bluuebunny/crossref_metadata_2025_split huggingface dataset:
The unsurpassed value of cardiopulmonary exercise testing in assessing the prognosis of heart failure
Authors: Avila D.X , Vivacqua R.C , Serra S , Montera M.W , Tinoco E , Siciliano A 
Published: November 2020

Abstract

Introduction
Cardiopulmonary exercise testing (CPET) has become an important clinical tool to predict outcome in patients with chronic heart failure (CHF) and help to select candidates for heart transplantation (HTx) or left ventricular assist devices (LVAD).

Purpose
To evaluate CPET measurements in advanced CHF patients that are being considered for HTx or LVAD and its association to early mortality regardless of the performed procedure.

Methods
Maximum intensity CPET was performed on a treadmil and ramp protocol in 65 patients with patients with CHF and reduced ejection fraction, NYHA functional classes III and IV between 2012 and 2018. Measurements derived from CPET were the following: peak V'O2, VO2 at the anaerobic threshold (AT), percentage of the VO2 of the anaerobic threshold in relation to the peak, the VE/VCO2 slope, maximum heart rate (HR), respiratory quotient (R), oxygen kinetics, circulatory power (CP), the recovery HR in the first minute and the oxygen uptake efficiency slope (OUES) and the relation (VE/VCO2 slope)/VO2 peak.

Results
Seventy-four percent were male. Mean age of 67±12 years. Amost half (47%) had ischemic etiology. There were no complications related to CPET. Ten patients were transplanted, six had an intracorporeal LVAD implanted and the reminder (49 patients) were kept in supervised physical rehabilitation program. There were 11 deaths, 2 in HTx, 2 in LVAD, 7 in the rehabilitation group. Mean follow-up among the survivors was 43 months ± 40.6 and it was 12.1±10.3 months in those who died. CPET derived measurements between survivors and non-survivors were as follows: V'O2 peak (mL kg–1 min–1): 12.6±4.6 and 8.6±2.7 (p=0.002); the VO2 AT (mL kg–1 min–1): 9.9±3.3 and 6.1±3.0 (p=0.002); VE/VCO2 slope: 34.2±12.1 and 68.1±68.7 (p=0.0003); R peak: 1.1±0.2 and 1.0±0.1 (p=0.009); t1/2, in seconds: 135.8±47.9 and 170.1±82.0 (p=0.03); HR at the first minute 16.6±13 and 7±5 (p=0.009); OUES (L min–1): 1.1±0.4 and 0.9±0.3 (p=0.04) and CP [(ml O2 kg–1 min–1) mmHg] 1.516.2±689. 3 and 960.6±363.6 (p=0.005). and the relation (VE/VCO2 slope)/V'O2 peak were 3.2±2.0 and 11.4±19.5 (p=0.001), respectively.

Conclusion
The predisposition to early death could be stratified by V'O2 peak, VO2 of the ventilatory threshold, VE/VCO2 slope, t1/2, recovery HR, OUES, CP, and by the relation (VE/VCO2 slope)/V'O2 peak.

Funding Acknowledgement
Type of funding source: Private hospital(s). Main funding source(s): own financing
Serially measured cytokines and cytokine receptors in relation to clinical outcome in patients with stable heart failure
Authors: Bouwens E , Schuurman A , Akkerhuis K.M , Baart S.J , Caliskan K , Brugts J.J , Van Ramshorst J , Germans T , Umans V.A.W.M , Boersma H , Kardys I 
Published: November 2020

Abstract

Background
Activation of the inflammatory response in heart failure (HF) may initially serve as a compensatory mechanism. However, on the longer term, this physiological phenomenon can become disadvantageous. Temporal patterns of inflammatory proteins other than CRP have not yet been investigated in patients with stable HF.

Purpose
We aimed to evaluate the association of 17 serially measured cytokines and cytokine receptors with clinical outcome in patients with stable heart failure.

