Differential sex-related effect of left ventricular ejection fraction trajectory on the risk of mortality and heart failure readmission following hospitalization for acute heart failure: A longitudinal study.

AIMS: There is limited information on the sex-specific longitudinal changes of left ventricular ejection fraction (LVEF) after an acute heart failure (AHF) hospitalization. We aimed to investigate whether LVEF trajectories over time and their impact on mortality and AHF readmission rates differ between men and women. METHODS AND RESULTS: We conducted a retrospective sex-specific analysis of longitudinal LVEF measurements (n = 9581) in 3383 patients with an index hospitalization for AHF in a single tertiary-level hospital. Statistical techniques suited for longitudinal data analysis were used. The mean age of the sample was 73.8 ± 11.2 years, and 47.9% were women. The mean LVEF was 49.4 ± 15.3%. At a median follow-up of 2.58 years (interquartile range 0.77-5.62), we registered 2197 deaths (64.9%) and 2597 AHF readmissions in 1302 (38.5%) patients. The longitudinal analysis showed that women had consistently higher LVEF values throughout the follow-up with both trajectories characterized by an early peak-approximately at 1 year-followed by decreasing values in men but a plateau in women. Multivariate between-sex comparisons across LVEF categories revealed that women had lower rates of AHF readmissions when LVEF ≤40%. On the contrary, women displayed an excess risk of AHF readmissions when LVEF >60%. A trend in the same direction was found for cardiovascular and all-cause mortality. CONCLUSION: Sex was a significant factor in determining the follow-up trajectory of LVEF and predicting differences in outcomes after an AHF admission. The findings suggest that women have a higher risk of AHF readmissions at higher LVEF values, while men have a higher risk at lower LVEF values. For all-cause and cardiovascular mortality, the same direction of the association was inferred but they were not significant.

ß-Blocker Withdrawal and Functional Capacity Improvement in Patients With Heart Failure With Preserved Ejection Fraction.

Importance: Increasing the patient's heart rate (HR) has emerged as a therapeutic option in patients with heart failure with preserved ejection fraction (HFpEF). However, the evidence is conflicting, and the profile of patients who benefit most from this strategy remains unclear. Objective: To assess the association of ß-blocker treatment withdrawal with changes in the percentage of predicted peak oxygen consumption (VO2) across indexed left ventricular diastolic (iLVEDV) and indexed left ventricular systolic volumes (iLVESV), and left ventricular ejection fraction (LVEF) in patients with HFpEF and chronotropic incompetence. Design, Setting, and Participants: This post hoc analysis was conducted using data from the investigator-blinded multicenter, randomized, and crossover clinical trial, PRESERVE-HR, that took place from October 1, 2018, through December 31, 2020, to investigate the short-term effects (2 weeks) of ß-blocker withdrawal on peak oxygen consumption (peak VO2). Patients with stable HFpEF (New York Heart Association functional class II to III) receiving treatment with ß-blocker and chronotropic incompetence were included. Intervention: Participants in the PRESERVE-HR trial were randomized to withdraw vs continue with ß-blocker treatment. After 2 weeks, they were crossed over to receive the opposite intervention. This crossover randomized clinical trial examined the short-term effect of ß-blocker withdrawal on peak VO2. Main Outcomes and Measures: The primary outcome was to evaluate the association between ß-blocker withdrawal and short-term changes in percentage of peak VO2 across iLVEDV, iLVESV, and LVEF in patients with HFpEF and chronotropic incompetence treated with ß-blocker. Results: A total of 52 patients (mean age, 73 [SD, 13] years; 60% female) were randomized. The mean resting HR, peak HR, peak VO2, and percentage of peak VO2 were 65 (SD, 9) beats per minute (bpm), 97 (SD, 15) bpm, 12.4 (SD, 2.9) mL/kg per minute, and 72.4% (SD, 17.7%), respectively. The medians (minimum-maximum) of iLVEDV, iLVESV, and LVEF were 44 mL/m2 (IQR, 19-82), 15 mL/m2 (IQR, 7-32), and 64% (IQR, 52%-78%), respectively. After stopping ß-blocker treatment, the median increase in peak HR was plus 30 bpm (95% CI, 25-35; P < .001). ß-Blocker cessation was differentially associated with change of percentage of peak VO2 across the continuum of iLVESV (P for interaction = .02), indicating a greater benefit in those with lower iLVESV. Conclusions and Relevance: In this study, results showed that in patients with HFpEF and chronotropic incompetence receiving treatment with ß-blocker, lower iLVESV may identify those with a greater short-term improvement in maximal functional capacity after stopping ß-blocker treatment. Further studies are warranted for further investigation. Trial Registration: ClinicalTrials.gov (NCT03871803).

