BACKGROUND:Studies on multiple serially measured blood biomarkers and adverse outcomes in patients with heart failure (HF) are scarce and restricted to research settings. Prognostic estimates based on serial measurements could provide a scientifically substantiated, uniform approach to risk stratification and timing of treatment. We use an exploratory and hypothesis-generating approach to assess the predictive ability of serially measured biomarkers, commonly collected during usual care, for adverse events in a real-world population of ambulant patients with HF with reduced ejection fraction (HFrEF) and HF with mildly reduced ejection fraction (HFmrEF). METHODS:We included ambulatory HFrEF-HFmrEF patients who attended an outpatient hospital visit between 2017 and 2022. Data on blood biomarkers, clinical characteristics and clinical outcome were extracted from electronic health records. Joint modelling was applied to investigate associations between time-varying blood biomarkers and the composite endpoint of mortality, LVAD implantation and heart transplant. RESULTS:We included 1353 patients; 66.8% men; median (P25, P75) age 62 (51, 71) years. During a median follow-up of 3.30 (1.62, 4.65) years, 387 (28.6%) experienced the endpoint. Temporal trajectories of 30 blood biomarkers were significantly associated with the endpoint. After correcting for clinical characteristics, associations persisted in multiple-biomarker models for serially measured NT-proBNP, hs-TnT, and CRP, as well as liver biomarkers, kidney biomarkers, and blood count parameters. Serial measurements increased model performance compared to baseline measurements, with AUCs up to 0.83 for multiple-biomarker models. CONCLUSION:Real-life, serially measured laboratory data predict adverse events in an ambulatory HFrEF-HFmrEF population, with good internal model performance. Thus, making use of laboratory values already present in electronic medical records, could inform risk stratification without any extra effort.

This article contextualises the 2023 European Society of Cardiology (ESC) guidelines for the management of cardiomyopathies for clinical practice in the Netherlands. The guideline addendum provides additional recommendations for situations where the ESC guidelines may not fully align with Dutch clinical practice. By endorsing the ESC guidelines through this addendum, the Netherlands Society of Cardiology (Nederlandse Vereniging Voor Cardiologie) supports its members in adhering to evidence-based management strategies for cardiomyopathies. As Dutch cardiologists generally adopt the ESC guidelines quickly, this contextualisation is essential for effective application thereof within the Dutch healthcare setting.

Epicardial adipose tissue (EAT) has garnered interest due to its important role in obesity-related heart failure with preserved ejection fraction. However, while bariatric surgery is known to both improve cardiac function and reduce EAT, the presence of any relation between these two remains unclear. This study aims to investigate the association between EAT changes and improvement of cardiac dysfunction following bariatric surgery. This prospective cohort study enrolled subjects aged 35-65years with a body mass index ≥ 35 kg/m² who underwent bariatric surgery, excluding those with known cardiac disease. Conventional transthoracic echocardiography and strain analyses were conducted before and one-year post-surgery. Improvement in cardiac function was defined as a composite outcome requiring improvement in three domains: systolic function (ejection fraction or global longitudinal strain), diastolic function (E/e’ratio or septal e’velocity), and cardiac remodeling (left atrial volume index or left ventricular mass index). In the 142 patients who completed one year follow-up, a significant reduction in EAT of 31 • EAT reduction post-bariatric surgery was associated with left ventricular function improvement one-year after bariatric surgery in individuals with obesity without established cardiac disease independent of change in body mass index. • EAT reduction post-bariatric surgery was not related to weight loss per se, further emphasizes the multifaceted benefits of bariatric surgery. • EAT thickness could serve as an easy, fast, and non-invasive marker for monitoring cardiac dysfunction in individuals with obesity without known cardiac disease.

