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.

Rosuvastatin treatment in stable chronic obstructive pulmonary disease (RODEO): a randomized controlled trial.

OBJECTIVES: The objective of this study was to examine whether statin therapy is associated with enhanced endothelium-dependent vascular function, improved pulmonary function and reduced systemic inflammation in patients with chronic obstructive pulmonary disease (COPD). DESIGN AND SETTING: This randomized, placebo-controlled, double-blind, parallel trial including patients with COPD was performed at two University hospitals in Norway. SUBJECTS, INTERVENTION AND MEASUREMENTS: Patients with stable COPD (n = 99) were assigned randomly to receive rosuvastatin 10 mg (n = 49) or matching placebo (n = 50) once daily for 12 weeks. The primary outcome measure was change in endothelium-dependent vascular function measured using peripheral arterial tonometry and expressed as the reactive hyperaemia index. Secondary end-points were change in pulmonary function, as assessed by forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC), and change in the circulating levels of the inflammatory markers interleukin-6 (IL6) and high-sensitivity C-reactive protein (hsCRP). RESULTS: In the overall study population, no significant between-group difference in change in endothelium-dependent vascular or pulmonary function was observed. Rosuvastatin therapy was associated with a reduction in hsCRP (-20% vs. 11%, P = 0.017) and an attenuation of the rise in IL6 concentration (8% vs. 30%, P = 0.028) compared with placebo. In a prespecified subgroup analysis of patients with a supra-median circulating hsCRP concentration (>1.7 mg L(-1) ), rosuvastatin was associated with improved endothelium-dependent vascular function (13% vs. 2%, P = 0.026). CONCLUSIONS: In stable COPD patients without the standard indications for statin therapy, rosuvastatin treatment is associated with a significant attenuation of systemic inflammation and improvement in endothelial-dependent vascular function in patients with evidence of systemic inflammation.

The liver-heart axis in patients with severe obesity: The association between liver fibrosis and chronic myocardial injury may be explained by shared risk factors of cardiovascular disease.

BACKGROUND: Severe obesity is associated with increased risk of non-alcoholic fatty liver disease and cardiovascular disease. We hypothesized that liver fibrosis as quantified by the Enhanced Liver Fibrosis (ELF) test would be predictive of myocardial injury and fibrosis, expressed by higher concentrations of cardiac troponin T and I measured by high-sensitivity assays (hs-cTnT and hs-cTnI, respectively). MATERIAL AND METHODS: We performed cross-sectional analyses of baseline data from 136 patients (mean age 45 years, 38 % male) with severe obesity participating in the non-randomized clinical trial Prevention of Coronary Heart Disease in Morbidly Obese Patients (ClinicalTrials.gov NCT00626964). Associations between ELF scores, hs-cTnT, and hs-cTnI concentrations were assessed using linear regression analysis. RESULTS: ELF scores were associated with hs-cTnT in the unadjusted model (B 0.381, 95 % Confidence Interval [CI] 0.247, 0.514), but the association was attenuated upon adjustment for potential confounders (B -0.031, 95 % CI -0.155, 0.093). Similarly, for hs-cTnI, an observed association with ELF scores in the unadjusted model was attenuated upon adjustment for potential confounders ((B 0.432, 95 % CI 0.179, 0.685) and (B 0.069, 95 % CI -0.230, 0.367), respectively). Age, sex, hypertension, and estimated glomerular filtration rate were amongst the shared predictors of ELF score, hs-cTnT, and hs-cTnI that provided the univariable models with the highest R-squared and lowest Akaike Information Criterion values. CONCLUSIONS: Contrary to our hypothesis, ELF score did not predict myocardial injury and fibrosis, but we rather demonstrated an association between liver fibrosis and myocardial injury and fibrosis may be explained by shared risk factors of cardiovascular disease.

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.

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.

