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Aims: Heart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF‐related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early‐stage intervention, since haemodynamic congestion precedes clinical symptoms. Methods: The BioMEMS study, a substudy of the MONITOR‐HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR‐HF trial were collected at baseline, 3‐, 6‐, and 12‐month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS‐HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death. Conclusion: Since the prognostic value of single baseline measurements of biomarkers like N‐terminal pro‐B‐type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively. [ABSTRACT FROM AUTHOR]

Background: Collagen cross-linking is a fundamental process in dilated cardiomyopathy (DCM) and occurs when collagen deposition exceeds degradation, leading to impaired prognosis. This study investigated the associations of collagen-metabolism biomarkers with left ventricular function and prognosis in DCM. Methods: DCM patients who underwent endomyocardial biopsy, blood sampling, and cardiac MRI were included. The primary endpoint included death, heart failure hospitalization, or life-threatening arrhythmias, with a follow-up of 6 years (5–8). Results: In total, 209 DCM patients were included (aged 54 ± 13 years, 65% male). No associations were observed between collagen volume fraction, circulating carboxy-terminal propeptide of procollagen type-I (PICP), or collagen type I carboxy-terminal telopeptide [CITP] and matrix metalloproteinase [MMP]-1 ratio and cardiac function parameters. However, CITP:MMP-1 was significantly correlated with global longitudinal strain (GLS) in the total study sample (R = −0.40, p < 0.0001; lower CITP:MMP-1 ratio was associated with impaired GLS), with even stronger correlations in patients with LVEF > 40% (R = −0.70, p < 0.0001). Forty-seven (22%) patients reached the primary endpoint. Higher MMP-1 levels were associated with a worse outcome, even after adjustment for clinical and imaging predictors (1.026, 95% CI 1.002–1.051, p = 0.037), but CITP and CITP:MMP-1 were not. Combining MMP-1 and PICP improved the goodness-of-fit (LHR36.67, p = 0.004). Conclusion: The degree of myocardial cross-linking (CITP:MMP-1) is associated with myocardial longitudinal contraction, and MMP-1 is an independent predictor of outcome in DCM patients. [ABSTRACT FROM AUTHOR]

Iron deficiency (ID) is the most common nutritional disorder worldwide. It is often observed in patients with chronic diseases, such as heart failure (HF), chronic kidney disease (CKD), inflammatory bowel disease (IBD) and cancer. ID is associated with poor clinical outcome, including poor performance, reduced quality of life, as well as increased hospitalization and mortality. The aim of this review is to provide an overview about the role of ID in chronic diseases (HF, CKD, IBD, cancer) regarding their current definitions and clinical relevance; diagnostic accuracy of iron parameters in chronic inflammatory conditions and its potential as prognostic markers. Due to different definitions and guideline recommendations of ID, various laboratory parameters for ID diagnostic exist and there is no general consensus about the definition of ID and its treatment. Still, a general trend can be observed across all investigated indications of this review (HF, CKD, IBD, cancer) that serum ferritin and transferrin saturation (TSAT) are the two parameters mentioned most often and emphasized in all guidelines to define ID and guide treatment. The most commonly used threshold values for the diagnosis of ID are TSAT of < 20% and serum ferritin of < 100–300 µg/L. Noteworthy, both TSAT and particularly ferritin are frequently applied, but both may vary due to inflammatory conditions. Studies showed that TSAT is less affected by inflammatory processes and may therefore be more accurate and reliable than serum ferritin, particularly in conditions with elevated inflammatory state. A low iron status and particularly a low TSAT value was associated with a poor outcome in all investigated indications, with the strongest evidence in HF patients. Routine surveillance of iron status in these groups of patients with chronic conditions is advisable to detect ID early. Depending on the inflammatory state, TSAT < 20% may be the more accurate diagnostic marker of ID than ferritin. Moreover, TSAT may also be the more reliable estimate for the prognosis, particularly in HF. [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]