Abstract The rising prevalence of obesity and its association with heart failure with preserved ejection fraction (HFpEF) highlight an urgent need for a diagnostic approach tailored to this population. Diagnosing HFpEF is hampered by the lack of a single non-invasive diagnostic criterion. While this makes a firm diagnosis of HFpEF already notoriously difficult in the general population, it is even more challenging in individuals with obesity. The challenges stem from a range of factors, including the use of body mass index as a conceptually suboptimal indicator of health risks associated with increased body mass, symptom overlap between HFpEF and obesity, limitations in physical examination, difficulties in electrocardiographic and echocardiographic evaluation, and reduced diagnostic sensitivity of natriuretic peptides in individuals with obesity. In this review, we examine these diagnostic challenges and propose a diagnostic algorithm specifically tailored to improve the accuracy and reliability of HFpEF diagnosis in this growing patient demographic. Graphical abstract Proposed obesity-adjusted HFpEF score. HFpEF, Heart failure with preserved ejection fraction. Created with BioRender.com.

Introduction This study investigates the interplay between the circulating plasma proteome and echocardiographic parameters in patients across the spectrum of heart failure (HF) (ranging from patients at risk of/with preserved (HFpEF) to reduced (HFrEF) ejection fraction). Methods Data from two cohort studies, HELPFul and Bio-SHiFT, were analyzed. We measured 4210 circulating plasma proteins in a total of 750 patients using SomaScan® proteomics. Echocardiographic parameters in both studies included left ventricular ejection fraction (LVEF) and the ratio of the peak early left ventricular (LV) filling velocity and early diastolic mitral annular velocity (E/e’). In further analyses, we classified patients in left ventricular diastolic dysfunction (LVDD) groups according to the prevailing guidelines. Results Out of the 4210 plasma proteins, 21 proteins were significantly associated with E/e’ in patients at risk of/with HFpEF, whereas 9 proteins were associated with LVEF. Approximately 43 % (n = 1822) of the proteins showed significant interactions between E/e’ and HF subtype. All of these proteins showed weaker associations with E/e’ in patients at risk of/with HFpEF compared to the ones with HFrEF. These proteins were related to the extracellular matrix, cellular processes, insulin-like growth factor (IGF) transport, metabolic and catabolic processes. Furthermore, comparisons between LVDD groups and those with normal diastolic function identified 40 proteins associated with grade 2 (top 5: Cystatin C, TMEDA, NT-proBNP, GDF-15 and PXDN) and 198 with grade 3 LVDD (top 5: NT-proBNP, Cystatin C, PXDN, RNasa1, and Factor D). Conclusion In patients at risk of/with HFpEF, biological processes and pathways showed weaker associations with E/e’ compared to patients with HFrEF. Varying pathways identified through proteomics were associated with deterioration of LVDD across the ejection fraction spectrum. Our results are in line with the mechanistic frameworks currently thought to underlie the various types of HF.

This article contextualises the 2023 European Society of Cardiology (ESC) guidelines for the management of cardiomyopathies for clinical practice in the Netherlands. The guideline addendum provides additional recommendations for situations where the ESC guidelines may not fully align with Dutch clinical practice. By endorsing the ESC guidelines through this addendum, the Netherlands Society of Cardiology (Nederlandse Vereniging Voor Cardiologie) supports its members in adhering to evidence-based management strategies for cardiomyopathies. As Dutch cardiologists generally adopt the ESC guidelines quickly, this contextualisation is essential for effective application thereof within the Dutch healthcare setting.