Elevated high-sensitivity cardiac troponin T is associated with increased mortality after acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Cardiovascular co-morbidities are common in chronic obstructive pulmonary disease (COPD). Retrospective studies on selected patients have indicated that cardiac troponin elevation is frequent during acute exacerbations of COPD (AECOPD), and that this is associated with poor survival. In the present prospective study the prevalence and prognostic value of elevated cardiac troponin T (cTnT) in unselected patients with AECOPD have been investigated, using a novel high-sensitivity assay (hs-cTnT assay). METHODS AND RESULTS: 99 patients hospitalised for AECOPD were included. They were followed until death or study termination. During a median follow-up time of 1.9 years, 57 patients (58%) died. 97 patients (98%) had measurable levels of hs-cTnT and 73 (74%) had hs-cTnT above the normal range (≥14.0 ng/l). The crude mortality rates in patients having hs-cTnT <14.0, 14.0-39.9 and ≥40 ng/l were 4.6, 30.2 and 58.3 per 100 patient-years, respectively. Adjusting for relevant covariables using an extended Cox regression analysis, the HRs (95% CI) for death were 4.5 (1.2 to 16) and 8.9 (2.4 to 32) among patients having hs-cTnT 14.0-39.9 and ≥40 ng/l, respectively, compared with patients with hs-cTnT <14.0 ng/l. The association between mortality and hs-cTnT was strongly modified by heart rate at admission (p<0.001)-that is, the association between mortality and hs-cTnT was stronger among patients with tachycardia. CONCLUSION: Elevated hs-cTnT during AECOPD is frequent, and it is associated with increased mortality. The effect is stronger among patients having tachycardia than among patients with normal heart rate.

Rationale and design of the PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA II) trial: a randomized, placebo-controlled, multicenter trial.

BACKGROUND: Recent advances in the treatment algorithms of early breast cancer have markedly improved overall survival. However, anthracycline- and trastuzumab-associated cardiotoxicity may lead to dose-reduction or halt in potentially life-saving adjuvant cancer therapy. Early initiated neurohormonal blockade may prevent or attenuate the cardiotoxicity-induced reduction in cardiac function, but prior studies have been inconclusive. The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan has been shown to be superior to traditional treatment in heart failure with reduced ejection fraction, but its cardioprotective effects in the cardio-oncology setting remains to be tested. OBJECTIVE: To assess if sacubitril/valsartan given concomitantly with early breast cancer treatment regimens including anthracyclines, with or without trastuzumab, may prevent cardiac dysfunction. METHODS: PRADA II is a randomized, placebo-controlled, double blind, multi-center, investigator-initiated clinical trial. Breast cancer patients from four university hospitals in Norway, scheduled to receive (neo-)adjuvant chemotherapy with epirubicin independently of additional trastuzumab/pertuzumab treatment, will be randomized 1:1 to sacubitril/valsartan or placebo. The target dose is 97/103 mg b.i.d. The patients will be examined with cardiovascular magnetic resonance (CMR), echocardiography, circulating cardiovascular biomarkers and functional testing at baseline, at end of anthracycline treatment and following 18 months after enrolment. The primary outcome measure of the PRADA II trial is the change in left ventricular ejection fraction (LVEF) by CMR from baseline to 18 months. Secondary outcomes include change in LV function by global longitudinal strain by CMR and echocardiography and change in circulating cardiac troponin concentrations. RESULTS: The study is ongoing. Results will be published when the study is completed. CONCLUSION: PRADA II is the first randomized, placebo-controlled study of sacubitril/valsartan in a cardioprotective setting during (neo-)adjuvant breast cancer therapy. It may provide new insight in prevention of cardiotoxicity in patients receiving adjuvant or neo-adjuvant therapy containing anthracyclines. Furthermore, it may enable identification of patients at higher risk of developing cardiotoxicity and identification of those most likely to respond to cardioprotective therapy. TRIAL REGISTRATION: The trial is registered in the ClinicalTrials.gov registry (identifier NCT03760588 ). Registered 30 November 2018.

New features of troponin testing in different clinical settings.

Cardiac troponin levels are routinely measured for diagnosing acute myocardial infarction. Cardiac troponin measurements also provide information concerning prognosis and the effect of early intervention in patients with acute coronary syndromes. The recent development of highly sensitive cardiac troponin assays permits detection of very low circulating levels. Use of sensitive troponin assays improves overall diagnostic accuracy in patients with suspected acute coronary syndromes, and these assays provide strong prognostic information in stable coronary artery disease and chronic heart failure. However, increased sensitivity comes with a cost of decreased specificity, and serial testing, as well as clinical context and judgment, is likely to become increasingly important in the interpretation of troponin assay results.

