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Despite the progress in the care of individuals with heart failure (HF), important sex disparities in knowledge and management remain, covering all the aspects of the syndrome, from aetiology and pathophysiology to treatment. Important distinctions in phenotypic presentation are widely known, but the mechanisms behind these differences are only partially defined. The impact of sex‐specific conditions in the predisposition to HF has gained progressive interest in the HF community. Under‐recruitment of women in large randomized clinical trials has continued in the more recent studies despite epidemiological data no longer reporting any substantial difference in the lifetime risk and prognosis between sexes. Target dose of medications and criteria for device eligibility are derived from studies with a large predominance of men, whereas specific information in women is lacking. The present scientific statement encompasses the whole scenario of available evidence on sex‐disparities in HF and aims to define the most challenging and urgent residual gaps in the evidence for the scientific and clinical HF communities. [ABSTRACT FROM AUTHOR]

Aims: To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post‐discharge outcomes. Methods and results: Of 8298 patients in the European Society of Cardiology Heart Failure Long‐Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non‐use of angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers and beta‐blockers. In‐hospital death occurred in 3.3%. The prevalence of hyponatraemia and in‐hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in‐hospital mortality 6.9%), 11% Yes/No (in‐hospital mortality 4.9%), 8% No/Yes (in‐hospital mortality 4.7%), and 72% No/No (in‐hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In‐hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12‐month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35–1.89), Yes/No 1.35 (1.14–1.59), and No/Yes 1.18 (0.96–1.45). For death or heart failure hospitalization they were 1.38 (1.21–1.58), 1.17 (1.02–1.33), and 1.09 (0.93–1.27), respectively. Conclusion: Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in‐hospital and post‐discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk. [ABSTRACT FROM AUTHOR]

Acute heart failure is a major cause of urgent hospitalizations. These are followed by marked increases in death and rehospitalization rates, which then decline exponentially though they remain higher than in patients without a recent hospitalization. Therefore, optimal management of patients with acute heart failure before discharge and in the early post‐discharge phase is critical. First, it may prevent rehospitalizations through the early detection and effective treatment of residual or recurrent congestion, the main manifestation of decompensation. Second, initiation at pre‐discharge and titration to target doses in the early post‐discharge period, of guideline‐directed medical therapy may improve both short‐ and long‐term outcomes. Third, in chronic heart failure, medical treatment is often left unchanged, so the acute heart failure hospitalization presents an opportunity for implementation of therapy. The aim of this scientific statement by the Heart Failure Association of the European Society of Cardiology is to summarize recent findings that have implications for clinical management both in the pre‐discharge and the early post‐discharge phase after a hospitalization for acute heart failure. [ABSTRACT FROM AUTHOR]

Episodes of worsening symptoms and signs characterize the clinical course of patients with chronic heart failure (HF). These events are associated with poorer quality of life, increased risks of hospitalization and death and are a major burden on healthcare resources. They usually require diuretic therapy, either administered intravenously or by escalation of oral doses or with combinations of different diuretic classes. Additional treatments may also have a major role, including initiation of guideline‐recommended medical therapy (GRMT). Hospital admission is often necessary but treatment in the emergency service or in outpatient clinics or by primary care physicians has become increasingly used. Prevention of first and recurring episodes of worsening HF is an essential component of HF treatment and this may be achieved through early and rapid administration of GRMT. The aim of the present clinical consensus statement by the Heart Failure Association of the European Society of Cardiology is to provide an update on the definition, clinical characteristics, management and prevention of worsening HF in clinical practice. [ABSTRACT FROM AUTHOR]

Natriuretic peptides, brain (B‐type) natriuretic peptide (BNP) and N‐terminal prohormone of brain natriuretic peptide (NT‐proBNP) are globally and most often used for the diagnosis of heart failure (HF). In addition, they can have an important complementary role in the risk stratification of its prognosis. Since the development of angiotensin receptor–neprilysin inhibitors (ARNIs), the use of natriuretic peptides as therapeutic agents has grown in importance. The present document is the result of the Trilateral Cooperation Project among the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America and the Japanese Heart Failure Society. It represents an expert consensus that aims to provide a comprehensive, up‐to‐date perspective on natriuretic peptides in the diagnosis and management of HF, with a focus on the following main issues: (1) history and basic research: discovery, production and cardiovascular protection; (2) diagnostic and prognostic biomarkers: acute HF, chronic HF, inclusion/endpoint in clinical trials, and natriuretic peptide‐guided therapy; (3) therapeutic use: nesiritide (BNP), carperitide (ANP) and ARNIs; and (4) gaps in knowledge and future directions. [ABSTRACT FROM AUTHOR]

Background: Circulating Neprilysin (sNEP) has emerged as a potential prognostic biomarker in heart failure (HF). In PARAGON-HF benefit of sacubitril/valsartan was only observed in patients with left ventricular ejection fraction (LVEF) ≤57%. We aimed to assess the prognostic value of sNEP in outpatients with HF and LVEF >57%, in comparison with patients with LVEF ≤57%. Methods: Consecutive HF outpatients were included from May-2006 to February-2016. The primary endpoint was the composite of all-cause death or HF hospitalization and the main secondary endpoint was the composite of cardiovascular death or HF hospitalization. For the later competing risk methods were used. Results: sNEP was measured in 1428 patients (age 67.7±12.7, 70.3% men, LVEF 35.8% ±14), 144 of which had a LVEF >57%. sNEP levels did not significantly differ between LVEF groups (p = 0.31). During a mean follow-up of 6±3.9 years, the primary endpoint occurred in 979 patients and the secondary composite endpoint in 714 (in 111 and 84 of the 144 patients with LVEF >57%, respectively). sNEP was significantly associated with both composite endpoints. Age- and sex- adjusted Cox regression analyses showed higher hazard ratios for sNEP in patients with LVEF >57%, both for the primary (HR 1.37 [1.16–1.61] vs. 1.04 [0.97–1.11]) and the secondary (HR 1.38 [1.21–1.55] vs. 1.11 [1.04–1.18]) composite endpoints. Conclusions: sNEP prognostic value in patients with HF and LVEF >57% outperforms that observed in patients with lower LVEF. Precision medicine using sNEP may identify HF patients with preserved LVEF that may benefit from treatment with sacubitril/valsartan. [ABSTRACT FROM AUTHOR]

The article discusses the association between inflammation and heart failure (HF) and the potential for personalized anti-inflammatory therapy in HF. The authors highlight the need for therapies targeting inflammation in HF, as elevated markers of inflammation are associated with impaired prognosis and disease progression. The study by Buckley et al. suggests that a composite neutrophil-related protein score can be used to identify individuals at higher risk of HF and may help in selecting patients who would benefit from anti-inflammatory drugs like colchicine. The article emphasizes the importance of incorporating personalized strategies in clinical research based on clinically meaningful biomarkers. [Extracted from the article]

