bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical impact of the determination of natriuretic peptides on long-term follow-up of patients treated in the Heart Failure Unit
Authors: Perea Armijo J , Lopez Aguilera J , Duran Torralba C , Castillo Dominguez J.C , Anguita Sanchez M 
Published: November 2020

Abstract

Introduction
The use of natriuretic peptides has spread in recent years as a diagnostic tool in patients with heart failure (HF). However, its influence on the prognosis of these patients has not been clearly established. Thus, our main aim was to know the characteristics of patients with increased levels of NT-proBNP and to analyze its impact on long-term prognosis in terms of mortality and readmissions due to heart failure.

Material and methods
We selected cases from the heart failure unit at HURS which had a NT-proBNP determination at first consultation. Patients were divided into two groups: GROUP 1 (NT-ProBNP &lt;10000) and GROUP 2 (NT-ProBNP &gt;10000). Clinical, echocardiographic and treatment variables were collected and patients were followed up for readmissions due to heart failure and all-cause mortality.

Results
A total of 280 patients were selected. The mean age of the cohort was 66.74±13.88 years and was male-dominated (64%). In group 1, there was a higher initial left ventricular ejection fraction (LVEF) (43.19% vs 40.36%; p=0.057), lower basal creatinine (1.13 mg/dL vs 1.53 mg/dL; p=0.001), lower creatinine at the end of follow-up (1.27 mg/dL vs 1.79 mg/dL; p=0.001) and a lower NT-proBNP at the end of follow-up (4039 pg/mL vs 17140 pg/mL; p=0.000) than in group 2. In addition, group 2 showed a higher percentage of chronic kidney disease (55% vs 29%; p=0.000) than group 1, with no differences in their main variables. With 110 months of follow-up, patients with NT-proBNP levels&gt;10000 had a similar hospital readmission rate compared to the group with lower NT-proBNP levels (81.2% vs 84.8% log rank p=0.133).With a mean of 130.01±9.11 months of follow-up, patients with NT-proBNP levels&gt;10000 had a tendency to higher mortality from any cause than those with lower NT-proBNP levels (84.4% vs 48.4%, log rank p=0.000).

Conclusion
Patients with NT-proBNP levels&gt;10000 are associated with a lower LVEF at baseline and a higher proportion of chronic kidney disease. In the long term, patients with NT-proBNP levels&gt;10000 had the same rate of readmissions for heart failure but a higher rate of death from any cause.
Kaplan-Meier analysis

Funding Acknowledgement
Type of funding source: None
Exploring sex-specific patterns of mortality predictors among patients undergoing cardiac resynchronization therapy: a machine learning approach
Authors: Tokodi M , Behon A , Merkel E.D , Kovacs A , Toser Z , Sarkany A , Csakvari M , Lakatos B.K , Schwertner W.R , Merkely B , Kosztin A 
Published: November 2020

Abstract

Background
The relative importance of variables explaining sex differences in outcomes is scarcely explored in patients undergoing cardiac resynchronization therapy (CRT).

Purpose
We sought to implement and evaluate machine learning (ML) algorithms for the prediction of 1- and 3-year all-cause mortality in patients undergoing CRT implantation. We also aimed to assess the sex-specific differences and similarities in the predictors of mortality using ML approaches.

Methods
A retrospective registry of 2191 CRT patients (75% males) was used in the current analysis. ML models were implemented in 6 partially overlapping patient subsets (all patients, females or males with 1- or 3-year follow-up data available). Each cohort was randomly split into a training (80%) and a test set (20%). After hyperparameter tuning with 10-fold cross-validation in the training set, the best performing algorithm was also evaluated in the test set. Model discrimination was quantified using the area under the receiver-operating characteristic curves (AUC) and the associated 95% confidence intervals. The most important predictors were identified using the permutation feature importances method.

Results
Conditional inference random forest exhibited the best performance with AUCs of 0.728 [0.645–0.802] and 0.732 [0.681–0.784] for the prediction of 1- and 3-year mortality, respectively. Etiology of heart failure, NYHA class, left ventricular ejection fraction and QRS morphology had higher predictive power in females, whereas hemoglobin was less important than in males. The importance of atrial fibrillation and age increased, whereas the relevance of serum creatinine decreased from 1- to 3-year follow-up in both sexes.