Methods
In 263 patients, 1984 serial, tri-monthly blood samples were collected during a median follow-up of 2.2 (IQR: 1.4–2.5) years. The primary endpoint (PE) composed of cardiovascular mortality, HF-hospitalization, heart transplantation, and LVAD. We selected baseline blood samples in all patients, as well as the two samples closest to the primary endpoint, and the last sample available in event-free patients. Thus, in 567 samples we measured 17 cytokines and cytokine receptors using the Olink Proteomics Cardiovascular III multiplex assay. Associations between biomarkers and PE were investigated by joint modelling.

Results
Median age was 68 (IQR: 59–76) years, with 72% men, 74% NYHA class I-II and a median ejection fraction of 30% (23–38%). 70 patients reached a PE. After adjustment for clinical characteristics (age, sex, diabetes, atrial fibrillation, NYHA class at baseline, diuretics and systolic blood pressure), 7 biomarkers were associated with the PE (Figure). Interleukin-1 receptor type 1 (IL1RT1) showed the strongest association: HR 2.65 [95% CI: 1.78–4.21]) per standard deviation change in level (NPX) at any point in time during follow-up, followed by Tumor necrosis factor receptor 1 (TNF-R1): 2.25 [1.66–3.08], and C-X-C motif chemokine 16 (CXCL16): 2.18 [1.59–3.04]. After adjustment for baseline N-terminal pro–B-type natriuretic peptide, high-sensitive troponin T and C-reactive protein however, only IL1RT1 and TNF-R1 remained significantly associated with the PE.

Conclusion
Repeatedly measured levels of several cytokines and cytokine receptors are independently associated with clinical outcome in stable HF patients. These results suggest that repeated measurements of these biomarkers, in addition to established cardiac biomarkers, may contribute to personalized risk assessment and herewith better identify high-risk patients.
Figure 1. Associations between levels of cytokines and cytokine receptors and the primary endpoint.

Funding Acknowledgement
Type of funding source: Other. Main funding source(s): This work was supported by the Jaap Schouten Foundation and the Noordwest Academie.
Estimation of left ventricular filling pressures in transplanted hearts by echocardiography – do current guidelines work?
Authors: Kubiak G.M , Ciarka A , Janssens S , Van Cleemput J , Voigt J.-U 
Published: November 2020

Abstract

Introduction
End-stage heart failure (HF) can be successfully treated with heart transplantation (HTx), which reduces mortality and improves quality of life (QoL). Diastolic dysfunction and subsequently increased left ventricular (LV) filling pressures can be an early sign of rejection, while later after HTx, they can be suggestive for other insults to the myocardium, for example related to transplant vasculopathy. Therefore, right heart catheterization (RHC) remains a standard follow-up examination in patients after HTx. It has been questioned, whether echocardiography can accurately predict the LV filling pressures in HTx patients, and whether echocardiographic diastolic parameters correlate with hemodynamics in this population. Therefore, our study aimed to investigate the correlation between invasive measurements and echocardiographic estimates of LV filling pressures in HTx patients.

Methods
We analyzed 461 consecutive HTx patients who underwent RHC and transthoracic echocardiography on the same day. Patients were classified as having elevated LV filling pressures when the pulmonary capillary wedge (PCWP) was ≥15 mmHg. Standard echocardiographic parameters of systolic and diastolic function were measured and the decision tree of the recommendations on diastolic dysfunction assessment of the American and European imaging societies (ASE/EACVI) was applied to detect elevated LV filling pressures and determine the diastolic dysfunction grade.