Intrarenal Venous Flow Pattern Changes Do Relate With Renal Function Alterations in Acute Heart Failure.

BACKGROUND: There is scarce evidence supporting the clinical utility of congestive intrarenal venous flow (IRVF) patterns in patients with acute heart failure. OBJECTIVES: This study aims to: 1) investigate the association between IRVF patterns and the odds of worsening renal function (WRF); 2) track the longitudinal changes of serum creatinine (sCr) across IRVF at predetermined points and its association with decongestion; and 3) explore the relationship between IRVF/WRF categories and patient outcomes. METHODS: IRVF was assessed at baseline (pre-decongestive therapy), 72 hours, and 30 and 90 days postdischarge. Changes in sCr trajectories across dynamic IRVF variations and parameters of decongestion were assessed using linear mixed effect models. The association between IRVF/WRF categories and outcomes was evaluated using univariable/multivariable models. RESULTS: In this prospective, multicenter study with 188 participants, discontinuous IRVF patterns indicated higher odds of WRF (OR: 3.90 [95% CI: 1.24-12.20]; P = 0.020 at 72 hours; and OR: 5.76 [95% CI: 1.67-19.86]; P = 0.006 at 30 days) and an increase in sCr (Δ-72 hours 0.14 mg/dL [95% CI: 0.06-0.22]; P = 0.001; Δ-discharge 0.13 mg/dL [95% CI: 0.03-0.23]; P = 0.007). However, the diuretic response and decongestion significantly influenced the magnitude of these changes. Patients exhibiting both WRF and discontinuous IRVF at 30 days experienced an increased hazard of adverse events (HR: 5.96 [95% CI: 2.63-13.52]; P < 0.001). CONCLUSIONS: Discontinuous IRVF identifies patients with higher odds of WRF during admission and postdischarge periods. Nonetheless, adequate diuretic response and decongestion could modify this association. Patients showing both WRF and discontinuous IRVF at 30 days had increased rates of adverse events.

Noncardiovascular morbidity and mortality across left ventricular ejection fraction categories following hospitalization for heart failure.

INTRODUCTION AND OBJECTIVES: Noncardiovascular events represent a significant proportion of the morbidity and mortality burden in patients with heart failure (HF). However, the risk of these events appears to differ by left ventricular ejection fraction (LVEF) status. In this study, we sought to evaluate the risk of noncardiovascular death and recurrent noncardiovascular readmission by LVEF status following an admission for acute HF. METHODS: We retrospectively assessed a cohort of 4595 patients discharged after acute HF in a multicenter registry. We evaluated LVEF as a continuum, stratified in 4 categories (LVEF ≤ 40%, 41%-49%, 50%-59%, and ≥ 60%). Study endpoints were the risks of noncardiovascular mortality and recurrent noncardiovascular admissions during follow-up. RESULTS: At a median follow-up of 2.2 [interquartile range, 0.76-4.8] years, we registered 646 noncardiovascular deaths and 4014 noncardiovascular readmissions. After multivariable adjustment including cardiovascular events as a competing event, LVEF status was associated with the risk of noncardiovascular mortality and recurrent noncardiovascular admissions. When compared with patients with LVEF ≤ 40%, those with LVEF 51%-59%, and especially those with LVEF ≥ 60%, were at higher risk of noncardiovascular mortality (HR, 1.31; 95%CI, 1.02-1,68; P=.032; and HR, 1.47; 95%CI, 1.15-1.86; P=.002; respectively), and at higher risk of recurrent noncardiovascular admissions (IRR, 1.17; 95%CI, 1.02-1.35; P=.024; and IRR, 1.26; 95%CI, 1.11-1.45; P=.001; respectively). CONCLUSIONS: Following an admission for HF, LVEF status was directly associated with the risk of noncardiovascular morbidity and mortality. Patients with HFpEF were at higher risk of noncardiovascular death and total noncardiovascular readmissions, especially those with LVEF ≥ 60%.

