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Aims: There is a lack of specific studies assessing the impact of natriuretic peptide monitoring in the post‐discharge management of patients with heart failure (HF) and preserved ejection fraction (HFpEF), throughout the vulnerable phase following acute HF hospitalization. The NICE study aims to assess the clinical benefit of incorporating N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) into the post‐discharge management of HFpEF patients. Methods and results: Individuals admitted with HFpEF (left ventricular ejection fraction >50%) were included in a multicentre randomized controlled study employing an open‐label design with event blinding (NCT02807168). Upon discharge, 157 patients were randomly allocated to either NT‐proBNP monitoring (n = 79) or no access to NT‐proBNP (control group, n = 78) during pre‐scheduled visits at 2, 4 and 12 weeks. Clinical endpoints were evaluated at 6 months. The primary endpoint of HF rehospitalizations occurred in 12.1% patients, without significant differences observed between the NT‐proBNP monitoring group (12.8%) and the control group (11.4%) (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.47–2.81, p = 0.760). Regarding secondary endpoints, the NT‐proBNP monitoring group demonstrated a significantly lower risk of death (1.3% vs. 10.1%; HR 0.12, 95% CI 0.02–0.98; p = 0.048), whereas non‐HF hospitalizations (12.8% vs. 19.0%, p = 0.171) and any adverse clinical event (26.9% vs. 36.7%, p = 0.17) did not reach statistical significance [Correction added on 29 April 2024, after first online publication: In the preceding sentence, "95% CI 0.02 ‐ 0.09" has been corrected to "95% CI 0.02 ‐ 0.98; p = 0.048" in this version.]. Awareness of NT‐proBNP levels were associated with higher doses of diuretics and renin–angiotensin system inhibitors (angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers) in the NT‐proBNP monitoring group. Conclusions: Post‐discharge monitoring of NT‐proBNP in HFpEF patients did not exhibit an association with reduced rates of HF hospitalization in this study. Nonetheless, it appears to enhance global clinical management by optimizing medical therapies and contributing to improved overall survival. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: Diabetes mellitus is associated with worse outcomes and lower attainment of disease‐modifying therapies in patients with heart failure with reduced ejection fraction (HFrEF). This post hoc analysis of TRANSITION compared the patterns of tolerability and uptitration of sacubitril/valsartan in patients with HFrEF stabilized after hospital admission due to acute decompensated HF depending on the presence or absence of diabetes as a co‐morbidity. Methods: TRANSITION, a randomized, open‐label study compared sacubitril/valsartan initiation pre‐discharge vs. post‐discharge (up to14 days) in 991 patients hospitalized for acutely decompensated HFrEF. The impact of diabetes status on tolerability and safety was studied at 10‐week and 26‐week post‐randomization. Results: Among the 991 patients analysed at baseline, 460 (46.4%) had diabetes and exhibited a higher risk profile. At 10 weeks, sacubitril/valsartan target dose (97/103 mg bid) was achieved in a similar proportion of patients in each subgroup, when initiated pre‐discharge or post‐discharge respectively [diabetes subgroup: 47% (n = 105/226) vs. 50% (n = 115/228); relative risk ratio (RRR), 0.923; P = 0.412; non‐diabetes subgroup: 45% (n = 119/267) vs. 51% (n = 133/261); RRR, 0.878; P = 0.155]. The proportions of patients achieving and maintaining either 49/51 mg or 97/103 mg bid [diabetes subgroup: 61.1% (n = 138/226) vs. 67.5% (n = 154/228); RRR, 0.909; P = 0.175; non‐diabetes subgroup: 62.9% [n = 168/267] vs 69.3% [n = 181/261]; RRR, 0.906; P = 0.118] or any dose for ≥2 weeks leading to Week 10 [diabetes subgroup: 85% (n = 192/226) vs. 88.2% (n = 201/228); RRR, 0.966; P = 0.356; non‐diabetes subgroup: 86.9% (n = 232/267) vs. 90.8% (n = 237/261); RRR, 0.963; P = 0.215] were also similar in each subgroup, when initiated pre‐discharge or post‐discharge, respectively. At 10 weeks, hypotension and renal dysfunction rates were similar, although hyperkalaemia was higher among patients with diabetes (15.9% vs. 9.5%). The rate of permanent discontinuation due to adverse events was similar in the diabetes and non‐diabetes subgroups at 10 weeks, respectively: pre‐discharge (7.5% vs. 7.1%) or post‐discharge (5.7% vs. 4.2%). Similar patterns of uptitration and tolerability were observed at 26 weeks. Cardiac biomarkers including NT‐proBNP (P < 0.005) and hs‐TnT (P < 0.005) reduced significantly from baseline levels in both subgroups at Weeks 4 and 10; however, the response was greater among patients without diabetes. Mortality (diabetes vs. non‐diabetes subgroups: 3.3% vs 4.0%; P = 0.438) and HF rehospitalization (diabetes vs. non‐diabetes subgroups: 36.3% vs. 33.0%; P = 0.295) did not differ between the groups at 26 weeks. Conclusions: Despite a higher risk profile among patients with diabetes, sacubitril/valsartan initiation either before or shortly after discharge in hospitalized patients with HFrEF resulted in comparable rates of dose up‐titration and tolerability as in those without diabetes. [ABSTRACT FROM AUTHOR]

