One hundred and twenty-one consecutive patients examined were submitted to dobutamine stress echocardiography. Treatment with anti-ischemic medication was not interrupted before the test.
The patients were randomly divided into three protocols of study (Figure 1): 1A) early administration of atropine at a dose of 10 mcg/kg/min of dobutamine; B) early administration of atropine at a dose of 20 mcg/kg/min of dobutamine, and; C) late or standard administration of atropine at a dose of 40 mcg/kg/min of dobutamine, in case heart rate obtained was below 85% of maximum rate expected for age (220 – age) and there was no criteria for interruption of test (such as: new abnormality in wall motion or a worsening of an existing one, heart rate = or > 85% of maximum rate expected for age, important increase of systolic or diastolic blood pressure (SBP > 220 mmHg and/or DBP > 110 mmHg), relevant cardiac arrhythmia (supraventricular arrhythmia with high response and/or malignant ventricular arrhythmia), intense angina (specially if associated with worsening of regional function), pronounced hypotension (decrease of SBP > 20 mmHg) followed by symptomatology, and conclusion of protocol. Groups A & B were considered belonging to the early dobutamine-atropine protocol (Figure 1) and group C belonged to the late protocol (conventional).
In group C, some patients did not require atropine during the test (which is part of the standard protocol). The patients of group C who did not receive atropine during the test (n = 16) were not taken into account for pertinent statistical analysis on the effects of atropine in the early or late phase of the echocardiogram. For a better understanding, we considered to be late protocol the patients of group C who received atropine and standard protocol the patients involved in group C who did or not require atropine.
The current research was approved by the Ethical and Research Committee of the hospital, and informal consent was obtained from all the patients.
Stress echocardiogram
Two kinds of equipments were used in the study: a HDI 5000 (digitalization – "Image View") and a Sonos HP 5500, both with 4,0 MHz transducers.
The patients were submitted to the two-dimensional echocardiograms and Doppler for full analysis of cardiac performance. The images obtained were of the long axis, short axis, apical four and two chambers which correspond to the viewing of the myocardial segments supplied by the main coronary arteries.
Dobutamine was diluted in a glucose solution and administered through an infusion pump initially at a dose of 5 mcg/kg/min and increased to 10, 20, 30 mcg/kg/min every 3 minutes up to maximum dose of 40 mcg/kg/min (according to each group). The atropine sulfate was initiated at a dose of 0,25 up to 0,50 mg and increased in intervals of 1 to 2 minutes respectively, until a maximum dose of 2 mg. This agent was administered intravenously in the last minute of the stage, whereas the dobutamine infusion remained continuous.
During the exam, a three derivation electrocardiogram (ECG) record was maintained, as well as a continuous check up of heart rate and blood pressure before and after the administration of atropine.
At the peak of test, after achieving the end points, the dobutamine and atropine infusions were interrupted and monitoring was continued during 5 to 10 minutes of the recovery phase (eventually, for a longer period if necessary), until heart rate was lower than 100 bpm and other clinical and hemodynamic parameters were normal. Metoprolol was given intravenously (1 to 5 mg) during recovery phase to revert the effects of the dobutamine-atropine combination.
Echocardiographic evaluation
The left ventricle was divided into 16 segments [2]. Each segment was described as: normal, hypokinetic, akinetic or dyskinetic. A normal dobutamine stress echocardiogram was defined as having normal wall motion at rest with an increase of its systolic thickening during stress (hyperkinesia). The presence of ischemia (positive test) was defined as the development of a new abnormality in wall-motion or a worsening of an existing one during stress (hypokinesia, akinesia or dyskinesia).
The echocardiograms were reviewed by two experienced examiners ("off line"), who had no access to clinical and angiographical data, and a consensus was reached whenever necessary.
Statistical analysis
The statistical methodology adopted for the comparison of proportions between continuous variables was the X
2 test or the Fisher exact Test, whenever the X
2 test could not be evaluated. For the comparison of means between the two groups the t de Student test was applied for independent samples, or the Mann-Whitney test (non-parametric test) whenever the variable did not present normal distribution.
In situations where three groups had to be analyzed, the comparison of means between the groups was made with the Analysis of Variance (ANOVA). In this case, the Tukey test of multiple comparisons was applied to identify which groups differed from each other; this is an ANOVA complementary test. The Analysis of Variance of Kruskal-Wallis (non-parametric test) was used for the comparative analysis of variables which did not present a normal distribution.
The adopted criteria for determining any significance was the level of 5% (in other words, whenever the p value of the statistical analysis was lower or equal to 0,05).
The analysis of all statistical tests was processed by the SAS® system (Statistical Analysis System).
