N-terminal pro-B-type natriuretic peptide for prediction of ventricular arrhythmias: Data from the SMASH study.

BACKGROUND: Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations predict heart failure (HF) and mortality, but whether NT-proBNP predicts ventricular arrhythmias (VA) is not clear. HYPOTHESIS: We hypothesize that high NT-proBNP concentrations associate with the risk of incident VA, defined as adjudicated ventricular fibrillation or sustained ventricular tachycardia. METHODS: In a prospective, observational study of patients treated with implantable cardioverter defibrillator (ICD), we analyzed NT-proBNP concentrations at baseline and after mean 1.4 years in association to incident VA. RESULTS: We included 490 patients (age 66 ± 12 years, 83% men) out of whom 51% had a primary prevention ICD indication. The median NT-proBNP concentration was 567 (25-75 percentile 203-1480) ng/L and patients with higher concentrations were older with more HF and ICD for primary prevention. During mean 3.1 ± 0.7 years, 137 patients (28%) had ≥1 VA. Baseline NT-proBNP concentrations were associated with the risk of incident VA (hazard ratio [HR]: 1.39, 95% confidence interval [95% CI]: 1.22-1.58, p < .001), HF hospitalizations (HR: 3.11, 95% CI: 2.53-3.82, p < .001), and all-cause mortality (HR: 2.49, 95% CI: 2.04-3.03, p < .001), which persisted after adjusting for age, sex, body mass index, coronary artery disease, HF, renal function, and left ventricular ejection fraction. The association with VA was stronger in secondary versus primary prevention ICD indication: HR: 1.59 (95% CI: 1.34-1.88 C-statistics 0.71) versus HR: 1.24, 95% CI: 1.02-1.51, C-statistics 0.55), p-for-interaction = 0.06. Changes in NT-proBNP during the first 1.4 years did not associate with subsequent VA. CONCLUSIONS: NT-proBNP concentrations are associated with the risk of incident VA after adjustment for established risk factors, with the strongest association in patients with a secondary prevention ICD indication.

Cardiac troponin is associated with cardiac outcomes in men and women with atrial fibrillation, insights from the ARISTOTLE trial.

BACKGROUND: Cardiac troponin T (cTnT) and I (cTnI) concentrations provide strong prognostic information in anticoagulated patients with atrial fibrillation (AF). Whether the associations between cardiac troponin concentrations and mortality and morbidity differ by sex is not known. OBJECTIVES: To assess whether men and women have different concentrations and prognostic value of cTnT and cTnI measurements in anticoagulated patients with AF. METHODS: cTnT and cTnI concentrations were measured with high-sensitivity (hs) assays in EDTA plasma samples obtained from the multicentre ARISTOTLE trial, which randomized patients with AF and at least one risk factor for stroke or systemic embolic event to warfarin or apixaban. Patients were stratified according to sex and the associations between hs-troponin concentrations, and all-cause death, cardiac death, myocardial infarction, stroke or systemic embolic event and major bleeding were assessed in multivariable regression models. RESULTS: We found higher cardiac troponin concentrations in men (n = 9649) compared to women (n = 5331), both for hs-cTnT (median 11.8 [Q1-3 8.1-18.0] vs. 9.6 [6.7-14.3] ng L-1 , P < 0.001) and hs-cTnI (5.8 [3.4-10.8] vs. 4.9 [3.1-8.8] ng L-1 , P < 0.001). Adjusting for baseline demographics, comorbidities and medications, men still had significantly higher hs-troponin concentrations than women. C-reactive protein and N-terminal pro-B-type natriuretic peptide concentrations were higher in female patients. Both hs-cTnT and hs-cTnI concentrations were associated with all clinical outcomes similarly in men and women (p-value for interaction >0.05 for all end-points). CONCLUSION: Men have higher hs-troponin concentrations than women in AF. Regardless of sex, hs-troponin concentrations remain similarly associated with adverse clinical outcomes in anticoagulated patients with AF.