Aims: Sacubitril/valsartan has shown efficacy and tolerability in patients with heart failure (HF) and reduced ejection fraction (HFrEF) in the ambulatory setting (PARADIGM-HF), and following stabilisation of acutely decompensated HF (ADHF) (PIONEER-HF and TRANSITION). However, data are lacking for the initiation of sacubitril/valsartan in newly diagnosed (de novo) HFrEF. Here, we assess the tolerability of initiating sacubitril/valsartan following ADHF in TRANSITION subgroups of patients with a de novo vs. prior diagnosis of HFrEF.Methods and Results: TRANSITION randomised 1002 patients to pre- and post-discharge initiation of sacubitril/valsartan (analysis set n = 991, following exclusions for mis-randomisation). In this post-hoc analysis, tolerability to sacubitril/valsartan [proportion of patients achieving target dose (97/103 mg b.i.d.) at 10 weeks post-randomisation], adverse events (AEs) and serious AEs (SAEs) were compared in de novo (n = 286) and prior HFrEF (n = 705) subgroups. More de novo than prior HFrEF patients achieved target dose at Week 10 (56% vs. 45%; relative risk ratio 1.30, 95% confidence interval 1.12-1.52, P < 0.001), and fewer had SAEs and permanent treatment discontinuations. Initiation of sacubitril/valsartan did not prevent the concomitant initiation and up-titration of guideline-directed HF therapies. De novo patients showed faster and greater decreases in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin-T, and lower rates of HF and all-cause rehospitalisation vs. prior HFrEF.Conclusions: After ADHF, first-line initiation of sacubitril/valsartan in de novo HFrEF, alongside the initiation of other guideline-directed therapies, is feasible and is associated with a better risk-benefit profile than in patients with prior HFrEF. Early intervention with sacubitril/valsartan may be considered to delay disease progression in patients with de novo HFrEF.Clinical Trial Registration: ClinicalTrials.gov, NCT02661217. [ABSTRACT FROM AUTHOR]

Background: Clonal hematopoiesis driven by somatic mutations in hematopoietic cells, frequently called clonal hematopoiesis of indeterminate potential (CHIP), has been associated with adverse cardiovascular outcomes in population-based studies and in patients with ischemic heart failure (HF) and reduced left ventricular ejection fraction (LVEF). Yet, the impact of CHIP on HF progression, including nonischemic etiology, is unknown.Objectives: The purpose of this study was to assess the clinical impact of clonal hematopoiesis on HF progression irrespective of its etiology.Methods: The study cohort comprised 62 patients with HF and LVEF <45% (age 74 ± 7 years, 74% men, 52% nonischemic, and LVEF 30 ± 8%). Deep sequencing was used to detect CHIP mutations with a variant allelic fraction >2% in 54 genes. Patients were followed for at least 3.5 years for various adverse events including death, HF-related death, and HF hospitalization.Results: CHIP mutations were detected in 24 (38.7%) patients, without significant differences in all-cause mortality (p = 0.151). After adjusting for risk factors, patients with mutations in either DNA methyltransferase 3 alpha (DNMT3A) or Tet methylcytosine dioxygenase 2 (TET2) exhibited accelerated HF progression in terms of death (hazard ratio [HR]: 2.79; 95% confidence interval [CI]: 1.31 to 5.92; p = 0.008), death or HF hospitalization (HR: 3.84; 95% CI: 1.84 to 8.04; p < 0.001) and HF-related death or HF hospitalization (HR: 4.41; 95% CI: 2.15 to 9.03; p < 0.001). In single gene-specific analyses, somatic mutations in DNMT3A or TET2 retained prognostic significance with regard to HF-related death or HF hospitalization (HR: 4.50; 95% CI: 2.07 to 9.74; p < 0.001, for DNMT3A mutations; HR: 3.18; 95% CI: 1.52 to 6.66; p = 0.002, for TET2 mutations). This association remained significant irrespective of ischemic/nonischemic etiology.Conclusions: Somatic mutations that drive clonal hematopoiesis are common among HF patients with reduced LVEF and are associated with accelerated HF progression regardless of etiology. [ABSTRACT FROM AUTHOR]