Results
The invasive measurements showed elevated LV filling pressures in 303 (66%) of HTx patients. Based on the echocardiographic parameters, HTx patients were classified into the following groups: normal diastolic function (n=151, 33%), grade I (n=87, 19%), grade II (n=21,5%), and grade III (n=151, 33%) diastolic dysfunction, and indetermined group (n=51, 11%). The PCWP values differed between the groups: 14.4±0.3 mmHg vs. 13.3±0.4 vs. 20.5±0.9 mmHg vs. 22.2±0.3 mmHg vs. 17.7±0.6 mmHg, p=0.0001, accordingly (Figure A). The PCWP showed moderate correlation with E/A (r=0.49, p=0.0001) and E/e' (r=0.40, p=0.0001) (Figures B and C, resp.). The decision tree of the ASE/EACVI recommendations predicted elevated LV filling pressures with a sensitivity of 64%, specificity of 98%, negative predictive value of 59% and positive predictive value (PPV) of 98%.

Conclusions
Our study is the first to demonstrate a correlation between the LV filling pressures estimated from echocardiography and invasively measured during RHC in large HTx population. Echocardiography alone can reliably describe elevated LV filling pressures with a high PPV. The sensitivity of the algorithm, however, is limited. Additional parameters need to be identified to increase the sensitivity of the current recommendations for detection of elevated filling pressures this patients population.
Figure 1

Funding Acknowledgement
Type of funding source: None
Right ventricular myocardial work: new method for non-invasive assessment of right ventricular function in HFrEF
Authors: Butcher S.C , Fortuni F , Montero J.M , Ajmone Marsan N , Delgado V , Bax J.J 
Published: November 2020

Abstract

Background
The prognostic significance of speckle tracking echocardiography derived right ventricular (RV) strain has been repeatedly demonstrated in the heart failure with reduced ejection fraction (HFrEF) patient group. Nevertheless, assessing RV systolic function in the context of afterload is vital as even minimal increases in pulmonary pressures may result in a substantial reduction in RV stroke volume. The novel assessment of Right Ventricular Myocardial Work (RVMW) through the evaluation of pressure-strain loops derived by echocardiography, provides a comprehensive evaluation of RV systolic function, integrating both RV strain and afterload.

Purpose
To explore the relationship between the non-invasive estimation of RVMW with invasive indices of right heart catherization (RHC) in a cohort of patients with HFrEF.

Methods
Noninvasive analysis of RVMW was performed in 23 HFrEF patients (median age 60.4 [58.0 to 66.0] years, 74% male) who underwent echocardiography and invasive RHC within 48 hours. The novel indices of RV global constructive work (RVGCW), RV global work index (RVGWI), RV wasted work (RVWW) and RV global work efficiency (RVGWE) were analysed utilizing proprietary software originally developed for the assessment of left ventricular myocardial work by speckle tracking echocardiography. These indices and other standard measurements of RV systolic function were then compared with invasively measured cardiac index (CI), derived by thermodilution during RHC.

Results
Mean left ventricular ejection fraction was 18.7% (±6.7), with a mean cardiac index of 2.2 L/min/m2(±0.7) and a mean pulmonary arterial pressure of 32 mm Hg (±13). None of the standard echocardiographic parameters of RV systolic function, including fractional area change, RV global longitudinal strain, RV free wall strain and TAPSE were significantly correlated with cardiac index in this cohort of HFrEF patients. In contrast, two of the novel indices derived non-invasively by pressure-strain loops, RVGCW and RVGWI, demonstrated a moderate correlation with invasively measured CI (r=0.55, p=0.006 and r=0.49, p=0.018).

Conclusion
RVGCW and RVGWI are novel parameters that provide integrative analysis of RV systolic function and correlate more closely with invasively measured CI than other standard echocardiographic parameters. Their potential role in aiding clinical decision-making merits further investigation.

Funding Acknowledgement
Type of funding source: None
Lung water quantification by cardiac magnetic resonance imaging: a novel prognostic tool in hf
Authors: Rocha B.M.L , Lopes Da Cunha G.J , Freitas P , Lopes P , Santos A.C , Guerreiro S , Tralhao A , Ventosa A , Andrade M.J , Aguiar C.M.T , Abecasis J , Saraiva C , Mendes M , Ferreira A 
Published: November 2020

Abstract

Background
Cardiac magnetic resonance (CMR) imaging has recently been proposed to quantify lung water density (LWD, %) non-invasively. Given that pulmonary congestion plays a key role in the pathophysiology of Heart Failure (HF), we designed a study to assess the prognostic significance of a simplified LWD measure in patients with HF and reduced left ventricular ejection fraction (LVEF).

