Therapeutic monitoring of class I antiarrhythmic agents using high-resolution electrocardiography instead of blood samples.

Antiarrhythmic therapy requires monitoring of serum drug concentrations to determine a patient's optimal oral dose of medication. Repeated examination of blood samples, however, is costly and time-consuming, so the present study evaluated whether changes in serum concentrations could be estimated from changes in electrocardiographic (ECG) parameters. Of 36 patients receiving antiarrhythmic drugs for supraventricular or ventricular arrhythmias, 12 were treated with flecainide, 12 with pilsicainide, and 12 with pirmenol. Signal-averaged ECG (SAECG) were recorded before starting drug administration, 1 month later, and twice during ongoing therapy. At the time of the 2nd to the 4th recordings, serum concentrations of the drugs were also measured. As previously reported, all agents, but especially flecainide and pilsicainide, prolonged the filtered QRS (f-QRS) and the duration of low-amplitude signals at the terminal portion of the QRS complex. The SAECG parameters varied between the recordings made during therapy. Differences in the duration of the f-QRS between 2 recordings correlated significantly with differences in serum drug concentrations (r=0.91 for flecainide, r=0.70 for pilsicainide, and r=0.61 for pirmenol). No significant correlation between drug concentration and other SAECG parameters was found. Changes in the serum concentration of flecainide, pilsicainide and pirmenol can be estimated from changes in the duration of the f-QRS on the SAECG and periodic monitoring of such could help reduce the number of repeat measurements of drug concentrations in blood samples.

Relationship between brain natriuretic peptide, myocardial wall stress, and ventricular arrhythmia severity.

We previously demonstrated that the severity of arrhythmias is reflected by circulating brain natriuretic peptide (BNP) concentrations in patients without signs of congestive heart failure. In the present study, we evaluated the relationships between the severity of the arrhythmia, BNP concentration, and echocardiographic findings. The subjects consisted of 52 patients with ventricular premature contractions (VPC) but no manifestations of heart failure and no digoxin or beta-blocker therapy. Patients underwent Holter monitoring, plasma sampling for BNP measurement, and transthoracic echocardiography (TTE). We scored the motion of 16 left ventricular segments, deriving a wall-motion score index (WMSI) by totaling the scores and dividing by the number of segments scored. Twenty-three patients with Lown grade I to II arrhythmias constituted group A while group B consisted of 29 Lown III to IV patients. Group B had BNP concentrations triple those in group A (57.2 versus 18.1 pg/mL, P < 0.01). Left ventricular ejection fraction (LVEF) was similar in groups A and B (65.2% versus 62.1%, NS). Although left ventricular end-diastolic dimension (LVEDD) was normal in both groups, group B exhibited a larger LVEDD than group A (50 versus 46 mm, P < 0.005). The correlation (r) between BNP and interventricular septum thickness (IVST) was 0.27 (P = 0.013) in group A and 0.37 (P < 0.0001) in group B. Between BNP and posterior wall thickness (PWT), the correlation was 0.23 (P = 0.014) in group A versus 0.33 (P < 0.0001) in group B. The WMSI in group B was higher than in group A (1.34 versus 1.11, P < 0.05). We believe that besides the changes in echocardiographic parameters, the BNP elevation in group B could be a response to abnormal wall stress from the severe ventricular arrhythmias.