Total Bilirubin Yields Prognostic Information Following a Myocardial Infarction in the Elderly.

Total bilirubin consists of an unconjugated form, solubilized by its binding to albumin, and a conjugated form representing a minor part of the circulating bilirubin. As total bilirubin in physiological concentrations is a powerful antioxidant, its concentration gradient may reflect the health status of an individual, and serve as a prognostic indicator of outcome in primary and secondary cardiovascular disease prevention. The aim of this study was to assess the association between total bilirubin and incident cardiovascular events following a myocardial infarction. Total bilirubin in serum was measured at baseline 2-8 weeks after hospitalization for an MI in 881 patients, aged 70 to 82 years, included in the OMEMI (Omega-3 Fatty acids in Elderly with Myocardial Infarction) study, where patients were followed-up for up to 2 years. The first major adverse clinical event (MACE) was the primary endpoint and consisted of nonfatal MI, unscheduled coronary revascularization, stroke, hospitalization for heart failure or all-cause death. As total bilirubin was non-normally distributed, log-transformed values and quartiles of bilirubin were analyzed using Cox regression models. The median (Q1, and Q3) baseline concentration of bilirubin was 11 (9, and 14) µmol/L, and higher log-transformed concentrations were associated with male sex, lower New York Heart Association (NYHA) class and non-smoking. MACE occurred in 177 (20.1%) patients during the follow-up. Higher concentrations of bilirubin were associated with a lower risk of MACE: HR 0.67 (95%CI 0.47-0.97) per log-unit increase, p = 0.032. Patients in the lowest quartile of bilirubin (<9 µmol/L) had the highest risk with HR 1.61 (95%CI 1.19-2.18), p = 0.002, compared to quartiles 2-4. This association remained significant even after adjusting for age, sex, body mass index (BMI), smoking status, NYHA class and treatment allocation: HR 1.52 (1.21-2.09), p = 0.009. Low concentrations of bilirubin (<9 µmol/L) are associated with increased nonfatal cardiovascular events or death in elderly patients with a recent myocardial infarction.

Screen-detected atrial fibrillation and 'micro-atrial fibrillation' and risk of cardiovascular events after myocardial infarction in elderly patients.

BACKGROUND: Incident atrial fibrillation (AF) occurs in 5-10% of patients after acute myocardial infarction (AMI) and is associated with adverse outcomes. Guidelines now recommend screening for AF in all elderly patients. However, the relevance of screen-detected AF and short episodes of irregular supraventricular ectopic beats ('micro-AF') after AMI is unknown. OBJECTIVES: To investigate the value of two-week intermittent ECG screening to detect incident AF and 'micro-AF' in elderly patients 12 months after an AMI, and its association with risk of cardiovascular events. METHODS: This was an investigator-initiated, multicenter substudy of the OMega-3 fatty acids in Elderly patients with Myocardial Infarction (OMEMI) trial, in Norway. Women and men aged 70-82 years, with a recent AMI, were recruited during 2012-2018. All participants had a 12-lead ECG performed at 3, 12 and 24 months. Patients without AF one year after the index AMI underwent 2 weeks of intermittent 30-second 'thumb ECG' screening. Incident AF and 'micro-AF' (episodes of ≥3 consecutive irregular supraventricular ectopic beats) were registered, and the association with risk of major cardiovascular events (MACE; non-fatal AMI, stroke, coronary revascularization, hospitalization for heart failure, or all-cause death) was analyzed with logistic regression. RESULTS: Among 1014 patients (198 (28.7%) women), 255 (25.1%) had known AF or AF identified at baseline. New-onset AF was detected clinically or at study visits in 39 (3.8%) patients. By screening participants without AF (n=567), unknown AF was identified in 4 (0.7%) and 'micro-AF' in 27 (4.8%) patients. Among 43 patients with incident AF, 21 (48.8%) experienced a MACE, which was significantly higher than those without AF (n=114, 15.9%; p<0.001), driven by a higher risk of AMI or revascularization. Nine (33.3%) patients with 'micro-AF' and 75 (13.9%) without 'micro-AF' experienced a MACE (p=0.002), explained mostly by a higher risk of heart failure hospitalization (p<0.001). Using patients without AF and 'micro-AF' as reference, 'micro-AF' was associated with an intermediate risk of MACE (OR 2.8; 95% CI 1.2-6.4) and new-onset AF with a high risk of MACE (OR 5.3; 95% CI 2.8-10.0). CONCLUSIONS: Two-week intermittent ECG screening identified few cases of new-onset AF, but a substantial number of patients with 'micro-AF'. 'Micro-AF' was associated with an increased risk of major cardiovascular events, albeit with an intermediate risk compared to those with new-onset AF.

