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Abstract Aims In low‐risk patients with severe aortic stenosis (AS), sutureless surgical aortic valve replacement (SU‐SAVR) may be an alternative to transcatheter aortic valve implantation (TAVI). The risk of heart failure hospitalization (HFH) after aortic valve replacement (AVR) in this population is incompletely characterized. This study aims to investigate the incidence, predictors, and outcomes of HFH in patients undergoing SU‐SAVR versus TAVI. Methods and results Patients referred for AVR between 2013 and 2020 at two centres were consecutively included. The decision for SU‐SAVR or TAVI was determined by a multidisciplinary Heart Team. Cox regression and competing risk analysis were conducted to assess adverse events. Of 594 patients (mean age 77.5 ± 6.4, 59.8% male), 424 underwent SU‐SAVR, while 170 underwent TAVI. Following a mean follow‐up of 34.1 ± 23.1 months, HFH occurred in 112 (27.8%) SU‐SAVR patients and in 8 (4.8%) TAVI patients (P

Abstract Aims Natriuretic peptide (NP) uptake varies in Emergency Departments (EDs) across Europe. The ‘Peptide for Life’ (P4L) initiative, led by Heart Failure Association, aims to enhance NP utilization for early diagnosis of heart failure (HF). We tested the hypothesis that implementing an educational campaign in Western Balkan countries would significantly increase NP adoption rates in the ED. Methods and results This registry examined NP adoption before and after implementing the P4L‐ED study across 10 centres in five countries: Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia, and Serbia. A train‐the‐trainer programme was implemented to enhance awareness of NP testing in the ED, and centres without access received point‐of‐care instruments. Differences in NP testing between the pre‐P4L‐ED and post‐P4L‐ED phases were evaluated. A total of 2519 patients were enrolled in the study: 1224 (48.6%) in the pre‐P4L‐ED phase and 1295 (51.4%) in the post‐P4L‐ED phase. NP testing was performed in the ED on 684 patients (55.9%) during the pre‐P4L‐ED phase and on 1039 patients (80.3%) during the post‐P4L‐ED phase, indicating a significant absolute difference of 24.4% (95% CI: 20.8% to 27.9%, P

Abstract Aims The prevalence of advanced heart failure (HF) is increasing due to the growing number of patients with HF and their better treatment and survival. There is a scarcity of data on the accuracy of HF web‐based risk scores in this selected population. This study aimed to assess mortality prediction performance of the Meta‐Analysis Global Group in Chronic HF (MAGGIC‐HF) risk score and the model of the Barcelona Bio‐HF Risk Calculator (BCN‐Bio‐HF) containing N terminal pro brain natriuretic peptide in HF patients receiving intermittent inotropic support with levosimendan as destination therapy. Methods and results Four hundred and three advanced HF patients from 23 tertiary hospitals in Spain receiving intermittent inotropic support with levosimendan as destination therapy were included. Discrimination for all‐cause mortality was compared by area under the curve (AUC) and Harrell's C‐statistic at 1 year. Calibration was assessed by calibration plots comparing observed versus expected events based on estimated risk by each calculator. The included patients were predominantly men, aged 71.5 [interquartile range 64–78] years, with reduced left ventricular ejection fraction (27.5 ± 9.4%); ischaemic heart disease was the most prevalent aetiology (52.5%). Death rate at 1 year was 26.8%, while the predicted 1‐year mortality by BCN‐Bio‐HF and MAGGIC‐HF was 17.0% and 22.1%, respectively. BCN‐Bio‐HF AUC was 0.66 (Harrell's C‐statistic 0.64), and MAGGIC‐HF AUC was 0.62 (Harrell's C‐statistic 0.61). Conclusions The two evaluated risk scores showed suboptimal discrimination and calibration with an underestimation of risk in advanced HF patients receiving levosimendan as destination therapy. There is a need for specific scores for advanced HF.

Abstract Aims Venoarterial extracorporeal membrane oxygenation (VA‐ECMO) is currently one of the most used devices in refractory cardiogenic shock. However, there is a lack of evidence on how to set the ‘optimal’ flow. We aimed to describe the evolution of VA‐ECMO flows in a cardiogenic shock population and determine the risk factors of ‘high‐ECMO flow’. Methods and results A 7 year database of patients supported with VA‐ECMO was used. Based on the median flow during the first 48 h of the VA‐ECMO run, patients were classified as ‘high‐flow’ or ‘low‐flow’, respectively, when median ECMO flow was ≥3.6 or

Aims: In low‐risk patients with severe aortic stenosis (AS), sutureless surgical aortic valve replacement (SU‐SAVR) may be an alternative to transcatheter aortic valve implantation (TAVI). The risk of heart failure hospitalization (HFH) after aortic valve replacement (AVR) in this population is incompletely characterized. This study aims to investigate the incidence, predictors, and outcomes of HFH in patients undergoing SU‐SAVR versus TAVI. Methods and results: Patients referred for AVR between 2013 and 2020 at two centres were consecutively included. The decision for SU‐SAVR or TAVI was determined by a multidisciplinary Heart Team. Cox regression and competing risk analysis were conducted to assess adverse events. Of 594 patients (mean age 77.5 ± 6.4, 59.8% male), 424 underwent SU‐SAVR, while 170 underwent TAVI. Following a mean follow‐up of 34.1 ± 23.1 months, HFH occurred in 112 (27.8%) SU‐SAVR patients and in 8 (4.8%) TAVI patients (P < 0.001). The SU‐SAVR cohort exhibited higher all‐cause mortality (138 [32.5%] patients compared with 30 [17.6%] in the TAVI cohort [P < 0.001]). These differences remained significant after sensitivity analyses with 1:1 propensity score matching for baseline variables. SU‐SAVR with HFH was associated with increased all‐cause mortality (61.6% vs. 23.1%, P < 0.001). Independent associates of HFH in SU‐SAVR patients included diabetes, atrial fibrillation, chronic obstructive pulmonary disease, lower glomerular filtration rate and lower left ventricular ejection fraction. SU‐SAVR patients with HFH had a 12‐month LVEF of 59.4 ± 12.7. Conclusions: In low‐risk AS, SU‐SAVR is associated with a higher risk of HFH and all‐cause mortality compared to TAVI. In patients with severe AS candidate to SU‐SAVR or TAVI, TAVI may be the preferred intervention. [ABSTRACT FROM AUTHOR]

Abstract Aims The criteria for patients with heart failure (HF) and improved ejection fraction (HFimpEF) are a baseline left ventricular ejection fraction (LVEF) ≤40%, a ≥10‐point increase from baseline LVEF, and a second LVEF measurement >40%. We aimed to (i) assess patients with HF and reduced LVEF (HFrEF) at baseline and compare quality of life (QoL) changes between those that fulfilled and those that did not fulfil the HFimpEF criteria 1 year later and (ii) assess the prognostic role of QoL in patients with HFimpEF. Methods We reviewed data from a prospective registry of real‐world outpatients with HF that were assessed for LVEF and QoL at a first visit to the HF clinic and 1 year later. QoL was evaluated with the Minnesota Living with Heart Failure Questionnaire (MLWHFQ). The primary prognostic endpoint was the composite of all‐cause death or HF hospitalization. Results Baseline and 1‐year LVEF and MLWFQ scores were available for 1040 patients with an initial LVEF ≤40% (mean age, 65.2 ± 11.7 years; 75.9% men). The main aetiology was ischaemic heart disease (52.9%), and patients were mostly in New York heart Association Classes II (71.1%) and III (21.6%). At baseline, the mean LVEF was 28.5% ± 7.3, and the mean MLWHFQ score was 30.2 ± 19.5. After 1 year, the mean LVEF increased to 38.0% ± 12.2, and the MLWHFQ scores improved to 17.4 ± 16.0. In 361 patients that fulfilled the HFimpEF criteria (34.7%), significant improvements were observed in both LVEF (from 28.7% ± 6.6 to 50.9% ± 7.6, P

Abstract Heart failure (HF) is a long‐term clinical syndrome, with increasing prevalence and considerable healthcare costs that are further expected to increase dramatically. Despite significant advances in therapy and prevention, mortality and morbidity remain high and quality of life poor. Epidemiological data, that is, prevalence, incidence, mortality, and morbidity, show geographical variations across the European countries, depending on differences in aetiology, clinical characteristics, and treatment. However, data on the prevalence of the disease are scarce, as are those on quality of life. For these reasons, the ESC‐HFA has developed a position paper to comprehensively assess our understanding of the burden of HF in Europe, in order to guide future policies for this syndrome. This manuscript will discuss the available epidemiological data on HF prevalence, outcomes, and human costs—in terms of quality of life—in European countries.

