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• Clear clinical guidance on the management of AF in the setting of AHF remains missing in the current AF and HF guidelines due to a paucity of data. • In patients hospitalized for AHF, only a few converted from AF to sinus rhythm or vice versa. This occurred mainly within the first 24 hours after hospital admission. • Although development of AF or persistent AF was associated with longer lengths of hospitalization, midterm mortality and readmission rates were similar in the AF groups. Atrial fibrillation (AF) is the most common sustained arrhythmia in acute heart failure (AHF), with a prevalence of approximately 35%. However, little is known about the clinical characteristics and outcomes of in-hospital conversion from AF to sinus rhythm and vice versa. In a post hoc secondary analysis of the randomized, double-blind, placebo-controlled PROTECT trial in patients with AHF, we identified 4 groups of patients: AF at admission and in-hospital conversion to sinus rhythm (n = 44); in-hospital development of AF (n = 31); persistent AF (n = 278); and continuous sinus rhythm (n = 410). Conversion from AF to sinus rhythm (13.7%) and from sinus rhythm to AF (7.0%) occurred only in a minority of patients. Patients with AF who converted to sinus rhythm were more often classified as being in New York Heart Association class IV, had higher heart rates and higher respiratory rates at hospital admission, whereas patients who developed AF were older, more likely to be female and had the highest ejection fractions compared to continuous sinus rhythm (all P < 0.05). Conversion to sinus rhythm or development of AF occurred mainly within the first 24 hours after hospital admission. Patients with persistent AF and those who developed AF had longer median lengths of hospital stay (8 vs 7 days; P < 0.001 and 9 vs 7 days; P < 0.001, respectively), compared to those with continuous sinus rhythm. In both univariable and multivariable analyses, there was no significant association between the AF groups and the primary clinical outcomes of either 180-day all-cause mortality or 60-day death or readmission for heart failure. In patients hospitalized for AHF, only few converted from AF to sinus rhythm or sinus rhythm to AF. Although development of AF or persistent AF was associated with longer lengths of hospitalization, midterm mortality and readmission rates were similar in the groups. [Display omitted] [ABSTRACT FROM AUTHOR]

Aims: Acute heart failure (AHF) is associated with end‐organ dysfunction. The effect of AHF on the pancreas has not been studied. We aim to evaluate serum markers of pancreatic damage during hospitalization for AHF. Methods and results: In data from the Pragmatic Urinary Sodium‐based treatment algoritHm in Acute Heart Failure (PUSH‐AHF) study, amylase and lipase values were extracted from available serum samples at baseline, and at 24 and 72 h after hospitalization. The differences between pancreatic enzymes between timepoints were evaluated using the Friedman test. Associations with N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) were tested using linear regression analysis. The study population consisted of 274 patients. Mean age was 73 ± 11 years, and 117 (43%) were women. Mean left ventricular ejection fraction (LVEF) was 38 ± 14%; 53 (19%) patients had HF with a preserved LVEF (≥50%). At baseline, median amylase and lipase were within normal range (47 [33–63] U/L and 30 [21–44] U/L, respectively). Both enzymes significantly increased in the first 72 h (P‐value for trend <0.001); mean change was 9 ± 22 U/L for amylase, and 10 ± 22 U/L for lipase. Moreover, NT‐proBNP at baseline showed a positive correlation with mean change in pancreatic enzymes in 72 h (P = 0.02 for amylase and P = 0.006 for lipase). Conclusion: Patients admitted for AHF exhibited a significant increase in serum values of pancreatic enzymes in the first 72 h, suggesting that an episode of AHF affects the pancreatic tissue. This rise in pancreatic enzymes was associated with HF severity, as reflected by NT‐proBNP. [ABSTRACT FROM AUTHOR]