Background: Testosterone deficiency is associated with heart failure (HF) progression and poor prognosis. Testosterone therapy has been shown to improve exercise capacity in patients with chronic HF, but no trial has evaluated the impact of replacement in patients with demonstrated testosterone deficiency.Methods: Prospective, randomized, double-blind, placebo-controlled, and parallel-group trial comparing testosterone replacement with placebo in males with chronic HF with reduced ejection fraction (HFrEF) and testosterone deficiency (NCT01813201). Long-acting undecanoate testosterone at a fixed dose of 1000 mg was supplied by intramuscular injection at inclusion and then every 3 months. The placebo group received isotonic saline serum. Patients were randomly allocated 1:1 to testosterone or placebo while receiving optimal medical therapy, and the study was conducted for 12 months.Results: The final sample comprised 29 patients, 15 in the placebo group and 14 in the testosterone group (aged 65 ± 8, 62% with an ischemic etiology, left ventricular ejection fraction [LVEF] 30% ± 6%, 69% New York Heart Association functional [NYHA II]). After 12 months, testosterone replacement increased testosterone levels ( P = .002) but was not associated with benefit in terms of clinical symptoms and functional capacity including NYHA class, Framingham score, Minnesota Living Heart Failure Questionnaire, 6-minute walk test, or LVEF and N-terminal pro-B-type natriuretic peptide levels. No significant side effects associated with testosterone treatment were observed. No effects were found in other hormonal, metabolic, and bone turnover biomarkers.Conclusion: In patients with HFrEF and testosterone deficiency, replacement therapy was not associated with any significant improvement. [ABSTRACT FROM AUTHOR]

Aims: Paradoxically, obesity is associated with survival in heart failure (HF). Whether this is true for HF patients with comorbid type-2 diabetes (T2D) remains uncertain. Our aim was to address this issue in diabetic patients by collecting correlates for body mass index (BMI) and long-term mortality.Method and Results: Both BMI and survival after a mean follow-up of 4.3 ± 3.0 years (up to 10 years) were assessed for 2527 ambulatory patients (66.3% men; mean age 69 ± 12.3 years). A total of 1102 (43.6%) patients had T2D and ischaemic aetiology of HF was present in 47.8%; mean left ventricular ejection fraction was 38 ± 16%. Based on BMI scores, patients were categorized as either underweight, normal, overweight, or obese. A significant survival interaction was observed between BMI and T2D. Smooth spline curves for the estimation of risk of all-cause and cardiovascular death showed the classic obesity paradox, with reduced mortality as BMI increased in non-diabetics; for T2D patients this pattern was lost. After adjustment for age and sex, hazard ratios for low-weight and obesity were: 2.04 [95% confidence intervals (CI) 1.50-2.78, P < 0.001] and 0.76 (95% CI 0.58-0.99, P = 0.04), respectively, for non-T2D patients; and 1.30 (95% CI 0.77-2.19, P = 0.32) and 0.99 (95% CI 0.78-1.26, P = 0.95), respectively, for T2D patients. Multivariate analyses for mortality (including BMI as a continuous variable) were significant for non-diabetic patients only.Conclusions: In patients with HF, but without T2D, the obesity paradox was present; however, T2D removed this phenomenon. Advice about weight loss for obese diabetic patients with HF requires further research. [ABSTRACT FROM AUTHOR]

Aims Prevention of hospital readmissions is one of the main objectives in the management of patients with heart failure ( HF). Most of the models predicting readmissions are based on data extracted from hospitalized patients rather than from outpatients. Our objective was to develop a validated score predicting 1-month and 1-year risk of readmission for worsening of HF in ambulatory patients. Methods and results A cohort of 2507 ambulatory patients with chronic HF was prospectively followed for a median of 3.3 years. Clinical, echocardiographic, ECG, and biochemical variables were used in a competing risk regression analysis to construct a risk score for readmissions due to worsening of HF. Thereafter, the score was externally validated using a different cohort of 992 patients with chronic HF ( MUSIC registry). Predictors of 1-month readmission were the presence of elevated natriuretic peptides, left ventricular (LV) HF signs, and estimated glomerular filtration rate ( eGFR) <60 mL/min/m2. Predictors of 1-year readmission were elevated natriuretic peptides, anaemia, left atrial size >26 mm/m2, heart rate >70 b.p.m., LV HF signs, and eGFR <60 mL/min/m2. The C-statistics for the models were 0.72 and 0.66, respectively. The cumulative incidence function distinguished low-risk (<1% event rate) and high-risk groups (>5% event rate) for 1-month HF readmission. Likewise, low-risk (7.8%), intermediate-risk (15.6%) and high-risk groups (26.1%) were identified for 1-year HF readmission risk. The C-statistics remained consistent after the external validation (<5% loss of discrimination). Conclusion The Redin- SCORE predicts early and late readmission for worsening of HF using proven prognostic variables that are routinely collected in outpatient management of chronic HF. [ABSTRACT FROM AUTHOR]

