bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dapagliflozin reduces the risk of hyperkalaemia in patients with heart failure and reduced ejection fraction: a secondary analysis DAPA-HF
Authors: Kristensen S.L , Docherty K.F , Jhund P.S , Bengtsson O , Demets D.L , Inzucchi S.E , Kober L , Kosiborod M.N , Langkilde A.M , Martinez F.A , Ponikowski P , Sabatine M.S , Sjostrand M , Solomon S.D , McMurray J.J.V 
Published: November 2020

Abstract

Background
Hyperkalaemia often limits the use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure and reduced ejection fraction (HFrEF), denying these patients a life-saving therapy.

Purpose
To determine whether treatment with the sodium-glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin reduces the risk of hyperkalaemia associated with MRA use in patients with HFrEF.

Methods
The risk of developing mild hyperkalaemia (potassium &gt;5.5 mmol/L) and moderate/severe hyperkalaemia (&gt;6.0 mmol/L) was examined in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF) according to background MRA use, and randomized treatment assignment, by use of Cox regression analyses.

Results
Overall, 3370 (70.1%) patients in DAPA-HF were treated with an MRA. Mild hyperkalaemia and moderate/severe hyperkalaemia occurred in 182 (11.1%) and 23 (1.4%) patients treated with dapagliflozin as compared to 204 (12.6%) and 40 (2.4%) of patients given placebo (Table and Figure). This yielded a hazard ratio (HR) of 0.86 (0.70–1.05) for mild hyperkalaemia and 0.50 (0.29, 0.85) for moderate/severe hyperkalaemia, comparing dapagliflozin to placebo.

Conclusions
Patients with HFrEF and taking a MRA who were randomized to dapagliflozin had half the incidence of moderate/severe hyperkalaemia, compared with those randomized to placebo.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): DAPA-HF study was funded by AstraZeneca
Chronic obstructive pulmonary disease in heart failure: influence on circulating biomarkers and outcome
Authors: Aimo A , Vergaro G , Januzzi J , Richards A.M , Lam C.S.P , Latini R , Anand I.S , Ueland T , Brunner-La Rocca H.P , Bayes-Genis A , De Boer R.A , Gaggin H.K , Huber K , Passino C , Emdin M 
Published: November 2020

Abstract

Background
Chronic obstructive pulmonary disease (COPD) is common in patients with chronic heart failure (CHF).

Purpose
We aimed to explore the impact of COPD on HF biomarkers (N-terminal fraction of pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T [hs-TnT], and soluble suppression of tumorigenesis-2 [sST2]) and outcome.

Methods
Individual data from 14 cohorts of patients with stable chronic HF and NT-proBNP and hs-TnT values were analysed. Patients with known COPD status were evaluated.

Results
Patients (n=13,178) were aged 67 years (58–75), 75% males, and 76%, 11%, 13% with HF with reduced, mid-range, or preserved ejection fraction (HFrEF/HFmrEF/HFpEF), respectively. Patients with COPD were older than those without COPD (age 71 years [64–77] vs. 66 [57–75]; p&lt;0.001), more frequently males (79% vs. 74%; p&lt;0.001), had more often ischaemic HF (54% vs. 52%; p&lt;0.001), and HFpEF (14% vs. 12%; p=0.011), but not HFpEF (12% vs. 11%; p=0.097). COPD patients had also more severe dyspnoea (44% in NYHA class III-IV vs. 31%; p&lt;0.001), and slightly worse renal function (median estimated glomerular filtration rate [eGFR] 58 mL/min/1.73 m2 [44–74] vs. 60 [46–67]; p&lt;0.001). Patients with COPD had higher NT-proBNP (1501 ng/L [642–3333] vs. 1225 ng/L [476–2902]; p&lt;0.001), hs-TnT (22 ng/L [13–38] vs. 17 ng/L [9–30]; p&lt;0.001), and sST2 (30 ng/mL [22–45] vs. 29 [21–43]; p&lt;0.001).
Over a median follow-up of 2.1 years (1.5–3.7, range 0–18 years), 3,865/12,489 patients (31%) died; among them, 2,443/12,450 (20%) died for cardiovascular causes; 3,373/12,469 patients (27%) were hospitalized for HF over 35 months (15–63, range 0–216 months). Patients with COPD had a significantly higher all-cause mortality, cardiovascular mortality, and worse survival free from HF hospitalization (all p&lt;0.001; Figure). In a model including age, gender, ischaemic vs. non-ischaemic aetiology, eGFR, HFrEF/HFmrEF/HFpEF, and NYHA class III-IV, COPD retained independent prognostic significance from NT-proBNP for 1-year all-cause (p=0.009) and cardiovascular mortality (p=0.022), 5-year all-cause (p&lt;0.001) and cardiovascular mortality (p=0.011) as well as 3- (p=0.033), 6- (p=0.019) and 12-month HF hospitalization (p=0.033). COPD lost its independent prognostic significance when hs-TnT and sST2 were included in the model.