Non-traditional risk factors predict coronary calcification in chronic kidney disease in a population-based cohort.

The increased burden of cardiovascular disease in chronic kidney disease cannot be explained by traditional risk factors alone. Here, we evaluated the impact of non-traditional factors on the association of chronic kidney disease with coronary artery calcification using logistic regression among 2672 Dallas Heart Study patients of whom 220 had chronic kidney disease. The prevalence of coronary calcification significantly increased across all chronic kidney disease stages and this remained independently associated with coronary calcification after adjusting for traditional factors. The calcium x phosphorus product, homocysteine, and osteoprotegerin each diminished the magnitude of association between kidney disease and coronary calcification. After adjustment for these, the association between kidney disease and coronary calcification was no longer significant with the effects most prominent in the stages 3-5 subgroup. Our study has identified three non-traditional independent predictors of coronary calcification that diminished the association between chronic kidney disease and coronary calcification. These factors may represent novel mechanistic links warranting further investigation.

Troponin T elevation and long-term mortality after chronic obstructive pulmonary disease exacerbation.

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease, exacerbations of which increase strain on the heart. The prognostic value of elevated circulating levels of cardiac Troponins seen during COPD exacerbations has been investigated. From the Akershus hospital database, 897 patients discharged after treatment for COPD exacerbation in the period 2000-2003 were identified and followed-up until June 30, 2005. Median observation time was 1.9 yrs. In 396 patients, measurements of cardiac-specific troponin T (cTnT) were available. Levels of cTnT >/=0.04 mug.L(-1) were considered elevated. Clinical data were retrieved from patient records and date of death was obtained from the Norwegian National Registry. In order to balance the nonrandomised nature of available cTnT measurements, an exposure propensity score (EPS) for cTnT sampling was calculated and used in regression analyses. After adjusting for EPS in Cox regression analyses, elevated cTnT was significantly associated with increased all-cause mortality in the observation period, with a hazard ratio of 1.64 (95% confidence interval 1.15-2.34). In conclusion, chronic obstructive pulmonary disease patients with elevated cardiac-specific Troponin T during exacerbation are at increased risk of death after discharge.

Prognostic merit of N-terminal-proBNP and N-terminal-proANP in mechanically ventilated critically ill patients.

BACKGROUND: Amino-terminal fragments of type-A and type-B natriuretic peptide prohormones (NT-proBNP, NT-proANP) are powerful prognostic markers in patients with cardiac disease, and NT-proBNP has been demonstrated to predict outcome in severe sepsis and septic shock. We assessed the prognostic value of NT-proBNP and NT-proANP in a consecutive series of mechanically ventilated intensive care patients and compared their prognostic merit. METHODS: Seventy unselected patients admitted to the intensive care unit (ICU) were included in the study 48 h after start of controlled mechanical ventilation. Venous blood was obtained on inclusion and assayed for NT-proBNP and NT-pro ANP. Univariate and multivariate logistic regression analysis was used to assess the association of NT-proBNP and NT-proANP levels with 30-day mortality. Established risk factors and possible confounders were used as covariates. Discrimination of different prognostic models was assessed calculating the area under the receiver-operating characteristics curve (ROC-AUC). RESULTS: NT-proBNP and NT-proANP levels were higher in non-survivors (n=25) than in 30-day survivors (n=45). Log NT-proBNP [odds ratio (OR) 2.34, 95% CI 1.17-4.66], and log NT-proANP (OR 2.44, 95% CI 1.12-5.30) were independently predictive of increased mortality. A prior diagnosis of chronic obstructive lung disease was predictive of decreased mortality (OR 0.29, 95% CI 0.08-1.00). The relative prognostic values, evaluated by the ROC-AUCs of NT-proBNP (AUC 0.74, 95% CI 0.61-0.86) and NT-proANP (AUC 0.73, 95% CI 0.61-0.86), were nearly identical. CONCLUSIONS: High NT-proANP and NT-proBNP levels associated with decreased short-term survival in unselected, mechanically ventilated ICU patients. NT-proANP performed equally well as a prognostic indicator as NT-proBNP, and may represent a clinically useful alternative to NT-proBNP.

Selection of medical treatment in stable angina pectoris: results of the International Multicenter Angina Exercise (IMAGE) Study.

