (62.5%), coronary heart disease (61.0%), dyslipidemia (50.6%), atrial fibrillation (41.0%), diabetes (34.3%), and chronic kidney disease (26.0%). Co-medications were beta-blockers (83.4%), MRAs (60.1%), loop diuretics (65.2%), and digitalis (7.5%).
S/V was discontinued due to an adverse event (AE) during the 12 months in 191 (4.1%) patients, of these in 180 (3.6%) due to AEs and 28 (0.6%) due to SAEs. The most frequent AE was hypotension, which was reported in 391 (7.9%) of patients, of these 74 (18.9%) discontinued S/V. Hypokalaemia was observed in 1.7% and an impairment of renal function in 1.0% of S/V patients, respectively. Total mortality was 3.8%, cardiovascular mortality 1.8% in the S/V group.

Conclusions
This is the first large prospective study on the use of S/V in patients with HFrEF in Europe. S/V was well tolerated with a safety profile comparable with that observed in clinical trials for S/V patients.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Novartis Pharma AG
Cardiac rehabilitation effectively reduces the number of deaths in the heart failure population (propensity score matched analysis)
Authors: Leszek P , Witczak K , Bartolik K , Was D , Maruszewski B , Brukalo K , Kleinork A , Rolska-Wojcik P , Zaleska-Kociecka M 
Published: November 2020

Abstract

Background
Numerous cardiac rehabilitation (CR) studies have demonstrated functional benefits, improvement in quality of life and clinical outcomes from exercise training in patients with heart failure (HF), so CR is consistently recommend for HF patients. However its influence on survival in HF population is unknown.

Purpose
To assess the influence of CR on survival rate in HF patients.

Methods
It is a retrospective analysis of 1 620 686 HF patients in Poland in years 2013–2018, based on nationwide Polish Ministry of Health registry, that provides public universal healthcare coverage to all residents and collects detailed information for the entire Polish population (38,495,659 in 2013) since 2009. Within registry, we identified the experimental group of 11 512 HF patients ≥18 years old who underwent CR in 2013–2018.
From entire HF population we identified a 1:1 propensity score matched cohort of HF patients, who did not get CR.

Results
After propensity-score matching, we identified 11,512 patient pairs who underwent/not CR. Average age was approximately 66 years (18–39: 2.1 vs 2.0%; 40–49: 491 – 4.3 vs 4.2%; 50–59: 17.0 vs 17.1%; 60–69: 34.9 vs 35.2%; 70–79: 31.3 vs 31.4%; 80+: 10.4 vs 10.3% respectively), 61% of the participants were males, mainly urban residence nearly 70%, with HF diagnose put during hospitalization 74.5%. Both groups were similar also by comorbidities evaluated by Charlson Comorbidity Index.
Patients subjected to CR compared CR negative significantly increased survival risk at 1st, 2nd, 3rd, 4th and 5th year (CR vs CR negative 97.4% vs. 84.9%; 93.9% vs. 77.9%; 89.9% vs. 71.9%; 85.2% vs 66.0%; 81.8% vs 62.1% respectively) – Figure 1.

Conclusion
Our analysis showed that in heart failure patients, CR was associated with an increased survival rate among HF patients as treated in routine health care system.
Figure1

Funding Acknowledgement
Type of funding source: Other. Main funding source(s): European Union from the European Social Fund
Regular training in a hospital in patients with left ventricle assist device (LVAD): influence on exercise capacity, muscular strength and complex coordination
Authors: Smolis-Bak E , Chwyczko T , Noszczak E , Bogucki M , Zalucka L , Kowalik I , Mierzynska A , Piotrowicz E , Szymanski J , Zielinski T , Sobieszczanska-Malek M , Kusmierczyk M , Dabrowski R , Szwed H , Piotrowicz R 
Published: November 2020

Abstract

Heart failure (HF) significantly reduces physical capacity and harms the overall functioning. In the end-stage cases of HF, the only options are surgical procedures including left ventricular assist devices (LVAD) implantation and heart transplant. Due to the insufficient number of available organs for transplantation, LVAD are used more and more frequently. Rehabilitation of patients with LVAD is a crucial element of therapy because of long-term immobilization of patients awaiting transplant or heart muscle regeneration.

Purpose
The aim of the study was to evaluate the impact of early hospital rehabilitation on exercise tolerance, muscles strength and complex coordination in LVAD patients.

Methods
The total of 20 LVAD patients were recruited to the study (all male, aged 19–66 years). All patients underwent standard cardiac rehabilitation in the postoperative and medical treatment wards. After the end of hospitalization, patients were admitted to the rehabilitation department for 4–5 weeks. During that period they performed endurance training, conditioning exercises with elements of resistance and coordination exercises. All patients were tested before and after the rehabilitation program using ergospirometry (CPX), 6-MWT, upper and lower limbs muscle strength (30 Second Chair Stand) and complex coordination (Up&Go test).

Results
A significant increase in the values of most of studied parameters was observed after exercise training in comparison to the results before rehabilitation process (VO2 peak) [ml/kg/min]: 11.1±2.2 vs. 12.5±2.7, p&lt;0.001; Watt: 42.6±12.4 vs. 54.1±13.1, p&lt;0.0001; 6- MWT [m]: 300.1±102.2 vs. 404.8±105.9, p&lt;0.0001; 30 Seconds Chair Stand [number of stands] 8.4±3.3 vs. 11.6±4.8, p&lt;0.0001; Up&Go [sec] 9.0±1.7 vs. 7.1±1.5, p&lt;0.0001; left hand grip strength [kg]: 31.5±8.4 vs. 34.8±8.1, ns; right hand grip strength [kg]: 33.6±11,2 vs. 36.0±9.0, ns. No adverse effects were observed during rehabilitation process.