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]

Open in new tab Download slide OBJECTIVES Sutureless aortic valve replacement (SU-SAVR) has been associated with higher rates of permanent pacemaker (PPM) compared with conventionally implanted aortic bioprostheses. The purpose of this study was to determine the incidence, predictors and mid-term prognostic impact of PPM after Perceval (Livanova, London, UK) SU-SAVR in low-risk patients. METHODS A total of 400 consecutive low-risk (EuroSCORE II < 4%) patients without prior pacemaker who underwent surgical aortic valve replacement with the Perceval prosthesis from 2013 to 2019 in 2 centres were included. Baseline, clinical and electrocardiographic parameters, procedural characteristics and follow-up data were collected. RESULTS PPM was required in 36 (9%) patients after SU-SAVR, with a median time between the procedure and PPM implantation of 7.5 (4.5–10.5) days. Older age and prior right bundle branch block (RBBB) were associated with an increased risk of PPM (P  < 0.05 for all), but only baseline RBBB was found to be an independent predictor of new PPM requirement (odds ratio: 2.60, 95% confidence interval: 1.15–5.81; P  = 0.022). At a median follow-up of 3.4 (2.3–4.5) years, there were no differences between groups in mortality (PPM: 36%, no PPM: 22%, P  = 0.105) or heart failure rehospitalization (PPM: 25%, no PPM: 21%, P  = 0.839). CONCLUSIONS About 1 out of 10 low-risk patients with aortic stenosis undergoing SU-SAVR with the Perceval prosthesis required PPM implantation. Prior RBBB determined an increased risk (close to 3-fold) of PPM following the procedure. PPM was not associated with a higher risk of clinical events at 3-year follow-up. [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]

Background: The Global Leadership Initiative on Malnutrition (GLIM) criteria were recently proposed to build a global consensus on the diagnostic criteria for malnutrition. This study aimed to evaluate the GLIM criteria for its prognostic significance in outpatients with heart failure (HF), and to compare them to a previous validated method, such as the Mini Nutritional Assessment (MNA). Methods: This was a post hoc observational analysis of a prospectively recruited cohort, which included 151 subjects that attended an outpatient HF clinic. At baseline, all patients completed the nutritional screening MNA short form and the nutritional assessment MNA. In a post hoc analysis, we evaluated the GLIM criteria at baseline. The outcomes were based on data from a five-year follow-up. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular (CV) mortality and recurrent HF-related hospitalizations. We also investigated whether the GLIM criteria had better prognostic power than the MNA. Results: Abnormal nutritional status was identified in 19.8% of the patients with the GLIM criteria and in 25.1% with the MNA. In the multivariate analyses (age, sex, NYHA functional class, diabetes, and Barthel index), nutritional status assessed by the MNA, but not by the GLIM criteria, was an independent predictor of all-cause mortality, CV mortality, and recurrent HF-related hospitalizations during the five-year follow-up. Conclusions: Malnutrition assessed by MNA, but not by the GLIM criteria, was an independent predictor of all-cause mortality, CV mortality, and recurrent HF-related hospitalization in our cohort of outpatients with HF. [ABSTRACT FROM AUTHOR]

Aims: Systolic pulmonary artery pressure (SPAP), tricuspid annular plane systolic excursion (TAPSE), and TAPSE/SPAP ratio trajectories are not fully characterized in chronic heart failure (HF). We assessed very long-term longitudinal SPAP, TAPSE and TAPSE/SPAP trajectories in HF patients, and their dynamic changes in outcomes.Methods and Results: Prospective, consecutive, observational registry of real-life HF patients, performing echocardiography studies at baseline and according to a prospectively structured schedule after 1 year, and then every 2 years, up to 15 years. Pulmonary hypertension (PH) was defined as SPAP ≥40 mmHg; right ventricular dysfunction (RVD) was defined at TAPSE ≤16 mm; and TAPSE/SPAP ratio was dichotomized at 0.36 mm/mmHg. The clinical endpoints were all-cause death, the composite endpoint of mortality or HF hospitalization and the number of recurrent HF hospitalizations. The study cohort included 1557 patients. Long-term SPAP trajectory Loess curves were U-shaped with a nadir at 7 years. TAPSE Loess curves showed a marked rise during the first year, with stabilization thereafter. TAPSE/SPAP ratio Loess splines were similar to the later with a smooth decline towards the end. Patients who died had higher SPAP, lower TAPSE and lower TAPSE/SPAP ratio in the preceding period than survivors. Baseline PH and/or RVD were independently associated with mortality and HF-related hospitalizations, and the persistence of one or both entities at 1 year conferred a worse long-term prognosis.Conclusions: Long-term trajectories for SPAP, TAPSE and TAPSE/SPAP ratio are reported in patients with chronic HF. An increasing SPAP and declining TAPSE and TAPSE/SPAP ratio in the preceding period is associated with higher mortality. [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]

Purpose: In ST-segment elevation myocardial infarction (STEMI) patients, longitudinal strain (LS) in remote non-infarcted myocardium (RNM) has not yet been characterized by tissue tracking (TT) cardiovascular magnetic resonance (CMR). In STEMI patients, we aimed to characterize RNM-LS by TT-CMR and to assess both its dynamics and its structural and prognostic implications.Methods: We recruited 271 patients with a first STEMI studied with TT-CMR 1 week after infarction. Of these patients, 145 underwent 1-week and 6-month TT-CMR and were used to characterize both the dynamics and the short-term and long-term structural implications of RNM-LS. Based on previously validated data, RNM areas were defined depending on the culprit coronary artery.Results: Reduced RNM-LS at 1 week (n = 70, 48%) was associated with larger infarct size and more depressed left ventricular ejection fraction (LVEF) at both the 1-week and 6-month TT-CMR (p value < 0.001). Late normalization of RNM-LS was frequent (28/70, 40%) and independently related to late recovery of LVEF (p value = 0.002). Patients with reduced RNM-LS at 1-week TT-CMR had more major adverse cardiac events (death, heart failure or re-infarction) in both the 271 patients included in the study group (26% vs. 11%, p value = 0.002) and in an external validation cohort made up of 177 STEMI patients (57% vs. 13%, p value < 0.001).Conclusion: After STEMI, reduced RNM-LS by TT-CMR is common and is associated with more severe short- and long-term structural damage. There is a beneficial tendency towards recovery of RNM-LS that parallels late recovery of LVEF. More events occur in patients with reduced RNM-LS. [ABSTRACT FROM AUTHOR]

