Risk stratification in emergency patients by copeptin.

BACKGROUND: Rapid risk stratification is a core task in emergency medicine. Identifying patients at high and low risk shortly after admission could help clinical decision-making regarding treatment, level of observation, allocation of resources and post discharge follow-up. The purpose of the present study was to determine short-, mid- and long-term mortality by plasma measurement of copeptin in unselected admitted patients. METHOD: Consecutive patients >40-years-old admitted to an inner-city hospital were included. Within the first 24 hours after admission, a structured medical interview was conducted and self-reported medical history was recorded. All patients underwent a clinical examination, an echocardiographic evaluation and collection of blood for later measurement of risk markers. RESULTS: Plasma for copeptin measurement was available from 1,320 patients (average age 70.5 years, 59.4% women). Median follow-up time was 11.5 years (range 11.0 to 12.0 years). Copeptin was elevated (that is, above the 97.5 percentile in healthy individuals).Mortality within the first week was 2.7% (17/627) for patients with elevated copeptin (above the 97.5 percentile, that is, >11.3 pmol/L) compared to 0.1% (1/693) for patients with normal copeptin concentrations (that is, ≤11.3 pmol/L) (P <0.01). Three-month mortality was 14.5% (91/627) for patients with elevated copeptin compared to 3.2% (22/693) for patients with normal copeptin. Similar figures for one-year mortality and for the entire observation period were 27.6% (173/627) versus 8.7% (60/693) and 82.9% (520/527) versus 57.5% (398/693) (P <0.01 for both), respectively.Using multivariable Cox regression analyses shows that elevated copeptin was significantly and independently related to short-, mid- and long-term mortality. Adjusted hazard ratios were 2.4 for three-month mortality, 1.9 for one-year mortality and 1.4 for mortality in the entire observation period. CONCLUSIONS: In patients admitted to an inner-city hospital, copeptin was strongly associated with short-, mid- and long-term mortality. The results suggest that rapid copeptin measurement could be a useful tool for both disposition in an emergency department and for mid- and long-term risk assessment.

Accuracy of a heart failure diagnosis in administrative registers.

BACKGROUND: The incidence of heart failure is frequently reported using hospital discharge diagnoses. The specificity of a diagnosis has been shown to be high but the sensitivity of a reported diagnosis is unknown. PURPOSE: To study the accuracy of a heart failure diagnosis reported to the Danish National Patient Registers during routine clinical work. METHODS: The patient population consisted of 3644 consecutive patients admitted to all departments in one hospital. Diagnoses reported to the National Patient Register were recorded. A study team evaluated each patient independently of routine care, performed an echocardiogram and evaluated whether clinical symptoms of heart failure were present. Heart failure was defined in accordance with current ESC guidelines as symptoms of heart failure and evidence of cardiac dysfunction. RESULTS: A registered diagnosis of heart failure (n=126) carried a specificity of 99% and a sensitivity of 29% for all patients. The positive predictive value was 81%, the negative predictive value 90%. CONCLUSION: The diagnosis of Heart Failure in the Danish National Registers is underreported, but very specific.

Heart murmur and N-terminal pro-brain natriuretic peptide as predictors of death in 2977 consecutive hospitalized patients.

BACKGROUND: Little is known about the prognostic importance of murmur in unselected patients. It is difficult to distinguish between innocent and significant murmurs. N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and BNP have recently been shown to be useful in small series of patients with valvular heart disease. We wanted to test whether murmur predicts mortality in unselected patients admitted to the hospital and whether NT-pro-BNP is capable of distinguishing between innocent and significant murmurs. METHODS: Consecutive patients (n = 2977) older than 40 years admitted to a local hospital were studied. Auscultation, echocardiography were performed and levels of natriuretic peptides were measured. RESULTS: A total of 21.8% of the 2977 patients had a murmur. After adjusting for sex and age there was a significant difference in the one-year mortality of patients with and without murmur (OR = 1.57, 95% CI = 1.27-1.94). NT-pro-BNP gave additional prognostic information for both patients with and without murmurs. Presence of a murmur was an independent predictor of 1-year mortality (OR = 1.36, 95% CI = 1.03-1.80) in a multivariate analysis. In patients with a murmur but normal NT-pro-BNP, discovery of valvular heart disease by echocardiography yielded no additional prognostic information. CONCLUSIONS: Detection of a cardiac murmur during routine medical examination of hospitalized patients is associated with increased risk of death within a year. A blood test for NT-pro-BNP gives significant additional prognostic information of a murmur and could obviate the need for echocardiography in selected patients with a murmur and normal NT-pro-BNP for whom surgery is not feasible.

Value of N-terminal pro brain natriuretic peptide in the elderly: data from the prospective Copenhagen Hospital Heart Failure study (CHHF).