OBJECTIVES: The present study was designed to investigate which characteristics of anginal symptoms or exercise test results could predict the favorable anti-ischemic effect of the beta-adrenergic blocking agent metoprolol and the calcium antagonist nifedipine in patients with stable angina pectoris. BACKGROUND: The characteristics of anginal symptoms and the results of exercise testing are considered of great importance for selecting medical treatment in patients with chronic stable angina pectoris. However, little information is available on how this first evaluation may be used to select the best pharmacologic approach in individual patients. METHODS: In this prospective multicenter study, 280 patients with stable angina pectoris were enrolled in 25 European centers. After baseline evaluation, consisting of an exercise test and a questionnaire investigating patients' anginal symptoms, the patients were randomly allocated to double-blind treatment for 6 weeks with either metoprolol (Controlled Release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) according to a parallel group design. At the end of this period, exercise tests were repeated 1 to 4 h after drug intake. RESULTS: Both metoprolol and nifedipine prolonged exercise tolerance over baseline levels; the improvement was greater in the patients receiving metoprolol (p < 0.05). Multivariate analysis revealed that low exercise tolerance was the only variable associated with a more favorable effect within each treatment group. Metoprolol was more effective than nifedipine in patients with a lower exercise tolerance or with a higher rate-pressure product at rest and at ischemic threshold. None of the characteristics of anginal symptoms or exercise test results predicted a greater efficacy of nifedipine over metoprolol. CONCLUSIONS: The results of a baseline exercise test, but not the characteristics of anginal symptoms, may offer useful information for selecting medical treatment in stable angina pectoris.

Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris. Results of the International Multicenter Angina Exercise (IMAGE) Study.

OBJECTIVES: This study was designed to investigate whether combination therapy with metoprolol and nifedipine provides a greater anti-ischemic effect than does monotherapy in individual patients with stable angina pectoris. BACKGROUND: Combination therapy with a beta-adrenergic blocking agent (which reduces myocardial oxygen consumption) and a dihydropyridine calcium antagonist (which increases coronary blood flow) is a logical approach to the treatment of stable angina pectoris. However, it is not clear whether, in individual patients, this combined therapy is more effective than monotherapy. METHODS: Two hundred eighty patients with stable angina pectoris were enrolled in a double-blind trial in 25 European centers. Patients were randomized (week 0) to metoprolol (controlled release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) for 6 weeks; placebo or the alternative drug was then added for a further 4 weeks. Exercise tests were performed at weeks 0, 6 and 10. RESULTS: At week 6, both metoprolol and nifedipine increased the mean exercise time to 1-mm ST segment depression in comparison with week 0 (both p < 0.01); metoprolol was more effective than nifedipine (p < 0.05). At week 10, the groups randomized to combination therapy had a further increase in time to 1-mm ST segment depression (p < 0.05 vs. placebo). Analysis of the results in individual patients revealed that 7 (11%) of 63 patients adding nifedipine to metoprolol and 17 (29%) of 59 patients (p < 0.0001) adding metoprolol to nifedipine showed an increase in exercise tolerance that was greater than the 90th percentile of the distribution of the changes observed in the corresponding monotherapy + placebo groups. However, among these patients, an additive effect was observed only in 1 (14%) of the 7 patients treated with metoprolol + nifedipine and in 4 (24%) of the 17 treated with nifedipine + metoprolol. CONCLUSIONS: The mean additive anti-ischemic effect shown by combination therapy with metoprolol and nifedipine in patients with stable angina pectoris is not the result of an additive effect in individual patients. Rather, it may be attributed to the recruitment by the second drug of patients not responding to monotherapy.

Serum homocysteine concentration as an indicator of survival in patients with acute coronary syndromes.