Background: Atrial fibrillation (AF) and heart failure (HF) are intertwined conditions with high mortality and impact on quality of life. The biological mechanisms at play in patients with HF with vs without AF may differ. Objectives: This study aimed to describe differences in circulating proteins with putative pathophysiological effects between HF with reduced ejection fraction (HFrEF) patients with and without AF. Methods: We examined 377 patients with ambulant HFrEF and measured 4210 circulating proteins in baseline blood samples using an aptamer-based multiplex proteomic approach. Associations between AF (AF history or on baseline electrocardiogram) and the proteins were assessed using regression models adjusted for age, sex, kidney function, and duration of HF at baseline. Associations of AF-related proteins with biological processes were evaluated using enrichment analyses. Results: The median age [25th–75th percentile] was 64 years [55–72], 73% [274 of 377] were male, 28% [104 of 375] had New York Heart Association class III/IV, and 37% [139 of 377] had AF (either AF history [36%, 137 of 377] or AF on baseline electrocardiogram [8%, 30 of 374]). We found 71 proteins significantly associated with AF (false discovery rate < .05), including well-studied (eg, troponin T, insulin-like growth factor-binding protein 7, microfibril-associated glycoprotein 4, bone morphogenetic protein 10, angiopoietin 2) and lesser-studied proteins (eg, olfactomedin−like protein 3, keratocan, basigin) in the AF domain. Our pathway analysis revealed modules of proteins related to various underlying mechanisms, such as nervous system development, elastic fiber assembly, protein glycosylation, and ether lipid metabolism. Conclusions: Patients with HFrEF with AF have distinct circulating proteomic profiles, and these differences are related to various biological mechanisms. This study provides an overview of the systemic biological pathways associated with AF in patients with HFrEF, confirms (pre-)clinical findings regarding AF-related proteins, and could inform future research in novel treatment targets and HFrEF-AF management after careful validation.

Background: Although obesity is a major risk factor for atrial fibrillation (AF), its mechanisms and the diagnostic yield of AF screening in severe obesity is unclear. This study aims to enhance our comprehension of AF susceptibility in severe obesity by investigating associations between left atrial (LA) cardiomyopathy and premature atrial contractions (PACs) and to explore the diagnostic yield of AF screening. Methods: This cross-sectional study included a total of 192 subjects aged 35-65 years with a BMI >= 35 kg/m2, alongside 50 non-obese controls, both without known cardiac disease. Prolonged heart rhythm registration was done with either 24-hours (n = 147) or 7-day Holter monitoring (n = 75) or an implantable loop recorder (ILR) (n = 10). Furthermore, we performed conventional transthoracic echocardiography and strain analyses. Results: In the obese cohort, LA enlargement was independently associated with PAC frequency. Each SD increment (10 ml/m2) of LA volume index corresponded with a 46 % increase in PACs. An increase of each SD (10 %) LA reservoir strain was associated with a decrease of 16 % in PAC frequency. There was no association found between LA cardiomyopathy and PACs in the control group. AF was not detected in any subject. Conclusion: LA enlargement was independently associated with more frequent PACs in severe obesity, a wellknown AF precursor. There was a noticeable trend suggesting a relation between impaired LA function and PACs. Considering our observed low diagnostic yield of AF screening within this population, further investigation is needed to determine whether incorporating LA cardiomyopathy as an additional risk measure could improve AF screening strategies for individuals with severe obesity.