QRS fragmentation is associated with increased risk of ventricular arrhythmias in high-risk patients; Data from the SMASH 1 Study.

INTRODUCTION: QRS fragmentation (fQRS), defined as the presence of additional spikes within the QRS complex, has been associated with myocardial conduction abnormalities and arrhythmogenicity. OBJECTIVE: We aimed to assess whether fQRS is associated with incident ventricular arrhythmias (VA) in high-risk patients treated with implantable cardioverter-defibrillator (ICD) for primary and secondary prevention. METHODS: In a prospective observational multicenter study, we included 495 patients treated with ICD. fQRS was analyzed according to previously validated criteria, by two physicians blinded for outcome data. Incident VA were obtained from ICD recordings. RESULTS: ECG recordings interpretable for fQRS were available in 459 patients (93%), aged 66 ± 12 years with left ventricular ejection fraction 40% ± 13%. fQRS was present in 52 patients (11%) with comparable baseline characteristics to patients without fQRS, except higher age, higher prevalence of coronary artery disease (CAD), lower prevalence of cardiomyopathy, and more frequently a secondary prevention ICD indication. Among patients with native QRS, those with fQRS had similar QRS duration and axis to those without fQRS. During 3.1 ± 0.7 years follow-up, 126 patients (28%) had ≥1 VA . fQRS was associated with increased risk of VA (HR 3.41 [95% CI 2.27-5.13], p < .001), which persisted after adjusting for age, gender, sex, BMI, CAD, heart failure, renal function, ICD indication, QRS duration, QRS axis, Q waves, and bundle branch block. fQRS was more strongly associated with VA in patients with a primary (HR 6.05 [95% CI 3.16-11.60]) versus secondary (HR 2.39 [95% CI 1.41-4.04]) ICD indication (p-for-interaction = .047). CONCLUSIONS: fQRS is associated with threefold increased risk of VA in high-risk patients, independent of established risk factors.

Soluble ST2 concentrations associate with in-hospital mortality and need for mechanical ventilation in unselected patients with COVID-19.

OBJECTIVE: Soluble ST2 (sST2) reflects inflammation, endothelial dysfunction and myocardial fibrosis, is produced in the lungs and is an established biomarker in heart failure. We sought to determine the role of sST2 in COVID-19 by assessing pathophysiological correlates and its association to in-hospital outcomes. METHODS: We enrolled 123 consecutive, hospitalised patients with COVID-19 in the prospective, observational COVID-19 MECH study. Biobank samples were collected at baseline, day 3 and day 9. The key exposure variable was sST2, and the outcome was ICU treatment with mechanical ventilation or in-hospital death. RESULTS: Concentrations of sST2 at baseline was median 48 (IQR 37-67) ng/mL, and 74% had elevated concentrations (>37.9 ng/mL). Higher baseline sST2 concentrations were associated with older age, male sex, white race, smoking, diabetes, hypertension and chronic kidney disease. Baseline sST2 also associated with the presence of SARS-CoV-2 viraemia, lower oxygen saturation, higher respiratory rate and increasing concentrations of biomarkers reflecting inflammation, thrombosis and cardiovascular disease. During the hospitalisation, 8 (7%) patients died and 27 (22%) survivors received intensive care unit (ICU) treatment. Baseline sST2 concentrations demonstrated a graded association with disease severity (median, IQR): medical ward 43 (36-59) ng/mL; ICU 67 (39-104) ng/mL and non-survivors 107 (72-116) ng/mL (p<0.001 for all comparisons). These associations persisted at day 3 and day 9 . CONCLUSIONS: sST2 concentrations associate with SARS-CoV-2 viraemia, hypoxaemia and concentrations of inflammatory and cardiovascular biomarkers. There was a robust association between baseline sST2 and disease severity that was independent of, and superior to, established risk factors. sST2 reflects key pathophysiology and may be a promising biomarker in COVID-19. TRIAL REGISTRATION NUMBER: NCT04314232.