Aims: N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), high‐sensitivity troponin T (hs‐TnT) and soluble suppression of tumorigenesis‐2 (sST2) predict outcome in chronic heart failure (HF). We assessed the influence of age on circulating levels and prognostic significance of these biomarkers. Methods and results: Individual data from 5301 patients with chronic HF and NT‐proBNP, hs‐TnT, and sST2 data were evaluated. Patients were stratified according to age: <60 years (n = 1332, 25%), 60–69 years (n = 1628, 31%), 70–79 years (n = 1662, 31%), and ≥ 80 years (n = 679, 13%). Patients (median age 66 years, 75% men, median left ventricular ejection fraction 28%, 64% with ischaemic HF) had median NT‐proBNP 1564 ng/L, hs‐TnT 21 ng/L, and sST2 29 ng/mL. Age independently predicted NT‐proBNP and hs‐TnT, but not sST2. The best NT‐proBNP and hs‐TnT cut‐offs for 1‐year and 5‐year all‐cause and cardiovascular mortality and 1‐ to 12‐month HF hospitalization increased with age, while the best sST2 cut‐offs did not. When stratifying patients according to age‐ and outcome‐specific cut‐offs, this stratification yielded independent prognostic significance over NT‐proBNP levels only, or the composite of NT‐proBNP and hs‐TnT, and improved risk prediction for most endpoints. Finally, absolute NT‐proBNP, hs‐TnT, and sST2 levels predicted outcomes independent of age, sex, left ventricular ejection fraction category, ethnic group, and other variables. Conclusions: Soluble ST2 is less influenced by age than NT‐proBNP or hs‐TnT; all these biomarkers predict outcome regardless of age. The use of age‐ and outcome‐specific cut‐offs of NT‐proBNP, hs‐TnT and sST2 allows more accurate risk stratification than NT‐proBNP alone or the combination of NT‐proBNP and hs‐TnT. [ABSTRACT FROM AUTHOR]

Background: We assessed the prognostic significance of absolute and percentage change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients hospitalised for acute decompensated heart failure with preservedejection fraction (HFpEF) versus heart failure with reduced ejection fraction (HFrEF).Methods: Patients with left ventricular ejection fraction ≥50% were categorised as HFpEF (n=283), while those with <40% as were categorised as HFrEF (n=776). Prognostic values of absolute and percentage change in NT-proBNP levels for 6 months all-cause mortality after discharge were assessed separately in patients with HFpEF and HFrEF by multivariable adjusted Cox regression analysis. Comorbidities were compared between heart failure groups.Results: Discharge NT-proBNP levels predicted outcome similarly in HFpEF and HFrEF: for any 2.7-factor increase in NT-proBNP levels, the HR for mortality was 2.14 for HFpEF (95% CI 1.48 to 3.09) and 1.96 for HFrEF (95% CI 1.60 to 2.40). Mortality prediction was equally possible for NT-proBNP reduction of ≤30% (HR 4.60, 95% CI 1.47 to 14.40 and HR 3.36, 95% CI 1.93 to 5.85 for HFpEF and HFrEF, respectively) and for >30%-60% (HR 3.28, 95% CI 1.07 to 10.12 and HR 1.79, 95% CI 0.99 to 3.26, respectively), compared with mortality in the reference groups of >60% reductions in NT-proBNP levels. Prognostically relevant comorbidities were more often present in patients with HFpEF than patients with HFrEF in low (≤3000 pg/mL) but not in high (>3000 pg/mL) NT-proBNP discharge categories.Conclusions: Our study highlights-after demonstrating that NT-proBNP levels confer the same relative risk information in HFpEF as in HFrEF-the possibility that comorbidities contribute relatively more to prognosis in patients with HFpEF with lower NT-proBNP levels than in patients with HFrEF. [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]

Biomarkers have emerged as indispensable tools for diagnosis and prognostication in a variety of cardiovascular diseases, and several are now standard of care. New markers are constantly being developed, but few are able to significantly improve upon already established markers. ST2 is a marker of cardiomyocyte stress and fibrosis, which provides incremental value to natriuretic peptides for risk stratification of patients across a wide spectrum of cardiovascular diseases. Based upon the totality of data, measurement of ST2 is now recommended for additive risk stratification in patients with acute or ambulatory heart failure in the 2013 American College of Cardiology Foundation and American Heart Association joint guidelines. Looking forward, ST2 levels may be useful for tailoring medical therapy in those with or at risk for developing heart failure. This paper provides an up-to-date overview of the clinical studies that led to the endorsement of ST2 as a cardiovascular prognostic marker, and provides insight into the application of ST2 now and in the future. [ABSTRACT FROM AUTHOR]

Context:Prognostic value of ST2 levels and dynamics has not been investigated in acute heart failure (AHF) using prospective real-life measurements. Objective:The objective of this study is to investigate the prognostic value of ST2 in AHF. Methods:ST2 levels were determined at admission (n = 182) and discharge (n = 85). Primary endpoint was the composite of all-cause death and HF rehospitalisation at one year. Results: Discharge ST2 (HR 2.42 [95% CI 1.46–4],p = 0.001) and ΔST2 (HR 2.32 [95% CI 1.21–4.57],p = 0.01) but not admission ST2, remained independently prognostic for the primary endpoint after comprehensive multivariable adjustment. ST2 significantly improved prognosis stratification on top of clinical variables and NTproBNP. Conclusions: Routine clinical use of discharge ST2 and ST2 dynamics provide independent prognostic information. [ABSTRACT FROM PUBLISHER]

Aims To address the incremental usefulness of biomarkers from different disease pathways for predicting risk of death in heart failure (HF). Methods and results We used data from consecutive patients treated at a structured multidisciplinary HF unit to investigate whether a combination of biomarkers reflecting ventricular fibrosis, remodelling, and stretch [ST2 and N-terminal pro brain natriuretic peptide (NTproBNP)] improved the risk stratification of a HF patient beyond an assessment based on established mortality risk factors (age, sex, ischaemic aetiology, left ventricular ejection fraction, New York Heart Association functional class, diabetes, glomerular filtration rate, sodium, haemoglobin, and beta-blocker and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker treatments). ST2 was measured with a novel high-sensitivity immunoassay. During a median follow-up time of 33.4 months, 244 of the 891 participants in the study (mean age 70.2 years at baseline) died. In the multivariable Cox proportional hazards model, both ST2 and NTproBNP significantly predicted the risk of death. The individual inclusion of ST2 and NTproBNP in the model with established mortality risk factors significantly improved the C statistic for predicting death [0.79 (0.76–0.81); P < 0.001]. The net improvement in reclassification after the separate addition of ST2 to the model with established risk factors and NTproBNP was estimated at 9.90% [95% confidence interval (CI) 4.34–15.46; P < 0.001] and the integrated discrimination improvement at 1.54 (95% CI 0.29–2.78); P = 0.015). Conclusions Our data suggest that in a real-life cohort of HF patients, the addition of ST2 and NTproBNP substantially improves the risk stratification for death beyond that of a model that is based only on established mortality risk factors. [ABSTRACT FROM AUTHOR]