Conclusions
COPD in HF is characterized by higher NT-proBNP, hs-TnT and sST2 levels. COPD adds prognostic significance over NT-proBNP alone, but not over the combination of NT-proBNP, hs-TnT, and sST2.

Funding Acknowledgement
Type of funding source: None
Heart failure hospitalization trends during a very long-term follow-up up to 18 years
Authors: Zamora E , De Antonio M , Domingo M , Santiago-Vacas E , Codina P , Santesmases J , Troya M.I , Diez-Quevedo C , Boldo M , Alonso N , Gonzalez B , Rivas C , Nunez J , Lupon J , Bayes-Genis A 
Published: November 2020

Abstract

Background
Heart Failure (HF) is the first cause of hospitalizations in people older than 65 years. Often patients suffer recurrent hospital admissions.

Objective
To assess recurrent HF-related hospitalizations during very long-term follow-up in a cohort of HF outpatients managed in an ambulatory structured HF Unit.

Methods
End of follow-up was 31.8.2019 (at least 1-year follow-up for alive patients, up to 18 years). Heart failure hospitalizations were defined as unplanned hospitalizations of at least 24 hours due to worsening heart failure and were identified from clinic records, hospital wards, or electronic Catalan history record. Death was recorded from the same sources and Spanish Health System and Spanish Death Registry. Lost information during follow-up was adequately censored (1 patient for survival status and 37 for HF-related hospitalizations).

Results
A total of 2355 patients were included. Follow-up span a total of 12,472 patients-years. 1682 HF-related hospitalizations were recorded in 725 patients (13.5 per 100 patients-years). Number of admissions ranged from 0 in 1630 patients to 22 in 1 patient (patients with hospitalizations, median 2 [Q1-Q3, 1–3]; 118 patients had 4 or more hospitalizations). HF hospitalization density incidence was higher during the 10 first years in patients with HF hospitalizations in the precedent year before HF Clinic baseline visit (table). By contrast, if only patients who died during follow-up were considered (N=1299), hospitalization trends significantly increased in their last period of life: 11.7%, 8.9%, 13.6%, 20.8% and 44.9% from the first to the last period (quintile) of their trajectory, respectively.

Conclusions
HF hospitalizations occur during the whole HF trajectory, with an increasing trend at the end of the every patient trajectory.

Funding Acknowledgement
Type of funding source: None
Patients with heart failure and a LVEF less than 40% present an overall lower health related quality of life than those with LVEF between 40% and 60%: a multinational real-world survey in EU
Authors: Proudfoot C , Fonseca A.F , Lahoz R , Corda S , Cotton S , Jackson J , Studer R 
Published: November 2020

Abstract

Background and purpose
Heart Failure (HF) is associated with symptoms such as dyspnoea and fatigue which can impact patients' health related quality of life (HRQoL). This study aimed to characterize and assess the HRQoL of patients with HF and left-ventricular ejection fraction (LVEF) &lt;40% versus those with ≥40%-60%.

Methods
A cross-sectional study of patients with HF was conducted in France, Germany, Italy, Spain and United Kingdom. Patient record forms (PRFs) were completed by 257 cardiologists and 158 general practitioners (GPs) for consecutively consulting patients. The same patients were invited to provide patient-reported outcomes including self-completion questionnaires, Minnesota Living with Heart Failure Questionnaire (MLHFQ) and EQ-5D-5L VAS.

Results
204 HF patients with LVEF &lt;40% (mean age 67.7 years) and 600 patients with LVEF ≥40–60% (mean age 68.9 years) were included. Proportion of males was significantly higher in the lower LVEF group (73.5% vs. 61.2%, p=0.0017). Overall, the patients with lower LVEF more frequently presented with comorbidities than those with LVEF ≥40–60% (p&lt;0.05, Figure 1). NYHA stage III/IV (35.8%/7.4% vs. 15.3%/0.8%) as well as self-reported HF symptoms were more frequently reported in the lower LVEF group (p&lt;0.05, Figure 1). Similarly, patients with LVEF &lt;40% reported statistically significantly worse HRQoL compared to those with LVEF ≥40–60% (Table 1).