Improvement in left atrial strain following ferric carboxymaltose in heart failure: an analysis of the Myocardial-IRON trial.

AIMS: Iron deficiency (ID) is associated with an impaired cardiac function and remodelling in heart failure (HF). Treatment with ferric carboxymaltose (FCM) has been showed recently to improve biventricular systolic function and ventricular strain parameters in patients with HF with reduced ejection fraction and ID, but there is no evidence on the benefit of FCM on the left atrium (LA). In this study, we aimed to evaluate the effect of FCM on LA longitudinal strain (LA-LS). METHODS AND RESULTS: This is a post hoc subanalysis of a double-blind, placebo-controlled, randomized clinical trial that enrolled 53 ambulatory patients with HF, left ventricular ejection fraction (LVEF) < 50%, and ID [Myocardial-IRON trial (NCT03398681)], treated with FCM or placebo. Cardiac magnetic resonance-featured tracking (CMR-FT) strain changes were evaluated before and 7 and 30 days after randomization using linear mixed regression analysis. The median age of the sample was 68 years (interquartile range: 64-76), and 20 (69%) were men. Mean ± standard deviation of LVEF was 39 ± 11%, and most (97%) were in stable New York Heart Association class II. At baseline, mean LA-LS was -8.9 ± 3.5%. At 30 days, and compared with placebo, LA-LS significantly improved in those allocated to FCM treatment arm (LA-LS = -12.0 ± 0.5 and -8.5 ± 0.6, respectively; - ∆ 3.55%, P < 0.001). CONCLUSIONS: In patients with stable HF, LVEF < 50%, and ID, treatment with FCM was associated with short-term improvements in LA-LS assessed by CMR-FT. Future works should assess the potential benefit of iron repletion on LA function.

Early glomerular filtration rates changes and risk of mortality in acute heart failure. The modifying role of admission renal function and decongestion.

BACKGROUND: The pathophysiology of changes in estimated glomerular filtration rate (eGFR) in acute heart failure (AHF) is complex and multifactorial. We evaluated the associated mortality risk of early changes in eGFR across baseline renal function on admission and early changes in natriuretic peptides in patients admitted with AHF. METHODS: We retrospectively evaluated 2,070 patients admitted with AHF. Renal dysfunction on admission was defined as eGFR<60 ml/min/1.73m2 and successful decongestion as NT-proBNP decreased >30% from baseline. We assessed the mortality risk associated with eGFR changes from baseline at 48-72 h after admission (ΔeGFR%) according to baseline renal function, and NT-proBNP changes at 48-72 h through Cox regression analyses. RESULTS: The mean age was 74.4 ± 11.2 years, and 930 (44.9%) were women. The proportion of admission eGFR<60 ml/min/1.73m2 and 48-72 h changes in NT-proBNP>30% were 50.5% and 32.8%, respectively. At a median follow-up of 1.75 years, 928 deaths were registered. In the whole sample, changes in renal function were not associated with mortality (p = 0.208). The adjusted analysis revealed that the risk of mortality related to ΔeGFR% was heterogeneous across baseline renal function and changes in NT-proBNP (p-value for interaction=0.003). ΔeGFR% was not associated with mortality in patients with baseline eGFR≥60 ml/min/1.73m2. In those with eGFR<60 ml/min/1.73m2, a decrease in eGFR was associated with higher mortality, particularly in those with a reduction in NT-proBNP<30%. CONCLUSION: In patients with AHF, early ΔeGFR% was associated with the risk of long-term mortality only in patients with renal dysfunction on admission and no early decline in NT-proBNP.

Impact of dapagliflozin on cardiac remodelling in patients with chronic heart failure: The DAPA-MODA study.