Abstract Background Atrial fibrillation (AF) and heart failure (HF) are intertwined conditions with high mortality rates and large impact on quality of life, and their coexistence is increasingly prevalent. Both conditions influence each other’s development and progression, and share many risk-factors—such as hypertension, obesity, diabetes mellitus and ischaemic heart disease. Moreover, their combined presence further increases the risk of hospitalization and mortality. The biological mechanisms at play in HF patients with AF may therefore differ from those in HF patients without AF. Purpose We aimed to describe the differences in pathophysiological pathways in HF patients with versus without AF, by identifying biomarkers associated with AF from a panel of 4210 circulating proteins and subsequently examining biological mechanisms related to these biomarkers. Methods We examined 377 ambulant HF patients with reduced ejection fraction from a longitudinal cohort study. We measured 4210 circulating proteins in baseline blood samples using an aptamer-based multiplex proteomic approach. Associations between AF (known AF history or AF on the baseline ECG) and the proteins were assessed using linear regression models adjusted for age, sex, kidney function and duration of HF at baseline. Associations of proteins significantly related to AF, with biological processes, were assessed using network-based clustering and subsequent enrichment analysis. Results The median [25th, 75th percentile] age was 64 [55, 72], 73% [274/377] were male, 28% [104/375] had NYHA-class III or IV, and 37% [139/377] had AF (either AF history: 36% [137/377] or AF on baseline ECG: 8% [30/374]). We found 71 proteins significantly associated with AF (FDR<0.05), including well-studied (e.g. troponin T, IGFBP7, MFAP4, BMP10, angiopoietin 2) and lesser studied (e.g. olfactomedin−like protein 3, keratocan, basigin) proteins in the AF domain. Our pathway analysis revealed clusters of proteins related to various underlying mechanisms, such as axon guidance, elastic fibre assembly, macrophage derived foam cell differentiation, ether lipid metabolism and amyloid-beta binding. Overviews of the significantly associated proteins and related biological mechanisms are provided in Figures 1 and 2. Conclusion HF patients with AF have distinct proteomic profiles and these differences are related to various biological mechanisms, many of which can be associated with atrial remodelling. This study provides an overview of the biological mechanisms behind AF in HF, confirms prior findings regarding AF-related proteins, and could guide future research in novel treatment targets and HF-AF management.Figure 1:Proteins associated with AFFigure 2:Biological mechanisms

AIMS:Examining the systemic biological processes in the heterogeneous syndrome of heart failure with reduced ejection fraction (HFrEF), as reflected by circulating proteins, in relation to echocardiographic characteristics, may provide insights into heart failure pathophysiology. We investigated the link of 4210 repeatedly measured circulating proteins with repeatedly measured echocardiographic parameters as well as with elevated left atrial pressure (LAP), in patients with HFrEF, to provide insights into underlying mechanisms. METHODS AND RESULTS:In 173 patients with HFrEF, we performed 6-monthly echocardiography and trimonthly blood sampling during a median follow-up of 2.7 (inter-quartile range: 2.5-2.8) years. We investigated circulating proteins in relation to echocardiographic parameters of left ventricular [left ventricular ejection fraction (LVEF), global longitudinal strain (GLS)] and left atrial function [left atrial reservoir strain (LASr)] and elevated LAP (E/e' ratio >15) and used gene enrichment analyses to identify underlying pathophysiological processes. We found 723, 249, 792, and 427 repeatedly measured proteins, with significant associations with LVEF, GLS, LASr, and E/e' ratio, respectively. Proteins associated with LASr reflected pathophysiological mechanisms mostly related to the extracellular matrix. Proteins associated with GLS reflected cardiovascular biological processes and diseases, whereas those associated with LVEF reflected processes involved in the sympathetic nervous system. Moreover, 49 proteins were associated with elevated LAP; after correction for LVEF, three proteins remained: cystatin-D, fibulin-5, and HSP40. CONCLUSION:Circulating proteins show varying associations with different echocardiographic parameters in patients with HFrEF. These findings suggest that pathways involved in atrial and ventricular dysfunction, as reflected by the plasma proteome, are distinct.

Aims Despite clear guideline recommendations for initiating four drug classes in all patients with heart failure (HF) with reduced ejection fraction (HFrEF) and the availability of rapid titration schemes, information on real-world implementation lags behind. Closely following the 2021 ESC HF guidelines and 2023 focused update, the TITRATE-HF study started to prospectively investigate the use, sequencing, and titration of guideline-directed medical therapy (GDMT) in HF patients, including the identification of implementation barriers. Methods and results TITRATE-HF is an ongoing long-term HF registry conducted in the Netherlands. Overall, 4288 patients from 48 hospitals were included. Among these patients, 1732 presented with de novo, 2240 with chronic, and 316 with worsening HF. The median age was 71 years (interquartile range [IQR] 63-78), 29% were female, and median ejection fraction was 35% (IQR 25-40). In total, 44% of chronic and worsening HFrEF patients were prescribed quadruple therapy. However, only 1% of HFrEF patients achieved target dose for all drug classes. In addition, quadruple therapy was more often prescribed to patients treated in a dedicated HF outpatient clinic as compared to a general cardiology outpatient clinic. In each GDMT drug class, 19% to 36% of non-use in HFrEF patients was related to side-effects, intolerances, or contraindications. In the de novo HF cohort, 49% of patients already used one or more GDMT drug classes for other indications than HF. Conclusion This first analysis of the TITRATE-HF study reports relatively high use of GDMT in a contemporary HF cohort, while still showing room for improvement regarding quadruple therapy. Importantly, the use and dose of GDMT were suboptimal, with the reasons often remaining unclear. This underscores the urgency for further optimization of GDMT and implementation strategies within HF management. [GRAPHICS]