Abstract Aims To define plasma concentrations, determinants, and optimal prognostic cut‐offs of soluble suppression of tumorigenesis‐2 (sST2), high‐sensitivity cardiac troponin T (hs‐cTnT), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in women and men with chronic heart failure (HF). Methods and results Individual data of patients from the Biomarkers In Heart Failure Outpatient Study (BIOS) Consortium with sST2, hs‐cTnT, and NT‐proBNP measured were analysed. The primary endpoint was a composite of 1 year cardiovascular death and HF hospitalization. The secondary endpoints were 5 year cardiovascular and all‐cause death. The cohort included 4540 patients (age 67 ± 12 years, left ventricular ejection fraction 33 ± 13%, 1111 women, 25%). Women showed lower sST2 (24 vs. 27 ng/mL, P

Abstract Aims Prior studies have not fully characterized the haemodynamic effects of the angiotensin receptor‐neprilysin inhibitor (ARNI) sacubitril/valsartan in heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF–PH). The aim of the Treatment of PH With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in HFpEF Patients With CardioMEMS Device (ARNIMEMS‐HFpEF) study is to assess pulmonary artery pressure (PAP) dynamics by means of implanted PAP monitors in patients with HFpEF–PH treated with sacubitril/valsartan. Methods and results This single‐arm, investigator‐initiated, interventional study included 14 consecutive ambulatory symptomatic HFpEF–PH patients who underwent CardioMEMS implantation prior to enrolment [mean ejection fraction 60.4 ± 7.2%, baseline mean PAP (mPAP) 33.9 ± 7.6 mmHg]. Daily PAP values were examined during three periods: a 6 week period after CardioMEMS implantation and before sacubitril/valsartan treatment (pre‐ARNI), a 6 week period with sacubitril/valsartan treatment (ARNI ON), and a 6 week period of sacubitril/valsartan withdrawal (ARNI OFF). The primary endpoint was change in mPAP with and without sacubitril/valsartan. Secondary endpoints included changes in 6 min walking distance, B‐line sum in lung ultrasound, and quality of life (QoL). During the study period, 1717 mPAP measurements were recorded. Between pre‐ARNI vs. ARNI ON, mPAP significantly declined by −4.99 mmHg [95% confidence interval (CI) −5.55 to −4.43]. Between ARNI ON vs. ARNI OFF, mPAP significantly increased by +2.84 mmHg [95% CI +2.26 to +3.42]. Between pre‐ARNI vs. ARNI ON, we found an improvement in 6 min walking distance, B‐lines, and QoL. Mean loop diuretic management did not differ between periods. Conclusions Sacubitril/valsartan significantly reduced mPAP in patients with HFpEF–PH, independent of loop diuretic management, together with improvement in functional capacity, lung congestion, and QoL. Sacubitril/valsartan may be a therapeutic alternative in HFpEF–PH.

Abstract Aims This study aimed to evaluate psychometric properties of the Spanish version of the Thirst Distress Scale for patients with Heart Failure (TDS‐HF) and to describe thirst distress‐associated factors in outpatients at a heart failure (HF) clinic in Spain. Thirst is common in patients with HF, but thirst distress has rarely been addressed and may significantly decrease quality of life. Methods and results A cross‐sectional study was performed assessing perceived thirst distress by patients with HF during the preceding 3 days, with the TDS‐HF (scores 8 to 40). Univariable and multivariable linear regression analyses were performed to identify variables independently associated with thirst distress. Three‐hundred two HF outpatients were included (age 67 ± 12 years, 74% male, HF duration 82 ± 75 months, left ventricular ejection fraction 42 ± 14%). Most patients were on treatment with fluid restriction (99%), sodium restriction (99%), and diuretics (70%). The psychometric evaluation of the Spanish version of the TDS‐HF showed satisfactory item‐total and inter‐item correlations (range from 0.77 to 0.85 and 0.60 to 0.84, respectively), and internal consistency was 0.95 (Cronbach's alpha). The majority perceived mild to moderate thirst distress, and 18% perceived it as high or severe. The mean score obtained was 16.2 ± 9.3 (median 13, Q1–Q3 8–20). Higher serum urea {beta coefficient 1.6 [95% confidence interval (CI) 0.267 to 2.92], P = 0.019} and lower potassium [beta coefficient −3.63 (85% CI −6.32 to −0.93), P = 0.009] remained significantly associated with thirst distress in the multivariable analysis, together with the dose of diuretics [beta coefficient 2.98 (95% CI 1.37 to 4.59), P

Abstract Aims Reverse remodelling (RR) is the recovery from left ventricular (LV) dilatation and dysfunction. Many arbitrary criteria for RR have been proposed. We searched the criteria with the strongest prognostic yield for the hard endpoint of cardiovascular death. Methods and results We performed a systematic literature search of diagnostic criteria for RR. We evaluated their prognostic significance in a cohort of 927 patients with LV ejection fraction (LVEF) 10 U and (ii) LVEF increase ≥1 category [severe (LVEF ≤ 30%), moderate (LVEF 31–40%), mild LV dysfunction (LVEF 41–55%), and normal LV function (LVEF ≥ 56%)]. The same two criteria yielded independent prognostic significance and improved risk reclassification even in patients with more severe systolic dysfunction, namely, those with LVEF 10 U and LVEF increase ≥1 category displayed a greater prognostic value than LVESV reduction ≥15%, both in the whole cohort and in the subgroups with LVEF 10 U independently predicted cardiovascular death over Model 1 and LVESV reduction ≥15% (hazard ratio 0.40, 95% confidence interval 0.18–0.90, P = 0.026), while LVESV reduction ≥15% did not independently predict cardiovascular death (P = 0.112). Conclusions Left ventricular ejection fraction increase >10 U and LVEF increase ≥1 category are stronger predictors of cardiovascular death than the most commonly used criterion for RR, namely, LVESV reduction ≥15%.

Aims: Natriuretic peptide (NP) uptake varies in Emergency Departments (EDs) across Europe. The 'Peptide for Life' (P4L) initiative, led by Heart Failure Association, aims to enhance NP utilization for early diagnosis of heart failure (HF). We tested the hypothesis that implementing an educational campaign in Western Balkan countries would significantly increase NP adoption rates in the ED. Methods and results: This registry examined NP adoption before and after implementing the P4L‐ED study across 10 centres in five countries: Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia, and Serbia. A train‐the‐trainer programme was implemented to enhance awareness of NP testing in the ED, and centres without access received point‐of‐care instruments. Differences in NP testing between the pre‐P4L‐ED and post‐P4L‐ED phases were evaluated. A total of 2519 patients were enrolled in the study: 1224 (48.6%) in the pre‐P4L‐ED phase and 1295 (51.4%) in the post‐P4L‐ED phase. NP testing was performed in the ED on 684 patients (55.9%) during the pre‐P4L‐ED phase and on 1039 patients (80.3%) during the post‐P4L‐ED phase, indicating a significant absolute difference of 24.4% (95% CI: 20.8% to 27.9%, P < 0.001). The use of both NPs and echocardiography significantly increased from 37.7% in the pre‐P4L‐ED phase to 61.3% in the post‐P4L‐ED phase. There was an increased prescription of diuretics and SGLT2 inhibitors during the post‐P4L‐ED phase. Conclusions: By increasing awareness and providing resources, the utilization of NPs increased in the ED, leading to improved diagnostic accuracy and enhanced patient care. [ABSTRACT FROM AUTHOR]

Aims: The prevalence of advanced heart failure (HF) is increasing due to the growing number of patients with HF and their better treatment and survival. There is a scarcity of data on the accuracy of HF web‐based risk scores in this selected population. This study aimed to assess mortality prediction performance of the Meta‐Analysis Global Group in Chronic HF (MAGGIC‐HF) risk score and the model of the Barcelona Bio‐HF Risk Calculator (BCN‐Bio‐HF) containing N terminal pro brain natriuretic peptide in HF patients receiving intermittent inotropic support with levosimendan as destination therapy. Methods and results: Four hundred and three advanced HF patients from 23 tertiary hospitals in Spain receiving intermittent inotropic support with levosimendan as destination therapy were included. Discrimination for all‐cause mortality was compared by area under the curve (AUC) and Harrell's C‐statistic at 1 year. Calibration was assessed by calibration plots comparing observed versus expected events based on estimated risk by each calculator. The included patients were predominantly men, aged 71.5 [interquartile range 64–78] years, with reduced left ventricular ejection fraction (27.5 ± 9.4%); ischaemic heart disease was the most prevalent aetiology (52.5%). Death rate at 1 year was 26.8%, while the predicted 1‐year mortality by BCN‐Bio‐HF and MAGGIC‐HF was 17.0% and 22.1%, respectively. BCN‐Bio‐HF AUC was 0.66 (Harrell's C‐statistic 0.64), and MAGGIC‐HF AUC was 0.62 (Harrell's C‐statistic 0.61). Conclusions: The two evaluated risk scores showed suboptimal discrimination and calibration with an underestimation of risk in advanced HF patients receiving levosimendan as destination therapy. There is a need for specific scores for advanced HF. [ABSTRACT FROM AUTHOR]

