Cohort study of plasma natriuretic peptides for identifying left ventricular systolic dysfunction in primary care

Introduction

Many studies have shown that the prognosis of patients with heart failure due to left ventricular systolic dysfunction can be improved by treatment with an angiotensin converting enzyme inhibitor.1Clinical outcome in patients with asymptomatic left ventricular dysfunction can also be improved by these drugs.2 The identification of these patients on clinical grounds is, however, unreliable. Three studies in symptomatic patients with a diagnosis of heart failure showed that only 25-40% of subjects actually had left ventricular systolic dysfunction.3,5Clinical identification of asymptomatic left ventricular systolic dysfunction is even more difficult.

As a result, it has been suggested that all patients with clinically suspected heart failure or at risk of asymptomatic left ventricular systolic dysfunction should be investigated to confirm the diagnosis.6Echocardiography has become the standard investigation for this purpose, but provision remains limited.6Twelve lead electrocardiography may help target echocardiography at those most likely to have left ventricular systolic dysfunction.7,9

Measurement of plasma concentrations of atrial and brain natriuretic peptides has also been advocated as a means of identifying patients with left ventricular systolic dysfunction.10 11These peptides are secreted in increased quantities by the failing heart, are stable in whole blood for up to three days at room temperature, and can be measured with a relatively simple, rapid, and inexpensive assay. 12 13Small clinical studies and epidemiological surveys have suggested that these peptides may be useful in identifying left ventricular systolic dysfunction in selected groups of patients.11 14,17 The true test of such an approach, however, is to use it in ordinary clinical practice and where it is likely to be most valuable—that is, primary care. We report a study carried out in general practice in the United Kingdom among survivors of myocardial infarction with a high prevalence of other illnesses.

Subjects and methods

The West Glasgow general practitioner audit group decided that, as part of good clinical practice, all patients with a history of myocardial infarction should be reviewed with respect to the use of secondary prevention measures such as aspirin, β blockers, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, and angiotensin converting enzyme inhibitors. As part of this review patients were recalled for echocardiography to determine whether left ventricular systolic dysfunction was present. We decided to evaluate the use of natriuretic peptides in identifying left ventricular systolic dysfunction in these patients. Referred patients were seen by a doctor (SJMcC), who took a standard medical and drug history and carried out a clinical examination. A 12 lead electrocardiogram was then recorded and 10 ml of blood taken from a forearm vein for measurement of brain natriuretic peptide and N-terminal atrial natriuretic peptide. All samples were taken into chilled potassium-EDTA tubes and placed on ice. Plasma was separated in a refrigerated centrifuge and stored at −20°C until assay. Both natriuretic peptides were measured as previously reported. 13 18 The peptides were measured in a single batch by an investigator without knowledge of the clinical or echocardiographic findings.

A standard echocardiographic examination was carried out by an experienced cardiac technician (LC). Two dimensional, M-mode, and colour flow and pulsed wave Doppler recordings were obtained with the patient in the left lateral decubitus position.

Results

Table 1shows the clinical characteristics of the 134 patients. A semiquantitative assessment of left ventricular function was made in all patients. The numbers of patients with preserved function and mild, moderate, and severe dysfunction were 68 (51%), 32 (24%), 26 (19%), and 8 (6%) respectively. M-mode could be measured in only 91 (68%) patients. Ten (11%) patients had substantially reduced fractional shortening (<25%).

Table 2shows the mean (95% confidence interval) plasma brain natriuretic peptide and N-terminal atrial natriuretic peptide concentrations in patients with and without left ventricular systolic dysfunction. Though the mean concentrations of both peptides tended to be highest in those with the most severe left ventricular dysfunction, considerable overlap existed between the range of values in these patients and those with preserved left ventricular function.

Table 3 shows the areas under the receiver operating curves for brain natriuretic peptide and N-terminal atrial natriuretic peptide. These indicate their diagnostic value for left ventricular systolic dysfunction. The area under the curve for patients with normal 12 lead electrocardiographic results was 0.93.

The optimal threshold concentrations of the two peptides were determined as those that gave the best combination of sensitivity and specificity for detection of left ventricular systolic dysfunction. These thresholds were used to calculate the positive and negative predictive values (table 4 ). Concentrations below the thresholds were useful in excluding severe left ventricular systolic dysfunction but could not discriminate between lesser degrees of systolic dysfunction and preserved function.Table 5 shows the likelihood ratios for each of the natriuretic peptides.

Discussion

We evaluated the potential role of two natriuretic peptides in detecting left ventricular systolic dysfunction in ordinary clinical practice. In our population brain natriuretic peptide and N-terminal atrial natriuretic peptide were of clinical value in identifying only patients with severe left ventricular systolic dysfunction, though this was a small subgroup.

Neither test was useful in discriminating between lesser degrees of systolic dysfunction and preserved function. The characteristics of, for example, our patients with moderately severe left ventricular dysfunction suggest that their ventricular impairment was real. Of the 26 patients in this category, 25 had a Q wave infarct pattern or left bundle branch block on their electrocardiogram, significant left ventricular dilatation (left ventricular end diastolic diameter>55 mm), or very low fractional shortening (<25%). Our findings therefore suggest that measurement of blood natriuretic peptide concentrations would not help in identifying most patients with important left ventricular dysfunction (who would be suitable for treatment with an angiotensin converting enzyme inhibitor).