Aim: Fibroblast growth factor 23 (FGF23) is an intensively studied biomarker at the crossroads of cardiovascular disease, heart failure (HF) and chronic kidney disease. Independent associations between increasing FGF23 levels and cardiovascular events were found in many, but not all studies. By analysing data from the TIME-CHF cohort, we sought to investigate the prognostic value of FGF23 in an elderly, multimorbid HF patient cohort. We determined differences between intact (iFGF23) and C-terminal FGF23 (cFGF23) regarding their prognostic value and their levels over time in different HF subgroups according to left ventricular ejection fraction (LVEF).Methods and Results: In this multicentre trial of 622 patients with symptomatic HF aged ≥60 years, we determined iFGF23 and cFGF23 at baseline, 3, 6 and 12-month follow-up. In unadjusted analyses, cFGF23 significantly predicted all HF-related outcomes at all time points. The predictive value of iFGF23 was less and not statistically significant at baseline. After multivariable adjustments, the association between both cFGF23 and iFGF23 and outcome lost statistical significance apart from cFGF23 at month 3. Overall, patients with preserved and mid-range LVEF had higher levels of iFGF23 and cFGF23 than those with reduced LVEF. Levels decreased significantly during the first 3 months in mid-range and reduced LVEF patients, but did not significantly change over time in those with preserved LVEF.Conclusions: Fibroblast growth factor 23 is of limited value regarding risk prediction in this elderly HF population. Potentially heterogeneous roles of FGF23 in different LVEF groups deserve further investigation. [ABSTRACT FROM AUTHOR]

Aims: To determine the prognostic value of multilevel assessment of fibrosis in dilated cardiomyopathy (DCM) patients. Methods and results: We quantified fibrosis in 209 DCM patients at three levels: (i) non‐invasive late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR); (ii) blood biomarkers [amino‐terminal propeptide of procollagen type III (PIIINP) and carboxy‐terminal propeptide of procollagen type I (PICP)], (iii) invasive endomyocardial biopsy (EMB) (collagen volume fraction, CVF). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization, or life‐threatening arrhythmias, after adjusting for known clinical predictors [adjusted hazard ratios: LGE 3.54, 95% confidence interval (CI) 1.90–6.60; P < 0.001 and PICP 1.02, 95% CI 1.01–1.03; P = 0.001]. The combination of LGE and PICP provided the highest prognostic benefit in prediction (likelihood ratio test P = 0.007) and reclassification (net reclassification index: 0.28, P = 0.02; and integrated discrimination improvement index: 0.139, P = 0.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+/PICP+) had the worst prognosis (log‐rank P < 0.001). RNA‐sequencing and gene enrichment analysis of EMB showed an increased expression of pro‐fibrotic and pro‐inflammatory pathways in patients with high levels of fibrosis (LGE+/PICP+) compared to patients with low levels of fibrosis (LGE‐/PICP‐). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated with distinct cardiac transcriptomic profiles. Conclusion: The combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro‐fibrotic and pro‐inflammatory transcriptomic profile in DCM patients with LGE and elevated PICP. [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]

This study sought to investigate the prevalence of systolic dysfunction using global longitudinal strain (GLS) and its prognostic value in relatives of dilated cardiomyopathy (DCM) patients that had normal left ventricular ejection fraction (LVEF). DCM relatives are advised to undergo cardiac assessment including echocardiography, irrespective of the genetic status of the index patient. Even though LVEF is normal, the question remains whether this indicates absence of disease or simply normal cardiac volumes. GLS may provide additional information regarding (sub)clinical cardiac abnormalities and thus allow earlier disease detection. A total of 251 DCM relatives and 251 control subjects with a normal LVEF (≥55%) were screened. Automated software measured the GLS on echocardiographic 2-, 3-, and 4-chamber views. The cutoff value for abnormal strain was >−21.5. Median follow-up was 40 months (interquartile range: 5 to 80 months). Primary outcome was the combination of death and cardiac hospitalization. A total of 120 relatives and 83 control subjects showed abnormal GLS (48% vs. 33%, respectively; p < 0.001). Abnormal GLS was independently associated with DCM relatives and cardiovascular risk factors, rather than genetic mutations. Subjects with abnormal GLS had more frequent cardiac hospitalizations and a higher mortality as compared with subjects with normal GLS (hazard ratio: 3.29; 95% confidence interval: 1.58 to 6.87; p = 0.001). Additionally, follow-up LVEF was measured in a subset of relatives, and it decreased significantly in those with abnormal as compared with normal GLS (p = 0.006). Relatives of DCM patients had a significantly higher prevalence of systolic dysfunction detected by GLS despite normal LVEF compared with control subjects, independent of age, sex, comorbidities, and genotype. Abnormal GLS was associated with LVEF deterioration, cardiac hospitalization, and death. [ABSTRACT FROM AUTHOR]