Aims: Venoarterial extracorporeal membrane oxygenation (VA‐ECMO) is currently one of the most used devices in refractory cardiogenic shock. However, there is a lack of evidence on how to set the 'optimal' flow. We aimed to describe the evolution of VA‐ECMO flows in a cardiogenic shock population and determine the risk factors of 'high‐ECMO flow'. Methods and results: A 7 year database of patients supported with VA‐ECMO was used. Based on the median flow during the first 48 h of the VA‐ECMO run, patients were classified as 'high‐flow' or 'low‐flow', respectively, when median ECMO flow was ≥3.6 or <3.6 L/min. Outcomes included rates of ventilator‐associated pneumonia, ECMO‐related complications, days on ECMO, days on mechanical ventilation, intensive care unit and hospitalization lengths of stay, and in‐hospital and 60 day mortality. Risk factors of high‐ECMO flow were assessed using univariate and multivariate cox regression. The study population included 209 patients on VA‐ECMO, median age was 51 (40–59) years, and 78% were males. The most frequent aetiology leading to cardiogenic shock was end‐stage dilated cardiomyopathy (57%), followed by acute myocardial infarction (23%) and fulminant myocarditis (17%). Among the 209 patients, 105 (50%) were classified as 'high‐flow'. This group had a higher rate of ischaemic aetiology (16% vs. 30%, P = 0.023) and was sicker at admission, in terms of worse Simplified Acute Physiology Score II score [40 (26–58) vs. 56 (42–74), P < 0.001], higher lactate [3.6 (2.2–5.8) mmol/L vs. 5.2 (3–9.7) mmol/L, P < 0.001], and higher aspartate aminotransferase [97 (41–375) U/L vs. 309 (85–939) U/L, P < 0.001], among others. The 'low‐flow' group had less ventilator‐associated pneumonia (40% vs. 59%, P = 0.007) and less days on mechanical ventilation [4 (1.5–7.5) vs. 6 (3–12) days, P = 0.009]. No differences were found in lengths of stay or survival according to the ECMO flow. The multivariate analysis showed that risk factors independently associated with 'high‐flow' were mechanical ventilation at cannulation [odds ratio (OR) 3.9, 95% confidence interval (CI) 2.1–7.1] and pre‐ECMO lactate (OR 1.1, 95% CI 1.0–1.2). Conclusions: In patients with refractory cardiogenic shock supported with VA‐ECMO, sicker patients had higher support since early phases, presenting thereafter higher rates of ventilator‐associated pneumonia but similar survival compared with patients with lower flows. [ABSTRACT FROM AUTHOR]

Aims: The criteria for patients with heart failure (HF) and improved ejection fraction (HFimpEF) are a baseline left ventricular ejection fraction (LVEF) ≤40%, a ≥10‐point increase from baseline LVEF, and a second LVEF measurement >40%. We aimed to (i) assess patients with HF and reduced LVEF (HFrEF) at baseline and compare quality of life (QoL) changes between those that fulfilled and those that did not fulfil the HFimpEF criteria 1 year later and (ii) assess the prognostic role of QoL in patients with HFimpEF. Methods: We reviewed data from a prospective registry of real‐world outpatients with HF that were assessed for LVEF and QoL at a first visit to the HF clinic and 1 year later. QoL was evaluated with the Minnesota Living with Heart Failure Questionnaire (MLWHFQ). The primary prognostic endpoint was the composite of all‐cause death or HF hospitalization. Results: Baseline and 1‐year LVEF and MLWFQ scores were available for 1040 patients with an initial LVEF ≤40% (mean age, 65.2 ± 11.7 years; 75.9% men). The main aetiology was ischaemic heart disease (52.9%), and patients were mostly in New York heart Association Classes II (71.1%) and III (21.6%). At baseline, the mean LVEF was 28.5% ± 7.3, and the mean MLWHFQ score was 30.2 ± 19.5. After 1 year, the mean LVEF increased to 38.0% ± 12.2, and the MLWHFQ scores improved to 17.4 ± 16.0. In 361 patients that fulfilled the HFimpEF criteria (34.7%), significant improvements were observed in both LVEF (from 28.7% ± 6.6 to 50.9% ± 7.6, P < 0.001) and QoL (from 32.9 ± 20.6 to 16.9 ± 16.0, P < 0.001). Patients that did not fulfil the HFimpEF criteria also showed significant improvements in LVEF (from 28.4% ± 7.6 to 31.1% ± 7.9, P < 0.001) and QoL (from 28.7 ± 18.8 to 17.6 ± 15.9, P < 0.001). However, the QoL improvement was significantly higher in the HFimpEF group (−16.0 ± 23.8 vs. −11.1 ± 20.3, P = 0.001), despite the worse mean baseline MLWHFQ score, compared with the non‐HFimpEF group (P = 0.001). The 1‐year QoL was similar between groups (P = 0.50). The 1‐year MLWHFQ score was independently associated with outcomes; the hazard ratio for the composite endpoint was 1.02 (95% CI: 1.01–1.03, P = 0.006). In contrast, the QoL improvement (with a cut‐off ≥5 points) was not independently associated with the composite outcome. Conclusions: Patients with HFrEF showed improved QoL after 1 year, regardless of whether they met the HFimpEF criteria. The similar 1‐year QoL perception between groups suggested that factors other than LVEF influenced QoL perception. The 1‐year QoL was superior to the QoL change from baseline for predicting prognosis in patients with HFimpEF. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a long‐term clinical syndrome, with increasing prevalence and considerable healthcare costs that are further expected to increase dramatically. Despite significant advances in therapy and prevention, mortality and morbidity remain high and quality of life poor. Epidemiological data, that is, prevalence, incidence, mortality, and morbidity, show geographical variations across the European countries, depending on differences in aetiology, clinical characteristics, and treatment. However, data on the prevalence of the disease are scarce, as are those on quality of life. For these reasons, the ESC‐HFA has developed a position paper to comprehensively assess our understanding of the burden of HF in Europe, in order to guide future policies for this syndrome. This manuscript will discuss the available epidemiological data on HF prevalence, outcomes, and human costs—in terms of quality of life—in European countries. [ABSTRACT FROM AUTHOR]

Aims: Prior studies have not fully characterized the haemodynamic effects of the angiotensin receptor‐neprilysin inhibitor (ARNI) sacubitril/valsartan in heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF–PH). The aim of the Treatment of PH With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in HFpEF Patients With CardioMEMS Device (ARNIMEMS‐HFpEF) study is to assess pulmonary artery pressure (PAP) dynamics by means of implanted PAP monitors in patients with HFpEF–PH treated with sacubitril/valsartan. Methods and results: This single‐arm, investigator‐initiated, interventional study included 14 consecutive ambulatory symptomatic HFpEF–PH patients who underwent CardioMEMS implantation prior to enrolment [mean ejection fraction 60.4 ± 7.2%, baseline mean PAP (mPAP) 33.9 ± 7.6 mmHg]. Daily PAP values were examined during three periods: a 6 week period after CardioMEMS implantation and before sacubitril/valsartan treatment (pre‐ARNI), a 6 week period with sacubitril/valsartan treatment (ARNI ON), and a 6 week period of sacubitril/valsartan withdrawal (ARNI OFF). The primary endpoint was change in mPAP with and without sacubitril/valsartan. Secondary endpoints included changes in 6 min walking distance, B‐line sum in lung ultrasound, and quality of life (QoL). During the study period, 1717 mPAP measurements were recorded. Between pre‐ARNI vs. ARNI ON, mPAP significantly declined by −4.99 mmHg [95% confidence interval (CI) −5.55 to −4.43]. Between ARNI ON vs. ARNI OFF, mPAP significantly increased by +2.84 mmHg [95% CI +2.26 to +3.42]. Between pre‐ARNI vs. ARNI ON, we found an improvement in 6 min walking distance, B‐lines, and QoL. Mean loop diuretic management did not differ between periods. Conclusions: Sacubitril/valsartan significantly reduced mPAP in patients with HFpEF–PH, independent of loop diuretic management, together with improvement in functional capacity, lung congestion, and QoL. Sacubitril/valsartan may be a therapeutic alternative in HFpEF–PH. [ABSTRACT FROM AUTHOR]

Aims: To define plasma concentrations, determinants, and optimal prognostic cut‐offs of soluble suppression of tumorigenesis‐2 (sST2), high‐sensitivity cardiac troponin T (hs‐cTnT), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in women and men with chronic heart failure (HF). Methods and results: Individual data of patients from the Biomarkers In Heart Failure Outpatient Study (BIOS) Consortium with sST2, hs‐cTnT, and NT‐proBNP measured were analysed. The primary endpoint was a composite of 1 year cardiovascular death and HF hospitalization. The secondary endpoints were 5 year cardiovascular and all‐cause death. The cohort included 4540 patients (age 67 ± 12 years, left ventricular ejection fraction 33 ± 13%, 1111 women, 25%). Women showed lower sST2 (24 vs. 27 ng/mL, P < 0.001) and hs‐cTnT level (15 vs. 20 ng/L, P < 0.001), and similar concentrations of NT‐proBNP (1540 vs. 1505 ng/L, P = 0.408). Although the three biomarkers were confirmed as independent predictors of outcome in both sexes, the optimal prognostic cut‐off was lower in women for sST2 (28 vs. 31 ng/mL) and hs‐cTnT (22 vs. 25 ng/L), while NT‐proBNP cut‐off was higher in women (2339 ng/L vs. 2145 ng/L). The use of sex‐specific cut‐offs improved risk prediction compared with the use of previously standardized prognostic cut‐offs and allowed to reclassify the risk of many patients, to a greater extent in women than men, and for hs‐cTnT than sST2 or NT‐proBNP. Specifically, up to 18% men and up to 57% women were reclassified, by using the sex‐specific cut‐off of hs‐cTnT for the endpoint of 5 year cardiovascular death. Conclusions: In patients with chronic HF, concentrations of sST2 and hs‐cTnT, but not of NT‐proBNP, are lower in women. Lower sST2 and hs‐cTnT and higher NT‐proBNP cut‐offs for risk stratification could be used in women. [ABSTRACT FROM AUTHOR]

