NT-proBNP can be used to detect right ventricular systolic dysfunction in pulmonary hypertension.

Right ventricular systolic dysfunction (RVSD) at baseline (pre-treatment) predicts early death in patients with pulmonary hypertension (PH). However, RVSD can only be detected reliably by prohibitively invasive or expensive techniques. N-terminal B-type natriuretic peptide concentration ([NT-proBNP]) correlates with RV function in PH; however, an [NT-proBNP] threshold that indicates RVSD in individual patients has not previously been determined. Twenty-five patients with PH (pulmonary arterial hypertension (n = 19) or chronic thromboembolic PH (n = 6)) underwent cardiovascular magnetic resonance (CMR) imaging and NT-proBNP measurement at baseline. [NT-proBNP] was correlated against RV dimensions and ejection fraction (RVEF) measured directly by CMR imaging. The ability of NT-proBNP to detect RVSD (defined as a CMR-derived RVEF >2 SDS below control values) was tested and predictors of [NT-proBNP] identified. [NT-proBNP] correlated negatively with RVEF. RVSD was present in nine out of 25 patients. An [NT-proBNP] threshold of 1,685 pg.mL(-1) was sensitive (100%) and specific (94%) in detecting RVSD. RVEF and RV mass index independently predicted [NT-proBNP]. In pulmonary hypertension, a baseline N-terminal B-type natriuretic peptide concentration of >1,685 ng.L(-1) suggests right ventricular systolic dysfunction, and thus an increased risk of early death. N-terminal B-type natriuretic peptide could prove useful as an objective, noninvasive means of identifying patients with pulmonary hypertension who have right ventricular systolic dysfunction at presentation.

Redefinition of uremic cardiomyopathy by contrast-enhanced cardiac magnetic resonance imaging.

Patients with end stage renal failure (ESRF) have an increased risk of premature cardiovascular disease. Left ventricular (LV) abnormalities, so called 'uremic cardiomyopathy', are associated with poorer outcome. Cardiac magnetic resonance imaging (CMR) accurately defines LV dimensions and identifies underlying myocardial pathology. We studied the relationship between LV function and myocardial pathology in ESRF patients with CMR. A total of 134 patients with ESRF underwent CMR. LV function was assessed with further images acquired after gadolinium-diethylentriaminepentaacetic acid (DTPA). The presence of myocardial fibrosis was indicated by late gadolinium enhancement (LGE). Two main myocardial pathologies were identified. A total of 19 patients (14.2%) displayed 'subendocardial LGE' representing myocardial infarction, which was associated with conventional cardiovascular risk factors including a history of ischemic heart disease (IHD) (P < 0.001), hypercholesterolemia (P < 0.05), and diabetes (P < 0.01). Patients with subendocardial LGE had greater LV mass (P < 0.05), LV dilation (P < 0.01), and LV systolic dysfunction (P < 0.001) compared to patients with no evidence of LGE. The second pattern, 'diffuse LGE', seen in 19 patients (14.2%) appeared to represent regional areas of diffuse myocardial fibrosis. Diffuse LGE was associated with greater LV mass compared to patients without LGE (P < 0.01) but not systolic dysfunction. In total, 28.4% of all patients exhibited evidence of myocardial fibrosis demonstrated by LGE. In contrast to published literature describing three forms of uremic cardiomyopathy - left ventricular hypertrophy (LVH), dilation, and systolic dysfunction, we have shown that LVH is the predominant cardiomyopathy specific to uremia, while LV dilation and systolic dysfunction are due to underlying (possibly silent) ischemic heart disease.

Comparison of the dual receptor endothelin antagonist enrasentan with enalapril in asymptomatic left ventricular systolic dysfunction: a cardiovascular magnetic resonance study.

OBJECTIVE: To compare the effect of the dual endothelin A/B receptor antagonist enrasentan with enalapril on left ventricular (LV) remodelling. METHODS: Multicentre, randomised, double blind, parallel group study of 72 asymptomatic patients with LV dysfunction. Patients received enrasentan (60-90 mg/day) or enalapril (10-20 mg/day). The primary end point was the change in LV end diastolic volume index (EDVI) after six months' treatment. RESULTS: LV EDVI increased with enrasentan but decreased with enalapril (3.9 (1.8) v -3.4 (1.4) ml/m2, p = 0.001). Enrasentan increased resting cardiac index compared with enalapril (0.11 (0.07) v -0.10 (0.07) l/m2, p = 0.04), as well as LV mass index (0.67 (1.6) v -3.6 (1.6) g/m2, p = 0.04). Other variables were comparable between groups. Enalapril lowered brain natriuretic peptide more than enrasentan (-19.3 (9.4) v -5.8 (6.9) pg/ml, p = 0.005). Noradrenaline (norepinephrine) (p = 0.02) increased more with enrasentan than with enalapril. Enrasentan was associated with more serious adverse events compared with enalapril (six (16.7%) patients v one (2.8%), p = 0.02); the rate of progression of heart failure did not differ. CONCLUSION: In asymptomatic patients with LV dysfunction, LV EDVI increased over six months with enrasentan compared with enalapril treatment, with adverse neurohormonal effects. This suggests that enrasentan at a dose of 60-90 mg/day over six months causes adverse ventricular remodelling despite an increase in the resting cardiac index.