BACKGROUND: Circulating homocysteine levels are predictive of survival in patients with stable coronary artery disease. The prognostic value of serum homocysteine levels, obtained in the acute phase in patients with myocardial infarction or unstable angina, is unknown. OBJECTIVES: To test the hypothesis that circulating homocysteine levels, obtained during the first 24 hours following hospital admission in patients with acute coronary syndromes, are predictive of long-term mortality. METHODS: To test this hypothesis we performed a prospective inception cohort study at a teaching hospital in Gothenburg, Sweden. A total of 579 patients (179 women and 400 men; median age, 67 years) were included (Q-wave myocardial infarction in 163 patients, non-Q-wave myocardial infarction in 210 patients, unstable angina pectoris in 206 patients). MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: During a median follow-up of 628 days, 65 patients died. The serum homocysteine level (mean [SD]) was significantly lower in long-term survivors (n = 514) than in nonsurvivors (n=65) (12.3 [7.0] vs 14.3 [5.9] pmol/L; P=.003). The relative risk (all-cause mortality) for patients with homocysteine levels in the upper quartile was 2.4 (95% confidence interval, 1.5-4.0) compared with that of patients in the 3 lower quartiles. After adjustment for relevant confounders, the relative risk estimate remained significant (relative risk= 1.69; 95% confidence interval, 1.02-2.80). In a stepwise model the homocysteine level provided prognostic information additional to that of patient age, diabetes mellitus, and diuretic usage prior to hospital admission (P=.03). CONCLUSION: The serum homocysteine level on hospital admission is an independent predictor of long-term survival in patients with acute coronary syndromes.

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.

Neurohumoral measurements as indicators of long-term prognosis after acute myocardial infarction.

The objective of this study was to evaluate the prognostic accuracy and usefulness of neurohumoral determination as a risk stratification tool after acute myocardial infarction (AMI) by comparing the long-term prognostic value of subacute neurohumoral measurements with other established indicators of adverse outcome. The study included 145 patients with documented AMI. During a median follow-up of 3.7 years, 30 cardiovascular and 6 noncardiovascular deaths occurred. By univariate analysis, plasma atrial natriuretic factor (ANF) and endothelin levels were strongly related to long-term cardiovascular mortality. In multivariate models, both peptides added prognostic information to that obtained from clinical evaluation, but not to that obtained from left ventricular ejection fraction (LVEF). Estimation of the area under the receiver-operating characteristic curve showed comparable prognostic accuracy for LVEF (0.7788), plasma ANF (0.7795), plasma endothelin (0.7493), and Killip classification (0.8203), meaning that for all these prognostic indicators, a randomly selected patient from the group of patients dying will have a test value larger than that of a randomly selected patient from the group of surviving patients 75% to 82% of the time. The clinical usefulness of neurohumoral determination in routine risk stratification after AMI appears to be limited since no additional prognostic information to that provided by objective evaluation of LV systolic function is obtained. However, in patients for whom objective assessment of LV performance is not readily available, measurement of plasma ANF and endothelin may be helpful in identifying asymptomatic patients at risk for cardiac death.

Prognostic value of plasma atrial natriuretic factor, norepinephrine and epinephrine in acute myocardial infarction.

Neurohumoral activation in acute myocardial infarction (AMI) may reflect the degree of hemodynamic compromise, contribute to the progression of heart failure and augment to the risk of serious ventricular arrhythmias. Consequently, assessment of neurohumoral variables may provide an index of prognostic value in AMI. Plasma levels of atrial natriuretic factor (ANF), norepinephrine and epinephrine were determined in 145 patients on day 3 after AMI. During the 360-day follow-up period 17 patients died. In univariate analysis, all 3 neurohormones were significantly related to 1-year mortality rates (ANF, p < 0.001; norepinephrine, p = 0.009; epinephrine, p = 0.048). After correction for age, sex, anamnestic, biochemical and clinical variables including signs of clinical heart failure in a multivariate model, ANF remained independently related to mortality. The association between plasma norepinephrine and survival failed to reach statistical significance after introduction of clinical heart failure in the model. Comparison of patients subdivided according to median hormone levels (ANF, 30.3 pmol/liter; norepinephrine, 2.29 nmol/liter) demonstrated a significantly increased mortality rate in patients with elevated ANF (p < 0.001), but not elevated norepinephrine levels. These results suggest that early plasma ANF levels are related to survival in patients with AMI, independently of signs of clinical heart failure.

Esomeprazole 20 mg maintains symptom control in endoscopy-negative gastro-oesophageal reflux disease: a controlled trial of 'on-demand' therapy for 6 months.

