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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]

Introduction: Heart failure is a serious burden on health care systems due to frequent hospital admissions. Early recognition of outpatients at risk for clinical deterioration could prevent hospitalization. Still, the role of signs and symptoms in monitoring heart failure patients is not clear. The heart failure coach is a web-based telemonitoring application consisting of a 9-item questionnaire assessment of heart failure signs and symptoms and developed to identify outpatients at risk for clinical deterioration. If deterioration was suspected, patients were contacted by a heart failure nurse for further evaluation. Methods: Heart failure coach questionnaires completed between 2015 and 2018 were collected from 287 patients, completing 18,176 questionnaires. Adverse events were defined as all-cause mortality, heart failure- or cardiac-related hospital admission or emergency cardiac care visits within 30 days after completion of each questionnaire. Multilevel logistic regression analyses were performed to assess the association between the heart failure coach questionnaire items and the odds of an adverse event. Results: No association between dyspnea and adverse events was observed (odds ratio 1.02, 95% confidence interval 0.79–1.30). Peripheral edema (odds ratio 2.21, 95% confidence interval 1.58–3.11), persistent chest pain (odds 2.06, 95% confidence interval 1.19–3.58), anxiety about heart failure (odds ratio 2.12, 95% confidence interval 1.44–3.13), and extensive struggle to perform daily activities (odds ratio 2.23, 95% confidence interval 1.38–3.62) were significantly associated with adverse outcome. Discussion: Regular assessment of more than the classical signs and symptoms may be helpful to identify heart failure patients at risk for clinical deterioration and should be an integrated part of heart failure telemonitoring programs. [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]

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]

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]

Background: The relationship between longitudinal clinical congestion pattern and heart failure outcome is uncertain. This study was designed to assess the prevalence of congestion over time and to investigate its impact on outcome in chronic heart failure.Methods: A total of 588 patients with chronic heart failure older than 60 years of age with New York Heart Association (NYHA) functional class ≥II from the TIME-CHF study were included. The endpoints for this study were survival and hospitalization-free heart failure survival. Orthopnea, NYHA ≥III, paroxysmal nocturnal dyspnea, hepatomegaly, peripheral pitting edema, jugular venous distension, and rales were repeatedly investigated and related to outcomes. These congestion-related signs and symptoms were used to design a 7-item Clinical Congestion Index.Results: Sixty-one percent of patients had a Clinical Congestion Index ≥3 at baseline, which decreased to 18% at month 18. During the median [interquartile range] follow-up of 27.2 [14.3-39.8] months, 17%, 27%, and 47% of patients with baseline Clinical Congestion Index of 0, 1-2, and ≥3 at inclusion, respectively, died (P <.001). Clinical Congestion Index was identified as an independent predictor of mortality at all visits (P <.05) except month 6 and reduced hospitalization-free heart failure survival (P <.05). Successful decongestion was related to better outcome as compared to persistent congestion or partial decongestion (log-rank P <0.001).Conclusions: The extent of congestion as assessed by means of clinical signs and symptoms decreased over time with intensified treatment, but it remained present or relapsed in a substantial number of patients with heart failure and was associated with poor outcome. This highlights the importance of appropriate decongestion in chronic heart failure. [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]

Aims: While the conditions of heart failure (HF) with reduced (HFrEF, LVEF < 40%) and preserved (HFpEF, LVEF ≥ 50%) left ventricular ejection fraction (LVEF) are well characterized, it is unknown whether patients with HF and mid-range LVEF (HFmrEF, LVEF 40-49%) have to be regarded as a separate clinical entity. The aim of this study was to characterize these three populations and to compare outcome and response to therapy.Methods and Results: The analysis was based on the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) comprising a population with established HF including the whole spectrum of LVEF. Of the 622 patients, 108 (17%) were classified as having HFmrEF. This group was in general found to be 'intermediate' regarding clinical characteristics with a comparable and high burden of comorbidities and equally impaired quality of life but was more likely to have coronary artery disease as compared with the HFpEF group. During a median follow-up of 794 days, mortality was 39.7% without significant differences between groups. N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided as compared with standard therapy resulted in improved survival free of HF hospitalizations in HFrEF and HFmrEF, but not in HFpEF.Conclusion: Although the 'intermediate' clinical profile of HFmrEF between HFrEF and HFpEF would support the conclusion that HFmrEF is a distinct clinical entity, we hypothesize that HFmrEF has to be categorized as HFrEF because of the high prevalence of coronary artery disease and the similar benefit of NT-proBNP-guided therapy in HFrEF and HFmrEF, in contrast to HFpEF. [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]