Methods
We conducted a single-center retrospective study of consecutive patients with HF and LVEF &lt;50% who underwent CMR on a 1.5T scanner. Those with severe interstitial lung disease or chronic liver disease were excluded. All measurements were performed in a parasagittal plane at the right midclavicular line on a standard HASTE sequence, which is widely available in all CMR studies. As previously reported, LWD was determined by the lung-to-liver signal ratio multiplied by 0.7. A cohort of 102 healthy controls was used to derive the upper limit of normal (mean ± 2SD) of the LWD (21.2%). The primary endpoint was a composite of all-cause death or HF hospitalization.

Results
A total of 290 HF patients (mean age 64±12 years, 74.8% male, 56.2% of ischemic etiology) with a mean LVEF of 34±10% were included. LWD measurement took on average 35±4 seconds and showed excellent inter-observer agreement (intra-class correlation coefficient &gt;0.90). LWD was increased in 65 (22.4%) patients. Compared to those with normal LWD, the former were more symptomatic (NYHA ≥III: 29.2% vs. 1.8%; p=0.017) and had higher median NT-proBNP [1973 (IQR: 809–3766) vs 802 (IQR: 355–2157pg/mL); p&lt;0.001]. During a median followup of 21 months (IQR: 13–29), 20 (6.9%) patients died and 40 (13.8%) had at least one HF hospitalization. In multivariate analysis, LVEF (HR per 1%: 0.96; CI-95%: 0.93–0.99; p=0.024), creatinine (HR per 1mg/dL: 2.43; CI-95%: 1.25–4.71; p=0.009) and LWD (HR per 1%: 1.06; CI-95%: 1.01–1.12; p=0.013) were independent predictors of the primary endpoint. The findings were mainly driven by an association between LWD and HF hospitalization (HR per 1%: 1.08; CI-95%: 1.03–1.13; p=0.002).

Conclusions
A CMR-derived method for LWD quantification independently predicts an increased risk of death or HF hospitalization in HF patients with LVEF &lt;50%. Our results support LWD measurement as a simple, reproducible and widely available method, further adding to the prognostic role of CMR in this population.

Funding Acknowledgement
Type of funding source: None
Death, hospitalization, emergency department visits and out-patient visits in patients with heart failure in contemporary practice: results from the prospective Europeam 9069-patient ARIADNE registry
Authors: Lund L.H , Zeymer U , Clark A.L , Barrios V , Damy T , Drozdz J , Fonseca C , Kalus S , Koch C , Maggioni A 
Published: November 2020

Abstract

Background
In Europe, heart failure (HF) is managed in variable settings and frequently in office-based practice. In HF with reduced ejection fraction (HFrEF) there is now extensive evidence based therapy, but implementation is inconsistent, variable and overall inadequate. The Assessment of Real lIfe cAre –Describing EuropeaN hEart failure management (ARIADNE) registry aimed to assess in detail how outpatients with HFrEF are managed in Europe in contemporary practice.

Methods
ARIADNE was a prospective non-interventional registry of patients with HFrEF (NYHA class II-IV) treated by office-based cardiologists or selected primary care physicians (recognized as HF specialists) in a real world setting. Patients were enrolled in 687 centres in 17 European countries, and studied at baseline and after 6 and 12 months. Key pre-specified outcomes were deaths, hospitalizations, emergency department visits, and office visits, and their primary reasons.