Aims: NT-proBNP is a strong predictor for readmissions and mortality in acute decompensated heart failure (ADHF) patients. We assessed whether absolute or relative NT-proBNP levels should be used as pre discharge treatment target.Methods and Results: Our study population was assembled from seven ADHF cohorts. We defined absolute (<1500, <3000, <5000, and <15 000 ng/L) and relative NT-proBNP targets (>30, >50, and >70%). Population attributable risk fraction (PARF) is the proportion of all-cause 6-month mortality in the population that would be reduced if all patients attain the NT-proBNP target. PARF was determined for each target as well as the percentage of patients attaining the NT-proBNP target. Attainability was investigated by logistic regression analysis. A total of 1266 patients [age 74 (64-80), 60% male] was studied. For every absolute NT-proBNP level, a corresponding percentage reduction was found that resulted in similar PARFs. The highest PARF (∼60-70%) was observed for <1500 or >70%, but attainability was low (27% and 22%, respectively). The strongest predictor for not attaining these targets was admission NT-proBNP. In admission NT-proBNP tertiles, PARFs were significantly different for absolute, but not for relative targets.Conclusion: In an ADHF population, pre-discharge absolute or relative NT-proBNP targets may both be useful as they have similar effects on PARF. However, depending on admission NT-proBNP, absolute targets show varying PARFs, while PARFs for relative targets were similar. A relative target is predicted to reduce mortality consistently across the whole spectrum of ADHF patients, while this is not the case using a single absolute target. [ABSTRACT FROM AUTHOR]

Background: Patients with diabetes mellitus (DM) have an increased risk of developing heart failure (HF). Further, DM is associated with poor prognosis in patients with HF. Our aim was to determine whether DM has any impact on the predictive value of a multi-biomarker panel in patients with HF. Methods: We included 1069 consecutive ambulatory HF patients in the study: age 66.2 ± 12.8 years, 33.5 ± 13.3 left ventricular ejection fraction, 36% diabetic patients. We measured serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), ST2, galectin-3, high-sensitivity C reactive protein (hs-CRP), cystatin-C, soluble transferrin receptor (sTfR), and neprilysin and followed patients for 4.9 ± 2.8 years. Primary endpoints were all-cause and cardiovascular death. Results: During follow-up, 534 patients died; 283 died of cardiovascular causes. Diabetic subjects had higher mortality (57.7 vs. 45.6%, p < 0.001). NTproBNP (p = 0.07), hs-TnT (p < 0.001), galectin-3 (p < 0.001), and cystatin-C (p = 0.001) concentrations were higher in diabetic patients, whereas sTfR levels were lower (p = 0.005). There were no interactions between DM and NTproBNP, hs-TnT, galectin-3, hs-CRP, cystatin-C, sTfR, and neprilysin relative to risk prediction for all-cause or cardiovascular death. By contrast, ST2 significantly interacted with DM for all-cause (p = 0.02) and cardiovascular (p = 0.03) death. In diabetic patients, HRs for ST2 were 1.27 (95% CI 1.16-1.40, p < 0.001) and 1.23 (95% CI 1.09-1.39, p = 0.001) for all-cause and cardiovascular death, respectively. In nondiabetic patients, HRs for ST2 were 1.53 (95% CI 1.35-1.73, p < 0.001) and 1.64 (95% CI 1.31-2.05, p < 0.001) for all-cause and cardiovascular death, respectively. The multivariable Cox regression analysis showed that hs-TnT and ST2 were the only markers that were independently associated with both all-cause and cardiovascular mortality in patients with HF and diabetes. Moreover, in these patients, the combination of these two markers significantly increased discrimination as assessed by the area under the curve. Conclusions: Biomarkers used in the general population to predict the clinical course of heart failure are also useful in patients with diabetes. In these patients, among all the biomarkers analysed only hs-TnT and ST2 were independently associated with both all-cause and cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Aims Heart failure (HF) is a chronic condition that typically affects a patient's quality of life (QoL). Little is known about long-term QoL monitoring in HF. This study aimed to evaluate the temporal changes and prognostic value of QoL assessment in a real-life cohort of HF patients. Methods and results The Minnesota Living with Heart Failure Questionnaire was used to monitor QoL at baseline and at 1, 3, and 5 years for 1151 consecutive patients {71.7% men, median age 69 years [25th–75th percentiles (P25–P75) 59–76]} in an HF unit. Follow-up for prognosis assessment was extended to 6 years. The number of answered questionnaires was 1151 at baseline, 746 at 1 year, 268 at 3 years, and 240 at 5 years. QoL scores showed a steep decrease (indicating QoL improvement) during the first year [29 (P25–P75 16–43) at baseline vs. 15 (P25–P75 8–27) at 1 year, P < 0.001], which was tempered, yet significant up to 5 years [12 (P25–P75 7–23) at 3 years vs. 10 (P25–P75 5–21) at 5 years, P = 0.012]. We recorded 457 deaths during follow-up. In a comprehensive multivariable Cox regression analysis, baseline QoL remained a significant prognosticator during follow-up [hazard ratio (HR)Cox for death 1.012, 95% confidence interval 1.006–1.018, P < 0.001]. QoL monitoring showed that a score increase ≥10% between consecutive assessments stratified high-risk patients within the next 12 months (P = 0.008). Conclusion Both baseline and follow-up QoL monitoring were useful for patient risk stratification in a real-life HF cohort. Worse QoL may warn of a worse prognosis. Widespread QoL monitoring in routine clinical practice is recommended. [ABSTRACT FROM PUBLISHER]