Aims: Reverse remodelling (RR) is the recovery from left ventricular (LV) dilatation and dysfunction. Many arbitrary criteria for RR have been proposed. We searched the criteria with the strongest prognostic yield for the hard endpoint of cardiovascular death. Methods and results: We performed a systematic literature search of diagnostic criteria for RR. We evaluated their prognostic significance in a cohort of 927 patients with LV ejection fraction (LVEF) < 50% undergoing two echocardiograms within 12 ± 2 months. These patients were followed for a median of 2.8 years (interquartile interval 1.3–4.9) after the second echocardiogram, recording 123 cardiovascular deaths. Two prognostic models were defined. Model 1 included age, LVEF, N‐terminal pro‐B‐type natriuretic peptide, ischaemic aetiology, cardiac resynchronization therapy, estimated glomerular filtration rate, New York Heart Association, and LV end‐systolic volume (LVESV) index, and Model 2 the validated Cardiac and Comorbid Conditions Heart Failure score. We identified 25 criteria for RR, the most used being LVESV reduction ≥15% (12 studies out of 42). In the whole cohort, two criteria proved particularly effective in risk reclassification over Model 1 and Model 2. These criteria were (i) LVEF increase >10 U and (ii) LVEF increase ≥1 category [severe (LVEF ≤ 30%), moderate (LVEF 31–40%), mild LV dysfunction (LVEF 41–55%), and normal LV function (LVEF ≥ 56%)]. The same two criteria yielded independent prognostic significance and improved risk reclassification even in patients with more severe systolic dysfunction, namely, those with LVEF < 40% or LVEF ≤ 35%. Furthermore, LVEF increase >10 U and LVEF increase ≥1 category displayed a greater prognostic value than LVESV reduction ≥15%, both in the whole cohort and in the subgroups with LVEF < 40% or LVEF ≤ 35%. For example, LVEF increase >10 U independently predicted cardiovascular death over Model 1 and LVESV reduction ≥15% (hazard ratio 0.40, 95% confidence interval 0.18–0.90, P = 0.026), while LVESV reduction ≥15% did not independently predict cardiovascular death (P = 0.112). Conclusions: Left ventricular ejection fraction increase >10 U and LVEF increase ≥1 category are stronger predictors of cardiovascular death than the most commonly used criterion for RR, namely, LVESV reduction ≥15%. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to evaluate psychometric properties of the Spanish version of the Thirst Distress Scale for patients with Heart Failure (TDS‐HF) and to describe thirst distress‐associated factors in outpatients at a heart failure (HF) clinic in Spain. Thirst is common in patients with HF, but thirst distress has rarely been addressed and may significantly decrease quality of life. Methods and results: A cross‐sectional study was performed assessing perceived thirst distress by patients with HF during the preceding 3 days, with the TDS‐HF (scores 8 to 40). Univariable and multivariable linear regression analyses were performed to identify variables independently associated with thirst distress. Three‐hundred two HF outpatients were included (age 67 ± 12 years, 74% male, HF duration 82 ± 75 months, left ventricular ejection fraction 42 ± 14%). Most patients were on treatment with fluid restriction (99%), sodium restriction (99%), and diuretics (70%). The psychometric evaluation of the Spanish version of the TDS‐HF showed satisfactory item‐total and inter‐item correlations (range from 0.77 to 0.85 and 0.60 to 0.84, respectively), and internal consistency was 0.95 (Cronbach's alpha). The majority perceived mild to moderate thirst distress, and 18% perceived it as high or severe. The mean score obtained was 16.2 ± 9.3 (median 13, Q1–Q3 8–20). Higher serum urea {beta coefficient 1.6 [95% confidence interval (CI) 0.267 to 2.92], P = 0.019} and lower potassium [beta coefficient −3.63 (85% CI −6.32 to −0.93), P = 0.009] remained significantly associated with thirst distress in the multivariable analysis, together with the dose of diuretics [beta coefficient 2.98 (95% CI 1.37 to 4.59), P < 0.001]. Treatment with angiotensin receptor blocker showed an independent protective effect [beta coefficient −3.62 (95% CI −6.89 to −0.345), P = 0.03]. Conclusions: The psychometric evaluation of the Spanish version of the TDS‐HF showed good psychometric properties. One in five patients experienced severe distress by thirst, but the majority had mild to moderate thirst distress. The dose of diuretics and angiotensin receptor blocker treatment influence thirst distress and could be clinically important targets to relieve thirst distress in patients with HF. [ABSTRACT FROM AUTHOR]

Aims: The role of microRNAs has not been studied in cardiogenic shock. We examined the potential role of miR‐423‐5p level to predict mortality and associations of miR‐423‐5p with prognostic markers in cardiogenic shock. Methods and results: We conducted a prospective multinational observational study enrolling consecutive cardiogenic shock patients. Blood samples were available for 179 patients at baseline to determine levels of miR‐423‐5p and other biomarkers. Patients were treated according to local practice. Main outcome was 90 day all‐cause mortality. Median miR‐423‐5p level was significantly higher in 90 day non‐survivors [median 0.008 arbitrary units (AU) (interquartile range 0.003–0.017) vs. 0.004 AU (0.002–0.009), P = 0.003]. miR‐423‐5p level above median was associated with higher lactate (median 3.7 vs. 2.4 mmol/L, P = 0.001) and alanine aminotransferase levels (median 68 vs. 35 IU/L, P < 0.001) as well as lower cardiac index (1.8 vs. 2.4, P = 0.04) and estimated glomerular filtration rate (56 vs. 70 mL/min/1.73 m2, P = 0.002). In Cox regression analysis, miR‐423‐5p level above median was associated with 90 day all‐cause mortality independently of established risk factors of cardiogenic shock [adjusted hazard ratio 1.9 (95% confidence interval 1.2–3.2), P = 0.01]. Conclusions: In cardiogenic shock patients, above median level of miR‐423‐5p at baseline is associated with markers of hypoperfusion and seems to independently predict 90 day all‐cause mortality. [ABSTRACT FROM AUTHOR]

Aims: The identification of subjects at higher risk for incident heart failure (HF) with preserved ejection fraction (EF) suitable for more intensive preventive programmes remains challenging. We applied phenomapping to the DAVID‐Berg population, comprising subjects with preclinical HF, aiming to refine HF risk stratification. Methods: The DAVID‐Berg study prospectively enrolled 596 asymptomatic outpatients with EF > 40% with hypertension, diabetes mellitus or known cardiovascular disease. In this cohort, we performed an unsupervised cluster analysis on 591 patients, including clinical, laboratory, electrocardiographic and echocardiographic parameters. We tested the association between each cluster and a composite outcome of HF/death. Results: The median age was 70 years, 55.5% were males and the median EF was 61.0%. Phenomapping provided three different clusters. Subjects in Cluster 3 were the oldest and had the highest prevalence of atrial fibrillation, the lowest estimated glomerular filtration rate (eGFR), the highest N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and the largest left atrium. During a median follow‐up of 5.7 years, 13.4% of subjects experienced HF/death events (N = 79). Compared with Clusters 1 and 2, Cluster 3 had the worst prognosis (log‐rank test: Cluster 3 vs. 1 P < 0.001; Cluster 3 vs. 2 P = 0.008). Cluster 3 was associated with a risk of HF/death 2.5 times higher than Cluster 1 [adjusted hazard ratio (HR) = 2.46, 95% confidence interval (CI) 1.24–4.90]. Conclusions: Based on phenomapping, older patients with lower kidney function and worse diastolic function might represent a subset of preclinical HF with EF > 40% who deserve more efforts to prevent clinical HF. [ABSTRACT FROM AUTHOR]