Serum Levels of Dihomo-Gamma (γ)-Linolenic Acid (DGLA) Are Inversely Associated with Linoleic Acid and Total Death in Elderly Patients with a Recent Myocardial Infarction.

Dihomo-gamma-linolenic acid (DGLA) is an n-6 polyunsaturated fatty acid (PUFA) derived from linoleic acid (LA). The LA:DGLA ratio reflects conversion from LA to DGLA. Low levels of DGLA in serum have been related to poor outcome in myocardial infarction (MI) patients. Aims: To assess the association of DGLA and LA:DGLA with total death as a primary aim and incident cardiovascular events as a secondary objective. Methods: Baseline samples from 1002 patients, aged 70 to 82 years, included 2-8 weeks after an MI and followed for 2 years, were used. Major adverse clinical events (MACE) consisted of nonfatal MI, unscheduled coronary revascularization, stroke, hospitalization for heart failure or all-cause death. Cox regression analysis was used to relate serum n-6 PUFA phospholipid levels (%wt) to the risk of MACE, adjusting for the following: (1) age, sex and body mass index (BMI); (2) adding baseline cod liver oil supplementation; (3) adding prevalent hypertension, chronic kidney disease and diabetes mellitus. Results: Median DGLA level in serum phospholipids was 2.89 (Q1-Q3 2.43-3.38) %wt. DGLA was inversely related to LA and LA:DGLA ratio. There were 208 incident cases of MACE and 55 deaths. In the multivariable analysis, the hazard ratio (HR) for the total death in the three higher quartiles (Q2-4) of DGLA as compared to Q1 was 0.54 (0.31-0.95), with p = 0.03 (Model-1), 0.50 (0.28-0.91), with p = 0.02 (Model-2), and 0.47 (0.26-0.84), with p = 0.012 (Model-3), and non-significant for MACE. Risk of MACE (Model 3) approached borderline significance for LA:DGLA in Q2-4 vs. Q1 [HR 1.42 (1.00-2.04), p = 0.052]. Conclusions: Low levels of DGLA were related to a high LA:DGLA ratio and risk of total death in elderly patients with recent MI.

Omega-3 supplements do not prevent cardiovascular disease. / Omega-3-tilskudd forebygger ikke hjertesykdom.

There is little evidence that omega-3 supplements can prevent cardiovascular disease. We should therefore hold back on recommending and marketing omega-3 supplements as a preventive treatment.

A single-centre, prospective cohort study of COVID-19 patients admitted to ICU for mechanical ventilatory support.