Among patients with chronic heart failure (HF), it is known that soluble concentrations of the interleukin receptor family member ST2 (sST2) are prognostic for adverse outcome, including risk for progression of HF and death. Considerably less was known about the merits of serial testing of sST2 and whether such testing provides incremental information beyond single measurements; additionally, the influence of HF therapies on sST2 concentrations and whether sST2 values predicted benefit of therapy changes remained unclear. Recently, several studies indicate that serial testing for sST2 increases the prognostic information gained compared with a single measurement. When measured in patients with chronic HF, concentrations of sST2 appear to predict worsening left ventricular remodeling, and serial measurements of sST2 appear particularly useful for predicting HF events, such as worsening HF and risk for either hospitalization or death from HF. Values for sST2 are lower in those treated with several HF therapies; in turn, sST2 concentrations may predict benefit from specific HF therapy changes. Using an upper reference limit of 35 ng/ml, serial testing for sST2 in chronic HF thus appears useful. The promising role of sST2 for serial chronic HF therapy monitoring will be discussed. [ABSTRACT FROM AUTHOR]

Hyperkalaemia is a growing concern in the treatment of patients with heart failure and reduced ejection fraction (HFrEF) as it limits the use of some prognostic-modifying drugs and has a negative impact on prognosis. The objective of the present study was to estimate the prevalence of hyperkalaemia in outpatients with HFrEF and its impact on achieving optimal medical treatment. For this purpose, a multicentre, prospective, and observational study was carried out on consecutive HFrEF patients who were monitored as outpatients in heart failure (HF) units and who, in the opinion of their doctor, received optimal medical treatment. A total of 565 HFrEF patients were included from 16 specialised HF units. The mean age was 66 ± 12 years, 78% were male, 45% had an ischemic cause, 39% had atrial fibrillation, 43% were diabetic, 42% had a glomerular filtration rate < 60 mL/min/1.7 m2, and the mean left ventricular ejection fraction was 31 ± 7%. Treatment at the study entry included: 76% on diuretics, 13% on ivabradine, 7% on digoxin, 18.9% on angiotensin-conversing enzyme inhibitors (ACEi), 11.3% on angiotensin receptors blockers (ARBs), 63.8% on angiotensin-neprilysin inhibitors (ARNi), 78.5% on mineralocorticoid receptor antagonists (MRAs), and 92.9% on beta-blockers. Potassium levels in the baseline analysis were: ≤5 mEq/L = 80.5%, 5.1–5.4 mEq/L = 13.8%, 5.5–5.9 mEq/L = 4.6%, and ≥6 mEq/L = 1.06%. Hyperkalaemia was the reason for not prescribing or reaching the target dose of an MRAs in 34.8% and 12.5% of patients, respectively. The impact of hyperkalaemia on not prescribing or dropping below the target dose in relation to ACEi, ARBs, and ARNi was significantly less. In conclusion, hyperkalaemia is a frequent problem in the management of patients with HFrEF and a limiting factor in the optimisation of medical treatment. [ABSTRACT FROM AUTHOR]

Aims Intraventricular conduction defects (IVCDs) can impair prognosis of heart failure (HF), but their specific impact is not well established. This study aimed to analyse the clinical profile and outcomes of HF patients with LBBB, right bundle branch block (RBBB), left anterior fascicular block (LAFB), and no IVCDs. Methods and results Clinical variables and outcomes after a median follow-up of 21 months were analysed in 1762 patients with chronic HF and LBBB (n = 532), RBBB (n = 134), LAFB (n = 154), and no IVCDs (n = 942). LBBB was associated with more marked LV dilation, depressed LVEF, and mitral valve regurgitation. Patients with RBBB presented overt signs of congestive HF and depressed right ventricular motion. The LAFB group presented intermediate clinical characteristics, and patients with no IVCDs were more often women with less enlarged left ventricles and less depressed LVEF. Death occurred in 332 patients (interannual mortality = 10.8%): cardiovascular in 257, extravascular in 61, and of unknown origin in 14 patients. Cardiac death occurred in 230 (pump failure in 171 and sudden