Aims: Burst steroid therapy, effective in acute respiratory diseases, may benefit patients with acute heart failure (AHF) in whom inflammatory activation is associated with adverse outcomes. Methods and results: CORTAHF assessed whether burst steroid therapy reduces inflammation and results in better quality of life and clinical outcomes in AHF. Patients with AHF, N‐terminal pro‐B‐type natriuretic peptide >1500 pg/ml, and high‐sensitivity C‐reactive protein (hsCRP) >20 mg/L were randomized 1:1 to oral, once daily 40 mg prednisone for 7 days or usual care, without blinding. Patients were followed for 90 days. A total of 101 patients were randomized. At day 7 the primary endpoint, hsCRP decreased in both arms – adjusted geometric mean ratios (GMRs) were 0.30 and 0.40 in the prednisone and usual care arms (ratio of GMRs 0.75, 95% confidence interval [CI] 0.56–1.00, p = 0.0498). The 90‐day risk of worsening heart failure (HF), HF readmission or death as reported by the unblinded investigators was significantly lower in the prednisone group (10.4%) than in usual care (30.8%) (hazard ratio 0.31, 95% CI 0.11–0.86, p = 0.016). The EQ‐5D visual analogue scale score as reported by the unblinded patients increased more in the prednisone group on day 7 (least squares mean difference 2.57, 95% CI 0.12–5.01 points, p = 0.040). All effects were statistically significant in the pre‐specified subgroup with centrally‐measured interleukin‐6 >13 pg/ml. Adverse events, particularly hyperglycaemia, occurred more in the prednisone group with no difference in infection rate. Conclusion: In this small open‐label study of patients with AHF, burst steroid therapy was associated with reduced inflammation as measured by hsCRP levels at day 7 (primary endpoint). Secondary endpoints showed improved quality of life at day 7 and reduced 90‐day risk of death or worsening HF. Large prospective studies are needed to evaluate these findings. [ABSTRACT FROM AUTHOR]

Aims: Inflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers shown to be highly predictive of adverse outcomes in these patients. The CORTAHF study builds on both these data and the fact that steroid burst therapy has been shown to be effective in the treatment of respiratory diseases and COVID‐19. Our hypothesis is that in patients with AHF and elevated C‐reactive protein (CRP) levels without symptoms or signs of infection, a 7‐day course of steroid therapy will lead to reduced inflammation and short‐term improvement in quality of life and a reduced risk of worsening HF (WHF) events. Methods and results: The study, which is currently ongoing, will include 100 patients with AHF ages 18–85, regardless of ejection fraction, screened within 12 h of presentation. Patients will be included who have NT‐proBNP > 1500 pg/mL and CRP > 20 mg/L at screening. Exclusion criteria include haemodynamic instability and symptoms and signs of infection. After signed consent, eligible patients will be randomized according to a central randomization scheme stratified by centre 1:1 to either treatment once daily for 7 days with 40 mg prednisone orally or to standard care. Patients will be assessed at study day 2, day 4 or at discharge if earlier, and at days 7 and 31 at the hospital; and at day 91 through a telephone follow‐up. The primary endpoint is the change in CRP level from baseline to day 7, estimated from a mixed model for repeated measures (MMRM) including all measured timepoints, in patients without a major protocol violation. Secondary endpoints include the time to the first event of WHF adverse event, readmission for HF, or death through day 91; and changes to day 7 in EQ‐5D visual analogue scale score and utility index. Additional clinical and laboratory measures will be assessed. Conclusions: The results of the study will add to the knowledge of the role of inflammation in AHF and potentially inform the design of larger studies with possibly longer duration of anti‐inflammatory therapies in AHF. [ABSTRACT FROM AUTHOR]