Background: To compare the prognostic value of estimated glomerular filtration rate, cystatin-C, an alternative renal biomarker, and their combination, in an outpatient population with heart failure. Estimated glomerular filtration rate is routinely used to assess renal function in heart failure patients. We recently demonstrated that the Cockroft-Gault formula is the best among the most commonly used estimated glomerular filtration rate formulas for predicting heart failure prognosis. Methodology/Principal Findings: A total of 879 consecutive patients (72% men, age 70.4 years [P25-75 60.5-77.2]) were studied. The etiology of heart failure was mainly ischemic heart disease (52.7%). The left ventricular ejection fraction was 34% (P25-75 26-43%). Most patients were New York Heart Association class II (65.8%) or III (25.9%). During a median followup of 3.46 years (P25-75 1.85-5.05), 312 deaths were recorded. In an adjusted model, estimated glomerular filtration rate and cystatin-C showed similar prognostic value according to the area under the curve (0.763 and 0.765, respectively). In Cox regression, the multivariable analysis hazard ratios were 0.99 (95% CI: 0.98-1, P = 0.006) and 1.14 (95% CI: 1.02-1.28, P = 0.02) for estimated glomerular filtration rate and cystatin-C, respectively. Reclassification, assessed by the integration discrimination improvement and the net reclassification improvement indices, was poorer with cystatin-C (20.5 [21.0;20.1], P = 0.024 and 24.9 [28.8;21.0], P = 0.013, respectively). The value of cystatin-C over estimated glomerular filtration rate for risk-stratification only emerged in patients with moderate renal dysfunction (eGFR 30-60 ml/min/1.73 m2, chi-square 12.9, P<0.001). Conclusions/Significance: Taken together, the results indicate that estimated glomerular filtration rate and cystatin-C have similar long-term predictive values in a real-life ambulatory heart failure population. Cystatin-C seems to offer improved prognostication in heart failure patients with moderate renal dysfunction. [ABSTRACT FROM AUTHOR]

Background: The prognostic value of the New York Heart Association classification (NYHAC) in acutely decompensated heart failure (ADHF) is unknown. Objectives: We sought to determine the relative value of NYHAC among patients with concomitantly measured amino-terminal pro-B type natriuretic peptide (NT-proBNP) at presentation with ADHF. Materials and methods: NYHAC was determined for 720 patients with ADHF and 1-year mortality status was examined. Cox-proportional hazards analysis compared the prognostic accuracy of NYHAC with other ADHF risk measures. Results: NYHAC had a significant univariate association with 1-year mortality status (HR 1.41, 95% confidence interval (CI) 1.03–1.94; p = 0.03) but was not a significant predictor of death in a multivariable model that included NT-proBNP (HR 2.14; 95% CI 1.65–2.81, p < 0.001). Conclusions: In contrast to objective measures such as NT-proBNP, the NYHAC appears to provide limited prognostic information among individuals with ADHF. [ABSTRACT FROM AUTHOR]

Aims: To study the relative prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) monitoring in addition to clinical disease severity scores (CDSSs) in outpatients with destabilized heart failure (HF). [ABSTRACT FROM PUBLISHER]

Aims Experience with amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing for evaluation of dyspnoeic patients with suspected acute heart failure (HF) is limited to single-centre studies. We wished to establish broader standards for NT-proBNP testing in a study involving four sites in three continents. [ABSTRACT FROM PUBLISHER]

In recent years, there has been growing interest in the risk stratification for heart failure, and the use of multiple biomarkers to identify different pathophysiological processes associated with this condition. One such biomarker is soluble suppression of tumorigenicity-2 (sST2), which has shown some potential for integration into clinical practice. sST2 is produced by both cardiac fibroblasts and cardiomyocytes in response to myocardial stress. Other sources of sST2 are endothelial cells of the aorta and coronary arteries and immune cells such as T cells. Indeed, ST2 is also associated with inflammatory and immune processes. We aimed at reviewing the prognostic value of sST2 in both chronic and acute heart failure. In this setting, we also provide a flowchart about its potential use in clinical practice. [ABSTRACT FROM AUTHOR]

Aims: Cardiogenic shock (CS) is an ominous complication of ST-elevation myocardial infarction (STEMI), despite the recent widespread use of reperfusion and invasive management. The Ruti-STEMI-Shock registry analysed the prevalence of and 30-day and 1-year mortality rates in ST-elevation myocardial infarction (STEMI) complicated by CS (STEMI-CS) over the last three decades. Methods and Results: From February 1989 to December 2018, 493 STEMI-CS patients were consecutively admitted in a well-defined geographical area of ~850,000 inhabitants. Patients were classified into six five-year periods based on their year of admission. STEMI-CS mortality trends were analysed at 30 days and 1 year across the six strata. Cox regression analyses were performed for comparisons. Mean age was 67.5 ± 11.7 years; 69.4% were men. STEMI-CS prevalence did not decline from period 1 to 6 (7.1 vs. 6.2%, p = 0.218). Reperfusion therapy increased from 22.5% in 1989–1993 to 85.4% in 2014–2018. Thirty-day all-cause mortality declined from period 1 to 6 (65% vs. 50.5%, p < 0.001), with a 9% reduction after multivariable adjustment (HR: 0.91; 95% CI: 0.84–0.99; p = 0.024). One-year all-cause mortality declined from period 1 to 6 (67.5% vs. 57.3%, p = 0.001), with an 8% reduction after multivariable adjustment (HR: 0.92; 95% CI: 0.85–0.99; p = 0.030). Short- and long-term mortality trends in patients aged ≥ 75 years remained ~75%. Conclusions: Short- and long-term STEMI-CS-related mortality declined over the last 30 years, to ~50% of all patients. We have failed to achieve any mortality benefit in STEMI-CS patients over 75 years of age. [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]

Objective: This study investigated the relationship of serum homocysteine (Hcy) and cystatin C (Cys C) levels with the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). Methods: A total of 178 patients with HFpEF who were admitted to our hospital between December 2019 and November 2020 were included. Patients were grouped based on their serum Hcy and Cys C levels: high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level. Cardiac function, ventricular remodeling indices, and prognosis were compared among patients in these groups. Additionally, the predictive value of serum Hcy and Cys C levels for adverse cardiovascular events in HFpEF patients was analyzed. Results: Patients' mean age in the high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level groups was 69.21 ± 4.17,67.74 ± 4.28,69.95 ± 4.98, and 67.06 ± 4.13 years old, respectively. The high Hcy level group exhibited a lower proportion of class II cardiac function according to the New York Heart Association (NYHA) classification and a higher proportion of class IV cardiac function than the normal Hcy level group, with statistically significant differences. Similarly, the high Cys C level group had a lower proportion of class II cardiac function and a higher proportion of class IV cardiac function compared with the normal Cys C level group, with statistically significant differences. Left ventricular end-diastolic internal diameter (LVEDD), left ventricular end-systolic internal diameter (LVESD), and left ventricular mass index (LVMI) were significantly higher in both the high Hcy level and high Cys C level groups compared with the normal group, with statistically significant differences. The rates of all-cause mortality and class I endpoint events were significantly higher in the high Hcy level and high Cys C level groups than in the normal group. Multifactorial logistic regression analysis demonstrated that adverse cardiovascular events were significantly associated with cardiac function class, LVEDD, LVESD, LVMI, Hcy, and Cys C in patients with HFpEF. The area under the curve (AUC) values for Hcy and Cys C, determined using receiver operating characteristic (ROC) curve analysis, were 0.778 (optimal critical value, 25.38) and 0.681 (optimal critical value, 1.56), respectively, for predicting adverse cardiovascular events. Both Hcy and Cys C serum levels were positively correlated with LVEDD, LVESD, LVMI, and NYHA classification. Conclusion: Serum levels of Hcy and Cys C were closely associated with cardiac function, ventricular remodeling indices, and prognosis in patients with HFpEF. These levels may serve as valuable indices for assessing HFpEF patients' health status and prognosis, providing important insights into their potential role as biomarkers for HFpEF management and prognosis. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) represents a complex clinical syndrome, often very difficult to diagnose using the available tools. As the global burden of this disease is constantly growing, surpassing the prevalence of heart failure with reduced ejection fraction, during the last few years, efforts have focused on optimizing the diagnostic and prognostic pathways using an immense panel of circulating biomarkers. After the paradigm of HFpEF development emerged more than 10 years ago, suggesting the impact of multiple comorbidities on myocardial structure and function, several phenotypes of HFpEF have been characterized, with an attempt to find an ideal biomarker for each distinct pathophysiological pathway. Acknowledging the limitations of natriuretic peptides, hundreds of potential biomarkers have been evaluated, some of them demonstrating encouraging results. Among these, soluble suppression of tumorigenesis-2 reflecting myocardial remodeling, growth differentiation factor 15 as a marker of inflammation and albuminuria as a result of kidney dysfunction or, more recently, several circulating microRNAs have proved their incremental value. As the number of emerging biomarkers in HFpEF is rapidly expanding, in this review, we aim to explore the most promising available biomarkers linked to key pathophysiological mechanisms in HFpEF, outlining their utility for diagnosis, risk stratification and population screening, as well as their limitations. [ABSTRACT FROM AUTHOR]