UNLABELLED: We describe the value of Nt-proBNP in relation to cardiac normality and risk of major adverse cardiac events (MACE) in consecutive hospitalised patients below and above 75 years of age. METHOD: During a 10 month period 2224 consecutive patients, admitted to all departments in a general city hospital, had a full cardiac examination and were prospectively followed for 1 year. We identified a normal group (without obvious heart disease) and a group with MACE (significant heart disease at admission or a cardiac event within the following 90 days). NT-proBNP measurements were done using an ELISA-a two-step sandwich assay with streptavidin coated microtitre plates. RESULTS: The age dependent 90th percentiles of Nt-proBNP in the normal group were approximately 3 times higher than values reported in previous community studies. Elderly patients had 3-fold higher absolute cut off values than did patients under the age of 75 years. One-hundred-and-sixteen patients had a MACE, and areas under the receiver operating curve (ROC) to predict a MACE were 0.83 (from 40 to 59 years), 0.82 (60 to 74) and 0.79 (from 75 years). In younger patients, the upper limit of Nt-proBNP in normal patients was similar to the value, which defined the top quintile of risk. In patients aged greater than 75 years the predictive cut point included more than 40% of the population. CONCLUSION: Nt-proBNP was useful at all ages but specificity was slightly lower in the elderly. Cut off values in hospitalised cardiac normal patients are approximately three times higher than community derived values.

Troponin T is a strong marker of mortality in hospitalized patients.

BACKGROUND: Cardiac troponins are diagnostic markers in acute coronary syndrome and prognostic markers in stable coronary disease. Small increases are occasionally observed in patients with non-cardiac disease, but the prevalence and prognostic value of increased troponin in the general hospitalized population are unknown. METHODS: Consecutive patients aged >40 years admitted to a district hospital between 1 April 1998 and 31 March 1999 were included. A comprehensive medical interview and clinical examination were performed including echocardiography and measurement of natriuretic peptides and troponin T with a high-sensitivity assay (hs-TnT). RESULTS: Serum for analyses of hs-TnT was available from 1176 patients. Patients were 73.7 years old on average (interquartile range, 64.5-80.0 years), 59.2% were women and median follow-up was 11.4 years. The prevalence of elevated hs-TnT (> 99(th) percentile) was 57.1% of the entire cohort and 52.3% of patients with non-cardiac diagnoses. hs-TnT above the median (17 ng/L) was associated in univariate analysis with a 3-fold higher mortality in the entire population (multivariate hazard rate (HR) from 1.3 to 1.8 for 1 and 11 year mortality, respectively). In patients without past or present ischemic heart disease hs-TnT in the upper quartile (above 34.8 ng/L) was associated in univariate analysis with a 5-fold higher mortality risk (multivariable HR 1.8 to 2.2 for 1 and 11 year mortality, respectively). CONCLUSION: More than half of the hospitalized patients had hs-TnT levels above the 99(th) percentile. Elevated hs-TnT is a strong mortality risk marker in general hospitalized older patients.

ProANP plasma measurement predicts all-cause mortality in acutely hospitalised patients: a cohort study.

IMPORTANCE: The association of natriuretic peptide measurement with all-cause mortality in a broad selection of acutely admitted patients has not yet been examined. OBJECTIVE: To test the risk association between pro-atrial natriuretic peptide (ANP) and short-term and long-term mortality and its predictive value in acutely hospitalised patients and compare this to N-terminal B-type natriuretic peptide (NT-proBNP). DESIGN, SETTING AND PATIENTS: Participants were selected from the Copenhagen Hospital Heart Failure Study (n=3644). Medical history, satisfactory echocardiography and blood samples were available on 2193 participants in 1998-1999 where NT-proBNP was measured. Vital status after discharge was obtained from national central data registers. A total of 1337 participants with eligible blood samples were selected in 2010-2011 for proANP measurement. Among these, 1255 (94%) were acutely hospitalised in 1998-1999. MAIN OUTCOME MEASURE(S): 1-year and long-term mortality. RESULTS: Median follow-up period was 11.5 years. At the end of follow-up, 926 patients had died, 239 during the first year. ProANP quartiles to 2-4 (median proANP levels 594 pmol/L, 990 pmol/L and 2052 pmol/L, respectively) associated with a stepwise increase in risk of 1-year and long-term mortality compared to the first quartile (336 pmol/L) in multivariable adjusted Cox proportional regression models (HR 1.53 95% CI 1.30 to 1.81 and HR 1.26 95% CI 1.17 to 1.36, respectively). An addition of NT-proBNP attenuated proANP's association with mortality in the models (HR 1.24 95% CI 1.01 to 1.53 and 1.14 95% CI 1.03 to 1.26, respectively). The increased risk was observed in participants with the highest proANP levels (fourth quartile). Similar results were observed in subgroups of participants with no evidence of cardiovascular disease (CVD). ProANP in quartiles improved discrimination when added to traditional risk factors in prediction models for 1-year (integrated discrimination improvement (IDI) 0.141 95% CI 0.085 to 0.197; C-index 0.753 95% CI 0.724 to 0.783, P for improvement 0.003) and long-term mortality (IDI 0.053 95% CI 0.032 to 0.074; C-index 0.736 95% CI 0.720 to 0.752, P for improvement <0.001) with similar results in subgroups. Discrimination was best in a combined model with proANP as well as NT-proBNP included. CONCLUSIONS AND RELEVANCE: High plasma proANP concentrations are associated with and predict short-term and long-term all-cause mortality in acutely hospitalised patients irrespective of CVD status at admission.

