Transsphenoidal surgery for pituitary tumours: frequency and predictors of delayed hyponatraemia and their relationship to early readmission.

OBJECTIVE: A major cause of readmission after transsphenoidal surgery (TSS) is delayed hyponatraemia. The purpose of this study was to identify predictors of hyponatraemia one week post surgery and predictors of 30-day readmissions for hyponatraemia. DESIGN: A retrospective cohort study including patients who had TSS performed for pituitary lesions. METHOD: The risk of readmission for hyponatraemia was assessed in consecutive patients between January 2008 and March 2016. The risk of hyponatraemia one week post surgery was assessed in patients admitted for TSS between July 2011 and March 2016. RESULTS: Of all included patients, 56/522 (10.7%) were readmitted within 30 days. Hyponatraemia was found in 14/56 (25%) of 30-day readmissions. We did not identify any predictive variable for hyponatraemia on readmission. The number of patients with hyponatraemia on the seventh post-operative day was 26/314 (8.3%). The risk of hyponatraemia one week post surgery was increased by an odds ratio of 2.40 (95% CI: 1.06-5.40) in patients with a tumour abutting the optic chiasm and by an odds ratio of 1.16 (1.04-1.31) per mmol/L decrease in sodium levels on the first post-operative day. CONCLUSIONS: Hyponatraemia occurred in 25% of readmissions; however, we did not identify any predictive variable for readmission with hyponatraemia. One week post surgery, 8.9% had hyponatraemia. Tumours pressing on the optic chiasm as well as a fall in sodium levels on the first post-operative day were associated with an increased risk of hyponatraemia one week post surgery. We suggest that a day 7 serum sodium <130 nmol/L should lead to concern and the provision of patient advice.

Prognostic significance of cardiovascular biomarkers and renal dysfunction in outpatients with systolic heart failure: a long term follow-up study.

OBJECTIVE: To assess whether the prognostic significance of cardiovascular (CV) biomarkers, is affected by renal dysfunction (RD) in systolic heart failure (HF). BACKGROUND: It is unknown, whether the prognostic significance of CV biomarkers, such as N-terminal-pro-brain-natriuretic-peptide (NT-proBNP), high-sensitive troponin T (hsTNT), pro-atrial natriuretic peptide (proANP), copeptin and pro-adrenomedullin (proADM), is affected by renal function in HF. METHODS: Clinical data and laboratory tests from 424 patients with systolic HF were collected prospectively. The patients were followed for 4.5 years (interquartile range: 2-7.7 years). CV biomarkers were analyzed on frozen plasma, and renal function was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Cox proportional hazard models for mortality risk were constructed and tests for interaction between each CV biomarker and RD were performed. RESULTS: Median age was 73 years (51-83), 29% were female, LVEF was 30% (13-45), 74% were NYHA classes I-II and estimated glomerular filtration rate (eGFR) was 68 ml/min/1.73 m(2) (18-157). A total of 252 patients died. All five biomarkers--log(NT-proBNP) (HR: 2.13, 95% CI: 1.57-2.87:, P<0.001), hsTNT (HR: 3.07, 95% CI: 1.90-4.96 P<0.001), proANP (HR: 1.02, 95% CI: 1.01-1.03, P<0.001), copeptin (HR: 1.02, 95% CI: 1.01-1.03, P=0.008) and proADM (HR: 2.37, 95% CI: 1.66-3.38, P<0.001)--were associated with mortality risk, but not affected by RD (P>0.05 for all interactions). CONCLUSION: Established and new CV biomarkers are closely associated with renal function in HF. However, their prognostic significance is not affected by RD, and all CV biomarkers can be used for risk stratification independently of renal function.

Prediction of outcome by highly sensitive troponin T in outpatients with chronic systolic left ventricular heart failure.

Our aim was to assess the prognostic impact of a high-sensitivity cardiac troponin T (hs-cTnT) assay in an outpatient population with chronic systolic left ventricular heart failure (HF). Four hundred sixteen patients with chronic HF and left ventricular ejection fraction ≤ 45% were enrolled in a prospective cohort study. In addition to hs-cTnT, plasma amino-terminal pro-B-type natriuretic peptide was measured at baseline. Mean age was 71 years, 29% were women, 62% had coronary artery disease (CAD), mean left ventricular ejection fraction was 31%, and 57% had abnormal level of hs-cTnT. During 4.4 years of follow-up, 211 (51%) patients died. In multivariate Cox regression models, hs-cTnT was categorized as quartiles or dichotomized by the 99th percentile of a healthy population. Adjusted hazard ratios for all-cause mortality for quartiles 2 to 4, with quartile 1 as reference, were 1.4 (95% confidence interval 0.9 to 2.4, p = 0.16) for quartile 2, 1.7 (0.9 to 2.5, p = 0.12) for quartile 3, and 2.6 (1.6 to 4.4, p <0.001) for quartile 4 and 1.7 (1.2 to 2.5, p = 0.003) for abnormal versus normal level of hs-cTnT. In patients without CAD, quartile 4 of hs-cTnT was associated with an adjusted hazard ratio of 6.8. In conclusion, hs-cTnT is increased in most outpatients with chronic systolic HF and carries prognostic information beyond clinical parameters and amino-terminal pro-B-type natriuretic peptide. Increased hs-cTnT indicated a particularly deleterious prognosis in patients without CAD.