Diagnostic and prognostic evaluation of left ventricular systolic heart failure by plasma N-terminal pro-brain natriuretic peptide concentrations in a large sample of the general population.

OBJECTIVE: To evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP) as a diagnostic and prognostic marker for systolic heart failure in the general population. DESIGN: Study participants, randomly selected to be representative of the background population, filled in a heart failure questionnaire and underwent pulse and blood pressure measurements, electrocardiography, echocardiography, and blood sampling and were followed up for a median (range) period of 805 (60-1171) days. SETTING: Participants were recruited from four randomly selected general practitioners and were examined in a Copenhagen university hospital. PATIENTS: 382 women and 290 men in four age groups (50-59 (n = 174); 60-69 (n = 204); 70-79 (n = 174); > or = 80 years (n = 120)). MAIN OUTCOME MEASURES: Value of NT-proBNP in evaluating patients with symptoms of heart failure and impaired left ventricular (LV) systolic function; prognostic value of NT-proBNP for mortality and hospital admissions. RESULTS: In 38 (5.6%) participants LV ejection fraction (LVEF) was < or = 40%. NT-proBNP identified patients with symptoms of heart failure and LVEF < or = 40% with a sensitivity of 0.92, a specificity of 0.86, positive and negative predictive values of 0.11 and 1.00, and area under the curve of 0.94. NT-proBNP was the strongest independent predictor of mortality (hazard ratio (HR) = 5.70, p < 0.0001), hospital admissions for heart failure (HR = 13.83, p < 0.0001), and other cardiac admissions (HR = 3.69, p < 0.0001). Mortality (26 v 6, p = 0.0003), heart failure admissions (18 v 2, p = 0.0002), and admissions for other cardiac causes (44 v 13, p < 0.0001) were significantly higher in patients with NT-proBNP above the study median (32.5 pmol/l). CONCLUSIONS: Measurement of NT-proBNP may be useful as a screening tool for systolic heart failure in the general population.

The influence of age, sex and other variables on the plasma level of N-terminal pro brain natriuretic peptide in a large sample of the general population.

OBJECTIVE: To identify potentially confounding variables for the interpretation of plasma N-terminal pro brain natriuretic peptide (NT-proBNP). DESIGN: Randomly selected subjects filled in a heart failure questionnaire and underwent pulse and blood pressure measurements, ECG, echocardiography, and blood sampling. SETTING: Subjects were recruited from four Copenhagen general practices located in the same urban area and were examined in a Copenhagen University Hospital. PATIENTS: 382 women and 290 men in four age groups: 50-59 years (n = 174); 60-69 years (n = 204); 70-79 years (n = 174); and > 80 years (n = 120). MAIN OUTCOME MEASURES: Associations between the plasma concentration of NT-proBNP and a range of clinical variables. RESULTS: In the undivided study sample, female sex (p < 0.0001), greater age (p < 0.0001), increasing dyspnoea (p = 0.0001), diabetes mellitus (p = 0.01), valvar heart disease (p = 0.002), low heart rate (p < 0.0001), left ventricular ejection fraction < or = 45% (p < 0.0001), abnormal ECG (p < 0.0001), high log10[plasma creatinine] (p = 0.0009), low log10[plasma glycosylated haemoglobin A1c] (p = 0.0004), and high log10[urine albumin] (p < 0.0001) were independently associated with a high plasma log10[plasma NT-proBNP] by multiple linear regression analysis. CONCLUSIONS: A single reference interval for the normal value of NT-proBNP is unlikely to suffice. There are several confounders for the interpretation of a given NT-proBNP concentration and at the very least adjustment should be made for the independent effects of age and sex.

Evaluation of impaired left ventricular ejection fraction and increased dimensions by multiple neurohumoral plasma concentrations.