BACKGROUND: Genetic evaluation is recommended in patients with unexplained dilated cardiomyopathy (DCM), but its diagnostic yield and prognostic relevance in unexplained isolated left ventricular dysfunction (LVdys) is unknown. METHODS AND RESULTS: A total of 127 LVdys and 262 DCM patients underwent genetic screening. Long-term outcome consisted of a combined end point of life-threatening arrhythmia, heart transplantation, and death. At baseline, LVdys patients were younger and had less frequently New York Heart Association class ≥3 when compared with DCM (55±13 versus 58±12; P=0.019 and 21% versus 36%; P=0.003, respectively). The prevalence of familial disease and pathogenic mutations was similar in LVdys and DCM (45% versus 40%; P=0.37 and 19% versus 17%; P=0.61, respectively). After a follow-up of 56 (31-82) months, outcome did not differ in LVdys compared with DCM patients (hazard ratio, 0.83; 95% confidence interval, 0.47-1.45; P=0.51). Overall, outcome was less favorable in patients with a genetic mutation or familial disease when compared with those without (hazard ratio, 2.7; 95% confidence interval, 1.07-7.7; P=0.048 and hazard ratio, 2.2; 95% confidence interval, 1.2-4.2; P=0.013, respectively). Thus, the diagnostic yield of genetic testing in LVdys and DCM is similarly high. The presence of a gene mutation or familial predisposition results in an equally worse prognosis. CONCLUSIONS: Genetic evaluation is advised in LVdys patients and should not merely be restricted to DCM. [ABSTRACT FROM AUTHOR]

Background: Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk. Methods: TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling. Results: Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78–2.57) unadjusted, 1.96 (1.49–2.53) after adjustment for clinical confounders and 1.44 (1.05–1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78–3.33) and 1.52 (1.15–2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785). Conclusions: Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice. Registration: URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.) [ABSTRACT FROM AUTHOR]

Over the last decade, parvovirus B19 (B19V) has frequently been linked to the pathogenesis of myocarditis (MC) and its progression towards dilated cardiomyopathy (DCM). The exact role of the presence of B19V and its load remains controversial, as this virus is also found in the heart of healthy subjects. Moreover, the prognostic relevance of B19V prevalence in endomyocardial biopsies still remains unclear. As a result, it is unclear whether the presence of B19V should be treated. This review provides an overview of recent literature investigating the presence of B19V and its pathophysiological relevance in MC and DCM, as well as in normal hearts. In brief, no difference in B19V prevalence is observed between MC/DCM and healthy control hearts. Therefore, the question remains open whether and how cardiac B19V may be of pathogenetic importance. Findings suggest that B19V is aetiologically relevant either in the presence of other cardiotropic viruses, or when B19V load is high and/or actively replicating, which both may maintain myocardial (low-grade) inflammation. Therefore, future studies should focus on the prognostic relevance of the viral load, replicative status and virus co-infections. In addition, the immunogenetic background of MC/DCM patients that makes them susceptible to develop heart failure upon presence of B19V should be more thoroughly investigated. [ABSTRACT FROM AUTHOR]

Background: Renal impairment is a major risk factor for mortality in various populations. Three formulas are frequently used to assess both glomerular filtration rate (eGFR) or creatinine clearance (CrCl) and mortality prediction: body surface area adjusted-Cockcroft-Gault (CG-BSA), Modification of Diet in Renal Disease Study (MDRD4), and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The CKD-EPI is the most accurate eGFR estimator as compared to a "gold-standard"; however, which of the latter is the best formula to assess prognosis remains to be clarified. This study aimed to compare the prognostic value of these formulas in predicting the risk of cardiovascular mortality (CVM) in population-based, cardiovascular risk, heart failure (HF) and post-myocardial infarction (MI) cohorts. Methods: Two previously published cohorts of pooled patient data derived from the partners involved in the HOMAGE-consortium and from four clinical trials - CAPRICORN, EPHESUS, OPTIMAAL and VALIANT - the high risk MI initiative, were used. A total of 54,111 patients were included in the present analysis: 2644 from populationbased cohorts; 20,895 from cardiovascular risk cohorts; 1801 from heart failure cohorts; and 28,771 from postmyocardial infarction cohorts. Participants were patients enrolled in the respective cohorts and trials. The primary outcome was CVM. Results: All formulas were strongly and independently associated with CVM. Lower eGFR/CrCl was associated with increasing CVM rates for values below 60 mL/min/m2. Categorical renal function stages diverged in a more pronounced manner with the CG-BSA formula in all populations (higher χ2 values), with lower stages showing stronger associations. The discriminative improvement driven by the CG-BSA formula was superior to that of MDRD4 and CKD-EPI, but remained low overall (increase in C-index ranging from 0.5 to 2 %) while not statistically significant in population-based cohorts. The integrated discrimination improvement and net reclassification improvement were higher (P < 0.05) for the CG-BSA formula compared to MDRD4 and CKD-EPI in CV risk, HF and post-MI cohorts, but not in population-based cohorts. The CKD-EPI formula was superior overall to MDRD4. Conclusions: The CG-BSA formula was slightly more accurate in predicting CVM in CV risk, HF, and post-MI cohorts (but not in population-based cohorts). However, the CG-BSA discriminative improvement was globally low compared to MDRD4 and especially CKD-EPI, the latter offering the best compromise between renal function estimation and CVM prediction. [ABSTRACT FROM AUTHOR]