AIMS: Dapagliflozin improves the prognosis of patients with heart failure (HF), regardless of left ventricular ejection fraction (LVEF). However, its effect on cardiac remodelling parameters, specifically left atrial (LA) remodelling, is not well established. METHODS AND RESULTS: The DAPA-MODA trial (NCT04707352) is a multicentre, single-arm, open-label, prospective and interventional study that aimed to evaluate the effect of dapagliflozin on cardiac remodelling parameters over 6 months. Patients with stable chronic HF receiving optimized guideline-directed therapy, except for any sodium-glucose cotransporter 2 inhibitor, were included. Echocardiography was performed at baseline, 30 and 180 days, and analysed by a central core-lab in a blinded manner to both patient and time. The primary endpoint was the change in maximal LA volume index (LAVI). A total of 162 patients (64.2% men, 70.5 ± 10.6 years, 52% LVEF >40%) were included in the study. At baseline, LA dilatation was observed (LAVI 48.1 ± 22.6 ml/m2 ) and LA parameters were similar between LVEF-based phenotypes (≤40% vs. >40%). LAVI showed a significant reduction at 180 days (-6.6% [95% confidence interval -11.1, -1.8], p = 0.008), primarily due to a decrease in reservoir volume (-13.8% [95% confidence interval -22.5, -4], p = 0.007). Left ventricular geometry improved with significant reductions in left ventricular mass index (-13.9% [95% confidence interval -18.7, -8.7], p < 0.001), end-diastolic volume (-8.0% [95% confidence interval -11.6, -4.2], p < 0.001) and end-systolic volume (-11.9% [95% confidence interval -16.7, -6.8], p < 0.001) at 180 days. N-terminal pro-B-type natriuretic peptide (NT-proBNP) showed a significant reduction at 180 days (-18.2% [95% confidence interval -27.1, -8.2], p < 0.001), without changes in filling Doppler measures. CONCLUSION: Dapagliflozin administration in stable out-setting patients with chronic HF and optimized therapy results in global reverse remodelling of cardiac structure, including reductions in LA volumes and improvement in left ventricular geometry and NT-proBNP concentrations.

An update on utilising brain natriuretic peptide for risk stratification, monitoring and guiding therapy in heart failure.

INTRODUCTION: Heart failure (HF) is a dominant health problem with an overall poor prognosis. Natriuretic peptides (NPs) are upregulated in HF as a compensatory mechanism. They have been extensively used for diagnosis and risk stratification. AREAS COVERED: This review addresses the history and physiology of NPs in order to understand their current role in clinical practice. It further provides a detailed and updated narrative review on the utility of those biomarkers for risk stratification, monitoring, and guiding therapy in HF. EXPERT OPINION: NPs show excellent predictive ability in heart failure patients, both in acute and chronic settings. Understanding their pathophysiology and their modifications in specific situations is key for an adequate interpretation in specific clinical scenarios in which their prognostic value may be weaker or less well evaluated. To better promote risk stratification in HF, NPs should be integrated with other predictive tools to develop multiparametric risk models. Both inequalities of access to NPs and evidence caveats and limitations will need to be addressed by future research in the coming years.

Maximal functional capacity in subjects with isolated left bundle branch block: A pilot study.

BACKGROUND: Left bundle branch block (LBBB) has been commonly associated with adverse cardiovascular (CV) events, but the effect of an isolated LBBB on maximal functional capacity is not well characterized. OBJECTIVE: To evaluate maximal functional capacity in adults with isolated LBBB and compare it to healthy population-derived predicted values (adjusted for sex, age, weight, and height). METHODS: This descriptive pilot study included subjects with isolated LBBB derived from outpatient clinics of two academic hospitals. All subjects underwent maximal cardiopulmonary exercise testing (CPET) and a Global Physical Activity Questionnaire (GPAQ). The primary outcome was to evaluate maximal functional capacity according to population-derived predicted values of peak oxygen consumption (peakVO2 ): pp-peakVO2 . The secondary outcome was to report adverse CV events (CV deaths or hospitalizations) at follow-up. RESULTS: A total of 27 (18 women and 9 men) participants were included. The median (interquartile range) age of the sample and time to screening from the first LBBB diagnosis were 62 (51-71) and 3.4 (1.1-8.4) years, respectively. The results of the GPAQ score showed that 19 patients were highly active, and 8 were moderately active. The median of peakVO2 and pp-peakVO2 were 19.3 (15-22.5) ml/kg/min and 88% (79.3%-104.4%), respectively. There were no adverse CV events at a median follow-up after CPET of 3.1 (2.7-3.4) years. CONCLUSION: In this pilot study, adults with isolated LBBB showed reduced maximal functional capacity, despite the absence of cardiac disease and a baseline moderate to highly active lifestyle.

Assessment of filling pressures and fluid overload in heart failure: an updated perspective.