BACKGROUND: A range of neurohumoral substances have been suggested as diagnostic markers in heart failure. It is, however, undetermined which marker has the greatest diagnostic potential, and whether additional information is gained by a comprehensive neurohumoral evaluation. AIMS: The purpose of the study was to compare the value of epinephrine, norepinephrine, renin activity, aldosterone (ALDO), atrial (ANP) and brain (BNP) natriuretic peptides, arginine-vasopressin and endothelin (ENDO) as markers for left ventricular (LV) dimensions and ejection fraction (LVEF) in patients with systolic heart failure. METHODS: Forty-eight patients with symptomatic heart failure were examined with blood samples and magnetic resonance imaging along with 20 age and gender-matched normal controls. RESULTS: In multiple regression analyses, BNP was the strongest independent marker for LV end-diastolic (r=0.71, P<0.0001), and end-systolic (r=0.75, P<0.0001) volumes, myocardial mass (r=0.69, P<0.0001), and LVEF (r=-0.78, P<0.0001). ANP was a supplementary independent marker for LV end-diastolic (r=0.76, P<0.0001) and end-systolic (r=0.78, P<0.0001) (ANP and BNP combined) volumes, ENDO for myocardial mass [r=0.71, P<0.0001 (ENDO/BNP)], and ALDO for LVEF [r=-0.81, P<0.0001 (ALDO/BNP)]. CONCLUSION: BNP is the strongest marker for LV dimensions and LVEF in patients with systolic heart failure. However, a comprehensive neurohumoral evaluation may add some information to the diagnosis.

Sustained postinfarction myocardial oedema in humans visualised by magnetic resonance imaging.

OBJECTIVE: To demonstrate postinfarction myocardial oedema in humans with particular reference to the longitudinal course, using magnetic resonance imaging (MRI). DESIGN: Prospective observational study. Subjects were studied one week, one month, three months, six months, and one year after presenting with a myocardial infarct. SETTING: Cardiology and magnetic resonance departments in a Danish university hospital. PATIENTS: 10 patients (three women, seven men), mean (SEM) age 58.2 (3.20) years, with a first transmural myocardial infarct. MAIN OUTCOME MEASURES: Location and duration of postinfarction myocardial oedema. RESULTS: All patients had signs of postinfarction myocardial oedema. The magnetic resonance images were evaluated by two blinded procedures, employing two MRI and two ECG observers: (1) MRI determined oedema location was compared with the ECG determined site of infarction and almost complete agreement was found; (2) the time course of postinfarction myocardial oedema was explored semiquantitatively, using an image ranking procedure. Myocardial oedema was greatest at the initial examination one week after the infarction, with a gradual decline during the following months (Spearman's rank correlation analysis: rho(observer 1) = 0.94 (p < 0.0001) and rho(observer 2) = 0.97 (p < 0.0001)). The median duration of oedema was six months. CONCLUSIONS: Postinfarction myocardial oedema seems surprisingly long lasting. This observation is of potential clinical interest because the oedema may have prognostic significance.

Antiremodeling effects on the left ventricle during beta-blockade with metoprolol in the treatment of chronic heart failure.

OBJECTIVES: The purpose of the study was to investigate the effects of beta1-blockade on left ventricular (LV) size and function for patients with chronic heart failure. BACKGROUND: Large-scale trials have shown that a marked decrease in mortality can be obtained by treatment of chronic heart failure with beta-adrenergic blocking agents. Possible mechanisms behind this effect remain yet to be fully elucidated, and previous studies have presented insignificant results regarding suspected LV antiremodeling effects. METHODS: In this randomized, placebo-controlled and double-blind substudy to the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF), 41 patients were examined with magnetic resonance imaging three times in a six-month period, assessing LV dimensions and function. RESULTS: Decreases in both LV end-diastolic volume index (150 ml/m2 at baseline to 126 ml/m2 after six months, p = 0.007) and LV end-systolic volume index (107 ml/m2 to 81 ml/m2, p = 0.001) were found, whereas LV ejection fraction increased in the metoprolol CR/XL group (29% to 37%, p = 0.005). No significant changes were seen in the placebo group regarding these variables. Left ventricular stroke volume index remained unchanged, whereas LV mass index decreased in both groups (175 g/m2 to 160 g/m2 in the placebo group [p = 0.005] and 179 g/m2 to 164 g/m2 in the metoprolol CR/XL group [p = 0.011). CONCLUSIONS: This study is the first randomized study to demonstrate that the beta1-blocker metoprolol CR/XL has antiremodeling effects on the LV in patients with chronic heart failure and consequently provides an explanation for the highly significant decrease in mortality from worsening heart failure found in the MERIT-HF trial.