Conclusions
The HRQoL of all HF patients with LVEF ≤60% appears impacted, while those with LVEF &lt;40% had significantly worse HRQoL than those with LVEF ≥40–60%. These differences in HRQoL may not only be related to the LVEF but also to the overall characteristics of these patients. Addressing the HRQoL burden for patients should be a key aspect of HF management strategies for all HF patients.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Novartis Pharma AG
Clinical significance of the relative apical sparing pattern of longitudinal strain in patients with cardiac amyloidosis
Authors: Saito M , Nakao Y , Higaki R , Kawachi Y , Yokomoto Y , Ogimoto A , Suzuki M , Kawakami H , Hiasa G , Okayama H , Inoue K , Ikeda S , Yamaguchi O 
Published: November 2020

Abstract

Background
The relative apical sparing pattern (RASP) of left ventricular (LV) longitudinal strain (LS) is frequently associated with cardiac amyloidosis (CA). However, some patients with CA do not show the RASP, and their clinical characteristics have not been fully clarified. We sought to investigate the clinical significance of RASP in patients with CA.

Methods
One hundred consecutive CA patients who were diagnosed by biopsy or myocardial pyrophosphate scintigraphy and evaluated for RASP (mean age: 76 years, male: 77%, LV mean wall thickness: 13.5 mm, light-chain [AL] type: 33 cases, transthyretin [TTR] type: 67 cases) were retrospectively enrolled. The RASP was semi-quantitatively and quantitatively assessed. Semi-quantitative RASP was defined as reduction of LS (≥−10%) in ≥5 (of 6) basal segments relative to preserved LS (&lt;−15%) in ≥1 apical segment. Quantitative RASP was calculated according to the following formula: Quantitative RASP = [Average apical LS] / [Average basal LS + Average mid LS]. We adapted three validated thresholds (&gt;1.00, &gt;0.90, and &gt;0.87) according to the literature.

Results
Semi-quantitative and binalized quantitative RASP (&gt;1.00, &gt;0.90, and &gt;0.87) were observed in 55, 55, 63, and 65 patients, respectively. RASP in each definition was more prevalent in the TTR group than in the AL group. Additionally, RASP was significantly associated with higher LV wall thickness even after adjustment for the CA subtypes (all, p&lt;0.05, Figure). After the RASP assessment, 35 all-cause deaths and 26 cardiac deaths were observed during the follow-up period (median, 1.1 years). Although these events were significantly associated with poor nutrition, lower blood pressure, higher New York Heart Association class, and the AL group, no association was found with RASP and LV wall thickness.

Conclusions
The incidence of RASP is low in the case of thin LV wall thickness in CA patients, which may indicate the difficulty of early diagnosis of CA using RASP in patients with mild LV hypertrophy. The prognostic prediction using RASP may be challenging in this cohort.
Figure 1

Funding Acknowledgement
Type of funding source: None
Impact of pulmonary wave reflection in heart failure: right ventricular-arterial coupling
Authors: Hayama H , Uejima T , Okazaki O , Hara H , Hiroi Y 
Published: November 2020

Abstract

Background
Pulmonary wave reflection, an important loading component on RV, would help better describe right ventricular (RV) – arterial uncouplingin type II pulmonary hypertension (PH).

Methods
This study included 105patients with type II PH (age = 72±13 years old, ejection fraction = 47±21%). Pulmonary wave reflection was characterised by estimating pressure and velocity profiles from Doppler measurement and separating pressure waveform into forward (Pf) and backward pressure (Pb) waves based on the concept of wave intensity. The relationship of RV strain against Pb or pulmonary artery systolic pressure (PASP) was compared between patients with and without subsequent event of worsening heart failure, using discriminant analysis.

Results
Sample profiles of pressure waveforms illustrated Pb accounted for a significant proportion of total pressure (figure A). When RV strain was plotted against Pb, the distribution of both group were clearly separated, indicating significant uncoupling in patients with events, whereas when plotted against PASP, the both groups were overlapped (figure B and C).

Conclusions
Pulmonary wave reflection can better describe RV-arterial uncoupling in type II PH.