Aims: Angiotensin receptor blockers have been shown to reduce heart failure hospitalization and cardiovascular mortality in men and women with heart failure with reduced ejection fraction (HFrEF). It is unknown whether there are differences between men and women in achieved dose and treatment discontinuation due to adverse events of candesartan. Methods and results: We conducted a post hoc analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. A total of 3172 men and 1106 women with HFrEF [left ventricular ejection fraction (LVEF) ≤ 40%] in New York Heart Association class II–IV were randomized to candesartan or placebo. Every 2 weeks, patients were up‐titrated from 4 or 8, to16, to 32 mg once daily, unless a higher dose was contraindicated or not tolerated. Women were older (66 vs. 64 years), had a higher LVEF (29.9% vs. 28.6%), and had more hypertension (54% vs. 47%) than men. The mean achieved dose of candesartan was 21.5 ± 12.6 mg in men and 20.7 ± 12.9 mg in women (P = 0.19). In both the candesartan and placebo groups, cardiovascular death and heart failure hospitalizations were higher in men and women who achieved lower dose levels. Event rates for achieved dose levels of 0, 4 or 8, 16, and 32 mg candesartan were 20.8, 17.2, 14.0, and 10.1 per 100 person‐years in men, respectively, and 23.6, 13.7, 14.0, and 9.1 per 100 person‐years in women, respectively. In each of the achieved dose levels, there was no sex difference in the proportion of patients with an event, neither in the candesartan group nor in the placebo group (P‐value for all > 0.05). There was no significant interaction between sex and treatment‐related discontinuation for hypotension (P = 0.520), an increase in creatinine (P = 0.102), and hyperkalaemia (P = 0.905). Conclusions: In a randomized clinical trial in patients with HFrEF, men and women achieved similar doses of candesartan. Primary event rates and treatment‐related discontinuation due to adverse events were also similar between men and women. [ABSTRACT FROM AUTHOR]

BackgroundPoor diuretic response in acute heart failure is related to poor clinical outcome. The underlying mechanisms and pathophysiology behind diuretic resistance are incompletely understood. We evaluated a combined approach using clinical characteristics and biomarkers to predict diuretic response in acute heart failure (AHF).Methods and resultsWe investigated explanatory and predictive models for diuretic response--weight loss at day 4 per 40 mg of furosemide--in 974 patients with AHF included in the PROTECT trial. Biomarkers, addressing multiple pathophysiological pathways, were determined at baseline and after 24 h. An explanatory baseline biomarker model of a poor diuretic response included low potassium, chloride, hemoglobin, myeloperoxidase, and high blood urea nitrogen, albumin, triglycerides, ST2 and neutrophil gelatinase-associated lipocalin (r(2) = 0.086). Diuretic response after 24 h (early diuretic response) was a strong predictor of diuretic response (β = 0.467, P < 0.001; r(2) = 0.523). Addition of diuretic response after 24 h to biomarkers and clinical characteristics significantly improved the predictive model (r(2) = 0.586, P < 0.001).ConclusionsBiomarkers indicate that diuretic unresponsiveness is associated with an atherosclerotic profile with abnormal renal function and electrolytes. However, predicting diuretic response is difficult and biomarkers have limited additive value. Patients at risk of poor diuretic response can be identified by measuring early diuretic response after 24 h.

Aim: To create and validate a prediction model to identify patients with type 2 diabetes (T2D) at high risk of new‐onset heart failure (HF), including those treated with a sodium‐glucose cotransporter‐2 (SGLT2) inhibitor. Methods: A prediction model was developed from the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE), a trial in T2D patients with albuminuria or cardiovascular disease. We included 5081 patients with baseline N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) measurement and no history of HF. The model was developed using Cox regression and validated externally in the placebo arm of the Canagliflozin Cardiovascular Assessment Study (CANVAS), which included 996 participants with T2D and established cardiovascular disease or high cardiovascular risk, and in patients treated with canagliflozin. Results: ALTITUDE participants (mean age 64 ± 9.8 years) had a median serum NT‐proBNP level of 157 (25th–75th percentile 70–359) pg/mL. Higher NT‐proBNP level, troponin T (TnT) level and body mass index (BMI) emerged as significant and independent predictors of new‐onset HF in both cohorts. The model further contained urinary albumin‐to‐creatinine ratio, glycated haemoglobin, age, haematocrit, and use of calcium channel blockers. A prediction model including these variables had a C‐statistic of 0.828 (95% confidence interval [CI] 0.801–0.855) in ALTITUDE and 0.800 (95% CI 0.720–0.880) in CANVAS. The C‐statistic of this model increased to 0.847 (95% CI 0.792–0.902) in patients after 1 year of canagliflozin treatment. Conclusion: In patients with T2D, higher NT‐proBNP level, TnT level and BMI are independent and externally validated predictors of new‐onset HF, including patients using an SGLT2 inhibitor. This newly developed model may identify patients at high risk of new‐onset HF, contributing to early recognition and possibly prevention. [ABSTRACT FROM AUTHOR]