Serological markers of extracellular matrix remodeling predict transplant-free survival in primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis is a progressive liver disease with a remarkably variable course. Biomarkers of disease activity or prognostic models predicting outcome at an individual level are currently not established. AIM: To evaluate the prognostic utility of four biomarkers of basement membrane and interstitial extracellular matrix remodeling in patients with primary sclerosing cholangitis. METHODS: Serum samples were available from 138 large-duct primary sclerosing cholangitis patients (of which 102 [74%] with IBD) recruited 2008-2012 and 52 ulcerative colitis patients (controls). The median follow-up time was 2.2 (range 0-4.3) years. Specific biomarkers of type III and V collagen formation (PRO-C3 and PRO-C5, respectively) and type III and IV collagen degradation (C3M and C4M, respectively) were assessed. The Enhanced Liver Fibrosis test, including procollagen type III N-terminal peptide, tissue inhibitor of metalloproteinase-1 and hyaluronic acid was assessed for comparison. RESULTS: All markers were elevated in primary sclerosing cholangitis compared to ulcerative colitis patients (P < 0.001). PRO-C3 showed the largest difference between the two groups with a threefold increase in primary sclerosing cholangitis compared to ulcerative colitis patients. Patients with high baseline serum levels of all markers, except C3M, had shorter survival compared to patients with low baseline serum levels (P < 0.001). Combining PRO-C3 and PRO-C5 the odds ratio for predicting transplant-free survival was 47 compared to the Enhanced Liver Fibrosis test's odds ratio of 11. CONCLUSIONS: Extracellular matrix remodeling is elevated in primary sclerosing cholangitis patients compared to ulcerative colitis patients. Furthermore, the interstitial matrix marker PRO-C3 was identified as a potent prognostic marker and an independent predictor of transplant-free survival in primary sclerosing cholangitis.

Troponins in heart failure.

The signs and symptoms of heart failure are frequently unspecific and correlate poorly with objective indices of cardiac function. Objective assessment of cardiac function by echocardiography or other imaging modalities also correlate poorly with symptomatic status and functional capacity. Accordingly, there is a need for circulating biomarkers that can provide incremental diagnostic and prognostic information to the existing armamentarium of tests. The introduction of more sensitive assays that allow determination of very low circulating concentrations of the myofibrillar proteins cardiac troponin I and T has not only resulted in improved diagnostic accuracy in the setting of acute coronary syndromes. The high sensitivity assays have also shown that cardiac troponins are frequently found chronically circulating in a variety of acute and chronic, cardiac and non-cardiac disease conditions, including acute heart failure and chronic symptomatic and asymptomatic left ventricular dysfunction. Cardiac troponin I and T provide may provide clinically useful prognostic information both concerning the future risk of developing heart failure in asymptomatic subjects and the risk of fatal events and hospital admissions in those with already established heart failure This review summarizes current literature on the clinical performance and utility of cardiac troponin measurements as diagnostic and prognostic tools in patients with symptomatic heart failure, as well as in those with asymptomatic left ventricular dysfunction, and clinical phenotypes at high risk for developing heart failure, including stable coronary artery disease, left ventricular hypertrophy, and aortic stenosis.

Lack of pro-inflammatory cytokine mobilization predicts poor prognosis in patients with acute heart failure.

AIMS: The aim of this study was to gain insight in the inflammatory response in acute heart failure (AHF) by assessing (1) plasma cytokine profiles and (2) prognostic value of circulating cytokines in AHF patients. METHODS AND RESULTS: Plasma levels of 26 cytokines were quantified by multiplex protein arrays in 36 patients with congestive AHF, characterized by echocardiographic, radiologic, and clinical examinations on admission, during hospitalization and at discharge. Recurrent AHF leading to death or readmission constituted the combined end point, and all patients were followed for 120 days after discharge. Levels of 15 of the measured cytokines were higher in AHF than in healthy subjects (n=22) on admission. Low levels of MCP-1, IL-1ß and a low IL-1ß/IL-1ra ratio predicted fatal and non-fatal AHF within 120 days. Patients with low circulating levels of IL-1ß had lower left ventricular ejection fraction and higher levels of N-terminal pro-B-type natriuretic peptide, while patients with low levels of MCP-1 had higher E/E' and inferior caval vein diameter, than patients with high levels. CONCLUSION: Immune activation, reflected in increased cytokine levels, is present in AHF patients. Interestingly, failure to increase secretion of IL-1ß and MCP-1 during AHF is associated with poor outcome.