Circulating proteins may provide insights into the varying biological mechanisms involved in heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). We aimed to identify specific proteomic patterns for HF, by comparing proteomic profiles across the ejection fraction spectrum. We investigated 4210 circulating proteins in 739 patients with normal (Stage A/Healthy) or elevated (Stage B) filling pressures, HFpEF, or ischemic HFrEF (iHFrEF). We found 2122 differentially expressed proteins between iHFrEF-Stage A/Healthy, 1462 between iHFrEF-HFpEF and 52 between HFpEF-Stage A/Healthy. Of these 52 proteins, 50 were also found in iHFrEF vs. Stage A/Healthy, leaving SLITRK6 and NELL2 expressed in lower levels only in HFpEF. Moreover, 108 proteins, linked to regulation of cell fate commitment, differed only between iHFrEF-HFpEF. Proteomics across the HF spectrum reveals overlap in differentially expressed proteins compared to stage A/Healthy. Multiple proteins are unique for distinguishing iHFrEF from HFpEF, supporting the capacity of proteomics to discern between these conditions.

BackgroundWe investigated whether repeatedly measured global longitudinal strain (GLS) has incremental prognostic value over repeatedly measured left ventricular ejection fraction (LVEF) and N-terminal pro B-type natriuretic peptide (NT-proBNP), and a single “baseline” GLS value, in chronic heart failure (HF) patients.MethodsIn this prospective observational study, echocardiography was performed in 173 clinically stable chronic HF patients every six months during follow up. During a median follow-up of 2.7 years, a median of 3 (25th–75th percentile:2–4) echocardiograms were obtained per patient. The endpoint was a composite of HF hospitalization, left ventricular assist device, heart transplantation, cardiovascular death. We compared hazard ratios (HRs) for the endpoint from Cox models (used to analyze the first available GLS measurements) with HRs from joint models (which links repeated measurements to the time-to-event data).ResultsMean age was 58 ± 11 years, 76% were men, 81% were in New York Heart Association functional class I/II, and all had LVEF < 50% (mean ± SD: 27 ± 9%). The endpoint was reached by 53 patients. GLS was persistently decreased over time in patients with the endpoint. However, temporal GLS trajectories did not further diverge in patients with versus without the endpoint and remained stable during follow-up. Both single measurements and temporal trajectories of GLS were significantly associated with the endpoint [HR per SD change (95%CI): 2.15(1.34–3.46), 3.54 (2.01–6.20)]. In a multivariable model, repeatedly measured GLS maintained its prognostic value while repeatedly measured LVEF did not [HR per SD change (95%CI): GLS:4.38 (1.49–14.70), LVEF:1.14 (0.41–3.23)]. The association disappeared when correcting for repeatedly measured NT-proBNP.ConclusionTemporal evolution of GLS was associated with adverse events, independent of LVEF but not independent of NT-proBNP. Since GLS showed decreased but stable values in patients with adverse prognosis, single measurements of GLS provide sufficient information for determining prognosis in clinical practice compared to repeated measurements, and temporal GLS patterns do not add prognostic information to NT-proBNP.