Purpose: One major issue is the therapeutic effect following chemotherapy for non–small cell lung cancer (NSCLC). Although numerous risk factors have been identified and novel therapies have been developed, improving patient overall survival (OS) remains a crucial postoperative issue. This study aimed to develop a nomogram for accurately predicting the OS of patients with Stage III–IV NSCLC treated with chemotherapy. Methods: The Department of Respiration at Tangdu Hospital, Air Force Medical University, prospectively collected data on 321 patients between January 2018 and December 2023. A week before treatment, the platelet‐to‐lymphocyte ratio (PLR), the neutrophil‐to‐lymphocyte ratio (NLR), and seven autoantibodies were measured using Youden's index, which was obtained using the ROC curve. The formula was used to compute the values of PLR and NLR. After using multifactor Cox regression analysis to identify risk factors, a nomogram was produced regarding the therapeutic effect following chemotherapy. The performance of the nomogram was assessed using a bootstrapped‐concordance index and calibration plots. Result: It was determined that NLR, sex‐determining region Y‐box 2 (SOX2), adenosine triphosphate binding RNA deconjugase 4–5 (GBU4‐5), and MAGE family member A1 (MAGEA1) were significantly associated factors that could be combined to accurately predict the therapeutic effect following chemotherapy. Utilizing these risk indicators, we were able to develop a nomogram that predicted the patients' survival at 1, 3, and 5 years. At 3 years, the area under the curve representing the expected survival probability was 0.762 (95% confidence interval 0.66–0.87). With a bootstrapped‐concordance index of 0.762, the nomogram demonstrated good calibration. Conclusions: Our nomogram proved to be a valuable instrument in accurately predicting the overall survival of patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to evaluate the prognostic value of the Stanniocalcin-2/PAPP-A/IGFBP-4 axis in patients with ST-segment elevation myocardial infarction (STEMI). Methods: Observational cohort study performed in 1085 consecutive STEMI patients treated with early reperfusion between February 2011 and August 2014. Stanniocalcin-2, PAPP-A, and IGFBP-4 were measured using state-of-the art immunoassays. The primary outcome was the composite endpoint of all-cause mortality and readmission due to heart failure (HF). Results: Median follow-up was 3.3 years (IQR 1.0–3.7), during which 176 patients (16.2%) presented a composite endpoint. Multivariable cox regression analysis revealed that Stanniocalcin-2 (HR 2.06; 95% CI 1.13–3.75; p = 0.018), IGFBP-4 (HR 1.73; 95% CI 1.14–2.64; p = 0.010), Killip–Kimball class III–IV (HR 1.40; 95% CI 1.13–1.74; p = 0.002), NT-ProBNP (HR 1.21; 95% CI 1.07–1.37; p = 0.002), age (HR 1.06; 95% CI 1.04–1.08; p < 0.001) and left ventricular ejection fraction (HR 0.97; 95% CI 0.95–0.98; p < 0.001) were independent predictors of the composite endpoint. A model containing Stanniocalcin-2 and IGFBP-4 on top of clinical variables significantly improved C-index discrimination (p = 0.036). Stanniocalcin-2 was also identified as independent predictor of all-cause mortality (HR 2.23; 95% CI 1.16–4.29; p = 0.017) and readmission due to HF (HR 3.42; 95% CI 1.22–9.60; p = 0.020). Conclusions: In STEMI patients, Stanniocalcin-2 and IGFBP-4 emerged as independent predictors of all-cause death and readmission due to HF. The Stanniocalcin-2/PAPP-A/IGFBP-4 axis exhibits a significant role in STEMI risk stratification. [ABSTRACT FROM AUTHOR]

The prognostic significance of pretransplant N‐terminal pro‐brain (B)‐type natriuretic peptide (NT‐proBNP) level has not been investigated in lung transplant recipients. The electronic files of 173 patients with chronic lung disease who underwent lung transplantation in 2018–2022 at a tertiary medical center were retrospectively reviewed. Right heart catheterization (RHC) and NT‐proBNP determination were performed preoperatively in all cases. Pretransplant demographic, clinical, and laboratory data were compared between posttransplant survivors and nonsurvivors. Correlations of NT‐proBNP values with lung function and RHC parameters and all‐cause mortality were analyzed. NT‐proBNP level correlated positively with mean pulmonary artery pressure (R = 0.51, p < 0.001) and pulmonary vascular resistance (PVR) (R = 0.45, p = 0.0013), and negatively with diffusing lung capacity for carbon monoxide (R = −0.25, p = 0.0017), cardiac index (R = −0.26, p = 0.001), and cardiac output (R = −0.23, p = 0.004). Over a median follow‐up time of 23.22 months, 74 patients died. On univariate analysis, mortality was significantly associated with higher log‐NT‐proBNP (hazard ratio [HR] = 0.54, 95% confidence interval [CI] 1.15–2.05, p = 0.016), older age at transplant registration (HR = 1.033, 95% CI 1.009–1.058, p = 0.0068), higher PVR (HR 1.15, 95% CI 1.07–1.23, p = 0.015), and lower cardiac output (HR = 0.62, 95% CI 0.42–0.92, p = 0.045). On multivariate analysis adjusted for age, sex, and body mass index, mortality significance was maintained only for higher log‐NT‐proBNP (HR = 1.54, 95% CI 1.12–2.11, p = 0.007). Among lung transplant recipients, pretransplant NT‐proBNP levels correlated well with RHC parameters and were strongly associated with posttransplantation mortality. Assessment of NT‐proBNP may improve risk stratification of lung transplant candidates. [ABSTRACT FROM AUTHOR]