Aims: Diagnosing acute heart failure (AHF) remains particularly challenging in older patients. Natriuretic peptides are recommended as valuable diagnostic tools in this context. This study aims to establish the diagnostic thresholds of B‐type natriuretic peptide (BNP) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) for AHF in patients aged over 75 years, both with and without co‐morbidities. Methods and results: In this retrospective longitudinal multicentre cohort study, data were gathered from 12 071 hospitalized patients aged 75 years or older, presenting with acute dyspnoea and undergoing BNP or NT‐proBNP measurement within 48 h of admission across 10 Assistance Publique‐Hôpitaux de Paris facilities between 2011 and 2022, encompassing geriatrics, cardiology, and pulmonology departments. Final diagnoses were categorized using ICD‐10 criteria as either AHF or other acute respiratory conditions such as COPD exacerbation, pulmonary embolism, and pneumonia. The mean (SD) age of the population was 84.0 (80.0, 89.0) years, with 52.7% being female. Out of these, 7946 (65.8%) were diagnosed with AHF upon discharge. For NT‐proBNP, the identified 'optimal' threshold for diagnosing AHF was 1748 ng/L, with a positive predictive value (PPV) of 84%. Among patients aged over 85 years, a threshold of 2235 pg/mL for NT‐proBNP was associated with an 84% PPV. In patients with atrial fibrillation (AF), a threshold of 2332 pg/mL for NT‐proBNP demonstrated a PPV of 90% for AHF diagnosis. Additionally, in patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min, a threshold of 3474 pg/mL for NT‐proBNP yielded a 90% PPV for AHF diagnosis. In male patients, a threshold of 1800 pg/mL showed an 85% PPV for AHF diagnosis, while in patients with obesity, a threshold of 1375 pg/mL demonstrated an 85% PPV for AHF diagnosis. Conclusions: In older patients, we found significant effects of co‐morbidities on natriuretic peptides results, particularly in patients over 85 years old, older patients with abnormal renal function, obesity, and atrial fibrillation. Despite the consideration of those co‐morbid conditions, NT‐proBNP and BNP level continue to demonstrate utility in the diagnosis of AHF in older patients. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to investigate the association of soluble suppression of tumorigenicity‐2 (sST2) measured by point‐of‐care testing assay with clinical outcomes in patients hospitalized with heart failure after adjusting for other predictors including N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and high‐sensitivity cardiac troponin T (hs‐cTnT). Methods: A total of 1726 consecutive patients hospitalized with heart failure from July 2015 to December 2021 were enrolled. Baseline serum sST2 concentrations were measured by immunofluorescence assay. Primary endpoint event was the composite of all‐cause death, heart transplantation, or left ventricular assist device. Results: During the median follow‐up duration of 682 days, 434 patients (25.1%) suffered from primary endpoint events. Baseline sST2 remained an independent predictor of the primary endpoint event in patients hospitalized with heart failure after adjusting for other predictors including NT‐proBNP and hs‐cTnT [per log (unit) increase, adjusted hazard ratio (HR) (95% confidence interval) (CI): 1.20 (1.09, 1.32), P < 0.001]. And baseline sST2 had a better prognostic value for patients with chronic decompensated heart failure [per log (unit) increase, adjusted HR (95% CI): 1.19 (1.07, 1.31)] than for those with acute new onset heart failure [per log (unit) increase, adjusted HR (95% CI): 1.28 (0.94, 1.75), P value for interaction <0.001], as well as a better prognostic value for patients with New York Heart Association (NYHA) functional class I–II [per log (unit) increase, adjusted HR (95% CI): 1.67 (1.11, 2.52)] than for those with NYHA functional class III‐IV [per log (unit) increase, adjusted HR (95% CI): 1.18 (1.07, 1.31), P value for interaction <0.001]. Baseline sST2 was also a good predictor of the primary endpoint event in patients hospitalized with heart failure at 1 month, 3 months, 1 year and 2 years (area under the curve: 0.789, 0.775, 0.736 and 0.733, respectively), and the best cut‐off values were 27.2 ng/ml, 27.1 ng/ml, 27.1 ng/ml and 25.1 ng/ml, respectively. Furthermore, baseline sST2 could provide additional prognostic value when added to baseline NT‐proBNP and hs‐cTnT (all P values <0.05). According to the category of elevated biomarkers (including NT‐proBNP, hs‐cTnT, and sST2), patients with three elevated biomarkers had a higher risk of the primary endpoint event compared with those with one or two elevated biomarkers (all P values <0.05). Conclusions: Baseline sST2 remained an independent predictor of adverse events after adjusting for other predictors including NT‐proBNP and hs‐cTnT, particularly in patients with chronic decompensated heart failure and NYHA functional class I–II. And in the basis of baseline NT‐proBNP and hs‐cTnT, adding baseline sST2 could provide additional prognostic value for patients hospitalized with heart failure. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to explore the causal relationships between cathepsins and cardiovascular diseases (CVDs) by Mendelian randomization (MR) analysis. Methods and results: Single nucleotide polymorphisms (SNPs) associated with nine cathepsin types (cathepsins B, E, F, G, H, O, S, L2, and Z) were obtained from the INTERVAL study (3301 individuals). CVDs data were acquired from the UK Biobank (coronary atherosclerosis: 14 334 cases, 346 860 controls) and a genome‐wide association study (GWAS) (myocardial infarction: 20 917 cases, 440 906 controls; myocarditis: 633 cases, 427 278 controls; chronic heart failure: 14 262 cases, 471 898 controls; angina pectoris: 30 025 cases, 440 906 controls; stable angina pectoris: 17 894 cases, 325 132 controls; unstable angina pectoris: 9481 cases, 446 987 controls; pericarditis: 1795 cases, 453 370 controls). Inverse variance weighted (IVW), MR‐Egger, weighted median methods were adopted to conduct univariable MR (UVMR), reverse MR, multivariable MR (MVMR) analyses to estimate causality. The UVMR analyses demonstrated significant causal relationships between higher cathepsin E levels and increased risk of coronary atherosclerosis [IVW: P = 0.0051, odds ratio (OR) = 1.0033, 95% confidence interval (CI) = 1.0010–1.0056] and myocardial infarction (IVW: P = 0.0097, OR = 1.0553, 95% CI = 1.0131–1.0993), while elevated cathepsin L2 levels were causally related to reduced risk of myocarditis (IVW: P = 0.0120, OR = 0.6895, 95% CI = 0.5158–0.9216) and chronic heart failure (IVW: P = 0.0134, OR = 0.9316, 95% CI = 0.8807–0.9854). Reverse MR analyses revealed that myocardial infarction increased cathepsin O levels (IVW: P = 0.0400, OR = 1.0708, 95% CI = 1.0031–1.1431). MVMR analyses treating nine cathepsins together revealed that the positive causality between cathepsin E levels and coronary atherosclerosis risk (IVW: P = 0.0390, OR = 1.0030, 95% CI = 1.0000–1.0060), and the protective effect of cathepsin L2 levels on myocarditis (IVW: P = 0.0030, OR = 0.6610, 95% CI = 0.5031–0.8676) and chronic heart failure (IVW: P = 0.0090, OR = 0.9259, 95% CI = 0.8737–0.9812) remained, as higher cathepsin O levels were found to be causally related to increased risks of myocarditis (IVW: P = 0.0030, OR = 1.6145, 95% CI = 1.1829–2.2034) and chronic heart failure (IVW: P = 0.0300, OR = 1.0779, 95% CI = 1.0070–1.1537). Conclusions: The study highlights the causalities of cathepsin E, L2, and O on CVDs, offering insights into their roles in cardiovascular biomarkers and therapeutic targets development. Further research is required to apply these genetic findings clinically. [ABSTRACT FROM AUTHOR]

Aims: This meta‐analysis investigated the dose–response relationship between circulating galectin‐3 levels and adverse outcomes in patients with heart failure (HF). Methods and results: PubMed and Embase were screened for studies on galectin‐3 and HF. The outcomes of interest were all‐cause mortality (ACM), and all‐cause mortality or HF‐related rehospitalization (ACM/HFR), with a follow‐up time of more than 6 months. For categorical variables, comparisons between groups with the highest and lowest galectin‐3 levels were pooled. For continuous variables, the risks of ACM and ACM/HFR increase per 1‐standard deviation (SD) and 1‐unit after logarithmic transformation galectin‐3 levels were pooled. A random‐effects model was employed to calculate the pooled results, and all pooled results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Besides, a dose–response analysis was performed. Twenty‐four cohort studies were included. In HF patients, higher circulating galectin‐3 levels were significantly associated with a higher risk of long‐term ACM (HR, 1.65; 95% CI 1.28–2.13; I2 = 66%), and 1 ng/mL increase in galectin‐3 was associated with a 4% (HR, 1.04; 95% CI 1.02–1.06; P = 0.002) increase in hazard. Similarly, higher circulating galectin‐3 levels were significantly associated with a higher risk of long‐term ACM/HFR (HR, 1.52; 95% CI, 1.15 to 2.00; I2 = 76%), and 1 ng/mL increase in galectin‐3 was associated with a 3% (HR, 1.03; 95% CI 1.02–1.04; P < 0.001) increase in hazard. An increase of 1‐SD in galectin‐3 units was associated with a 29% increased hazard of long‐term ACM (HR 1.29; 95% CI 1.13–1.48; I2 = 42%) and a 22% increased hazard of ACM/HFR (HR 1.22; 95% CI 1.07–1.38; I2 = 60%). Similarly, an increase of 1‐log in galectin‐3 units was associated with a 98% higher hazard of long‐term ACM (HR 1.98; 95% CI 1.48–2.65; I2 = 41%) and an 83% higher hazard of ACM/HFR in HF patients (HR 1.83; 95% CI 1.02–3.28; I2 = 7%). Correlation analysis showed a moderate positive correlation between baseline galectin‐3 and N terminal pro brain natriuretic peptide levels (r = 0.48, P = 0.045) and a weak negative correlation with eGFR (r = −0.39, P = 0.077). Conclusions: Higher circulating galectin‐3 levels after hospitalization of HF patients are linearly and positively associated with the risk of long‐term ACM and ACM/HFR. [ABSTRACT FROM AUTHOR]