BACKGROUND: Mortality rates in COVID-19 patients in need of mechanical ventilation are high, with wide variations between countries. Most studies were retrospective, and results may not be generalizable due to differences in demographics, healthcare organization and surge capacity. We present a cohort of mechanically ventilated COVID-19 patients from a resource-rich, publicly financed healthcare system. METHODS: Prospective study from a tertiary hospital. Consecutive SARS-CoV-2 positive adult patients admitted to the ICU for mechanical ventilation from 10 March 2020 to 04 May 2020 were included. Triage and treatment were protocolized. High-dose dalteparin was adjusted by D-dimer. Demographics, treatments and high-resolution physiological variables were collected. Outcomes were 30-day and hospital mortality. Data are medians (quartiles). RESULTS: Of the 1484 persons in the hospital catchment area testing positive for SARS-CoV-2, 201 (13.5%) were hospitalized. Thirty-eight (19%) patients were mechanically ventilated, of whom five (13%) died. Of the 163 patients treated with supplemental oxygen, eight (5%) died. In ventilated patients (75% males, age 61 (53-70) years), severe, moderate and mild ARDS was present in 25%, 70% and 5%. Tidal volume ≤8 mL/kg ideal bodyweight was achieved in 34 (94%) patients. Proning and neuromuscular blockers were used in 19 (54%) and 20 (61%) patients. Duration of ventilation was 12 days (8-23). D-dimer peaked at 3.8 mg/L (2.1-5.3), and maximum dalteparin dose was 15 000 IU/24 h (10 000-15 000). Despite organizational changes, a high degree of adherence to treatment protocols was achieved. CONCLUSION: In a prospective cohort study of mechanically ventilated COVID-19 patients treated in a resource-rich, publicly financed healthcare system, mortality was considerably lower than previously reported in retrospective studies.

High-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide in acute heart failure: Data from the ACE 2 study.

BACKGROUND: To assess if cardiac troponins can improve diagnostics of acute heart failure (AHF) and provide prognostic information in patients with acute dyspnea. METHODS: We measured cardiac troponin T with a high-sensitivity assay (hs-cTnT) in 314 patients hospitalized with acute dyspnea. The index diagnosis was adjudicated and AHF patients were stratified into AHF with reduced or preserved ejection fraction (HFrEF/HFpEF). The prognostic and diagnostic merit of hs-cTnT was compared to the merit of N-terminal pro-B-type natriuretic peptide (NT-proBNP). RESULTS: In the total population, median age was 73 (quartile [Q] 1-3 63-81) years and 48% were women. One-hundred-forty-three patients were categorized as AHF (46%) and these patients had higher hs-cTnT concentrations than patients with non-AHF-related dyspnea: median 38 (Q1-3 22-75) vs. 13 (4-25) ng/L; p < 0.001. hs-cTnT concentrations were similar between patients with HFrEF and HFpEF (p = 0.80), in contrast to NT-proBNP, which was higher in HFrEF (p < 0.001). C-statistics for discriminating HFpEF from non-AHF-related dyspnea was 0.80 (95% CI 0.73-0.86) for hs-cTnT, 0.79 (0.73-0.86) for NT-proBNP, and 0.83 (0.76-0.89) for hs-cTnT and NT-proBNP in combination. Elevated hs-cTnT remained associated with HFpEF in logistic regression analysis after adjusting for demographics, comorbidities and renal function. During median 27 months of follow-up, 114 (36%) patients died in the total population. Higher hs-cTnT concentrations were associated with increased risk of all-cause mortality after adjustment for clinical variables and NT-proBNP: hazard ratio 1.30 (95% CI 1.07-1.58), p = 0.009. CONCLUSION: hs-cTnT measurements improve diagnostic accuracy for HFpEF and provide independent prognostic information in unselected patients with acute dyspnea.

Effects of n-3 Fatty Acid Supplements in Elderly Patients After Myocardial Infarction: A Randomized, Controlled Trial.