Funding Acknowledgement
Type of funding source: None
Apical sparing strain pattern observed in danon disease: insights from a global registry
Authors: Bui Q , Ma G , Kraushaar M , Escobedo V , Le B , Covarrubias E , Brambatti M , Kahn A , Bougault C , Hong K , Taylor M , Adler E 
Published: November 2020

Abstract

Background
Danon Disease (DD) is a rare X-linked autophagic disorder due to mutations in the Lysosomal Associated Membrane Protein 2 (LAMP-2) gene and causes severe cardiac manifestations. Measurement of longitudinal strain (LS) has been shown to provide diagnostic insights into different etiologies of hypertrophic cardiomyopathies compared to conventional echocardiographic parameters.

Purpose
The aim of this study was to describe the pattern of global and regional LS in DD.

Methods
A retrospective, international registry, using medical records provided by patients, was formed to describe the natural history of DD. Complete echocardiogram images were available for review and LS was analyzed globally and regionally (basal, mid, apex).

Results
A total of eighteen DD patients (male 72%, mean age 17.2±10 years) had sufficient quality echocardiographic images for both traditional and myocardial strain evaluation. Notable traditional echocardiographic parameters included a mean EF of 60±11%, LV mass index 200±159 g/m2, intraventricular septal diameter 17.7±10.3 mm, LV posterior wall diameter 16.1±7.7 mm, LA volume index 21.9±13 mL/m2. Global longitudinal strain was reduced with a mean of −12.1±4.9% with an observed regional strain gradient: apex (−16.6±6.6%), mid (−10.9±4.7%) and basal (−9.2±4.5%). Bull's eye plot patterns reflected an apical sparing pattern that was similar to that described in cardiac amyloidosis.

Conclusion
In this DD cohort, we describe for the first time a strain pattern characterized by reduction in global longitudinal strain with apical sparing, which was originally pathognomonic for cardiac amyloidosis. This strain pattern in conjunction with a paradoxically normal LA volume may discriminate patients with DD from other hypertrophic conditions.

Funding Acknowledgement
Type of funding source: None
Effect of tolvaptan on long-term prognosis in Japanese patients with heart failure: a systematic review and meta-analysis
Authors: Nakao Y , Saito M , Yamaguchi O 
Published: November 2020

Abstract

Background
Tolvaptan (TLV), a vasopressin antagonist, can promote water diuresis and overcome various disadvantages associated with conventional diuretics by ameliorating congestive symptoms and improving hyponatremia while maintaining haemodynamics and renal function. Large-scale clinical trials conducted primarily in Western countries (e.g. EVEREST trial) failed to demonstrate the beneficial effect of TLV on prognosis in patients with heart failure (HF). However, even after these clinical trials, studies on the use of TLV add-on therapy and resultant prognosis have been reported in Asian countries. Racial differences can greatly affect drug efficacy and dosing.

Purpose
We sought to investigate the long-term prognostic effect of TLV add-on therapy in Asian patients with HF.

Methods
We searched MEDLINE, Scopus, Cochrane Central, and Google Scholar for articles published till 31 December 2019. Randomized controlled trials (RCTs) and matched case-control studies that had a follow-up period of at least 6 months and that compared TLV add-on therapy and conventional therapy (control group) in Asian patients with acute decompensated HF were included. Primary and secondary outcomes analysed were all-cause mortality and HF readmission, respectively. Pooled analysis was performed using univariate effect size with random effect models. Meta-regression was performed to assess the impact of potential covariates.

Results
Nine articles that enrolled 1010 patients (the range of patients in the enrolled studies: 58–217) were included in the systematic review. All studies were performed in Japan. The weighted mean follow-up period was 15 months. The weighted mean of sodium level and ejection fraction was 139 mEq/L and 47%, respectively. TLV dose at discharge was available only in five articles, and its weighted mean value was 8.8 mg/day. In the pooled analysis, TLV add-on therapy did not improve the incidence of all-cause mortality (OR: 1.02, 95% CI: 0.69–1.52, p=0.92, I2=23) and HF readmission (OR: 0.73, 95% CI: 0.24–2.22, p=0.58, I2=89) (Figure). Furthermore, the effect of TLV add-on therapy on all-cause mortality was significantly moderated by furosemide dose at discharge in the control group (p=0.03).