death in 59). An adjusted Cox model showed higher risk of cardiac death and pump failure death in the LBBB and RBBB than in the LAFB and the no IVCD groups. Conclusion LBBB and RBBB are associated with different clinical profiles and both are independent predictors of increased risk of cardiac death in patients with HF. A more favourable prognosis was observed in patients with LAFB and in those free of IVCDs. Further research in HF patients with RBBB is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hematologic abnormalities such as elevated red blood cell distribution width (RDW) as well as anemia are prognostically meaningful among heart failure (HF) patients. The inter-relationship between these hematologic abnormalities in HF is unclear, however. We therefore aimed to assess whether RDW is predicting changes in hemoglobin concentrations as well as onset of anemia. Methods: 268 consecutive non-anemic patients with acutely decompensated HF (ADHF) were enrolled at hospital discharge and RDW was measured. At 6month follow-up, change in hemoglobin as well as new-onset anemia was studied as a function of RDW at discharge. Results: RDW at discharge correlated negatively with hemoglobin values at 6months (r=−0.220; p<0.001); a greater decrease in hemoglobin concentration occurred in those with higher values of RDW at discharge (p=0.004), independently of baseline hemoglobin concentration and other risk factors. At 6months, 54 patients (20%) developed new-onset anemia. RDW values at discharge were significantly higher among patients who developed new-onset anemia (15.1±2.2 vs. 14.2±1.4, p=0.005). In integrated discrimination improvement analyses, the addition of RDW measurement improved the ability to predict new-onset anemia (IDI 0.0531, p<0.001), beyond known risk factors as hemoglobin, renal function, age, diabetes mellitus, sex and HF symptom severity. In adjusted analyses, patients with RDW>15% (derived from receiver operating characteristic analysis) had a tripling of the risk of new-onset anemia (OR=3.1, 95% CI 1.5–5.1, p=0.002). Conclusion: Among non-anemic patients with ADHF, RDW measurement at the time of hospital discharge independently predicts lower hemoglobin concentrations and new-onset anemia over a 6-month follow up period. [Copyright &y& Elsevier]

The precise mechanism explaining the increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations among patients with concomitant acute heart failure (AHF) and kidney dysfunction is not fully understood. The aim of this study was to assess the impact of kidney dysfunction on simultaneous measures of plasma and urinary NT-proBNP in an unselected cohort of patients with AHF. One hundred thirty-eight consecutive hospitalized patients (median age: 74 years; interquartile range: 67-80 years; 54% male) with a diagnosis of AHF were prospectively studied. Blood and urine samples were collected on hospital arrival to determine NT-proBNP concentrations. Both plasma and urinary NT-proBNP concentrations increased with declining estimated glomerular filtration rate (eGFR; P <.001 for both). However, after multivariate adjustment, eGFR was found to be an independent predictor of plasma (but not urinary)NT-proBNP concentration (eGFR: β=-0.19; P=.016). Indeed, plasma NT-proBNP was the main independent determinant of its urinary concentration (β=0.42; P<.001), and the ratio of urine/plasma NT-proBNP was independent of kidney function and similar across the range of eGFR examined (P=.368). In patients with AHF and concomitant kidney dysfunction, the increased circulating NT-proBNP may be mainly related to increased cardiac secretion and not decreased renal clearance. [ABSTRACT FROM AUTHOR]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: We studied whether the measurement of the soluble form of ST2 (sST2), an interleukin-1 receptor family member, could identify heart failure (HF) patients at risk of sudden cardiac death (SCD). Background: The prediction of SCD remains an important challenge in patients with mild-to-moderate chronic HF. Concentrations of sST2 have been found increased and related to worse long-term outcomes in patients with acute HF. Whether sST2 has a prognostic role in SCD is unknown. Methods: A nested case-control study was performed on 36 cases of SCD and 63 control patients (matched for age, sex, and left ventricular ejection fraction) obtained from the MUSIC (MUerte Súbita en Insuficiencia Cardíaca) registry, a 3-year multicenter registry of ambulatory HF patients (New York Heart Association functional class II to III, left ventricular ejection fraction ≤45%). Demographic, clinical, echocardiographic, electrical, and biochemical data were collected at enrollment. Results: Concentrations of sST2 were greater