BACKGROUND: High intake of marine n-3 polyunsaturated fatty acids (PUFA) has been associated with reduced risk of cardiovascular events; however, this has not been confirmed in patients with a recent acute myocardial infarction (AMI). Elderly patients are at particularly increased cardiovascular risk after myocardial infarction, but few trials address this group specifically. Omega-3 fatty acids hold the potential to reduce cardiovascular events with limited adverse effects in this vulnerable group. The hypothesis was that daily addition of 1.8g n-3 PUFA to standard of care secondary prophylaxis in elderly patients who have survived an AMI would reduce the risk of subsequent cardiovascular events during 2 years follow-up. METHODS: The OMEMI trial (Omega-3 Fatty acids in Elderly with Myocardial Infarction) is an investigator-initiated, multicenter, randomized clinical trial adding 1.8 g n-3 PUFA (930 mg eicosapentaenoic acid and 660 mg docosohexaenoic acid) versus placebo (corn oil) daily to standard of care in patients aged 70 to 82 years with recent (2-8 weeks) AMI. The primary endpoint was a composite of nonfatal AMI, unscheduled revascularization, stroke, all-cause death, heart failure hospitalization after 2 years. The secondary outcome was new atrial fibrillation. The safety outcome was major bleeding. Serum fatty acids were measured as biomarkers of adherence. RESULTS: In total, 1027 patients were randomized. Follow-up data were available for 1014 patients who were included in the intention-to-treat analysis. Mean±SD age was 75±3.6 years, 294 (29%) were female, and mean triglycerides were 111.4±61.9 mg/dL. The primary endpoint occurred in 108 (21.4%) patients on n-3 PUFA versus 102 (20.0%) on placebo (hazard ratio, 1.08 [95% CI, 0.82-1.41]; P=0.60). The secondary endpoint occurred in 28 (7.2%) patients on n-3 PUFA versus 15 (4.0%) on placebo (1.84 [0.98-3.45]; P=0.06). Median changes in eicosapentaenoic acid and docosahexaenoic acid were +87% and +16% for n-3 PUFA versus -13% and -8% for placebo. Major bleeding occurred in 54 (10.7%) and 56 (11.0%) in the n-3 PUFA and placebo groups, respectively (P=0.87). Similar results were found in per-protocol analysis (n=893). CONCLUSIONS: We could not detect reduction in clinical events in our elderly patients with recent AMI who were treated with 1.8 g n-3 PUFAs daily for 2 years. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01841944.

B-Type Natriuretic Peptide During Treatment With Sacubitril/Valsartan: The PARADIGM-HF Trial.

BACKGROUND: Natriuretic peptides are substrates of neprilysin; hence, B-type natriuretic peptide (BNP) concentrations rise with neprilysin inhibition. Thus, the clinical validity of measuring BNP in sacubitril/valsartan-treated patients has been questioned, and use of N-terminal pro-B-type natriuretic peptides (NT-proBNP) has been preferred and recommended. OBJECTIVES: The purpose of this study was to determine the prognostic performance of BNP measurements before and during treatment with sacubitril/valsartan. METHODS: BNP and NT-proBNP were measured before and after 4 to 6 weeks, 8 to 10 weeks, and 9 months of treatment with sacubitril/valsartan in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. We assessed the association of levels of these natriuretic peptides with the subsequent risk of cardiovascular death or hospitalization for HF. RESULTS: Median BNP concentration (before treatment: 202 ng/l [Q1 to Q3: 126 to 335 ng/l]) increased to 235 ng/l (Q1 to Q3: 128 to 422 ng/l) after 8 to 10 weeks of treatment. BNP concentrations doubled in 141 (18%) patients and tripled in 49 (6%) patients during the first 8 to 10 weeks of sacubitril/valsartan. In contrast, such striking increases in NT-proBNP following the use of the neprilysin inhibitor were extremely rare. Treatment with sacubitril/valsartan caused a rightward shift in the distribution of BNP when compared with NT-proBNP, but both peptides retained their prognostic accuracy (C-statistics of 63% to 67% for BNP and C-statistics of 64% to 70% for NT-proBNP) with no difference between the 2 biomarkers. Increases in both BNP and NT-proBNP during 8 to 10 weeks of sacubitril/valsartan were associated with worse outcomes (p = 0.003 and p = 0.005, respectively). CONCLUSIONS: Circulating levels of BNP may increase meaningfully early after initiation of sacubitril/valsartan. In comparison, NT-proBNP is not a substrate of neprilysin inhibition, and thus may lead to less clinical confusion when measured within 8 to 10 weeks of drug initiation. However, during treatment, either biomarker predicts the risk of major adverse outcomes in patients treated with angiotensin receptor-neprilysin inhibitors. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255).

Novel biomarkers of cardiovascular disease: Applications in clinical practice.