Prevalence and prognosis of heart failure with preserved ejection fraction and elevated N-terminal pro brain natriuretic peptide: a 10-year analysis from the Copenhagen Hospital Heart Failure Study.

AIMS: The aim of this study was to assess the epidemiological features and prognosis of heart failure with preserved ejection fraction (HFPEF) and to compare these findings with those from patients with reduced ejection fraction. Furthermore the effects of N-terminal pro brain natriuretic peptide (NT-proBNP) requirement in the heart failure diagnosis were assessed by repeating the analyses in the subgroup of patients with elevated NT-proBNP. METHODS AND RESULTS: In 1844 patients admitted, a clinical diagnosis of heart failure was made in 433; amongst these 61% had HFPEF. An elevated NT-proBNP applied to the heart failure diagnosis reduced the number of heart failure patients to 191, and amongst these 29% had preserved ejection fraction. Use of NT-proBNP reduced clinical differences between heart failure patients with preserved and reduced ejection fraction. When not using NT-proBNP, patients with reduced ejection fraction had higher mortality [hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.01-1.52; P = 0.04], even after adjustment for other significant predictors of mortality, except NT-proBNP (HR 1.29, 95% CI 1.04-1.59; P = 0.02). However, no difference in mortality was observed when NT-proBNP was adjusted for (HR 0.90, 95% CI 0.71-1.15; P = 0.4), or used for the heart failure diagnosis (HR 0.96; 95% CI 0.71-1.29; P = 0.8). CONCLUSION: Using a heart failure diagnosis requiring elevated NT-proBNP reduces the prevalence of HFPEF and results in a survival similar to that of heart failure with reduced ejection fraction. In contrast, when NT-proBNP is not used for the heart failure diagnosis or adjusted for, HFPEF is associated with a lower mortality in both univariate and multivariate analysis.

[Choriocarcinoma causing a pulmonary embolus]. / Pulmonal saddelembolus forårsaget af gestationelt koriokarcinom.

A 32 year-old women experienced dyspnea and thoracic pain that persisted with variable intensity over a course of eight months until acute worsening necessitated admission. A CT scan demonstrated a central pulmonary embolus. Subsequent surgical embolectomy produced a grained substance that was histologically compatible with a choriocarcinoma. Trophoblast tumors are rare, but unspecific symptoms from lungs, liver, kidney or brain warrant control of S-hCG in women, even when pregnancy has not been recognized or menopause has been reached.

Pregnancy-associated plasma protein A in non-cardiac conditions.

OBJECTIVE: PAPP-A is a promising new marker in coronary heart disease. It is important to investigate its specificity in order to establish its clinical utility as a marker of coronary heart disease. DESIGN AND METHODS: PAPP-A was measured within 24 h following hospital admission in 1448 consecutive patients admitted with diagnoses other than acute coronary syndromes. RESULTS: PAPP-A was detectable (> or = 4.0 mIU/L) in 278 (19.2%) patients, among whom the mean level was 6.3 mIU/L (95% C.I., 6.1-6.5 mIU/L). The 95 and 99 percentiles for PAPP-A were 7.3 and 9.4 mIU/L, respectively. There was no difference in the mean PAPP-A of different diagnoses (p=0.33). None of the specific diagnoses known to influence established coronary markers appeared to influence the level of circulating PAPP-A. CONCLUSION: PAPP-A is low in patients without known coronary heart disease. PAPP-A levels seem to be a potentially highly specific marker for heart disease.

[Heart murmur and echocardiographic findings in 2,907 non-selected patients admitted to hospital]. / Mislyde og ekkokardiografiske fund hos 2.907 uselekterede, indlagte patienter.

INTRODUCTION: Since the introduction and increased availability of echocardiography, the importance of heart auscultation in diagnosing valvular heart disease has been reduced. Nevertheless, auscultation is still important when deciding whether to refer a patient for further examination. MATERIALS AND METHODS: A retrospective analysis was done of 2,907 consecutive patients admitted to a hospital in Copenhagen from 1 April 1998 to 31 March 1999. Auscultation, clinical history and echocardiography were performed within 24 hours of admittance. RESULTS: The prevalence of heart murmurs was 20.5%. The sensitivity and specificity of murmur found by auscultation and echocardiographic findings were 0.52 and 0.93, respectively. We found a positive predictive value of auscultation of 0.76 and a negative predictive value of 0.82. CONCLUSION: The relationship between auscultation and echocardiography in diagnosing heart murmurs in non-selected patients admitted to hospital has not previously been described. Auscultation has a high specificity, indicating that such patients should be referred for echocardiography. Its sensitivity, however, is low, indicating that it is insufficient as a means of screening for valvular heart disease.