Results
Over 20 months, we enrolled 9069 patients; median age 69 (19–96) years, 24% women, with 30% older than 75 years, 61% NYHA class II, with a median EF 35% (30–40%).
Over a median follow-up of 353 (1–631) days, 382 patients (4.3%) died, with 171 cardiovascular deaths (1.9%). The rates of total hospitalizations overall, for HF, and for non-HF cardiovascular reasons were 19.3, 8.1, and 4.8 per 100 patient years, respectively; and rates of emergency department visits overall, for HF reasons, and for non-HF CV reason were 7.7, 1.6, and 1.8, respectively. The number of HF office visits were on average 1.0 per patient.

Conclusions
In this large multinational HFrEF registry with detailed data on cause-specific outcomes and health care utilization, incidence of death was low and outpatient HF visits were few, but incidence of HF and CV hospitalization and emergency department visits was high.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Novartis AG, Switzerland
Psychosocial and clinical factors associated with poor self-care in patients with chronic heart failure
Authors: Calero E , Hidalgo E , Rosenfeld L , Fernandez I , Garay A , Alcoberro L , Jimenez S , Yun S , Guerrero C , Moliner P , Delso C , Alcober L , Enjuanes C , Comin-Colet J 
Published: November 2020

Abstract

Background
Self care is a crucial factor in the education of patients with heart failure (HF) and directly impacts in the progression of the disease.
Beyond heart failure related factors, the role of psychosocial determinants and its interaction with clinical aspects has not been fully explored.

Aims
The aim of the study was to analyze both clinical and psychosocial factors associated with poor self care in patients with chronic HF.

Methods
Self care was evaluated at baseline with the 9 item European HFR Self Care Behaviour Scale (9 item ESCBS).
Scores were standardized and reversed from 0 (worst self care) to 100 (better self care). This study we analysed the associations between poor self care (defined as scores in the lower tertile of the 9 item ESCBS) with demographic, HF-related (clinical) and psychosocial factors in all patients at baseline.

Results
We included 1123 patients: mean age 72±11, 639 (60%) were male, mean LVEF 45±17 and 454 (40%) were in NYHA class III or IV. Mean score of the 9-item ESCBS was 69±28. In the clinical multivariate analyses HF-related factors associated with poor self-care were serum albumins level, ckd level and previous admission due to heart failure. In the psychosocial multivariate analyses poor social support, depressive symptoms and needing a caregiver were independently associated with poor self care. In combined models, only psychosocial factors were independently associated with poor self care whereas no clinical factors remain in the model.

Conclusion
Our study showed that psychosocial conditions are the main factors independently associated with poor self-care in patients with chronic heart failure

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): Hospital del Bellvitge
Population based study to compare the trends, risk factors and outcomes associated with gastrointestinal bleeding in patients with left ventricular assist devices in the US
Authors: Gonuguntla K , Patil S.P , Rojulpote C , Cowden R.G , Nasir M , Koa B , Zhang V , Schulman P 
Published: November 2020

Abstract

Introduction
Prior to the utilization of continuous flow devices in 2010, Gastrointestinal (GI) bleeding was a common adverse event related to LVADs.

Background
Given the drastic increase in the use of new LVADs with continuous flow (CF), we sought to determine if CF-LVADs are associated with an increased number of GI bleeds and higher mortality.

Methods
We analysed the data from a national inpatient sample database using the International Classification of Disease (ICD)-9 procedure code for LVAD use in end-stage heart failure among patients 18 years or older. Included were 2,359 patients with a mean age of 55±13.7 years and 77% males and 59% Caucasians.