Measurement of biomarkers has revolutionized the work-up of patients with suspected cardiovascular disease. The most widely used contemporary cardiovascular biomarkers are the natriuretic peptides in the diagnosis and prognosis of heart failure and cardiac troponins in the diagnosis of acute myocardial infarction. Numerous other biomarkers pertaining to diagnosis, prognosis, and risk prediction have been identified, but few have made their way to clinical practice. In this review, we will initially describe the fundamental approach to evaluate a novel biomarker. Before implementation of a biomarker into clinical practice, several stringent criteria related to its clinical utility are required. Essential statistical metrics such as discrimination, calibration, and reclassification are required to properly evaluate prediction models. We will then discuss the biomarkers according to main groups of cardiovascular pathology:1. myocardial injury (cardiac troponins, heart-type fatty acid-binding protein, cardiac myosin binding protein-C);2. myocardial stress (A-type and B-type natriuretic peptides, mid-regional pro-adrenomedullin, copeptin); 3. inflammation (C-reactive protein, interleukin 6, growth differentiation factor 15, soluble suppressor of tumorigenicity 2, galectin-3);4. platelet activation (soluble CD40 ligand, P-selectin);5. plaque instability (lipoprotein-associated phospholipase A2, matrix metalloproteinase-9);6. systemic stress (catecholamines, granin proteins);7. calcium homeostasis (secretoneurin). Finally, we will discuss novel applications of cardiovascular biomarkers, more specifically prediction of ventricular arrhythmias, and the use of biomarkers in composite risk prediction models.

Association of Natriuretic Peptides With Cardiovascular Prognosis in Heart Failure With Preserved Ejection Fraction: Secondary Analysis of the TOPCAT Randomized Clinical Trial.

Importance: Contemporary clinical trials of heart failure with preserved ejection fraction (HFpEF) apply natriuretic peptide (NP) thresholds to identify patients who are more likely to have the disease of interest and to enrich the baseline risk of the enrolled cohort. Objective: To determine whether age, race/ethnicity, obesity, renal function, and atrial fibrillation (AF) affect the levels of NPs in HFpEF and whether the prognostic significance of NPs varies in these clinically important subgroups. Design, Setting, and Participants: This secondary analysis of the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT) evaluated the distribution and prognostic significance of NPs across 6 subgroups comprising 1057 adult patients (60%) in the Americas region of TOPCAT with symptomatic heart failure (HF) and a left ventricular ejection fraction of 45% or more with available NPs at baseline. Exposures: Natriuretic peptides were log-transformed and standardized (expressed per 1 SD, z score) and assessed in 6 subgroups: age (cutoff, 70 years), black race, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared; cutoff, 30 kg/m2), waist circumference (cutoff, 102 cm for men, 88 cm for women), estimated glomerular filtration rate (cutoff, 60 mL/min/1.73 m2), and a history of AF. Main Outcomes and Measures: Time to composite cardiovascular death, hospitalization for HF, or aborted cardiac arrest at mean (SD) 2.4-year (1.5) follow-up. Results: Of 1057 participants, the mean (SD) age was 72 (10) years, 183 (17.3%) were black, the mean (SD) BMI was 33.4 (8.6) kg/m2, the mean (SD) estimated glomerular filtration rate was 64.6 (21.8) mL/min/1.73 m2, and 472 (45%) had a history of AF. Median B-type NP (n = 698) and N-terminal pro-B-type NP concentrations (n = 359) were 257 (interquartile range, 149-443) ng/L and 959 (interquartile range, 554-2015) ng/L, respectively. Natriuretic peptide concentrations varied by up to 0.5 SD within the 6 subgroups, being higher in older patients with nonblack race, a lower BMI, a lower waist circumference, a lower estimated glomerular filtration rate, and a history of AF. Elevated NP levels (per 1-SD increase) were independently associated with an increased risk of the primary outcome (adjusted hazard ratio, 1.36; 95% CI, 1.22-1.54; P < .001) consistently across all investigated subgroups (interaction P > .05). In TOPCAT Americas (n = 1767), 791 (45%) were enrolled based on elevated NP levels as the qualifying criterion (as opposed to a history of HF hospitalization). This proportion was 31% (93 of 302), 34% (258 of 760), and 39% (443 of 1144) for black race, younger than 70 years, and a BMI of 30 kg/m2 or greater, respectively. Conclusions and Relevance: Natriuretic peptides remain important biomarkers of prognosis in HFpEF, even in subgroups who tend to have lower NP levels. A single, absolute NP threshold for inclusion in contemporary HFpEF trials may lead to an underrepresentation of certain demographic and clinical subgroups. Trial Registration: ClinicalTrials.gov Identifier: NCT00094302.