Conclusions
Using advanced ML techniques in combination with easily obtainable clinical features, our models effectively predicted 1- and 3-year all-cause mortality in patients undergoing CRT implantation. The in-depth analysis of features has revealed marked sex differences in mortality predictors. These results support the use of ML-based approaches for the risk stratification of patients undergoing CRT implantation.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Research, Development and Innovation Office of Hungary
Myocardial work – new insights from deformation imaging in patients with advanced heart failure
Authors: Spinka G , Bartko P.E , Heitzinger G , Prausmueller S , Pavo N , Arfsten H , Kastl S , Hengstenberg C , Huelsmann M , Goliasch G 
Published: November 2020

Abstract

Background
The evaluation of myocardial contractility appears to be a major determinant for the prognosis and allocation of treatment strategies in advanced systolic heart failure (HFrEF). Non-invasive measurement of myocardial work is currently emerging as a new promising method for the assessment of myocardial contractility, as it additionally accounts for hemodynamic loading conditions of the ventricle.

Objectives
This study sought to assess the prognostic impact of myocardial work in patients with advanced heart failure and to compare it with routinely used deformation imaging parameters.

Methods
We included 234 patients with HFrEF under guideline directed therapy and comprehensively assessed myocardial work, as well as global longitudinal strain (GLS) by speckle tracking echocardiography. The primary endpoint was all-cause mortality.

Results
Median age of the patients was 68 years (IQR 60–75) and 78% were male. Over a 5-year follow-up period, 107 patients died. Median GWI was 526 mmHg% (IQR 366–779) and median GCW was 730 mmHg% (IQR 523–988). Parameters of myocardial work displayed a strong and independent association with long-term mortality, even after careful adjustment for clinical and echocardiographic confounders (Table 1). Additionally, we observed a significantly better calibration towards long-term mortality for GCW compared to GLS as the current golden standard for myocardial deformation imaging (AUC 0.63 vs. 0.60; P=0.007).

Conclusion
This is the first study to comprehensively assess global myocardial work in patients with advanced heart failure. Important treatment decisions rely on the assessment of myocardial contractility and risk stratification, specifically in late stages of the disease where exact guiding of treatment success and timely allocation of more aggressive treatment strategies are warranted. By incorporating loading conditions, myocardial work seems to be able to sensitively detect changes in myocardial contractility thath predict a dismal course of the disease. Furthermore, our data suggests that global constructive work is a more sensitive parameter to predict long-term outcome compared to the currently used echocardiographic deformation imaging parameters (i.e. GLS).

Funding Acknowledgement
Type of funding source: None
Limitations of sexual activity in patients with chronic heart failure
Authors: Barquinha S , Alves J.A , Franco C.F , Trindade M.T , Silva T.P.S , Goncalves A.P.G , Ferreira V.F , Moreira R.M , Timoteo A.T.T , Soares R.S , Ferreira R.F 
Published: November 2020

Abstract

Background
Limitation of sexual activity may potentially have a great impact in the quality of life of patients with chronic heart failure (HF), although the burden of sexual limitation and its clinical drivers are not completely understood. We aimed to characterize the impact of sexual limitation and how it relates to different measures of HF severity, in patients with HF.

Methods
We prospectively selected a cohort of patients followed in our ambulatory HF Clinics, with HF and currently or previously documented left ventricular ejection fraction (LVEF) ≤40%, aged between 18 and 80 years, with NYHA class I-IV. Clinical, laboratorial, imaging and ergometric data was collected. A questionnaire characterizing sexual activity of the patient was filled by her/himself before consultation with the physician, while alone in a private room.

Results
A total of 65 patients were selected, 75% of which were male, with mean age 61±11 years, 32% were in NYHA I or II, and 21% had a resynchronization system. Mean BNP was 520±850 pg/mL, LVEF was 39±12% and peak oxygen consumption (pVO2) was 17.2±5.3 mL/min/m2. Limitations of sexual activity were reported in 40 (62%) patients, including erectile dysfunction (25%), fatigue (11%), reduction of libidum (8%), fear of HF symptoms during sexual activity (5%), absence of sexual partner (5%), and other reasons (8%). Of these 40 patients, 22 (55%) reported severe or very severe sexual limitation. Only 2 (3%) patients actively searched for clinical aid. Patients with sexual limitations were older (63±12 vs 56±11 years), were in higher NYHA classes (One-Way ANNOVA), had higher levels of BNP (775±1051 vs 181±212 pg/mL) and lower glomerular filtration rates (66±19 vs 86±23 mL/min) (all p&lt;0.05). Other major variables such as ischemic etiology, diabetes, resynchronization therapy, LVEF and pVO2 were not associated with the presence or severity of sexual limitations, although there was a numerical trend for lower pVO2 (16.5±5.8 vs 19.0±4.0 mL/l/min/m2, p=0.20). NYHA class ≥II (β 6.5, 95% CI 0.4–10.5) and BNP levels (β 1.03, 95% CI 1.01–1.06) were independent predictors of sexual dysfunction.