Aims Renal failure is a major challenge in treating heart failure ( HF) patients. HF medication may deteriorate renal function, but the impact thereof on outcome is unknown. We investigated the effects of HF medication on worsening renal function ( WRF) and the relationship to outcome. Methods and results This post-hoc analysis of TIME-CHF ( NT-proBNP-guided vs. symptom-guided management in chronic HF) included patients with LVEF ≤45% and ≥1 follow-up visit ( n = 462). WRF III was defined as a rise in serum creatinine ≥0.5 mg/ dL (i.e. 44.2 µmol/L) at any time during the first 6 months. Four classes of medication were considered: loop diuretics, beta-blockers, renin-angiotensin system ( RAS)-blockers, and spironolactone. Functional principal component analysis of daily doses was used to comprehend medication over time. All-cause mortality after 18 months was the primary outcome. Interactions between WRF, medication, and outcome were tested. Patients with WRF III received on average higher loop diuretic doses ( P = 0.0002) and more spironolactone ( P = 0.02), whereas beta-blockers ( P = 0.69) did not differ and lower doses of RAS-blockers were given ( P = 0.09). There were significant interactions between WRF III, medicationn and outcome. Thus, WRF III was associated with poor prognosis if high loop diuretic doses were given ( P = 0.001), but not with low doses ( P = 0.29). The opposite was found for spironolactone (poor prognosis in the case of WRF III with no spironolactone, P <0.0001; but not with spironolactone, P = 0.31). Beta-blockers were protective in all patients ( P <0.001), but most in those with WRF III ( P <0.05 for interaction). RAS-blockade was associated with improved outcome ( P = 0.006), irrespective of WRF III. Conclusion Based on this analysis, it may be hypothesized that high doses of loop diuretics might have detrimental effects, particularly in combination with significant WRF, whereas spironolactone and beta-blockers might be protective in patients with WRF. [ABSTRACT FROM AUTHOR]

Therapy guided by N-terminal-pro-B-type natriuretic peptide (NT-proBNP) levels may improve outcomes in patients with chronic heart failure (HF), especially in younger patients with reduced left ventricular ejection fraction. It remains unclear whether treatment effects persist after discontinuation of the NT-proBNP-guided treatment strategy.Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure randomized 499 patients with HF aged ≥60 years with left ventricular ejection fraction 45% to intensified, NT-proBNP-guided versus standard, symptom-guided therapy into prespecified age groups (60-74 and ≥75 years) during 18 months. A total of 329 patients (92%) alive at 18 months agreed to long-term follow-up. HF medication was intensified to a larger extent in the NT-proBNP-guided group. During long-term, NT-proBNP-guided therapy did not improve hospital-free (primary end point: hazard ratio, 0.87; 95% confidence interval, 0.71-1.06; P=0.16) or overall survival (hazard ratio, 0.85; 95% confidence interval, 0.64-1.13; P=0.25) but did improve HF hospitalization-free survival (hazard ratio, 0.70; 95% confidence interval, 0.55-0.90; P=0.005). Patients aged 60 to 74 years had benefit from NT-proBNP-guided therapy on the primary end point and HF hospitalization-free survival, whereas patients aged ≥75 years did not (P<0.10 for interaction). In landmark analysis, there was no regression to the mean after cessation of the NT-proBNP-guided strategy. More intensified HF medication at month 12 was associated with better long-term HF hospitalization-free and overall survival.Intensified, NT-proBNP-guided therapy did not improve the primary end point compared with symptom-guided therapy but did improve HF hospitalization-free survival. Within the subgroup of patients aged 60 to 74 years, it improved clinical outcome including the primary end point. These effects did not disappear after cessation of the NT-proBNP-guided strategy on the long-term. This is possibly attributable to a more intensified HF medical therapy in the NT-proBNP-guided group.URL: http://www.isrctn.org. Unique identifier: ISRCTN43596477. [ABSTRACT FROM AUTHOR]