Aims: Patients with HFrEF and worsening HF events (WHFE) are at particularly high risk and urgently need disease‐modifying therapy. CHART‐HF assessed treatment patterns and reasons for medication decisions among HFrEF patients with and without WHFE. Methods and results: CHART‐HF collected retrospective electronic medical records of outpatients with HF and EF < 45% between 2017–2019 from a nationwide panel of 238 cardiologists (458 patients) and the Geisinger Health System (GHS) medical record (1000 patients). The index visit in the WHFE cohort was the first outpatient cardiologist visit ≤6 months following the WHFE, and in the reference cohort was the last visit in a calendar year without WHFE. Demographic characteristics were similar between patients with and without WHFE in both the nationwide panel and GHS. In the nationwide panel, the proportion of patients with versus without WHFE receiving ≥50% of guideline‐recommended dose on index visit was 35% versus 40% for beta blocker, 74% versus 83% for ACEI/ARB/ARNI, and 48% versus 49% for MRA. The proportion of patients receiving ≥50% of guideline‐recommended dose was lower in the GHS: 29% versus 34% for beta‐blocker, 16% versus 31% for ACEI/ARB/ARNI, and 18% versus 22% for MRA. For patients with and without WHFE, triple therapy on index date was 42% and 44% of patients from the nationwide panel, and 14% and 17% in the GHS. Comparing end of index clinic visit with 12‐month follow‐up in the GHS, the proportion of patients on no GDMT increased from 14% to 28% in the WHFE cohort and from 14 to 21% in the non‐WHFE group. Conclusions: Major gaps in use of GDMT, particularly combination therapy, remain among US HFrEF patients. These gaps persist during longitudinal follow‐up and are particularly large among patients with recent WHFE. [ABSTRACT FROM AUTHOR]

Aims: The objective of this study was to perform a cost–benefit analysis of the CardioMEMS HF System (Abbott Laboratories, Abbott Park, IL, USA) in a heart failure (HF) clinic in Spain by evaluating the real‐time remote monitoring of pulmonary artery pressures, which has been shown to reduce HF‐related hospitalizations and improve the quality of life for selected HF patients. Particularly, the study aimed to determine the value of CardioMEMS in Southern Europe, where healthcare costs are significantly lower and its effectiveness remains uncertain. Methods and results: This single‐centre study enrolled all consecutive HF patients (N = 43) who had been implanted with a pulmonary artery pressure sensor (CardioMEMS HF System); 48.8% were females, aged 75.5 ± 7.0 years, with both reduced and preserved left ventricular ejection fraction; 67.4% of them were in New York Heart Association Class III. The number of HF hospitalizations in the year before and the year after the sensor implantation was compared. Quality‐adjusted life years gained based on a literature review of previous studies were calculated. The rate of HF hospitalizations was significantly lower at 1 year compared with the year before CardioMEMS implantation (0.25 vs. 1.10 events/patient‐year, hazard ratio 0.22, P = 0.001). At the end of the first year, the usual management outperformed the CardioMEMS HF System. By the end of the second year, the CardioMEMS system is estimated to reduce costs compared with usual management (net benefits of €346). Conclusions: Based on the results, we suggest that remote monitoring of pulmonary artery pressure with the CardioMEMS HF System represents a midterm and long‐term efficient strategy in a healthcare setting in Southern Europe. [ABSTRACT FROM AUTHOR]

Aims: The current literature provides limited guidance on the best diuretic strategy post‐hospitalization for acute heart failure (AHF). It is postulated that the efficacy and safety of the outpatient diuretic regimen may be significantly influenced by the degree of fluid overload (FO) encountered during hospitalization. We hypothesize that in patients with more pronounced FO, reducing their regular oral diuretic dosage might be associated with an elevated risk of unfavourable clinical outcomes. Methods and results: It was a retrospective observational study of 410 patients hospitalized for AHF in which the dose of furosemide at admission and discharge was collected. Patients were categorized across diuretic dose status into two groups: (i) the down‐titration group and (ii) the stable/up‐titration group. FO status was evaluated by a clinical congestion score and circulating biomarkers. The endpoint of interest was the composite of time to all‐cause death and/or heart failure readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 86 (78–92) years, 256 (62%) were women, and 80% had heart failure with preserved ejection fraction. After multivariate adjustment, the down‐titration furosemide equivalent dose remained not associated with the risk of the combined endpoint in the whole sample (hazard ratio 1.34, 95% confidence interval 0.86–2.06, P = 0.184). The risk of the combination of death and/or worsening heart failure associated with the diuretic strategy at discharge was significantly influenced by FO status, including clinical congestion scores and circulating proxies of FO like BNP and cancer antigen 125. Conclusions: In patients hospitalized for AHF, furosemide down‐titration does not imply an increased risk of mortality and/or heart failure readmission. However, FO status modifies the effect of down‐titration on the outcome. In patients with severe congestion or residual congestion at discharge, down‐titration was associated with an increased risk of mortality and/or heart failure readmission. [ABSTRACT FROM AUTHOR]

Heart failure is a devastating syndrome affecting an increasingly high number of patients worldwide. Its aetiology and pathogenesis are complex with the involvement of factors ranging from the genetic material through valvular dysfunctions to numerous organs beyond the entire cardiovascular system. Based on continuous efforts of the heart failure scientific community we have witnessed major advances in many related disciplines during the last year. For example, epidemiological aspects—paving the road for improved risk prevention—have been thoroughly analysed for various geographical regions. Additionally, evidence‐based approaches now allow the introduction of novel guideline recommended medical therapies (i.e. sodium‐glucose transporter 2 inhibitors, and iron supplementation) while basic and translational research aim to explore additional molecular targets for future heart failure diagnostics and medications. All above aspects are addressed in this article, where a selection of articles published in the ESC Heart Failure journal in 2023 are highlighted. The editors are confident that the scientific contributions of ESC Heart Failure effectively served a highly relevant area of cardiovascular research last year. [ABSTRACT FROM AUTHOR]

Worsening heart failure (HF) is a vulnerable period in which the patient has a markedly high risk of death or HF hospitalization (up to 10% and 30%, respectively, within the first weeks after episode). The prognosis of HF patients can be improved through a comprehensive approach that considers the different neurohormonal systems, with the early introduction and optimization of the quadruple therapy with sacubitril–valsartan, beta‐blockers, mineralocorticoid receptor antagonists, and inhibitors. Despite that, there is a residual risk that is not targeted with these therapies. Currently, it is recognized that the cyclic guanosine monophosphate deficiency has a negative direct impact on the pathogenesis of HF, and vericiguat, an oral stimulator of soluble guanylate cyclase, can restore this pathway. The effect of vericiguat has been explored in the VICTORIA study, the largest chronic HF clinical trial that has mainly focused on patients with recent worsening HF, evidencing a significant 10% risk reduction of the primary composite endpoint of cardiovascular death or HF hospitalization (number needed to treat 24), after adding vericiguat to standard therapy. This benefit was independent of background HF therapy. Therefore, optimization of treatment should be performed as earlier as possible, particularly within vulnerable periods, considering also the use of vericiguat. [ABSTRACT FROM AUTHOR]

Aim: This paper describes the trajectory during 1 year of four patient‐reported outcomes (PROs), namely, sleep, depressive symptoms, health‐related quality of life (HrQoL), and well‐being, in patients with heart failure (HF), their relationship and the patient characteristics associated with changes in these PROs. Methods and results: Data analyses of PROs from 603 patients (mean age 67 years; 29% female, 60% NYHA II) enrolled in the HF‐Wii study. On short term, between baseline and 3 months, 16% of the patients experienced continuing poor sleep, 11% had sustained depressive symptoms, 13% had consistent poor HrQoL, and 13% consistent poor well‐being. Across the entire 1‐year period only 21% of the patients had good PRO scores at all timepoints (baseline, 3, 6, and 12 months). All others had at least one low score in any of the PROs at some timepoint during the study. Over the 12 months, 17% had consistently poor sleep, 17% had sustained symptoms of depression, 15% consistently rated a poor HrQoL, and 13% poor well‐being. Different patient characteristics per PRO were associated with a poor outcomes across the 12 months. Age, education, New York Heart Association, and length of disease were related to two PRO domains and submaximal exercise capacity (6 min test), co‐morbidity, and poor physical activity to one. Conclusion: In total, 79% of the patients with HF encountered problems related to sleep, depressive symptoms, HrQoL, and well‐being at least once during a 1‐year period. This underscores the need for continuous monitoring and follow‐up of patients with HF and the need for dynamic adjustments in treatment and care regularly throughout the HF trajectory. [ABSTRACT FROM AUTHOR]