Congestion plays a major role in the pathogenesis, presentation, and prognosis of heart failure and is an important therapeutic target. However, its severity and organ and compartment distribution vary widely among patients, illustrating the complexity of this phenomenon. Although clinical symptoms and signs are useful to assess congestion and manage volume status in individual patients, they have limited sensitivity and do not allow identification of congestion phenotype. This leads to diagnostic uncertainty and hampers therapeutic decision-making. The present article provides an updated overview of circulating biomarkers, imaging modalities (ie, cardiac and extracardiac ultrasound), and invasive techniques that might help clinicians to identify different congestion profiles and guide the management strategy in this diverse population of high-risk patients with heart failure.

Long-Term Prognostic Impact of Estimated Glomerular Filtration Rate on Admission in Patients Hospitalized for Acute Heart Failure.

INTRODUCTION: Although small-sample size studies have shown that basal alterations of estimated glomerular filtration rate (eGFR) are related to short- and mid-term higher mortality in acute heart failure (AHF), there is scarce information on the influence of an altered eGFR on long-term mortality and readmissions. Therefore, this multicenter study sought to investigate the relationship between eGFR on admission for AHF and both long-term mortality and readmissions in a large sample of patients. METHODS: We retrospectively evaluated 4,595 patients consecutively discharged after admission for AHF at three tertiary-care hospitals from January 1, 2008, to January 1, 2020. To investigate the effect of eGFR on admission with long-term morbimortality, we stratified the patients according to four eGFR categories: <30 mL·min-1·1.73 m-2 (G4 and G5 patients, n = 534), 30-44 mL·min-1·1.73 m-2 (G3b patients, n = 882), 45-59 mL·min-1·1.73 m-2 (G3a patients, n = 1,080), and ≥60 mL·min-1·1.73 m-2 (G1 and G2 patients, n = 2,099). eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation within the first 24 h following admission. RESULTS: At a median follow-up of 2.20 years, multivariate analyses revealed that compared to G1 and G2 patients, G4 and G5 patients exhibited a higher risk of all-cause (HR = 1.15, 95% CI: 01.02-1.30, p = 0.020) and cardiovascular (CV) (HR = 1.20, 95% CI: 1.04-1.39, p = 0.013) mortality. Similarly, multivariate analyses also showed that the lower the eGFR, the higher the risk of readmissions. In fact, compared to G1 and G2 patients, G4 and G5 patients displayed significantly increased incident rate ratios of total all-cause (28%), CV (26%), and HF-related (30%) readmissions. CONCLUSION: Data from this large study provide evidence that an eGFR below 30 mL·min-1·1.73 m-2 on admission could be an independent predictor for long-term mortality and readmissions in patients with AHF.

Quantification and treatment of congestion in heart failure: A clinical and pathophysiological overview.

Renal sodium and water retention with resulting extracellular volume expansion and redistribution are hallmark features of heart failure syndromes. However, congestion assessment, monitoring, and treatment represent a real challenge in daily clinical practice. This document reviewed historical and contemporary evidence of available methods for determining volume status and discuss pharmacological aspects and pathophysiological principles that underlie diuretic use.

Bending oxygen saturation index and risk of worsening heart failure events in chronic heart failure.

AIMS: Bendopnea is a clinical symptom of advanced heart failure with uncertain prognostic value. We aimed to evaluate whether bendopnea and the change in oxygen saturation when bending forward (bending oxygen saturation index [BOSI]) are associated with adverse outcomes in ambulatory chronic heart failure (CHF) patients. METHODS AND RESULTS: We prospectively evaluated 440 subjects with symptomatic CHF. BOSI was defined as the difference between sitting and bending oxygen saturation (SpO2 ). The endpoint was the total number of worsening heart failure (WHF) events (heart failure hospitalization or urgent heart failure visit requiring parenteral diuretic therapy). The mean age was 74 ± 10 years, 257 (58.6%) were male, and 226 (51.4%) had a left ventricular ejection fraction <50%. Bendopnea was present in 94 (21.4%) patients, and 120 (27.3%) patients had a BOSI ≥-3%. The agreement between BOSI ≥-3% and bendopnea was moderate (Gwet's AC 0.482, p < 0.001). At a median (p25%-p75%) follow-up of 2.17 years (0.88-3.16), we registered 441 WHF events in 148 patients. After multivariable adjustment, BOSI was independently associated with the risk for total WHF episodes (overall, p < 0.001). Compared to improvement/no change in SpO2 when bending (BOSI 0%), those with BOSI ≥-3% showed an increased risk of WHF events (incidence rate ratio [IRR] 2.16, 95% confidence interval [CI] 1.67-2.79; p < 0.001). In contrast, bendopnea was not associated with the risk of total WHF episodes (IRR 1.04, 95% CI 0.83-1.31; p = 0.705). CONCLUSIONS: In ambulatory and stable CHF patients, BOSI ≥-3% and not bendopnea was independently associated with an increased risk of total (first and recurrent) WHF episodes. Awareness of SpO2 while assessing bendopnea may be a useful tool for predicting heart failure decompensations.