Background: Soluble suppression of tumorigenesis-2 (sST2) is a biomarker related to inflammation and fibrosis.Objectives: This study assessed the independent prognostic value of sST2 in chronic heart failure (HF).Methods: Individual patient data from studies that assessed sST2 for risk prediction in chronic HF, together with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT), were retrieved.Results: A total of 4,268 patients were evaluated (median age 68 years, 75% males, 65% with ischemic HF, 87% with left ventricular ejection fraction [LVEF] <40%). NT-proBNP, hs-TnT, and sST2 were 1,360 ng/l (interquartile interval: 513 to 3,222 ng/l), 18 ng/l (interquartile interval: 9 to 33 ng/l), and 27 ng/l (interquartile interval: 20 to 39 ng/l), respectively. During a 2.4-year median follow-up, 1,319 patients (31%) experienced all-cause death (n = 932 [22%] for cardiovascular causes). Among the 4,118 patients (96%) with available data, 1,029 (24%) were hospitalized at least once for worsening HF over 2.2 years. The best sST2 cutoff for the prediction of all-cause and cardiovascular death and HF hospitalization was 28 ng/ml, with good performance at Kaplan-Meier analysis (log-rank: 117.6, 61.0, and 88.6, respectively; all p < 0.001). In a model that included age, sex, body mass index, ischemic etiology, LVEF, New York Heart Association functional class, glomerular filtration rate, HF medical therapy, NT-proBNP, and hs-TnT, the risk of all-cause death, cardiovascular death, and HF hospitalization increased by 26%, 25%, and 30%, respectively, per each doubling of sST2. sST2 retained its independent prognostic value across most population subgroups.Conclusions: sST2 yielded strong, independent predictive value for all-cause and cardiovascular mortality, and HF hospitalization in chronic HF, and deserves consideration to be part of a multimarker panel together with NT-proBNP and hs-TnT. [ABSTRACT FROM AUTHOR]

Background: Most patients with chronic heart failure have detectable troponin concentrations when evaluated by high-sensitivity assays. The prognostic relevance of this finding has not been clearly established so far. We aimed to assess high-sensitivity troponin assay for risk stratification in chronic heart failure through a meta-analysis approach.Methods: Medline, EMBASE, Cochrane Library, and Scopus were searched in April 2017 by 2 independent authors. The terms were "troponin" AND "heart failure" OR "cardiac failure" OR "cardiac dysfunction" OR "cardiac insufficiency" OR "left ventricular dysfunction." Inclusion criteria were English language, clinical stability, use of a high-sensitivity troponin assay, follow-up studies, and availability of individual patient data after request to authors. Data retrieved from articles and provided by authors were used in agreement with the PRISMA statement. The end points were all-cause death, cardiovascular death, and hospitalization for cardiovascular cause.Results: Ten studies were included, reporting data on 11 cohorts and 9289 patients (age 66±12 years, 77% men, 60% ischemic heart failure, 85% with left ventricular ejection fraction <40%). High-sensitivity troponin T data were available for all patients, whereas only 209 patients also had high-sensitivity troponin I assayed. When added to a prognostic model including established risk markers (sex, age, ischemic versus nonischemic etiology, left ventricular ejection fraction, estimated glomerular filtration rate, and N-terminal fraction of pro-B-type natriuretic peptide), high-sensitivity troponin T remained independently associated with all-cause mortality (hazard ratio, 1.48; 95% confidence interval, 1.41-1.55), cardiovascular mortality (hazard ratio, 1.40; 95% confidence interval, 1.33-1.48), and cardiovascular hospitalization (hazard ratio, 1.42; 95% confidence interval, 1.36-1.49), over a median 2.4-year follow-up (all P<0.001). High-sensitivity troponin T significantly improved risk prediction when added to a prognostic model including the variables above. It also displayed an independent prognostic value for all outcomes in almost all population subgroups. The area under the curve-derived 18 ng/L cutoff yielded independent prognostic value for the 3 end points in both men and women, patients with either ischemic or nonischemic etiology, and across categories of renal dysfunction.Conclusions: In chronic heart failure, high-sensitivity troponin T is a strong and independent predictor of all-cause and cardiovascular mortality, and of hospitalization for cardiovascular causes, as well. This biomarker then represents an additional tool for prognostic stratification. [ABSTRACT FROM AUTHOR]