Aim Epicardial adipose tissue (EAT) plays a role in obesity-related heart failure with preserved ejection fraction. However, the association of EAT thickness with the development of cardiac dysfunction in subjects with severe obesity without known cardiovascular disease is unclear. The aim of this study was to determine the association between EAT thickness and cardiac dysfunction and describe the potential value of EAT as an early marker of cardiac dysfunction Methods and results Subjects with body mass index >= 35 kg/m(2) aged 35 to 65 years, who were referred for bariatric surgery, without suspicion of or known cardiac disease, were enrolled. Conventional transthoracic echocardiography and strain analyses were performed. A total of 186 subjects were divided into tertiles based on EAT thickness, of whom 62 were in EAT-1 (EAT <3.8 mm), 63 in EAT-2 (EAT 3.8- 5.4 mm), and 61 in EAT-3 (EAT >5.4 mm). Parameters of systolic and diastolic function were comparable between tertiles. Patients in EAT-3 had the lowest global longitudinal strain (GLS) and left atrial contractile strain (LASct). Linear regression showed that a one-unit increase in EAT thickness (mm) was independently associated with a decrease in GLS (%) (beta coefficient-0.404, p = 0.002), and a decrease in LASct (%) (beta coefficient-0.544, p = 0.027). Furthermore, EAT-3 independently predicted cardiac dysfunction as defined by a GLS <18% (odds ratio 2.8, p = 0.013) and LASct <14% (odds ratio 2.5, p = 0.045) Conclusions Increased EAT thickness in subjects with obesity without known cardiac disease was independently associated with subclinical cardiac dysfunction. Our findings suggest that EAT might play a role in the early stages of cardiac dysfunction in obesity before this may progress to overt clinical disease. [GRAPHICS] .

We investigated whether repeatedly measured left atrial reservoir strain (LASr) in heart failure with reduced ejection fraction (HFrEF) patients provides incremental prognostic value over a single baseline LASr value, and whether temporal patterns of LASr provide incremental prognostic value over temporal patterns of other echocardiographic markers and NT-proBNP. In this prospective observational study, 153 patients underwent 6-monthly echocardiography, during a median follow-up of 2.5 years. Speckle tracking echocardiography was used to measure LASr. Hazard ratios (HRs) were calculated for LASr from Cox models (baseline) and joint models (repeated measurements). The primary endpoint (PEP) comprised HF hospitalization, left ventricular assist device, heart transplantation, and cardiovascular death. Mean age was 58 ± 11 years, 76

INTRODUCTION:The prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 25% in the general population to 90% in patients with obesity scheduled for bariatric surgery. NAFLD can progress towards non-alcoholic steatohepatitis (NASH) associated with complications such as cirrhosis, hepatocellular carcinoma and cardiovascular disease. To date, losing weight and lifestyle modifications are the best known treatments for NASH. Bariatric surgery significantly improves NAFLD/NASH in the short term. However, the extent of this improvement is not yet clear and long-term data on the natural course of NAFLD/NASH after bariatric surgery are lacking. The factors involved in NAFLD/NASH regression after bariatric surgery have not been elucidated.METHODS AND ANALYSIS:This is an observational prospective cohort study including patients scheduled for bariatric surgery. Extensive metabolic and cardiovascular analyses will be carried out including measurements of carotid intima media thickness and pulse wave velocity. Genomic, proteomic, lipidomic and metabolomic studies will be done. Microbioma analyses before and 1 year after surgery will be done. Transient elastography measurements will be performed before and at 1, 3 and 5 years after surgery. For those with an elevated preoperative transient elastography measurement by Fibroscan, a laparoscopic liver biopsy will be performed during surgery. Primary outcome measures are the change of steatosis and liver fibrosis 5 years after surgery. Secondary outcome measure is the comparison of the transient elastography measurements with the NAFLD Activity Score from the biopsies.ETHICS AND DISSEMINATION:The protocol has been approved by the Medical Research Ethics Committees United, Nieuwegein, on 1 March 2022 (registration code R21.103/NL79423.100.21). The study results will be submitted for publication in peer-reviewed journals and data will be presented at scientific meetings.TRIAL REGISTRATION NUMBER:NCT05499949.