Conclusions
Sexual limitation was highly prevalent among patients with HF, was often severe and the most frequent reason was erectile dysfunction. Simple and highly accessible parameters, such as age, NYHA class, BNP levels and renal function, are related to the presence of sexual limitation. More attention should be payed to sexual limitation in patients with HF considering the high burden and the large room for improvement.

Funding Acknowledgement
Type of funding source: None
Donepezil markedly prevents the progression of chronic heart failure and renal dysfunction in renal artery stenosis-induced hypertensive rats
Authors: Li M , Zheng C , Kawada T , Uemura K , Inagaki M , Nishikawa T , Sugimachi M 
Published: November 2020

Abstract

Introduction
Parasympathetic activation by donepezil has been shown to improve prognosis in chronic heart failure (CHF) rats following myocardial infarction. We examined whether donepezil is effective in the treatment of another CHF model complicated with renal artery stenosis (RAS)-induced hypertension.

Methods
RAS was created by ligating the left renal artery up to 50% in SD rats, at the same time, we implanted a blood pressure (BP) transmitter for confirming RAS-induced hypertension (7-week post-RAS: systolic BP = 154±7 mmHg; diastolic BP = 115±8 mmHg). In the 11th week after induction of RAS, surviving animals were randomly assigned to untreated (UT, n=10) or donepezil treated [DT, n=10, dissolved in drinking water (3mg/kg/day)] group. After a 6-week treatment, the effects of donepezil were evaluated by hemodynamics, blood levels of neurohumoral markers, and morphology.

Results
Compared with UT, DT significantly prevented the progression of the left kidney atrophy (2.38±0.13 vs. 1.51±0.34 g/kg, P&lt;0.05) and kidney fibrosis (left: −64%, P&lt;0.001; right: −55%, P&lt;0.01). DT also significantly prevented the progression of CHF, through suppressing cardiac hypertrophy (2.30±0.06 vs. 2.57±0.08 g/kg, P&lt;0.01), cardiac fibrosis (−70%, P&lt;0.01), and cardiac dysfunction [cardiac index: 102±3 vs. 86±3 ml/min/kg, P&lt;0.05; left ventricular (LV) end-diastolic pressure: 12±2 vs. 20±2 mmHg, P&lt;0.05; LV dp/dtmin: 5856±259 vs. 4924±227 mmHg/sec, P&lt;0.05]. DT not only decreased serum levels of creatinine (0.54±0.02 vs. 0.63±0.03 mg/dl, P&lt;0.05) and uric acid (1.4±0.2 vs. 1.9±0.2 mg/dl, P&lt;0.05); but also decreased plasma levels of norepinephrine (273±38 vs. 846±242, P&lt;0.01), AVP (2729±347 vs. 4783±695 pg/ml, P&lt;0.05), BNP (360±13 vs. 460±39 pg/ml, P&lt;0.05), angiotensin II and aldosteron, and suppressed the systemic inflammation.

Conclusions
Donepezil treatment markedly prevented the progression of CHF and renal dysfunction, and improved the neurohumoral markers in the CHF rat model complicated with RAS-induced hypertension, suggesting that donepezil may be used as a new pharmacotherapy for CHF patients complicated with RAS-induced hypertension.

Funding Acknowledgement
Type of funding source: None
Serum uric acid, influence of sacubitril/valsartan, and cardiovascular outcomes in heart failure with preserved ejection fraction: PARAGON-HF
Authors: Selvaraj S , Claggett B.L , Veldhuisen D.V , Anand I.S , Pieske B , Rouleau J.L , Zile M.R , Shi V.C , Lefkowitz M.P , McMurray J.J.V , Solomon S.D 
Published: November 2020

Abstract

Background
Serum uric acid (SUA) is a biomarker of several pathobiologies relevant to the pathogenesis of heart failure with preserved ejection fraction (HFpEF), though by itself may also worsen outcomes. In HF with reduced EF, SUA is independently associated with adverse outcomes and sacubitril/valsartan reduces SUA compared to enalapril. These effects in HFpEF have not been delineated.

Purpose
To determine the prognostic value of SUA, relationship of change in SUA to quality of life and outcomes, and influence of sacubitril/valsartan on SUA in HFpEF.