Background: The multifactorial pathogenesis leading to dilated cardiomyopathy (DCM) makes stratification difficult. The recent MOGE(S) (morphofunctional, organ involvement, genetic or familial, etiology, stage) classification addresses this issue.Objectives: The purpose of this study was to investigate the applicability and prognostic relevance of the MOGE(S) classification in patients with DCM.Methods: This study used patients from the Maastricht Cardiomyopathy Registry in the Netherlands and excluded patients with ischemic, valvular, hypertensive, and congenital heart disease. All other patients underwent a complete diagnostic work-up, including genetic evaluation and endomyocardial biopsy.Results: A total of 213 consecutive patients with DCM were included: organ involvement was demonstrated in 35 (16%) and genetic or familial DCM in 70 (33%) patients, including 16 (8%) patients with a pathogenic mutation. At least 1 cause was found in 155 (73%) patients, of whom 48 (23%) had more than 1 possible cause. Left ventricular reverse remodeling was more common in patients with nongenetic or nonfamilial DCM than in patients with genetic or familial DCM (40% vs. 25%; p = 0.04). After a median follow-up of 47 months, organ involvement and higher New York Heart Association functional class were associated with adverse outcome (p < 0.001 and p = 0.02, respectively). Genetic or familial DCM per se was of no prognostic significance, but when it was accompanied by additional etiologic-environmental factors such as significant viral load, immune-mediated factors, rhythm disturbances, or toxic triggers, a worse outcome was revealed (p = 0.03). A higher presence of MOGE(S) attributes (≥2 vs. ≤1 attributes) showed an adverse outcome (p = 0.007).Conclusions: The MOGE(S) classification in DCM is applicable, and each attribute or the gene-environment interaction is associated with outcome. Importantly, the presence of multiple attributes was a strong predictor of adverse outcome. Finally, adaptation of the MOGE(S) involving multiple possible etiologies is recommended. [ABSTRACT FROM AUTHOR]

Objectives: The study aim was to determine the prognostic value of a multimarker strategy for risk-assessment in patients presenting to the emergency department (ED) with dyspnea. Background: Combining biomarkers with different pathophysiological backgrounds may improve risk stratification in dyspneic patients in the ED. Methods: The study prospectively investigated the prognostic value of the biomarkers N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), Cystatin-C (Cys-C), high-sensitivity C-reactive protein (hs-CRP), and Galectin-3 (Gal-3) for 90-day mortality in 603 patients presenting to the ED with dyspnea as primary complaint. Results: hs-CRP, hs-cTnT, Cyst-C, and NT-proBNP were independent predictors of 90-day mortality. The number of elevated biomarkers was highly associated with outcome (odds ratio: 2.94 per biomarker, 95% confidence interval [CI]: 2.29 to 3.78, p < 0.001). A multimarker approach had incremental value beyond a single-marker approach. Our multimarker emergency dyspnea-risk score (MARKED-risk score) incorporating age ≥75 years, systolic blood pressure <110 mm Hg, history of heart failure, dyspnea New York Heart Association functional class IV, hs-cTnT ≥0.04 μg/l, hs-CRP ≥25 mg/l, and Cys-C ≥1.125 mg/l had excellent prognostic performance (area under the curve: 0.85, 95% CI: 0.81 to 0.89), was robust in internal validation analyses and could identify patients with very low (<3 points), intermediate (≥3, <5 points), and high risk (≥5 points) of 90-day mortality (2%, 14%, and 44% respectively; p < 0.001). Conclusions: A multimarker strategy provided superior risk stratification beyond any single-marker approach. The MARKED-risk score that incorporates hs-cTnT, hs-CRP, and Cys-C along with clinical risk factors accurately identifies patients with very low, intermediate, and high risk. [ABSTRACT FROM AUTHOR]