Oral glucose tolerance testing in an outpatient heart failure clinic reveals a high proportion of undiagnosed diabetic patients with an adverse prognosis.

AIMS: We evaluated the applicability and prognostic importance of oral glucose tolerance testing (OGTT) among outpatients with systolic heart failure (SHF). METHODS AND RESULTS: Consecutive patients with SHF and left ventricular ejection fraction (LVEF) ≤ 45% referred to a heart failure clinic (n= 413) were included in this study. An OGTT was conducted in patients without a history of diabetes. Information on NYHA class, aetiology of SHF, LVEF, treatment, and biochemical parameters were collected at baseline. The survival status was obtained after a median follow-up time of 591 days. Of the 413 patients, 82 (20%) had known diabetes. Of the remaining 331 patients, 227 (69%) agreed to undergo an OGTT. Among the tested subjects, 136 (60%) were classified as having normal glucose tolerance (NGT), 51 (23%) impaired glucose tolerance (IGT), and 40 (18%) newly diagnosed diabetes. Assuming a similar prevalence of unrecognized diabetes among the patients who refused OGTT, the prevalence of diabetes in the total population was 34%. If only fasting blood glucose had been used, 16 of the 40 newly diagnosed diabetic patients would have been undiagnosed. During follow-up, 24 (29%) patients with known diabetes, 6 (15%) of the newly diagnosed diabetic patients, 9 (18%) of those with IGT, and 13 (9%) patients with NGT died. Patients with diabetes had higher mortality rate compared with non-diabetic patients [multivariate hazard ratio 1.89 (1.02-3.59); P = 0.047]. CONCLUSION: It is feasible to perform diabetes screening using OGTT in outpatients with SHF. A substantial proportion of patients tested were found to have unrecognized diabetes. The presence of diabetes was associated with a higher mortality rate.

Prognostic usefulness of anemia and N-terminal pro-brain natriuretic peptide in outpatients with systolic heart failure.

N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and anemia are predictors of outcome in systolic heart failure. It is currently unclear how these 2 markers interact in particular with regard to the prognostic information carried by each risk marker. We therefore tested the hypothesis that anemia (World Health Organization criteria, hemoglobin levels <7.5 mmol/L for women and <8.0 mmol/L for men) and NT-pro-BNP are associated and evaluated how a possible association affects the prognostic value of each risk marker. Clinical data from 345 patients with systolic heart failure were obtained prospectively at the baseline visit to our heart failure clinic (inclusion criterion left ventricular ejection fraction <0.45, no exclusion criteria). Follow-up was 30 months (median), and 70 events (mortality) occurred. Prevalence of anemia was 27%. In a multivariate logistic regression model, anemia (p = 0.041) was closely associated with NT-pro-BNP levels above the median (1,381 pg/ml) after adjustment for traditional confounders (left ventricular ejection fraction, age, body mass index, atrial fibrillation, chronic kidney disease). In an adjusted Cox proportional hazard model, the 2 parameters were associated with mortality after adjustment for traditional confounders (hazard ratio for anemia 1.73, 95% confidence interval 1.06 to 2.83, p = 0.029; hazard ratio for NT-pro-BNP >1,381 pg/ml 2.68, 95% confidence interval 1.58 to 4.66, p <0.001). Patients with anemia and high NT-pro-BNP levels had a fivefold increased risk for mortality (hazard ratio 4.77, 95% confidence interval 2.47 to 9.18, p <0.001). In conclusion, anemia is closely associated with NT-pro-BNP in patients with systolic heart failure, and anemia and NT-pro-BNP carry independent prognostic information. Patients with anemia and high levels of NT-pro-BNP have a markedly increased mortality risk.

Effects of body mass index and age on N-terminal pro brain natriuretic peptide are associated with glomerular filtration rate in chronic heart failure patients.