Results
The Incidence of GI bleed from 2010 to 2014 was 7.46%. There was no significant yearly change in the incidence over five years (p=0.793). After controlling for age, sex, and length of stay (LOS), hierarchical multivariate logistic regression revealed that significant predictors of GI bleed were acute kidney injury (AOR=1.87, 95% CI: 1.26, 2.80), peripheral vascular disease (AOR=1.77, 95% CI: 1.02, 2.94), body mass index ≥25 (AOR=0.46, 95% CI: 0.22, 0.87), hemiplegia and paraplegia (AOR=3.01, 95% CI: 1.17, 7.05), moderate or severe liver disease (AOR=2.40, 95% CI: 0.97, 5.34), peptic ulcer disease (PUD) (AOR=18.13, 95% CI: 7.86, 42.38), surgical aortic valve replacement (AOR=2.46, 95% CI: 1.12, 5.15), and venous thromboembolism (AOR=2.58, 95% CI: 1.57, 4.15).

Conclusion
Earlier studies showed an increase in the rate of GI bleed in CF-LVADs when compared to pulsatile flow devices. However, our study has indicated that CF-LVADs display no improvement in rates of GI bleed over five years, but that there was an increased likelihood of mortality in patients with GI bleed. These findings pose further questions in regard to considering newer device designs and improved patient selection criteria.

Funding Acknowledgement
Type of funding source: None
Changes in circulating levels and cardiac expression of adiponectin system in children with heart failure after Ventricular Assist Device support
Authors: Ragusa R , Di Molfetta A , Del Turco S , Basta G , Cabiati M , Del Ry S , Amodeo A , Trivella M.G , Caselli C 
Published: November 2020

Abstract

Background
Ventricular Assist Device (VAD) is increasingly used as bridge to transplantation for the treatment adult and pediatric patients with end-stage Heart Failure (HF). Unloading of heart by VAD can lead to significant molecular, structural and functional changes of cardiac muscle in HF adult patients, including an improvement of the inflammatory process. Adiponectin (ADN), an anti-inflammatory adipokine, exerts anti-hypertrophic, anti-fibrotic and anti-apoptotic effects after binding to AdipoR1, AdipoR2 and T-CAD receptors. There is an apparently paradoxical increase of ADN levels in HF adult patients, probably due ADN resistance. VAD treatment leads to an increased cardiac expression of ADN receptors in HF adults. However, little is known about the role of ADN in HF children and the effects of VAD support on ADN system in these patients.

Purpose
The aims of this study were to evaluate: 1) the circulating ADN levels from HF children and a control group of healthy children; 2) the effects of VAD treatment both on circulating levels of ADN and on the cardiac expression of ADN system in pediatric patients with HF.

Methods
Circulating levels of ADN were measured in plasma samples collected from 8 HF children [age:57±33 (mean±SD) months; 2 males; 14.2±13.5 weight; 29±8 LVEF%] before and at 4 hrs, 1, 3, 7, 14 and 30 days after VAD implant. The ADN levels of paediatric patients at baseline were compared with a group of 107 [58±7 months; 67 males] healthy children. Expression levels of AdipoR1, AdipoR2, T-CAD were determined by real-time PCR in cardiac biopsies collected from HF children at the time of VAD implant (Pre-VAD) and at the time of heart transplantation (Post-VAD).

Results
Circulating levels of ADN were significantly higher in HF compared to healthy children (Figure 1A). In HF children, plasma ADN decreased significantly in early post-operative time-course (up to 3 days Post-VAD implant) and returned to pre-operative levels in 1 month (Figure 1B). In cardiac biopsies, mRNA expression of AdipoR1, AdipoR2, T-CAD increased significantly after VAD treatment compared to Pre-VAD (Figure 2A–C).

Conclusion
In pediatric patients, high circulating levels of ADN were associated with presence of HF and were modified by VAD implant, but remained significantly abnormal. On the other hand, an increased cardiac mRNA expression of ADN receptors was observed after VAD. These results could suggest the existence of a fine tuning of the ADN system at cardiac tissue level, able to mitigate plasma abnormality and favour the cardio-protective effect of ADN.

Funding Acknowledgement
Type of funding source: Public grant(s) – EU funding. Main funding source(s): SensorART-A Remote Controlled Sensorized ARTificial Heart Enabling Patients Empowerment and New Therapy Approaches