Venous Leg Compression for Tissue Decongestion in Patients With Worsening Congestive Heart Failure.

Aims: Venous leg compression (VLC) with elastic bandages has been proposed as a potentially useful strategy for decreasing tissue congestion. We aimed to evaluate the effect of VLC on short-term changes on intravascular refill, assessed by inferior vena cava (IVC) diameter in patients with worsening heart failure (WHF) requiring parenteral furosemide. Additionally, we sought to evaluate whether early changes in IVC were related to short-term decongestion. Methods: This is a prospective study in which we included 20 consecutive ambulatory patients with WHF treated with subcutaneous furosemide and VLC for at least 72 h. The endpoints were (a) short-term changes in IVC, (b) the association between decongestion and 3-h IVC changes following VLC. Changes in continuous endpoints and their longitudinal trajectories were estimated with linear mixed regression models. All analyses were adjusted for multiple comparisons. Results: Following administration of subcutaneous furosemide and VLC, we found a significant increase in 3-h IVC diameter (ΔIVC = 1.6 mm, CI 95%: 0.7-2.5; p < 0.001), with a greater increase in those with baseline IVC≤21 mm (2.4 vs. 0.8 mm; p < 0.001). 3-h intravascular refill (increase in IVC≥2 mm) was associated with greater decongestion (natriuresis, weight, peripheral edemas, and dyspnea) in those with baseline IVC≤21 mm but not when IVC>21 mm (p < 0.05 for all comparisons). Conclusions: In this cohort of patients with congestive WHF treated with subcutaneous furosemide and VLC, we found a greater increase in short-term IVC in those with IVC ≤21 mm at baseline. In this subset of patients, a 3-h increase in IVC≥2 mm was associated with greater short-term decongestion.

Infective Endocarditis in the Elderly: Challenges and Strategies.

The specific management of infective endocarditis (IE) in elderly patients is not specifically addressed in recent guidelines despite its increasing incidence and high mortality in this population. The term "elderly" corresponds to different ages in the literature, but it is defined by considerable comorbidity and heterogeneity. Cancer incidence, specifically colorectal cancer, is increased in older patients with IE and impacts its outcome. Diagnosis of IE in elderly patients is challenging due to the atypical presentation of the disease and the lower performance of imaging studies. Enterococcal etiology is more frequent than in younger patients. Antibiotic treatment should prioritize diminishing adverse effects and drug interactions while maintaining the best efficacy, as surgical treatment is less commonly performed in this population due to the high surgical risk. The global assessment of elderly patients with IE, with particular attention to frailty and geriatric profiles, should be performed by multidisciplinary teams to improve disease management in this population.

Short-term effects of dapagliflozin on maximal functional capacity in heart failure with reduced ejection fraction (DAPA-VO2 ): a randomized clinical trial.