among decedents (0.23 ng/ml [interquartile range 0.16 to 0.43 ng/ml] vs. 0.12 ng/ml [interquartile range 0.06 to 0.23 ng/ml], p = 0.001) and were predictive of experiencing SCD (+0.1 ng/ml, odds ratio: 1.39, 95% confidence interval: 1.09 to 1.78, p = 0.006). On the basis of a combined biomarker status, only 4% of patients experienced SCD for neither sST2 nor N-terminal pro–B-type natriuretic peptide (NT-proBNP) above receiver-operator characteristic-derived cut-off points (0.15 ng/ml and 2,000 ng/l, respectively), 34% for either biomarker above, and 71% for both biomarkers above (p < 0.001 for trend). This combined variable added incremental prognostic value to the multivariable regression model (p < 0.001). Conclusions: Elevated sST2 concentrations are predictive of SCD in patients with chronic HF and provide complementary information to NT-proBNP levels. A combined biomarker approach may have an impact on clinical decision-making. [Copyright &y& Elsevier]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The benefit of sacubitril/valsartan (S/V) in patients with chronic heart failure and reduced ejection fraction (HFrEF) is associated with a reduction of biomarkers of myocardial stretch and necrosis. S/V initiation after an acute decompensation of HFrEF (ADHF) has not been studied and the impact of a pre-discharge (d/c) vs. post-d/c strategy on cardiac biomarkers is unknown Hypothesis: S/V initiation in the hospital after stabilization from ADHF is safe and well tolerated and results in early biomarker response. Methods: TRANSITION (NCT02661217) is a randomized, open-label study comparing S/V start pre- vs. 1-14 days post-d/c in HFrEF patients admitted for ADHF after hemodynamic stabilization. Patients were stratified by pre-admission treatment: on ACE-I, ARB, or ACE-I/ARB-naïve. Randomization occurred after hemodynamic stabilization 1:1 per stratum for initiation of S/V pre-d/c or post-d/c. NT-proBNP and cardiac troponin T were measured at randomization, discharge, 4 weeks (w) and 10w post-randomization. Results: 983 patients were included in the safety analysis (24% ACE-I/ARB naïve, 29% de novo HFrEF). Median NT-proBNP at randomization was 1902 pg/mL (Q1-Q3 [IQR]: 945-3883) in the pre-d/c arm (n=478) and 1669 pg/mL (IQR: 706-3577) in the post-d/c arm (n=473). At discharge, patients in the pre-d/c arm exhibited a significant reduction of NT-proBNP levels (change from randomization: 0.719, 95%CI: 0.677-0.762) which was greater than in the post-d/c arm (0.966, 95%CI: 0.905-1.031) (p<0.001 for comparison). After 10w the reduction was significant and comparable in both arms: pre-d/c (0.619, 95%CI 0.564-0.679) vs. post-d/c 0.663 (95CI%: 0.603-0.728) (p=0.239 for comparison). At randomization, median hsTnT was 29 pg/mL (IQR: 19-45) in the pre-d/c arm vs. 28 pg/mL (IQR: 17-43) in the post-d/c arm. At discharge, only patients in the pre-d/c arm showed a significant reduction in hsTnT (0.946, 95%CI 0.906-0.989), albeit not significantly greater than the reduction observed in the post-d/c arm (0.961, 95%CI 0.916-1.007) (p=0.440). After 10w, both strategies showed a significant reduction in hsTnT concentrations (pre-d/c: 0.743, 95%CI: 0.699-0.790; vs. post-d/c: 0.715, 95%CI 0.673-0.759; p=0.276). Conclusions: In hospitalized patients with ADHF, initiation of S/V after hemodynamic stabilization and before discharge is feasible and associated with a rapid reduction of NT-proBNP. After discharge, both S/V initiation strategies were associated with comparable reductions in cardiac biomarkers levels after 10w. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine whether the risk of mortality associated with the concentration of soluble ST2 (sST2) differs in patients with acutely decompensated heart failure with preserved ejection fraction (HFpEF) compared to patients with systolic heart failure. We prospectively enrolled 447 patients with acutely decompensated heart failure. Blood samples were collected at presentation to determine the sST2 concentration. HFpEF was defined as symptoms or signs of acutely decompensated heart failure and left ventricular ejection fraction of ≥50% on the echocardiogram. The patients were followed up for 1 year, and the vital status was obtained for all. The sST2 concentrations were greater in the patients with systolic heart failure (n = 250) than in those with HFpEF (n = 197) at 0.55 versus 0.38 ng/ml (p <0.001). Receiver operating characteristic curve analyses showed different cutoff point values for sST2 for the prediction of 1-year mortality in patients with HFpEF (>0.35 ng/ml) and systolic heart failure (>0.56 mg//ml). These cutoff points had similar prognostic accuracy (area under the curve of 0.69 vs 0.73; p >0.05). In the adjusted analyses that