BACKGROUND: Most patients with gastro-oesophageal reflux disease (GERD), regardless of endoscopic status, suffer symptomatic relapse within 6 months of stopping acid suppressant therapy. AIM: To assess the efficacy of 'on-demand' treatment of GERD with esomeprazole, the first proton pump inhibitor developed as an optical isomer. METHODS: In this multicentre, double-blind study, 342 endoscopy-negative GERD patients demonstrating complete resolution of heartburn during the final week of a 4-week treatment period with esomeprazole 20 mg or omeprazole 20 mg once daily were randomized to receive esomeprazole 20 mg or placebo on demand (maximum of one dose per day) for a further 6 months. Use of rescue antacids was permitted. RESULTS: All 342 patients (191 males), aged 19-79 (mean 49) years, were evaluable in the intention-to-treat analysis. The proportion of patients who discontinued treatment due to insufficient control of heartburn was significantly higher among placebo compared to esomeprazole recipients (51% vs. 14%; P < 0.0001). Patients randomized to esomeprazole on-demand therapy remained in the study longer than those in the placebo group (mean 165 vs. 119 days). Over 50% took the study medication for periods of 1--3 consecutive days (esomeprazole) or 4--13 consecutive days (placebo). Use of antacids was > 2-fold higher among placebo recipients. The frequency of adverse events was similar in the two groups, when adjusted for time spent in the study, as were the clinical laboratory profiles. CONCLUSIONS: On-demand therapy with esomeprazole 20 mg is effective and well tolerated in maintaining symptom control in endoscopy-negative GERD.

Legionella antibodies in human and animal populations in Kenya.

Using a microagglutination method, domestic and wild animal sera, together with human patient and healthy blood donor sera, have been analysed for titres against various Legionella species, comprising fourteen different serogroups. Generally, the level of moderately elevated titres, i.e. greater than or equal to 64, was low for all the aforementioned serum groups. Within the domesticated animals, cattle, pigs and dogs presented a much lower prevalence in Kenya than found elsewhere, whereas it was the other way round for goats. Human sera, either from patients or from healthy donors, did not react against L. pneumophila serogroups 1, 6, or 3, which in that sequence are the most common L. pneumophila serogroups in Europe, and in other geographic areas where legionellosis is common. High titres of greater than or equal to 256 against L. pneumophila serogroup 6 (two cattle) or against L. bozemanii strain Mi-15 (two cattle, one dog) indicate that although the epidemiological picture may be different from other parts of the world, Legionella infections exist in Kenya as well.

Plasma cardiac natriuretic peptide determination as a screening test for the detection of patients with mild left ventricular impairment.

OBJECTIVE: To determine the usefulness of measuring the cardiac natriuretic peptides, atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and brain natriuretic peptide, as screening tests for identifying patients with mild left ventricular impairment. DESIGN: Cross-sectional evaluation of the diagnostic accuracy of the cardiac natriuretic peptides. SETTING: Cardiac catheterisation unit, Norwegian central hospital. PATIENTS: A consecutive series of 254 patients undergoing diagnostic left-sided cardiac catheterisation. One hundred and twenty eight of these patients had a history of previous myocardial infarction. MAIN OUTCOME MEASURES: The presence of normal and impaired left ventricular function, as evaluated by logistic regression analysis and estimation of the area under the receiver operating characteristic (ROC) curve (an index of overall diagnostic accuracy). Ventricular function was assessed by the measurement of left ventricular end diastolic pressure and angiographically determined left ventricular ejection fraction. RESULTS: Logistic regression analysis showed that plasma brain natriuretic peptide was the best predictor of increased left ventricular end diastolic pressure (> or = 15 mm Hg) (P < 0.001), decreased left ventricular ejection fraction (< or = 45%) (P < 0.001), and the combination of left ventricular ejection fraction < or = 45% and left ventricular end diastolic pressure > or = 15 mm Hg (P < 0.001). The areas under the ROC function for the detection of left ventricular dysfunction were 0.789 for brain natriuretic peptide, 0.665 for atrial natriuretic factor, and 0.610 for N-terminal pro-atrial natriuretic factor. CONCLUSIONS: Plasma brain natriuretic peptide seemed to be a better indicator of left ventricular function than plasma atrial natriuretic factor or N-terminal pro-atrial natriuretic factor. However, the overall diagnostic accuracy of circulating atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and brain natriuretic peptide as indicators of normal and impaired ventricular function in an unselected group of patients with coronary heart disease and a high frequency of previous myocardial infarction was relatively modest.