AIMS: This study aimed to evaluate the effect of dapagliflozin on 1 and 3-month maximal functional capacity in patients with stable heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: In this multicentre, randomized, double-blind clinical trial, 90 stable patients with HFrEF were randomly assigned to receive either dapagliflozin (n = 45) or placebo (n = 45). The primary outcome was a change in peak oxygen consumption (peakVO2 ) at 1 and 3 months. Secondary endpoints were changes at 1 and 3 months in 6-min walk test (6MWT) distance, quality of life (Minnesota Living with Heart Failure Questionnaire [MLHFQ]), and echocardiographic parameters (diastolic function, left chamber volumes, and left ventricular ejection fraction). We used linear mixed regression analysis to compare endpoint changes. Estimates were adjusted for multiple comparisons. The mean age was 67.1 ± 10.7 years, 69 (76.7%) were men, 29 (32.2%) had type 2 diabetes, and 80 (88.9%) were in New York Heart Association class II. Baseline means of peakVO2 , 6MWT and MLHFQ were 13.2 ± 3.5 ml/kg/min, 363 ± 110 m, and 23.1 ± 16.2, respectively. The median (25th-75th percentile) of N-terminal pro-brain natriuretic peptide was 1221 pg/ml (889-2100). Most patients were on treatment with sacubitril/valsartan (88.9%), beta-blockers (91.1%), and mineralocorticoid receptor antagonists (74.4%). PeakVO2 significantly increased in patients on treatment with dapagliflozin (1 month: +Δ 1.09 ml/kg/min, 95% confidence interval [CI] 0.14-2.04; p = 0.021, and 3 months: +Δ 1.06 ml/kg/min, 95% CI 0.07-2.04; p = 0.032). Similar positive findings were found when evaluating changes from baseline. No significant differences were observed in secondary endpoints. CONCLUSIONS: Among patients with stable HFrEF, dapagliflozin resulted in a significant improvement in peakVO2 at 1 and 3 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04197635.

Short-Term Changes in Left and Right Ventricular Cardiac Magnetic Resonance Feature Tracking Strain Following Ferric Carboxymaltose in Patients With Heart Failure: A Substudy of the Myocardial-IRON Trial.

Background The mechanisms explaining the clinical benefits of ferric carboximaltose (FCM) in patients with heart failure, reduced or intermediate left ventricular ejection fraction, and iron deficiency remain not fully clarified. The Myocardial-IRON trial showed short-term cardiac magnetic resonance (CMR) changes suggesting myocardial iron repletion following administration of FCM but failed to find a significant increase in left ventricular ejection fraction in the whole sample. Conversely, the strain assessment could evaluate more specifically subtle changes in contractility. In this subanalysis, we aimed to evaluate the effect of FCM on the short-term left and right ventricular CMR feature tracking derived strain. Methods and Results This is a post hoc subanalysis of the double-blind, placebo-controlled, randomized clinical trial that enrolled 53 ambulatory patients with heart failure and left ventricular ejection fraction <50%, and iron deficiency [Myocardial-IRON trial (NCT03398681)]. Three-dimensional left and 2-dimensional right ventricular CMR tracking strain (longitudinal, circumferential, and radial) changes were evaluated before, 7 and 30 days after randomization using linear mixed-effect analysis. The median (interquartile range) age of the sample was 73 years (65-78), and 40 (75.5%) were men. At baseline, there were no significant differences in CMR feature tracking strain parameters across both treatment arms. At 7 days, the only global 3-dimensional left ventricular circumferential strain was significantly higher in the FCM treatment-arm (difference: -1.6%, P=0.001). At 30 days, and compared with placebo, global 3-dimensional left ventricular strain parameters significantly improved in those allocated to FCM treatment-arm [longitudinal (difference: -2.3%, P<0.001), circumferential (difference: -2.5%, P<0.001), and radial (difference: 4.2%, P=0.002)]. Likewise, significant improvements in global right ventricular strain parameters were found in the active arm at 30 days (longitudinal [difference: -3.3%, P=0.010], circumferential [difference: -4.5%, P<0.001], and radial [difference: 4.5%, P=0.027]). Conclusions In patients with stable heart failure, left ventricular ejection fraction <50%, and iron deficiency, treatment with FCM was associated with short-term improvements in left and right ventricular function assessed by CMR feature tracking derived strain parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03398681.

Hospitalization following an emergency-department visit for worsening heart failure: The role of left ventricular ejection fraction.