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Background: Cardiac troponin release is related to the cardiomyocyte loss occurring in heart failure (HF). The prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) in several settings of HF is under investigation. The aim of the study is to assess the prognostic role of intrahospital hs-cTnT in patients admitted due to HF. Methods: In this observational, single center, prospective study, patients hospitalized due to HF have been enrolled. Admission, in-hospital peak, and discharge hs-cTnT have been assessed. Patients were followed up for 6 months. Cardiovascular (CV) death, HF hospitalization (HFH), and worsening HF (WHF) (i.e., urgent ambulatory visit/loop diuretics escalation) events have been assessed at 6-month follow up. Results: 253 consecutive patients have been enrolled in the study. The hs-cTnT median values at admission and discharge were 0.031 ng/mL (IQR 0.02–0.078) and 0.031 ng/mL (IQR 0.02–0.077), respectively. The risk of CV death/HFH was higher in patients with admission hs-cTnT values above the median (p = 0.02) and in patients who had an increase in hs-cTnT during hospitalization (p = 0.03). Multivariate Cox regression analysis confirmed that hs-cTnT above the median (OR: 2.06; 95% CI: 1.02–4.1; p = 0.04) and increase in hs-cTnT during hospitalization (OR:1.95; 95%CI: 1.006–3.769; p = 0.04) were predictors of CV death/HFH. In a subgroup analysis of patients with chronic HF, hs-cTnT above the median was associated with increased risk of CV death/HFH (p = 0.03), while in the subgroup of patients with HFmrEF/HFpEF, hs-cTnT above the median was associated with outpatient WHF events (p = 0.03). Conclusions: Inpatient hs-cTnT levels predict CV death/HFH in patients with HF. In particular, in the subgroup of chronic HF patients, hs-cTnT is predictive of CV death/HFH; while in patients with HFmrEF/HFpEF, hs-cTnT predicts WHF events. [ABSTRACT FROM AUTHOR]

The associations of plasma metabolites with adverse cardiovascular (CV) outcomes are still underexplored and may be useful in CV risk stratification. We performed a systematic review and meta-analysis to establish correlations between blood metabolites and adverse CV outcomes in patients with heart failure (HF). Four cohorts were included, involving 83 metabolites and 37 metabolite ratios, measured in 1158 HF patients. Hazard ratios (HR) of 42 metabolites and 3 metabolite ratios, present in at least two studies, were combined through meta-analysis. Higher levels of histidine (HR 0.74, 95% CI [0.64; 0.86]) and tryptophan (HR 0.82 [0.71; 0.96]) seemed protective, whereas higher levels of symmetric dimethylarginine (SDMA) (HR 1.58 [1.30; 1.93]), N-methyl-1-histidine (HR 1.56 [1.27; 1.90]), SDMA/arginine (HR 1.38 [1.14; 1.68]), putrescine (HR 1.31 [1.06; 1.61]), methionine sulfoxide (HR 1.26 [1.03; 1.52]), and 5-hydroxylysine (HR 1.25 [1.05; 1.48]) were associated with a higher risk of CV events. Our findings corroborate important associations between metabolic imbalances and a higher risk of CV events in HF patients. However, the lack of standardization and data reporting hampered the comparison of a higher number of studies. In a future clinical scenario, metabolomics will greatly benefit from harmonizing sample handling, data analysis, reporting, and sharing. [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]

Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure (HF) with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) affects around 60 million individuals worldwide. The primary aim of this study was to evaluate the efficacy of lung ultrasound (LUS) in managing HF with the goal of reducing hospital readmission rates. Methods: A systematic search was conducted on PubMed, Embase, Google Scholar, Web of Science, and Scopus, covering clinical trials, meta-analyses, systematic reviews, and original articles published between 1 January 2019 and 31 December 2023, focusing on LUS for HF assessment in out-patient settings. There is a potential for bias as the effectiveness of interventions may vary depending on the individuals administering them. Results: The PRISMA method synthesized the findings. Out of 873 articles identified, 33 were selected: 19 articles focused on prognostic assessment of HF, 11 centred on multimodal diagnostic assessments, and two addressed therapeutic guidance for HF diagnosis. LUS demonstrates advantages in detecting subclinical congestion, which holds prognostic significance for readmission and mortality during out-patient follow-up post-hospital-discharge, especially in complex scenarios, but there is a lack of standardization. Conclusions: there are considerable uncertainties in their interpretation and monitoring changes. The need for an updated international consensus on the use of LUS seems obvious. [ABSTRACT FROM AUTHOR]