Aims: In patients with heart failure (HF), we aimed to assess (i) the time trends in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) testing; (ii) patient characteristics associated with NT‐proBNP testing; (iii) distribution of NT‐proBNP levels, focusing on the subgroups with (WHFE) vs. without (NWHFE) a worsening HF event, defined as an HF hospitalization; and (iv) changes of NT‐proBNP levels over time. Methods and results: NT‐proBNP testing and levels were investigated in HF patients enrolled in the Swedish Heart Failure Registry (SwedeHF) linked with the Stockholm CREAtinine Measurements project from January 2011 to December 2018. Index date was the first registration in SwedeHF. Patterns of change in NT‐proBNP levels before (in the previous 6 ± 3 months) and after (in the following 6 ± 3 months) the index date were categorized as follows: (i) <3000 ng/L at both measurements = stable low; (ii) <3000 ng/L at the first measurement and ≥3000 ng/L at the second measurement = increased; (iii) ≥3000 ng/L at the first measurement and <3000 ng/L at the second measurement = decreased; and (iv) ≥3000 ng/L at both measurements = stable high. Univariable and multivariable logistic regression models, expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs), were performed to assess the associations between (i) clinical characteristics and NT‐proBNP testing and (ii) changes in NT‐proBNP from 6 months prior to the index date and the index date and a WHFE. Consistency analyses were performed in HF with reduced ejection fraction (HFrEF) alone. A total of 4424 HF patients were included (median age 74 years, women 34%, HFrEF 53%), 33% with a WHFE. NT‐proBNP testing increased over time, up to 55% in 2018, and was almost two‐fold as frequent, and time to testing was less than half, in patients with WHFE vs. NWHFE. Independent predictors of testing were WHFE, higher heart rate, diuretic use, and preserved ejection fraction. Median NT‐proBNP was 3070 ng/L (Q1–Q3: 1220–7395), approximately three‐fold higher in WHFE vs. NWHFE. Compared with stable low NT‐proBNP levels, increased (OR 4.27, 95% CI 2.47–7.37) and stable high levels (OR 2.48, 95% CI 1.58–3.88) were independently associated with a higher risk of WHFE. Results were consistent in the HFrEF population. Conclusions: NT‐proBNP testing increased over time but still was only performed in half of the patients. Testing was associated with a WHFE, with features of more severe HF and for differential diagnosis purposes. Increased and stable high levels were associated with a WHFE. Overall, our data highlight the potential benefits of carrying further implementation of NT‐proBNP testing in clinical practice. [ABSTRACT FROM AUTHOR]

Aims: An elevated risk of adverse events persists for years in cardiogenic shock (CS) survivors with high mortality rate and physical/mental disability. This study aims to link clinical CS‐survivor phenotypes with distinct late host‐response patterns at intensive care unit (ICU) discharge and long‐term outcomes using model‐based clustering. Methods and results: In the original prospective, observational, international French and European Outcome Registry in Intensive Care Units (FROG‐ICU) study, ICU patients with CS on admission were identified (N = 228). Among them, 173 were discharged alive from the ICU and included in the current study. Latent class analysis was applied to identify distinct CS‐survivor phenotypes at ICU discharge using 15 readily available clinical and laboratory variables. The primary endpoint was 1 year of mortality after ICU discharge. Secondary endpoints were readmission and physical/mental disability [short form‐36 questionnaire (SF‐36) score] within 1 year after ICU discharge. Two distinct phenotypes at ICU discharge were identified (A and B). Patients in Phenotype B (38%) were more anaemic and had higher circulating levels of lactate, sustained kidney injury, and persistent elevation in plasma markers of inflammation, myocardial fibrosis, and endothelial dysfunction compared with Phenotype A. They had also a higher rate of non‐ischaemic origin of CS and right ventricular dysfunction on admission. CS survivors in Phenotype B had higher 1 year of mortality compared with Phenotype A (P = 0.045, Kaplan–Meier analysis). When adjusted for traditional risk factors (i.e. age, severity of illness, and duration of ICU stay), Phenotype B was independently associated with 1 year of mortality [adjusted hazard ratio = 2.83 (95% confidence interval 1.21–6.60); P = 0.016]. There was a significantly lower physical quality of life in Phenotype B patients at 3 months (i.e. SF‐36 physical component score). Conclusions: A phenotype with sustained inflammation, myocardial fibrosis, and endothelial dysfunction at ICU discharge was identified from readily available data and was independently associated with poor long‐term outcomes in CS survivors. [ABSTRACT FROM AUTHOR]

Aims: This study aims to provide insight into sex‐specific cardiovascular protein profiles and their associations with adverse outcomes, which may contribute to a better understanding of heart failure (HF) pathophysiology and the optimal use of circulating proteins for prognostication in women and men. Methods and results: In 250 stable patients with HF with reduced ejection fraction (HFrEF), we performed trimonthly blood sampling (median follow‐up: 26 [17–30] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or one sample closest to censoring and applied the Olink Cardiovascular III panel. We used linear regression to study sex‐based differences in baseline levels and joint models to study differences in the prognostic value of serially measured proteins. In 66 women and 184 men (mean age of 66 and 67 years, respectively), 21% and 28% reached the PEP, respectively. Mean baseline levels of fatty acid‐binding protein 4, secretoglobin family 3A member 2, paraoxonase 3, and trefoil factor 3 were higher in women (Pinteraction: 0.001, 0.007, 0.018, and 0.049, respectively), while matrix metalloproteinase‐3, interleukin 1 receptor‐like 1, and myoglobin were higher in men (Pinteraction: <0.001, 0.001, and 0.049, respectively), independent of clinical characteristics. No significant differences between sexes were observed in the longitudinal associations of proteins with the PEP. Only peptidoglycan recognition protein 1 showed a suggestive interaction with sex for the primary outcome (Pinteraction = 0.028), without multiple testing correction, and was more strongly associated with adverse outcome in women {hazard ratio [HR] 3.03 [95% confidence interval (CI), 1.42 to 6.68], P = 0.008} compared with men [HR 1.18 (95% CI, 0.84 to 1.66), P = 0.347]. Conclusions: Although multiple cardiovascular‐related proteins show sex differences at baseline, temporal associations with the adverse outcome do not differ between women and men with HFrEF. [ABSTRACT FROM AUTHOR]

Acute heart failure (AHF) classification and management are primarily based on lung congestion and/or hypoperfusion. The quantification of the vascular and tissue lung damage is not standard practice though biomarkers of lung injury may play a relevant role in this context. Haemodynamic stress promotes alveolar and vascular derangement with loss of functional units, impaired lung capillary permeability and fluid swelling. This culminates in a remodelling process with activation of inflammatory and cytokines pathways. Four families of lung surfactant proteins (i.e., SP-A, SP-B, SP-C, and SP-D), essential for the membrane biology and integrity are released by alveolar type II pneumocites. With deregulation of fluid handling and gas exchange pathways, SPs become sensitive markers of lung injury. We report the pathobiology of lung damage; the pathophysiological and clinical implications of alveolar SPs along with the newest evidence for some classical HF biomarkers that have also shown to reflect a vascular and/or a tissue lung-related activity., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: The HeartLogic multisensor index has been found to be a sensitive predictor of worsening heart failure (HF). However, there is limited data on this index's association and its constituent sensors with HF readmissions. Methods and results: The PREEMPT‐HF study is a global, multicentre, prospective, observational, single‐arm, post‐market study. HF patients with an implantable defibrillator device or cardiac resynchronization therapy with defibrillator with HeartLogic capabilities were eligible if sensor data collection was turned on and the HeartLogic feature was not enabled. Thus, the HeartLogic Index/alert and heart sounds sensor trends were unavailable via the LATITUDE remote monitoring system to clinicians (blinded). Evaluation of subject medical records at 6 months and a final in‐clinic visit at 12 months was required for collection of all‐cause hospitalizations and HF outpatient visits. The purpose of this study is exploratory, no formal hypothesis tests are planned, and no adjustment for multiple testing will be performed. A total of 2183 patients were enrolled at 103 sites between June 2018 and June 2020. A significant proportion of the patients were implanted with implantable defibrillator devices (39%) versus cardiac resynchronization therapy with defibrillator (61%); were female (27%); over 65 (61%); New York Heart Association class I (13%), II (53%), and III (33%); ejection fraction < 25% (21%); ischaemic (50%); and with a history of renal dysfunction (23%). Conclusions: The PREEMPT study will provide clinical data and blinded sensor trends for the characterization of sensor changes with HF readmission, tachyarrhythmias, and event subgroups. These data may help to refine the clinical use of HeartLogic and to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Aims: How different degrees of adherence to guideline‐directed medical therapy (GDMT) affect mortality risk in patients with heart failure (HF) in a real‐world clinical setting is poorly understood. This study sought to investigate how different levels of adherence to GDMT were associated with the risk of all‐cause mortality in patients with HF across a spectrum of left ventricular ejection fractions (LVEFs) in a real‐world clinical setting. Methods and results: A total of 64 610 HF patients with no missing value of LVEF from the Swedish Heart Failure Registry were included in the study. Patients were divided according to different LVEFs (<30%, 30–39%, 40–49%, and≥50%) and stratified by an adherence score (good, moderate, or poor) according to the triple, double, and single one usage of GDMT: angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, beta‐blockers, and mineralocorticoid receptor antagonists. The outcome is time to all‐cause mortality. The mean age of the whole cohort was 73.9 ± 12.1 years, and the proportion of patients in LVEF < 30%, 30–39%, 40–49%, and≥50% groups was 27.6%, 26.9%, 22.1%, and 23.3%, respectively. Patients with LVEF < 30% had the highest mortality rate, almost 20% higher than those with LVEF ≥ 50% {hazard ratio [HR] [95% confidence interval (CI)]: 0.80 [0.71–0.90], P < 0.001}. After treatment of GDMT with good adherence, patients with LVEF < 30% had similar mortality to those with LVEF ≥ 50% [HR (95% CI): 0.97 (0.86–1.10), P = 0.664]. However, the percentage of moderate or poor GDMT was alarmingly high, with good adherence only in 20% of the patients. Conclusions: Good adherence to GDMT works best in patients with LVEF < 50%, whereas moderate adherence to GDMT varies in efficacy depending on the components of the drug combinations. [ABSTRACT FROM AUTHOR]