Conclusions
Similar to findings of previous RCTs completed in Western countries, we found that TLV add-on therapy did not improve long-term mortality and HF readmission in Japanese patients with HF; however, mostly small-scale studies were included in our review. TLV add-on therapy might contribute to the improvement in prognosis in HF patients taking large doses of furosemide.
Forest plot of tolvaptan's effect

Funding Acknowledgement
Type of funding source: Private hospital(s). Main funding source(s): Kitaishikai
Gender differences in heart failure: results from disease-management-programs
Authors: Macare C , Groos S , Kretschmann J , Weber A , Hagen B 
Published: November 2020

Abstract

Introduction
Among cardiovascular conditions, heart failure shows the highest rate of mortality. Despite increased awareness, striking differences in prognosis between men and women with HF still exist in ambulatory health care. In Germany, disease-management-programs (DMP) recognized this need and launched a structured treatment program especially for HF. Indicators assessing successful prevention and quality of care within DMP include among others, referral and prescription rates of prognosis-relevant medications (beta-blockers, AC-I, AT-1-antagonists).

Aim
To evaluate gender differences in heart failure therapy in the State of North-Rhine Westfalia, Germany.

Methods
Cross sectional analysis of the 2018 cohort (n=84.398, mean age 79±10.2 yrs., male 61.5%). Logistic regression analyses were run on referrals and prescription of beta-blockers, ACE-I and AT-1-antagonists (all, yes/no). Models tested for gender effects and included known covariates e.g. age and duration of participation (in yrs.) and comorbidities (diabetes, lipid disorder, hypertension, smoking, all yes/no).

Results
Logistic regression models indicated that gender significantly affected referral rates, OR 1.15, CI-95% 1.09–1.20 and OR 1.15, CI-95% 1.09–1.20, for referrals to hospitals and other physicians. Men received higher rates of referrals to other physicians and other institutions (26.5 vs. 14.2%) and (6.4 vs. 3.5%) than women. Prescription rates were also significantly associated with gender: OR 1.23, CI-95% 1.19–1.27, OR 1.36, CI-95% 1.29–1.43, and OR 0.79, CI-95% 0.72–0.87, for beta-blockers, ACE-I and AT-1-antagonists, respectively. Men received beta-blocker and ACE-I more often (33.8 vs. 4.4% and 28.6 and 8.1%); women had higher rates of AT-1- antagonist prescription (1.2 vs. 5.5%).

Conclusion
Although, as previously shown work indicated, differences decrease over time, marked gender differences in referral and prescription rates in heart failure still exist in ambulatory health care settings. These results indicate that secondary prevention in women with HF needs to improve.

Funding Acknowledgement
Type of funding source: None
Technology-supported home monitoring in heart failure patients
Authors: Rahimi K , Nazarzadeh M , Pinho-Gomes A.C , Woodward M , Salimi-Khorshidi G.H , Ohkuma T , Fitzpatrick R , Tarassenko L , Denis M , Cleland J 
Published: November 2020

Abstract

Background
Digital health promises to enhance the prevailing episodic models of chronic heart failure (HF) care.

Purpose
We aimed to test the hypothesis that digital home monitoring with centralised specialist support for remote management of HF and major vascular comorbidities is more effective in optimising medical therapy and improving patients' quality of life than digital home monitoring alone.

Methods and results
In a two-armed partially blinded parallel randomised controlled trial, seven sites in the United Kingdom recruited a total of 202 adults with HF (71.3 years SD 11.1; mean left ventricular ejection fraction 32.9% SD 15.4). Participants were selected for being at high risk of adverse outcomes or high potential to benefit from remote management. Participants in both study arms were given an internet-enabled tablet computer, Bluetooth-enabled blood pressure monitor and weighing scales for health monitoring. After a run-in period, participants randomized to intervention received additional regular feedback to support self-management and their primary care doctors received instructions on blood investigations and pharmacological treatment. The primary outcome was the use of recommended medical therapy, for chronic HF and major comorbidities, measured as a composite opportunity score. Co-primary outcome was change in physical score of Minnesota Living with Heart failure questionnaire.
At the end of the trial, the weighted opportunity score was 0.54 (CI 95% 0.46, 0.62) in the control group and 0.61 (CI 95% 0.52, 0.70) in the intervention arm (p for mean difference=0.25). Physical well-being of participants did not differ significantly between the groups either (p=0.55).

Conclusions
Central provision of tailored specialist management in a multimorbid HF population was feasible. However, there was no strong evidence for improvement in use of evidence-based therapies nor health-related quality of life.
Figure 1

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): National Institute for Health Research (NIHR) Health Services Research and Delivery; NIHR Career Development Fellowship