included amino terminal B-type natriuretic peptide concentrations, elevated sST2 concentrations were associated with a greater mortality risk in both populations (HFpEF, per ng/ml, hazard ratio 1.41, 95% confidence interval 1.14 to 1.76, p = 0.002; and systolic heart failure, per ng/ml, hazard ratio 1.20, 95% confidence interval 1.10 to 1.32, p <0.001). The determination of the sST2 concentration improved the clinical risk prediction compared to amino terminal B-type natriuretic peptide, as assessed by both the improved C-statistic and an improvement in the net reclassification index and integrated discrimination improvement analyses. In conclusion, in the present multicenter study, sST2 concentrations were lower in patients with HfpEF; however, sST2 remained an independent predictor of mortality, regardless of the left ventricular ejection fraction. [Copyright &y& Elsevier]

Background: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure.Methods: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin <100 μg/L, or 100-299 μg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%. Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments. The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point. Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation. Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT02937454, and has now been completed.Findings: Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57·2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72·5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0·79, 95% CI 0·62-1·01, p=0·059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0·80, 95% CI 0·64-1·00, p=0·050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0·96, 95% CI 0·70-1·32, p=0·81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0·74; 95% CI 0·58-0·94, p=0·013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0·80, 95% CI 0·66-0·98, p=0·030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0·67, 95% CI 0·47-0·97, p=0·035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group.Interpretation: In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death.Funding: Vifor Pharma. [ABSTRACT FROM AUTHOR]

Abstract: Aim: This study aims to evaluate the incremental value of plasma biomarkers to traditional clinical variables for risk stratification of 30-day and one-year mortality in acutely decompensated heart failure (ADHF). Methods and results: Through an international collaborative network, individual patient data on 5306 patients hospitalized for ADHF were collected. The all-cause mortality rate was 11.7% at 30days and 32.9% at one year. The clinical prediction model (age, gender, blood pressure on admission, estimated glomerular filtration rate <60mL/min/1.73m2, sodium and hemoglobin levels, and heart rate) had a c-statistic of 0.74 for 30-day mortality and 0.73 for one-year mortality. Several biomarkers measured at presentation improved risk stratification when added to the clinical model. At 30days, the net reclassification improvement (NRI) was 28.7% for mid-regional adrenomedullin (MR-proADM; p<0.001) and 25.5% for soluble (s)ST2 (p<0.001). At one year, sST2 (NRI 10.3%), MR-proADM (NRI 9.1%), amino-terminal pro-B-type natriuretic peptide (NT-proBNP; NRI 9.1%), mid-regional proatrial natriuretic peptide (MR-proANP; NRI 7.4%), B-type natriuretic peptide (NRI 5.5%) and C-reactive protein (CRP; NRI 5.3%) reclassified patients with ADHF (p<0.05 for all). CRP also markedly improved risk stratification of patients with ADHF as a dual biomarker combination with MR-proADM (NRI 36.8% [p<0.001] for death at 30days) or with sST2 (NRI 20.3%; [p<0.001] for one-year mortality). Conclusion: In this study, biomarkers provided incremental value for risk stratification of ADHF patients. Biomarkers such as sST2, MR-proADM, natriuretic peptides and CRP, reflecting different pathophysiologic pathways, add prognostic value to clinical risk factors for predicting both short-term and one-year mortality in ADHF. [Copyright &y& Elsevier]

The purpose of this study was to establish the role of hormonal anabolic deficiencies in exercise intolerance in patients with chronic heart failure One hundred four consecutive men (mean age 53.1 ± 10.6 years) with established diagnoses of chronic heart failure were included. At enrollment, blood samples were taken, and echocardiography and cardiopulmonary exercise testing were carried out. Exercise capacity was expressed as peak oxygen consumption (Vo 2), predicted peak Vo 2, and the ventilatory response to exercise (VE/Vco 2) slope. The mean left ventricular ejection fraction was 29.7 ± 11.9%, and most patients (86%) were in New York Heart Association class I or II, with a mean peak Vo 2 of 18 ml/min/kg. According to the