Aims: It has been reported that circulating soluble neprilysin (sNEP), which catalyses the degradation of several vasodilator peptides such as natriuretic peptides, predicts prognosis in heart failure patients with reduced ejection fraction. Hypoxia‐induced decrease in NEP expression in lungs has been reported. However, the associations between sNEP and haemodynamic parameters, as well as the prognostic impact of sNEP in pulmonary hypertension (PH), remain unclear. We aimed to clarify the relationships between sNEP and natriuretic peptide, haemodynamics (e.g. parameters of echocardiography and right heart catheter) or prognosis in PH patients. Methods and results: First, we examined the associations between sNEP levels and natriuretic peptide, echocardiography, or right heart catheter in PH patients (mean pulmonary artery pressure ≥ 25 mmHg and pulmonary artery wedge pressure ≤ 15 mm Hg on the basis of right heart catheterization, n = 79). Next, we followed up the patients for all‐cause mortality. Laboratory data revealed no significant correlations between sNEP and B‐type natriuretic peptide (R = 0.022, P = 0.872), N‐terminal proBNP (R = −0.018, P = 0.872), and high‐sensitivity troponin I (R = 0.206, P = 0.107). Regarding the parameters of echocardiography and right heart catheter, there were no significant correlations between sNEP and left ventricular ejection fraction (R = −0.036, P = 0.764), right ventricular fractional area change (R = −0.259, P = 0.064), tricuspid valve pressure gradient (R = −0.037, P = 0.767), and any of the right heart catheter parameters. In the Kaplan–Meier analysis (mean follow‐up, 1284 days, log‐rank P = 0.531), all‐cause mortality rates were comparable between the higher NEP group (sNEP ≥ median levels of 1.45 ng/mL, n = 39) and the lower NEP group (sNEP < 1.45 ng/mL, n = 40). In the Cox proportional hazard analysis, sNEP was not a predictor of all‐cause mortality (hazard ratio 0.902, 95% CI 0.674–1.207, P = 0.487) in PH patients. Conclusions: Circulating sNEP does not correlate with natriuretic peptide, haemodynamic parameters, or prognosis in patients with PH. [ABSTRACT FROM AUTHOR]

Heart failure (HF) represents one of the greatest healthcare burdens worldwide, and Egypt is no exception. HF healthcare programmes in Egypt still require further optimization to enhance diagnosis and management of the disease. Development of specialized HF clinics (HFCs) and their incorporation in the healthcare system is expected to reduce HF hospitalization and mortality rates and improve quality of care in Egypt. We conducted a literature search on PubMed on the requirements and essential infrastructure of HFCs. Retrieved articles deemed relevant were discussed by a panel of 10 expert cardiologists from Egypt and a basic HFC model for the Egyptian settings was proposed. A multidisciplinary team managing the HFC should essentially be composed of specialized HF cardiologists and nurses, clinical pharmacists, registered nutritionists, physiotherapists, and psychologists. Other clinical specialists should be included according to patients' needs and size and structure of individual clinics. HFCs should receive patients referred from primary care settings, emergency care units, and physicians from different specialties. A basic HFC should have the following fundamental investigations available: resting electrocardiogram, basic transthoracic echocardiogram, and testing for N‐terminal pro‐B‐type natriuretic peptide. Fundamental patients' functional assessments are assessing the New York Heart Association functional classification and quality of life and conducting the 6 min walking test. guideline‐directed medical therapy should be implemented, and device therapy should be utilized when available. In the first visit, once HF is diagnosed and co‐morbidities assessed, guideline‐directed medical therapy should be started immediately. Comprehensive patient education sessions should be delivered by HF nurses or clinical pharmacists. The follow‐up visit should be scheduled during the initial visit rather than over the phone, and time from the initial visit to the first follow‐up visit should be determined based on the patient's health status and needs. Home and virtual visits are only recommended in limited and emergency situations. In this paper, we provide a practical and detailed review on the essential components of HFCs and propose a preliminary model of HFCs as part of a comprehensive HF programme model in Egypt. We believe that other low‐to‐middle income countries could also benefit from our proposed model. [ABSTRACT FROM AUTHOR]

Aims: Left ventricular (LV) remodelling after acute myocardial infarction (AMI) is associated with heart failure and increased mortality. There was no consensus on the definition of LV remodelling, and the prognostic value of LV remodelling with different definitions has not been compared. We aimed to find the optimal definition and develop a prediction nomogram as well as online calculator that can identify patients at risk of LV remodelling. Methods and results: This prospective, observational study included 829 AMI patients undergoing percutaneous coronary intervention from January 2015 to January 2020. Echocardiography was performed within the 48 h of admission and at 6 months after infarction to evaluate LV remodelling, defined as a 20% increase in LV end‐diastolic volume (LVEDV), a 15% increase in LV end‐systolic volume (LVESV), or LV ejection fraction (LVEF) < 50% at 6 months. The impact of LV remodelling on long‐term outcomes was analysed. Lasso regression was performed to screen potential predictors, and multivariable logistic regression analysis was conducted to establish the prediction nomogram. The area under the curve, calibration curve and decision curve analyses were used to determine the discrimination, calibration and clinical usefulness of the remodelling nomogram. The incidences of LV remodelling defined by LVEDV, LVESV and LVEF were 24.85% (n = 206), 28.71% (n = 238) and 14.60% (n = 121), respectively. Multivariable Cox regression models demonstrated that different definitions of LV remodelling were independently associated with the composite endpoint. However, only remodelling defined by LVEF was significantly connected with long‐term mortality (hazard ratio = 2.78, 95% confidence interval 1.41–5.48, P = 0.003). Seven variables were selected to construct the remodelling nomogram, including diastolic blood pressure, heart rate, AMI type, stent length, N‐terminal pro brain natriuretic peptide, troponin I, and glucose. The prediction model had an area under the receiver operating characteristics curve of 0.766. The calibration curve and decision curve analysis indicated consistency and better net benefit in the prediction model. Conclusions: LV remodelling defined by LVEDV, LVESV and LVEF were independent predictors for long‐term mortality or heart failure hospitalization in AMI patients after percutaneous coronary intervention. However, only remodelling defined by LVEF was suitable for predicting all‐cause death. In addition, the nomogram can provide an accurate and effective tool for the prediction of postinfarct remodelling. [ABSTRACT FROM AUTHOR]

Aims: The prognostic value of 'high dose' loop diuretics in advanced heart failure outpatients is unclear. We aimed to assess the prognosis associated with loop diuretic dose in ambulatory patients awaiting heart transplantation (HT). Methods and results: All ambulatory patients (n = 700, median age 55 years and 70% men) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 were included. Patients were divided into 'low dose', 'intermediate dose', and 'high dose' loop diuretics corresponding to furosemide equivalent doses of ≤40, 40–250, and >250 mg, respectively. The primary outcome was a combined criterion of waitlist death and urgent HT. N‐terminal pro‐B‐type natriuretic peptide, creatinine levels, pulmonary capillary wedge pressure, and pulmonary pressures gradually increased with higher diuretic dose. At 12 months, the risk of waitlist death/urgent HT was 7.4%, 19.2%, and 25.6% (P = 0.001) for 'low dose', 'intermediate dose', and 'high dose' patients, respectively. When adjusting for confounders, including natriuretic peptides, hepatic, and renal function, the 'high dose' group was associated with increased waitlist mortality or urgent HT [adjusted hazard ratio (HR) 2.23, 1.33 to 3.73; P = 0.002] and a six‐fold higher risk of waitlist death (adjusted HR 6.18, 2.16 to 17.72; P < 0.001) when compared with the 'low dose' group. 'Intermediate doses' were not significantly associated with these two outcomes in adjusted models (P > 0.05). Conclusions: A 'high dose' of loop diuretics is strongly associated with residual congestion and is a predictor of outcome in patients awaiting HT despite adjustment for classical cardiorenal risk factors. This routine variable may be helpful for risk stratification of pre‐HT patients. [ABSTRACT FROM AUTHOR]