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]

Objective Cardiac troponins T (cTnT) and I (cTnI) are the preferred biomarkers to detect myocardial damage. The present study explores the value of measuring cardiac troponins (cTn) in nursing home residents, by investigating its relation to heart failure and 1-year mortality using 1 cTnT and 2 cTnI assays that are widely used in clinical practice. Design All participants underwent extensive clinical examinations and echocardiographic assessment for the diagnosis of heart failure. cTn was measured using high-sensitive (hs)- cTnT (Roche), hs-cTnI (Abbott), and sensitive cTnI (Beckman) assays. The glomerular filtration rate was estimated (eGFR) using serum creatinine and cystatin C concentrations. Data on all-cause mortality were collected at 1-year follow-up. Participants and Setting Participants were 495 long-term nursing home residents, older than 65 years, of 5 Dutch nursing home organizations. Results Median (IQR) concentrations were 20.6 (17.8–30.6), 6.8 (4.1–12.5), and 4.0 (2.0–8.0) ng/L for hs-cTnT, hs-cTnI, and cTnI, respectively. In total, 79% had elevated hs-cTnT concentrations, whereas only 9% and 5% of hs-cTnI and cTnI concentrations were elevated. Most important and independent determinants for higher hs-cTnT and hs-cTnI concentrations were heart failure and renal dysfunction. Whereas both heart failure (odds ratio [OR] 3.4) and eGFR lower than 60 mL/min/1.73 m 2 (OR 3.6) were equal contributors to higher hs-cTnT concentrations (all P < .001), hs-cTnI and cTnI were less associated with renal dysfunction (OR of, respectively, 1.9 and 2.1; P < .01) in comparison with heart failure (OR 4.3 and 4.7, respectively, P < .001). Furthermore, residents with higher hs-cTnT or hs-cTnI concentrations (fourth quartile) had respectively 4 versus 2 times more risk of 1-year mortality compared with lower concentrations. Conclusion Regardless of their cardiac health, hs-cTnT but not hs-cTnI concentrations were elevated in almost all aged nursing home residents, questioning the use of the current diagnostic cutoff in elderly with high comorbidity. Nonetheless, measuring cardiac troponins, especially hs-cTnT, had a promising role in assessing future risk of mortality. [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]

Objectives: In patients with heart failure (HF), peak oxygen consumption (peak VO2), the relationship between minute ventilation and carbon dioxide production (VE/VCO2 slope) and heart rate recovery (HRR) are established prognostic predictors. However, treadmill exercise has been shown to elicit higher peak VO2 values than bicycle exercise. We sought to assess whether the VE/VCO2 slope and HRR in HF also depend on the exercise mode. Methods: Twenty-one patients with mild HF on chronic β-blocker therapy underwent treadmill and bicycle cardiopulmonary exercise testing for measurement of peak VO2 and the VE/VCO2 slope. In patients with sinus rhythm (n = 16), HRR at 1 (HRR-1) and 2 min (HRR-2) after exercise termination was assessed. Results: Peak VO2 was higher during treadmill as compared with bicycle testing (21.7 ± 4.6 vs. 19.6 ± 3.4 ml/kg/min; p = 0.006). HRR-1 tended to be slower (15 bpm, interquartile range 8–19, vs. 18 bpm, interquartile range 11–22; p = 0.16), and HRR-2 was significantly slower after treadmill exercise (26 bpm, interquartile range 20–39, vs. 31 bpm, interquartile range 22–41; p = 0.04). In contrast, VE/VCO2 slope values did not differ between the test modes (32.9 ± 5.5 vs. 32.3 ± 5.0; p = 0.56). Conclusions: In contrast to peak VO2 and HRR, the VE/VCO2 slope is not affected by the exercise mode in patients with mild HF. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]