BACKGROUND: Obesity is a state characterized by glomerular hyperfiltration and age-related decreases in glomerular filtration rate (GFR). Body mass index (BMI), age, and GFR are associated with plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) patients. We hypothesized that the effects of BMI and age on plasma concentrations of NT-proBNP are associated with GFR. METHODS: We obtained clinical data and laboratory test results from 345 CHF patients at the baseline visit in our heart failure clinic and examined the hypothesis using multiple linear regression models. RESULTS: Age (P = 0.0184), BMI (P = 0.0098), hemoglobin (P = 0.0043), heart rhythm (P <0.0001), and left ventricular ejection fraction (P <0.0001) were associated with log(NT-proBNP). After adjustment for GFR estimated by the Cockcroft and Gault equation, the parameter estimates for BMI (P = 0.3807) and age (P = 0.7238) changed markedly and became insignificant. In another model, after adjustment for GFR estimated by the 4-component Modification of Diet in Renal Disease formula (eGFR(MDRD)), the parameter estimates for age (P = 0.0674) changed markedly and became insignificant, but BMI (P = 0.0067) remained significant and unchanged. The eGFR(MDRD) is adjusted for body surface area, which may explain the difference. CONCLUSIONS: In CHF patients, the effect of age on NT-proBNP is associated with estimates for GFR derived from serum creatinine, and the significance of the effects of BMI on NT-proBNP depends on the method by which GFR is estimated.

Unrecognized glycometabolic disturbance as measured by hemoglobin A1c is associated with a poor outcome after acute myocardial infarction.

BACKGROUND: Glycated hemoglobin A1c (HbA1c) is a measure of the average blood glucose levels over 2 months and is minimally affected by acute hyperglycemia often observed in myocardial infarction (MI). In a large population of high-risk patients with MI, we examined the prognostic impact of HbA1c in patients with and without a history of diabetes. METHODS: In the OPTIMAAL trial, patients with MI complicated with heart failure were randomized to losartan or captopril. Of the 2841 patients who had HbA1c measured at randomization, 495 (17%) reported a history of diabetes. The remaining patients without diabetes history were stratified into 3 categories according to HbA1c level: HbA1c, <4.9% (n = 1642); HbA1c, 4.9% to 5.1% (n = 432); and HbA1c, >5.1% (n = 272). Mean follow-up time was 2.5 years. RESULTS: Mortality rate during follow-up was 18% in patients with a history of diabetes. Increasing HbA1c levels were associated with higher mortality rate among patients without diabetes history (13% in patients with HbA1c <4.9%, 17% in patients with HbA1c 4.9%-5.1%, 22% in patients with HbA1c >5.1%). Among patients with no prior history of diabetes, a 1% absolute increase in HbA1c level at baseline resulted in a 24% increase in mortality, whereas the level of HbA1c had no impact on mortality among the patients with well-known diabetes (multivariate analyses). CONCLUSIONS: In this high-risk MI population, HbA1c level was a potent predictor of mortality in patients without previously known diabetes.

The relationship between N-terminal pro-brain natriuretic peptide and risk for hospitalization and mortality is curvilinear in patients with chronic heart failure.

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) carries prognostic information in patients with chronic heart failure and predicts risk for mortality and cardiovascular events. It is unknown whether NT-proBNP predicts risk for hospitalization for any cause. Furthermore, a clinically useful algorithm for risk stratification based on NT-proBNP as a continuous variable has not yet been described. We therefore evaluated NT-proBNP as a risk marker for mortality and hospitalization and developed a simple algorithm for risk stratification based on NT-proBNP as a continuous variable. METHODS: Data from 345 patients with chronic heart failure were collected prospectively in our heart failure clinic, and the patients were followed for 28 months (median). Seventy patients died, and 201 patients were hospitalized. Cox proportional hazard models for mortality and hospitalization were constructed with NT-proBNP as a dichotomous (median 1381 pg/mL) and a continuous variable (log2 NT-proBNP). RESULTS: Patients with supramedian levels of NT-proBNP had a 2.40-fold (95% CI 1.40-4.10) increased risk for mortality and 1.71-fold (95% CI 1.24-2.36) increased risk for hospitalization. The effect of doubling NT-proBNP on adjusted hazard ratios was 1.56 (95% CI 1.32-1.85) for mortality and 1.19 (95% CI 1.09-1.31) for hospitalization. We observed a curvilinear relationship between NT-proBNP and risk for mortality and hospitalization in the whole range of NT-proBNP. CONCLUSIONS: N-terminal pro-brain natriuretic peptide predicts risk for hospitalization and mortality. A simple algorithm indicates that every time NT-proBNP is doubled, estimated hazard ratio for death increases by a factor of 1.56 (56%) and by a factor of 1.19 (19%) for hospitalization. Finally, the relationship between NT-proBNP and risk is curvilinear if NT-proBNP is considered as a continuous variable.