BACKGROUND:The aim of this study was to assess heart failure (HF) treatment in patients with and without obesity in a large contemporary real-world Western European cohort.METHODS:Patients with a left ventricular ejection fraction (LVEF) <50% and available information on body mass index (BMI) were selected from the CHECK-HF registry. The CHECK-HF registry included chronic HF patients in the period between 2013 and 2016 in 34 Dutch outpatient clinics. Patients were divided into BMI categories. Differences in HF medical treatment were analysed, and multivariable logistic regression analysis (dichotomized as BMI <30 kg/m2 and ≥30 kg/m2 ) was performed.RESULTS:Seven thousand six hundred seventy-one patients were included, 1284 (16.7%) had a BMI ≥30 kg/m2 , and 618 (8.1%) had a BMI ≥35 kg/m2 . Median BMI was 26.4 kg/m2 . Patients with obesity were younger and had a higher rate of comorbidities such as diabetes mellitus, hypertension and obstructive sleep apnoea (OSAS). Prescription rates of guideline-directed medical therapy (GDMT) increased significantly with BMI. The differences were most pronounced for mineralocorticoid receptor antagonists (MRAs) and diuretics. Patients with obesity more often received the guideline-recommended target dose. In multivariable logistic regression, obesity was significantly associated with a higher likelihood of receiving ≥100% of the guideline-recommended target dose of beta-blockers (OR 1.34, 95% CI 1.10-1.62), renin-angiotensin system (RAS)-inhibitors (OR 1.34, 95% CI 1.15-1.57) and MRAs (OR 1.40, 95% CI 1.04-1.87).CONCLUSIONS:Guideline-recommended HF drugs are more frequently prescribed and at a higher dose in patients with obesity as compared to HF patients without obesity.

AIMS:In a large proportion of heart failure with reduced ejection fraction (HFrEF) patients, echocardiographic estimation of left atrial pressure (LAP) is not possible when the ratio of the peak early left ventricular filling velocity over the late filling velocity (E/A ratio) is not available, which may occur due to several potential causes. Left atrial reservoir strain (LASr) is correlated with LV filling pressures and may serve as an alternative parameter in these patients. The aim of this study was to determine whether LASr can be used to estimate LAP in HFrEF patients in whom E/A ratio is not available.METHODS AND RESULTS:Echocardiograms of chronic HFrEF patients were analysed and LASr was assessed with speckle tracking echocardiography. LAP was estimated using the current ASE/EACVI algorithm. Patients were divided into those in whom LAP could be estimated using this algorithm (LAPe) and into those in whom this was not possible because E/A ratio was not available (LAPne). We assessed the prognostic value of LASr on the primary endpoint (PEP), which comprised the composite of hospitalization for the management of acute or worsened HF, left ventricular assist device implantation, cardiac transplantation, and cardiovascular death, whichever occurred first in time. We studied 153 patients with a mean age of 58 years of whom 76% men and 82% who were in NYHA class I-II. A total of 86 were in the LAPe group and 67 in the LAPne group. LASr was significantly lower in the LAPne group as compared with the LAPe group (15.8% vs. 23.8%, P < 0.001). PEP-free survival at a median follow-up of 2.5 years was 78% in LAPe versus 51% in LAPne patients. An increase in LASr was significantly associated with a reduced risk of the PEP in LAPne patients (adjusted hazard ratio: 0.91 per %, 95% confidence interval 0.84-0.98). An abnormal LASr (<18%) was associated with a five-fold increase in reaching the PEP.CONCLUSIONS:In HFrEF patients in whom echocardiographic estimation of LAP is not possible due to due to unavailability of E/A ratio, assessing LASr potentially carries added clinical and prognostic value.