Purpose: The levels of human epididymis protein 4 (HE4) is associated not only with the prognosis of patients with acute heart failure (AHF), but also with chronic kidney disease (CKD). Our study aims to understand the prediction value of HE4 on prognosis in patients with AHF combined with CKD. Patients and Methods: This study prospectively enrolled patients diagnosed with AHF combined with CKD at the Department of Cardiology of Hunan Provincial People's Hospital from March 2019 to December 2022. Serum levels of HE4 were measured using a chemiluminescence microparticle immunoassay. The endpoint events included heart failure readmission and cardiovascular death. Results: A total of 130 patients with AHF combined with CKD were included in the stud. The median age is 73 years (interquartile range: 65– 79 years). Among the patients, 94 experienced the endpoint events. The multivariable Cox analysis reveals that LnHE4 (HR=2.280, 95% CI 1.300– 3.998, P = 0.004) and age (HR=1.024, 95% CI 1.003– 1.045, P = 0.025) are independent predictors of the endpoint events. The Kaplan-Meier survival curve demonstrates that patients with HE4 levels> 276.15 pmol/L has a significantly higher incidence of endpoint events compared to those with HE4 levels≤ 276.15 pmol/L (Log rank test: χ 2=19.689, P < 0.001). After adjusting for age and gender, the HR is 2.520 (95% CI: 1.626– 3.906, P < 0.001). Conclusion: HE4 is an independent predictor of heart failure readmission and cardiovascular death in patients with AHF combined with CKD. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) and diabetes are associated with increased incidence and worse prognosis of each other. The prognostic value of global longitudinal strain (GLS) measured by cardiovascular magnetic resonance (CMR) has not been established in HF patients with diabetes. Methods: In this prospective, observational study, consecutive patients (n = 315) with HF underwent CMR at 3T, including GLS, late gadolinium enhancement (LGE), native T1, and extracellular volume fraction (ECV) mapping. Plasma biomarker concentrations were measured including: N-terminal pro B-type natriuretic peptide(NT-proBNP), high-sensitivity troponin T(hs-TnT), growth differentiation factor 15(GDF-15), soluble ST2(sST2), and galectin 3(Gal-3). The primary outcome was a composite of all-cause mortality or HF hospitalisation. Results: Compared to those without diabetes (n = 156), the diabetes group (n = 159) had a higher LGE prevalence (76 vs. 60%, p < 0.05), higher T1 (1285±42 vs. 1269±42ms, p < 0.001), and higher ECV (30.5±3.5 vs. 28.8±4.1%, p < 0.001). The diabetes group had higher NT-pro-BNP, hs-TnT, GDF-15, sST2, and Gal-3. Diabetes conferred worse prognosis (hazard ratio (HR) 2.33 [95% confidence interval (CI) 1.43–3.79], p < 0.001). In multivariable Cox regression analysis including clinical markers and plasma biomarkers, sST2 alone remained independently associated with the primary outcome (HR per 1 ng/mL 1.04 [95% CI 1.02–1.07], p = 0.001). In multivariable Cox regression models in the diabetes group, both GLS and sST2 remained prognostic (GLS: HR 1.12 [95% CI 1.03–1.21], p = 0.01; sST2: HR per 1 ng/mL 1.03 [95% CI 1.00-1.06], p = 0.02). Conclusions: Compared to HF patients without diabetes, those with diabetes have worse plasma and CMR markers of fibrosis and a more adverse prognosis. GLS by CMR is a powerful and independent prognostic marker in HF patients with diabetes. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is a serious public health concern whose incidence has been on a rise and is projected by the World Health Organization to be the leading global cause of mortality by 2030. Heart failure (HF) is a complicated syndrome resulting from various CVDs of heterogeneous etiologies and exhibits varying pathophysiology, including activation of inflammatory signaling cascade, apoptosis, fibrotic pathway, and neuro-humoral system, thereby leading to compromised cardiac function. During this process, several biomolecules involved in the onset and progression of HF are released into circulation. These circulating biomolecules could serve as unique biomarkers for the detection of subclinical changes and can be utilized for monitoring disease severity. Hence, it is imperative to identify these biomarkers to devise an early predictive strategy to stop the deterioration of cardiac function caused by these complex cellular events. Furthermore, measurement of multiple biomarkers allows clinicians to divide HF patients into sub-groups for treatment and management based on early health outcomes. The present article provides a comprehensive overview of current omics platform available for discovering biomarkers for HF management. Some of the existing and novel biomarkers for the early detection of HF with special reference to endothelial biology are also discussed. [ABSTRACT FROM AUTHOR]

Effective intercellular communication is essential for cellular and tissue balance maintenance and response to challenges. Cellular communication methods involve direct cell contact or the release of biological molecules to cover short and long distances. However, a recent discovery in this communication network is the involvement of extracellular vesicles that host biological contents such as proteins, nucleic acids, and lipids, influencing neighboring cells. These extracellular vesicles are found in body fluids; thus, they are considered as potential disease biomarkers. Cardiovascular diseases are significant contributors to global morbidity and mortality, encompassing conditions such as ischemic heart disease, cardiomyopathies, electrical heart diseases, and heart failure. Recent studies reveal the release of extracellular vesicles by cardiovascular cells, influencing normal cardiac function and structure. However, under pathological conditions, extracellular vesicles composition changes, contributing to the development of cardiovascular diseases. Investigating the loading of molecular cargo in these extracellular vesicles is essential for understanding their role in disease development. This review consolidates the latest insights into the role of extracellular vesicles in diagnosis and prognosis of cardiovascular diseases, exploring the potential applications of extracellular vesicles in personalized therapies, shedding light on the evolving landscape of cardiovascular medicine. [ABSTRACT FROM AUTHOR]

Atrioventricular coupling has recently emerged as an outcome predictor. Our aim was to assess, through three-dimensional (3D) echocardiography, the role of the left atrioventricular coupling index (LACI), right atrioventricular coupling index (RACI) and a novel combined atrioventricular coupling index (CACI) in a cohort of patients with dilated cardiomyopathy (DCM). One hundred twenty-one consecutive patients with DCM underwent comprehensive 3D echocardiographic acquisitions. LACI was defined as the ratio between left atrial and left ventricular 3D end-diastolic volumes. RACI was defined as the ratio between right atrial and right ventricular 3D end-diastolic volumes. CACI was defined as the sum of LACI and RACI. Patients were prospectively followed for death, heart transplant, nonfatal cardiac arrest and hospitalization for heart failure. Fifty-five patients reached the endpoint. All three coupling indices were significantly more impaired in patients with events, with CACI showing the highest area under the curve (AUC = 0.66, p = 0.003). All three indices were independent outcome predictors when tested in multivariable Cox regression (HR = 2.62, p = 0.01 for LACI; HR = 2.58, p = 0.004 for RACI; HR = 2.37, p = 0.01 for CACI), but only CACI showed an incremental prognostic power over traditional risk factors such as age, left ventricular strain, right ventricular strain and mitral regurgitation severity (likelihood ratio χ2 test = 28.2, p = 0.03). CACI assessed through 3D echocardiography, reflecting both left and right atrioventricular coupling, is an independent predictor of adverse events in DCM, yielding an incremental prognostic power over traditional risk factors. [ABSTRACT FROM AUTHOR]

Introduction: Soluble suppression of tumorigenicity-2 (sST2) has been considered as a prognostic factor of cardiovascular disease. However, the prognostic value of sST2 concentration in chronic heart failure remains to be summarized. Methods: We searched PubMed, Embase, and Web of Science for eligible studies up to January 1, 2020. Data extracted from articles and provided by authors were used in agreement with the PRISMA statement. The endpoints were all-cause mortality (ACM), cardiovascular mortality (CVM)/heart failure-related hospitalization (HFH), and all-cause mortality (ACM)/heart failure-related readmission (HFR). Results: A total of 11 studies with 5,121 participants were included in this analysis. Higher concentration of sST2 predicted the incidence of long-term ACM (hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 1.02–1.04), long-term ACM/HFR (HR: 1.42, CI: 1.27–1.59), and long-term CVM/HFH (HR: 2.25, CI: 1.82–2.79), regardless of short-term ACM/HFR (HR: 2.31, CI: 0.71–7.49). Conclusion: Higher sST2 concentration at baseline is associated with increasing risk of long-term ACM, ACM/HFR, and CVM/HFH and can be a tool for the prognosis of chronic heart failure. [ABSTRACT FROM AUTHOR]