Mid-regional pro-adrenomedullin in patients with acute dyspnea: Data from the Akershus Cardiac Examination (ACE) 2 Study.

BACKGROUND: Mid-regional pro-adrenomedullin (MR-proADM) is a surrogate marker for adrenomedullin; a hormone that attenuates myocardial remodeling. Accordingly, we hypothesized that MR-proADM could provide diagnostic and prognostic information in patients with acute dyspnea. METHODS AND RESULTS: We measured MR-proADM by a commercial ELISA on hospital admission in 311 patients with acute dyspnea and compared the utility of MR-proADM with N-terminal pro-B-type natriuretic peptide (NT-proBNP). Blood samples were also available after 24h (n=232) and before discharge (n=94). The principal diagnosis of the index hospitalization was determined by an adjudication committee. MR-proADM concentrations on hospital admission were higher in patients with acute heart failure (HF; n=143) vs. patients hospitalized with non-HF-related dyspnea (n=168): 1.31 (Q1-3 0.97-1.89) vs. 0.85 (0.59-1.15) nmol/L; p<0.001. The receiver-operating characteristics area under the curve (ROC-AUC) for MR-proADM to diagnose HF was 0.77 (95% CI 0.72-0.82) and 0.86 (0.82-0.90) for NT-proBNP. During a median follow-up of 816days, 66/143 patients (46%) with acute HF and 35/84 patients (42%) with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) died; p=0.58 between groups. In multivariate Cox regression analyses, admission MR-proADM concentrations were associated with mortality in patients with acute HF (HR 5.90 [3.43-10.13], p<0.001), but not in patients with AECOPD. Admission MR-proADM concentrations also improved risk stratification in acute HF as assessed by the net reclassification index. MR-proADM concentrations decreased from admission to later time points. CONCLUSION: Admission MR-proADM concentrations provide strong prognostic information in patients with acute HF, but modest diagnostic information in patients with acute dyspnea.

Circulating chromogranin B levels in patients with acute respiratory failure: data from the FINNALI Study.

PURPOSE: Circulating chromogranin B (CgB) levels are increased in situations characterized by systemic and myocardial stress, but whether CgB provides prognostic information in patients with acute respiratory failure (ARF) is unknown. METHODS: We included 584 patients with ARF, defined as ventilatory support >6 h, and with blood samples available on Intensive Care Unit (ICU) admission and day 3 (n = 479). CgB levels were measured by radioimmunoassay and follow-up was 90 days. RESULTS: One-hundred-sixty-nine patients (29%) died during follow-up. Admission CgB levels separated non-survivors from survivors: median 1234 (Q1-3 989-1742) vs. 917 (753-1224) pmol/L, respectively, p < 0.001. CgB levels on ICU admission (logarithmically transformed) were associated with time to death after adjustment for established risk indices available on ICU admission, including N-terminal pro-B-type natriuretic levels: HR 2.62 (95%C.I. 1.82-3.77), p < 0.001. Admission CgB levels also improved prognostication on top of SOFA and SAPS II scores as assessed by Cox regression analyses and the category-free net reclassification index. The area under the curve (AUC) for admission CgB levels to separate survivors and non-survivors was 0.72 (95%CI 0.67-0.76), while the AUC on day 3 was 0.60 (0.54-0.66). CONCLUSIONS: CgB levels measured on ICU admission provided additional prognostic information to established risk indices in ARF patients.