Conclusions
Hospital-based rehabilitation is safe and effective in LVAD patients. Rehabilitation after LVAD implantation brings significant benefits in terms of exercise capacity and tolerance, muscle strength and complex coordination in this group of patients.

Funding Acknowledgement
Type of funding source: Public grant(s) – EU funding. Main funding source(s): NATIONAL RESEARCH AND DEVELOPMENT CENTER
A multiparametric ICD algorithm for heart failure risk stratification: an analysis in clinical practice
Authors: Calo L , Manzo M , Santini L , Dello Russo A , Santobuono V.E , Pecora D , Talarico A , Nicolis D , Costa A , Petracci B , Campari M , Valsecchi S , D'Onofrio A 
Published: November 2020

Abstract

Purpose
A novel multiparametric algorithm based on implantable cardioverter defibrillator (ICD) sensors has been recently developed. The HeartLogic index combines multiple parameters, i.e. heart sounds, intrathoracic impedance, respiration pattern, night heart rate, and patient activity, in a single index. In the validation study, the HeartLogic alert condition was shown to identify patients during periods of significantly increased risk of heart failure (HF) events. We sought to evaluate the risk stratification ability of the algorithm in a group of patients who received the system in clinical practice.

Methods
The HeartLogic feature was activated in 257 ICD and cardiac resynchronization therapy ICD patients (186 male, 70±11 years, left ventricular ejection fraction 30±8%) at 11 centers. The median follow-up duration was 14 months [25–75 percentile: 7–19]. The HeartLogic algorithm automatically calculates a daily HF index and identifies periods in or out of an alert state relative to a configurable threshold (in this analysis set to 16).

Results
Patients experienced 40 HF hospitalizations requiring at least 1 overnight stay (0.14/patient-year) during the observation period (285 patient-years). The HeartLogic index crossed the threshold value 191 times in 105 patients. The time in the alert state was 27 patient-years, i.e. 9.5% of the total observation period. HF hospitalization rate while in alert was 0.96/patient-year and 0.05/patient-year while out of alert. The occurrence of ≥1 index crossing during follow-up was associated with the risk of HF hospitalization (odds ratio: 4.70, CI 95%: 1.79–12.4, p=0.002), independently from other baseline clinical variables.

Conclusions
Our analysis of data collected in clinical practice confirms that the multiparametric ICD algorithm is an independent predictor of higher risk of HF. In particular, it allows dynamic identification of time-intervals when patients are at significantly increased risk of worsening HF. This potentially helps better triage resources to a more vulnerable patient population.

Funding Acknowledgement
Type of funding source: None
Determinants of sudden cardiac death after heart transplantation
Authors: Bonnet G , Coutance G , Waldmann V , Aubert O , Asselin A , Raynaud M , Racape M , Bories M.C , Varnous S , Bruneval P , Leprince P , Marijon E , Loupy A , Jouven X 
Published: November 2020

Abstract

Background
Heart transplant recipients are at high-risk of sudden cardiac death (SCD). However, risk factors of SCD in heart recipients remained poorly described.

Objective
To assess the predictors of SCD beyond the first-year post-transplant.

Methods
We enrolled consecutive patients transplanted between 2004 and 2017 in two French referral centers. We excluded patients deceased during the first year. Patients underwent an evaluation at the day of transplantation and during the first year, comprising clinical, biological, histological, immunological (circulating anti-HLA DSA) and interventional (cardiac allograft vasculopathy assessment) parameters. Echocardiographies were routinely performed in all included patients according to a prespecified protocol. According to the last consensus, SCD was defined as an unexpected out-of-hospital cardiac arrest without obvious non-cardiac cause, in the first hour after initiation of symptoms. Cox model analysis was used to determine the parameters associated with sudden death risk.

Results
A total of 913 patients were included. The median follow-up post-HT was 5.9 years (IQR=2.9–8.5). Among the 213 deaths after one year, 44 patients (21%) died from SCD. In this population, the incidence rate of SCD was 0,82 per 100 person-year (95% CI: 0,51–2,05). Among the 60 parameters tested in univariate analysis, we identified 2 independent factors of sudden death after 1 year post-HT: left ventricular ejection fraction (LVEF) ≤55% any time after transplantation ( HR 4.07, 95% CI 1.94–8.53, p&lt;0.001) and the presence of circulating anti-HLA DSA at the time of transplantation (HR 2.79, 95% CI 1.37–5.68, p=0.005). The incidence rate of SCD was 2.17 per 100 person-year (95% CI: 1.42; 4.60) and 1.21 per 100 person-year (95% CI: 0.80; 2.58) in patients with FEVG&lt;55% (n=73) and in patients with pre-formed DSA (n=260), respectively.

Conclusion
In a large multicentric and highly phenotyped cohort of heart transplant recipients, we identified two independent factors associated with SCD beyond the first year. This study provides fresh evidence of SCD assessment for improving risk stratification of HT recipients.

Funding Acknowledgement
Type of funding source: None