INTRODUCTION AND OBJECTIVES: Patients with worsening heart failure (WHF) are frequently hospitalized. However, some of the patients with WHF are discharged from the emergency department without hospitalization. The factors influencing the decision of admission are heterogeneous and, in most cases, remain not well-defined. This study aimed to analyze whether left ventricular ejection fraction (LVEF) influences admission decisions following a visit to the emergency department for WHF. PATIENTS AND METHODS: This is a retrospective analysis of 3168 patients discharged from a hospitalization for acute heart failure in a single-center in Spain. During follow-up, visits to the emergency department for WHF, including those hospitalized (WHF-readmissions) and episodes of WHF directly discharged without hospitalization in 24h (WHF-DDWH), were recorded. The association between the LVEF categories (<50% and ≥50%) and recurrent WHF-DDWH was evaluated by negative binomial regression. Estimates of risk were expressed as incidence rate ratios (IRR). RESULTS: The mean age (SD) of the study sample was 73.5 (11.2) years, and 1658 (52.3%) showed LVEF>50%. At a median (percentile 25% to percentile 75%) follow-up of 2.7 (1.0-5.8) years, 3341 episodes of WHF in 1439 patients were recorded. Of them, we registered 743 episodes of WHF-DDWH in 468 patients (22.2%). Compared to patients with LVEF<50%, those with LVEF≥50% exhibited an adjusted increased risk of recurrent WHF-DDWH (IRR: 1.36, CI 95%: 1.13-1.62, p=0.001). CONCLUSIONS: Following an acute heart failure admission, patients with LVEF≥50% showed an increased risk of same-day discharge for WHF.

Carbohydrate antigen 125 and risk of heart failure readmissions in patients with heart failure and preserved ejection fraction.

We aimed to assess the association between CA125 and the long-term risk of total acute heart failure (AHF) admissions in patients with an index hospitalization with AHF and preserved ejection fraction (HFpEF). We prospectively included 2369 patients between 2008 and 2019 in three centers. CA125 and NT-proBNP were measured during early hospitalization and evaluated as continuous and categorized in quartiles (Q). Negative binomial regressions were used to assess the association with the risk of recurrent AHF admission. The mean age of the sample patients was 76.7 ± 9.5 years and 1443 (60.9%) were women. Median values of CA125 and NT-proBNP were 38.3 (19.0-90.0) U/mL, and 2924 (1590-5447) pg/mL, respectively. During a median follow-up of 2.2 (0.8-4.6) years, 1200 (50.6%) patients died, and 2084 AHF admissions occurred in 1029 (43.4%) patients. After a multivariate adjustment, CA125, but not NT-proBNP, was positively and non-linearly associated with the risk of cumulative AHF-readmission (p < 0.001). Compared to Q1, patients belonging to Q2, Q3, and Q4 showed a stepwise risk increase (IRR = 1.29, 95% CI 1.08-1.55, p = 0.006; IRR = 1.35, 95% CI 1.12-1.63, p = 0.002; and IRR = 1.62, 95% CI 01.34-1.96, p < 0.001, respectively). In conclusion, CA125 predicted the risk of long-term AHF-readmission burden in patients with HFpEF and a recent admission for AHF.

Optimal carbohydrate antigen 125 cutpoint for identifying low-risk patients after admission for acute heart failure.

INTRODUCTION AND OBJECTIVES: Carbohydrate antigen 125 (CA125) has been shown to be useful for risk stratification in patients admitted with acute heart failure (AHF). We sought to determine a CA125 cutpoint for identifying patients at low risk of 1-month death or the composite of death/HF readmission following admission for AHF. METHODS: The derivation cohort included 3231 consecutive patients with AHF. CA125 cutoff values with 90% negative predictive value (NPV) and sensitivity up to 85% were identified. The adequacy of these cutpoints and the risk of 1-month death/HF readmission was then tested using the Royston-Parmar method. The best cutpoint was selected and externally validated in a cohort of patients hospitalized from BIOSTAT-CHF (n=1583). RESULTS: In the derivation cohort, the median [IQR] CA125 was 57 [25.3-157] U/mL. The optimal cutoff value was <23 U/mL (21.5% of patients), with NPVs of 99.3% and 94.1% for death and the composite endpoint, respectively. On multivariate survival analyses, CA125 <23 U/mL was independently associated with a lower risk of death (HR, 0.20; 95%CI, 0.08-0.50; P <.001), and the combined endpoint (HR, 0.63; 95%CI, 950.45-0.90; P=.009). The ability of this cutpoint to discriminate patients at a low 1-month risk was confirmed in the validation cohort (NPVs of 98.6% and 96.6% for death and the composite endpoint). The predicted ability of this cutoff remained significant at 6 months of follow-up. CONCLUSIONS: In patients admitted with AHF, CA125 <23 U/mL identified a subgroup at low risk of short-term adverse events, a population that may not require intense postdischarge monitoring.