Methods
We analyzed 4,795 participants from the Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction (PARAGON-HF) trial. We related baseline hyperuricemia to the primary outcome (CV death and total HF hospitalization), its components, myocardial infarction or stroke, and a renal composite outcome. At the 4-month visit, the relationship between SUA change and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) and several biomarkers including N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also assessed. We simultaneously adjusted for baseline and time-updated SUA to determine whether lowering SUA was associated with clinical benefit.

Results
Average age was 73±8 years and 52% were women. After multivariable adjustment, hyperuricemia was associated with increased risk for most outcomes (primary outcome HR 1.61, 95% CI 1.37, 1.90, Fig 1A). The treatment effect of sacubitril/valsartan for the primary outcome was not modified by baseline SUA (interaction p=0.11). Sacubitril/valsartan reduced SUA −0.38 mg/dL (95% CI: −0.45, −0.31) compared with valsartan (Fig 1B), with greater effect in those with baseline hyperuricemia (−0.50 mg/dL) (interaction p=0.013). Change in SUA was independently and inversely associated with change in KCCQ-OSS (p=0.019) and eGFR (p&lt;0.001), but not NT-proBNP (p=0.52). Time-updated SUA was a stronger predictor of adverse outcomes over baseline SUA.

Conclusions
SUA independently predicts adverse outcomes in HFpEF. Sacubitril/valsartan significantly reduces SUA compared to valsartan, an effect that was stronger in those with higher baseline SUA, and reducing SUA was associated with improved outcomes.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Novartis
Right ventricular free wall strain and effect of implantable defibrillator in non-ischemic heart failure
Authors: Jensen D.H , Elming M.B , Risum R , Haarbo J , Philbert B , Svendsen J.H , Pehrson S , Kober L , Thune J.J 
Published: November 2020

Abstract

Background
Patients with left ventricular systolic heart failure have a significantly increased risk of all-cause mortality and sudden cardiac death. A cardiac magnetic resonance (CMR) sub-study of the Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators (ICDs) in Patients with Nonischemic Systolic Heart Failure on Mortality (DANISH) trial found that in patients who also had reduced right ventricular ejection fraction, ICD implantation significantly increased survival. Recent studies have found that right ventricular free wall strain (RV-FWS) assessed by echocardiography has a similar prognostic power as right ventricular ejection fraction assessed by CMR and RV-FWS determined by echocardiographic may be a more accessible imaging modality to identify patients more likely to benefit from ICD implantation.

Purpose
To investigate if echocardiographic RV-FWS is related to risk of all-cause death in patients with heart failure and left ventricular systolic dysfunction and whether RV-FWS can identify a sub-group of patients more likely to benefit from ICD implantation.

Methods
RV-FWS was measured in 343 patients with left ventricular systolic heart failure included in the DANISH trial at our hospital, who underwent an echocardiographic examination before randomization. Cox regression was used to assess the effects of RV-FWS and ICD implantation on all-cause mortality. Impaired RV-FWS was defined as RV-FWS &gt;−20% according to guidelines.

Results
Median RV-FWS was −19% (quartiles: −24% to −14%). Impaired RV-FWS was present in 186 (54%) patients, and 70 (20.4%) patients died. RV-FWS was related to all-cause mortality both univariably, hazard ratio (HR) 1.07 (95% confidence interval [CI], 1.03–1.11), P=0.001, and adjusted for age, gender, tricuspid annular plane systolic excursion and left ventricular ejection fraction, HR 1.06 (95% CI 1.01–1.10), P=0.009. There was a significant interaction between impaired RV-FWS and effect of ICD, P for interaction=0.045 and ICD implantation significantly reduced mortality in patients with impaired RV-FWS, HR 0.52 (95% CI 0.28–0.96), P=0.04, but not in patients with normal RV-FWS, HR 1.34 (95% CI 0.64–2.82), P=0.44.

Conclusion
RV-FWS was independently related to all-cause mortality and associated with effect of ICD implantation. With validation in larger studies, impaired RV-FWS may potentially become a candidate for selecting patients for ICD implantation.
Impaired RVFWS and effect of ICD

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Danish Heart Foundation
First-phase ejection fraction predicts response to cardiac resynchronization therapy and adverse outcomes
Authors: Gu H , Baldeep S , Fang L , Webb J , Jackson T , Claridge S , Razavi R , Chowienczyk P , Rinaldi C 
Published: November 2020

Abstract

Background
Cardiac Resynchronization Therapy (CRT) is an important therapeutic treatment for chronic heart failure. However, even in carefully selected cases up to 40% of patient fail to respond. First-phase ejection fraction (EF1), the ejection fraction up to the time of maximal ventricular contraction, is a novel and more sensitive echocardiographic measure of early systolic function.