age-adjusted reference values, hormonal deficiencies were present in 29% for total testosterone, 39% for estimated free testosterone, 34% for insulin-like growth factor–1, and 61% for dehydroepiandrosterone sulfate. Dehydroepiandrosterone sulfate showed a significant correlation with peak Vo 2 (r = 0.29, p = 0.007), predicted peak Vo 2 (r = 0.28, p = 0.006), and VE/Vco 2 slope (r = −0.39, p <0.001), whereas total testosterone, estimated free testosterone, and insulin-like growth factor–1 were not significantly correlated. After adjusting in a multivariable model, dehydroepiandrosterone sulfate remained an independent predictor of each exercise parameter. In conclusion, in a cohort of patients with mild chronic heart failure, exercise capacity objectively measured using cardiopulmonary exercise testing was related to anabolic impairment of the adrenal rather than the somatotropic or peripheral axis. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to evaluate the prognostic importance of novel markers of renal dysfunction among patients with acutely destabilized heart failure (ADHF). Background: β-trace protein (BTP) and cystatin C are newer biomarkers for renal dysfunction; the prognostic importance of these tests, particularly BTP, relative to standard measures of renal function remains unclear. Methods: A total of 220 consecutive hospitalized patients with ADHF were prospectively studied. Blood samples were collected on presentation. In-hospital worsening renal function, as well as mortality and/or heart failure (HF) hospitalization, over a median follow-up period of 500 days was examined as a function of BTP or cystatin C concentrations; results were compared with creatinine, estimated glomerular filtration rate, and blood urea nitrogen. Results: Neither BTP nor cystatin C was associated with worsening renal function during the index hospitalization. A total of 116 patients (53%) either died or were hospitalized for HF during follow-up. Those with adverse outcomes had higher BTP (1.04 mg/l [range 0.80 to 1.49 mg/l] vs. 0.88 mg/l [range 0.68 to 1.17 mg/l], p = 0.003) and cystatin C (1.29 mg/l [range 1.00 to 1.71 mg/l] vs. 1.03 mg/l [range 0.86 to 1.43 mg/l], p = 0.001). After multivariable adjustment, both BTP (hazard ratio: 1.41, 95% confidence interval: 1.06 to 1.88; p = 0.018) and cystatin C (hazard ratio: 1.50, 95% confidence interval: 1.13 to 2.01; p = 0.006) were significant predictors of death/HF hospitalization, whereas serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen were no longer significant. In patients with an estimated glomerular filtration rate >60 ml/min/1.73 m2, elevated concentrations of BTP and cystatin C were still associated with significantly higher risk of adverse clinical events (p < 0.05). Net reclassification index analysis suggested cystatin C and BTP deliver comparable information regarding prognosis. Conclusions: Among patients hospitalized with ADHF, BTP and cystatin C predict risk of death and/or HF hospitalization and are superior to standard measures of renal function for this indication. [Copyright &y& Elsevier]

The purpose of this study was to compare the diagnostic sensitivity of 1-day Holter monitoring versus 7-day Holter monitoring (7DH) to detect atrial and ventricular arrhythmias in a population of stable patients with chronic heart failure and left ventricular dysfunction. Sixty-three consecutive stable patients with chronic heart failure with left ventricular ejection fractions ≤50% were included. Blood samples were obtained, the Minnesota Living With Heart Failure Questionnaire was administered, and echocardiography, 6-minute walk tests, and 7DH were performed at enrollment. The mean ejection fraction was 35.8 ± 9.8%, and the mean age was 55.5 ± 13.9 years. Seven-day Holter monitoring did not significantly increase the detection of nonsustained atrial tachycardia or atrial fibrillation. In contrast, the incidence of nonsustained ventricular tachycardia increased in nonischemic patients from 35.1% on day 1 to 54.1% on day 7 (p = 0.01). In ischemic patients, the sensitivity increased from 11.5% to 46.2% (p = 0.004). Two patients without nonsustained ventricular tachycardia on day 1 had episodes of 13 and 16 beats on days 3 and 6 of monitoring. In patients with left ventricular ejection fractions >35% and N-terminal–pro-brain natriuretic peptide levels <1,000 pg/ml, no episodes of nonsustained ventricular tachycardia were detected on day 1 in nonischemic and ischemic patients, but 7DH detected 3 new patients in each group. In conclusion, 7DH clearly improves the detection and allows a better characterization of ventricular arrhythmic episodes but seems to be less useful for supraventricular events. [ABSTRACT FROM AUTHOR]