Purpose
We examined the value of EF1, to predict response to CRT and clinical outcomes after CRT.

Methods
We analysed echocardiograms from 197 patients who underwent CRT between 2009 and 2018 and were followed to determine clinical outcomes.

Results
Volumetric response rate (reduction in end-systolic volume ≥15%) was 92.3% vs. 12.1%, for those with EF1 in the highest vs. lowest tertiles (p&lt;0.001). A cut-off value of 11.9% for EF1 had &gt;85% sensitivity and specificity for prediction of response to CRT; on multivariate logistic regression analysis incorporating previously defined predictors, EF1 was the strongest predictor of response (OR: 1.563, 95% CI: 1.371–1.782, p&lt;0.001) (table 1). EF1 was also the strongest predictor of a clinical composite score (OR: 1.115, 95% CI: 1.044–1.191, p=0.001). Improvement in EF1 at 6 months after CRT implantation (6.5±5.8% vs 1.8±4.3% in responders vs. non-responders, p&lt;0.001) was the best predictor of heart failure re-hospitalization and death after median follow-up of 29.2 months (HR: 0.819, 95% CI:0.765–0.876, p&lt;0.001).

Conclusion
EF1 is a promising marker to identify patients likely to respond to CRT and most likely provides a measure of myocardial viability that determines response.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): British Heart Foundation, Wellcome/EPSRC Centre for Medical Engineering
Validation of the EUROMACS right-sided heart failure risk score in left ventricular assist device patients: a single center experience
Authors: Valente F , Vachiery J.L , Dewachter C , Stefanidis C , Vanden Eyden F , De Maertelaer V , Roussoulieres A 
Published: November 2020

Abstract

Background
Right Heart failure (RHF) is a severe complication after left ventricular assist device (LVAD) implantation, increasing early and late mortality. A simple 5-item score, the EUROMACS-RHF risk score, was developed to predict early RHF and mortality after implantation.

Purpose
The aim of the study was to investigate whether EUROMACS-RHF risk score was applicable in a single center to predict early (&lt;30 days) post-operative RHF.

Methods
From February 2011 to October 2019 all LVAD implanted patients in our institution were retrospectively reviewed. Only patients with complete data for risk score calculation and RHF analysis were included. Baseline characteristics and hospitalization data, including preoperative clinical, biological, echocardiographic and hemodynamic data were obtained. Based on these informations, EUROMACS-RHF risk score was calculated and classified in low, intermediate and high.
The link between the EUROMACS-RHF risk score and early severe RHF was investigated using Pearson's exact chi-square tests.

Results
The analysis included 88 patients (67 males; 49±2 years). Etiology of HF was ischemic in 36 patients (41%), dilated cardiomyopathy in 21 (24%) and others causes in 31 (35%). A Heart Ware LVAD (94%) was implanted as bridge to transplantation in 96% of the patients; 81 patients (90%) had severe INTERMACS (1–3) profile.
RHF was identified in 21 patients (24.1%), of which 15 (18%) were treated with inotropes for ≥14 days, 8 (9%) had an RVAD, and 11 (13%) were treated with inhaled NO for ≥48 hours. Patients with severe RHF had a significantly longer length of ICU stay compared to patients without (median 20 days versus 6,5 days). The early (&lt;30 days) post-operatory mortality was of 43% (n=9/21) in the RHF group and 6% (n=4/69) in patients without RHF (p&lt;0.001). Three of the twelve patients alive in the RHF group had an emergency transplant.
The prediction of RHF from the EUROMACS-RHF risk score and the observed severe RHF are presented in the table. A high preoperative EUROMACS-RHF score was able to predict the presence of RHF in 52% of patients (p=0.005), while a low score predicted the absence of RHF in 52% of patients (p&lt;0.001). In contrast, an intermediate EUROMACS risk score was not found to predict early RHF (p=0.283).

Conclusion
In our cohort, the EUROMACS-RHF risk score was effective in predicting early severe RHF, in particular for patients with preoperatory low (no RHF) and high (RHF) scores. This external validation confirms the clinical usefulness in risk prediction before LVAD implantation.
Figure 1

Funding Acknowledgement
Type of funding source: None