Thallium reinjection versus standard stress/delay redistribution imaging for prediction of cardiac events.

OBJECTIVES: The purpose of this study was to compare thallium reinjection with standard stress/delay redistribution for the prediction of cardiac events. BACKGROUND: Although thallium reinjection enhances the detection of viable myocardium, its contribution to prognosis over stress/delay redistribution in a general referral population has not been clearly evaluated. METHODS: This retrospective analysis included 366 consecutive patients with coronary artery disease who underwent stress/delay redistribution imaging and thallium reinjection scintigraphy, with a mean follow-up of 33+/-12 months. RESULTS: Cardiac events occurred in 48 patients (40 deaths, 8 myocardial infarctions). Of the 366 original patients, 159 demonstrated ischemia by stress/delay redistribution, 107 showed ischemia by reinjection only, and 100 showed infarction only. Cardiac events occurred in 20 patients (12.6%) with stress/delay redistribution, 13 patients (12%) with ischemia detected by thallium reinjection only and 15 patients (15%) with infarction only. The size of the reversible thallium defect by either stress/delay redistribution imaging or reinjection scintigraphy did not predict cardiac events. Independent predictors of cardiac events included left ventricular cavity size, the size of the abnormal perfusion defect and patient age. CONCLUSIONS: Thallium reinjection does not contribute independent prognostic utility for cardiac events when compared with stress/delay redistribution. Left ventricular dilation and the size of the post-stress defect were predictors of cardiac events.

Persistent ST segment depression in precordial leads V5-V6 after Q-wave anterior wall myocardial infarction is associated with restrictive physiology of the left ventricle.

OBJECTIVES: To examine the relationship between the persistence of ST segment depression in leads V5-V6 after Q-wave anterior wall myocardial infarction (MI) and the filling pattern of the left ventricle (LV). BACKGROUND: Precordial ST segment depression predominantly in leads V5-V6 is associated with increased in-hospital morbidity and mortality after acute myocardial ischemia, perhaps due to reduced diastolic distensibility of the LV. METHODS: We prospectively studied 19 patients after Q-wave anterior wall MI (>6 months). All patients underwent 12-lead ECG recording, symptom-limited treadmill exercise testing with single photon emission computed tomography thallium-201 imaging, transthoracic Doppler echocardiography, cardiac catheterization and measurement of circulating atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels. Patients were classified based on the presence of ST segment depression in leads V5-V6: Group I = ST segment depression <0.1 mV (n = 10); Group II = ST segment depression > or =0.1 mV (n = 9). RESULTS: Patients in Group II had greater LV end diastolic pressures (32.4 +/- 6.5 mm Hg vs. 14.8 +/- 6.1 mm Hg; p = 0.0001), higher plasma ANP (44.4 +/- 47.1 pg/ml vs. 10.7 +/- 14 pg/ml; p = 0.04) and BNP levels (89.4 +/- 62.7 pg/ml vs. 23.6 +/- 33.1 pg/ml; p = 0.01), greater left atrium area (20.6 +/- 3.1 cm2 vs. 17.8 +/- 2.4 cm2; p = 0.05), lower peak atrial (A), higher early (E) mitral inflow velocities, a higher E/A ratio and a lower deceleration time (167 +/- 44 ms vs. 220 +/- 40 ms; p = 0.05). Lung thallium uptake during exercise was more common in Group II (78% vs. 10%, p = 0.04). CONCLUSIONS: Persistent ST segment depression in leads V5-V6 in survivors of Q-wave anterior wall MI is associated with increased LV filling pressure and a restrictive LV filling pattern.

Evaluation of ventricular function with first-pass iridium-191m radionuclide angiocardiography.

Iridium-191m would appear to be a highly useful agent for first-pass radionuclide angiocardiography (FPNA), with its very short half-life (4.96 sec), dual photopeaks (65 and 129 keV), and high injectable activity levels (greater than 100 mc). In order to compare 191mIr FPNA to current methods used to define cardiac function, 20 patients referred for cardiac catheterization were studied. Count rate data, right ventricular (RV), and left ventricular ejection fraction (LVEF), LV and diastolic volume (EDV), and end diastolic long axis (AXIS) were evaluated. Count rate data using 191mIr FPNA was consistently better than similar data obtained by 99mTc FPNA. There were acceptable correlations between 191mIr and 99mTc FPNA RVEF (r = 0.848), 191mIr FPNA and contrast angiography LVEF (r = 0.944), LVEDV (r = 0.917), and LV AXIS (r = 0.866). The data thus suggests that 191mIr FPNA has great potential in the evaluation of cardiac function.

Dipyridamole first-pass radionuclide ventriculography: prediction of future cardiac events.

Dipyridamole thallium myocardial perfusion imaging is a useful alternative to stress testing in the diagnostic and prognostic assessment of patients with coronary artery disease. The diagnostic use of dipyridamole radionuclide ventriculography is much more controversial, but no long-term prognostic studies have been reported. Imaging results of 159 consecutive patients who were referred for dipyridamole first-pass radionuclide ventriculography were correlated with subsequent cardiac events over a mean follow-up period of 11 months. An abnormal response to dipyridamole infusion (any reduction in wall motion or absolute decrease in global left ventricular ejection fraction of > or = 5 ejection fraction units) was associated with an increased incidence of nonfatal myocardial infarction (4.5% vs 0%, p < 0.05) and cardiac-related death (9% vs 1%, p < 0.001). The sensitivity, specificity, and negative predictive value of dipyridamole first-pass radionuclide ventriculography in predicting future cardiac events were 86%, 71%, and 98%, respectively, with a relative risk of 15 (confidence interval 12.06 to 18.1). In conclusion, dipyridamole first-pass radionuclide ventriculography demonstrated significant prognostic value in a large unselected patient population. This technique may provide a widely applicable and useful alternative to dipyridamole thallium perfusion imaging in the assessment of cardiac risk in patients with coronary artery disease.

Usefulness of dobutamine radionuclide ventriculography for prediction of left ventricular function improvement after coronary artery bypass grafting for ischemic cardiomyopathy.

Ventricular function may improve after coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy depending on the amount of contractile myocardial reserve. Based on the studies using dobutamine echocardiography to predict regional wall improvement after revascularization, we investigated the benefit of low-dose dobutamine radionuclide ventriculography for assessing functional contractile reserve in this population. The study group included 56 patients with ischemic cardiomyopathy (mean left ventricular [LV] ejection fraction [EF] of 23 +/- 5%) and multivessel disease, who were referred for viability assessment. All underwent radionuclide ventriculography before and during infusion of 5 and 10 microg/kg/min of dobutamine. An increase in global LVEF from rest to dobutamine was calculated, and 10% was considered the cutoff value to predict ventricular improvement after CABG. Of the 35 patients who underwent CABG 1 month later, 29 were available for repeated radionuclide ventriculography after 12 +/- 5 months. Of these, 15 showed improvement (delta LVEF > or = 5%, mean 10 +/- 5%) and 14 did not (delta LVEF < 5%, mean -1 +/- 3%). The increase in EF with dobutamine had the highest univariate predictive value of all parameters evaluated. The sensitivity, specificity, and positive and negative predictive values of dobutamine radionuclide ventriculography were 67%, 93%, 91%, and 72%, respectively. We conclude that dobutamine radionuclide ventriculography is a useful method to assess contractile reserve and predict ventricular functional improvement after CABG in patients with ischemic cardiomyopathy.

Ventricular fibrillation complicating temporary ventricular pacing in acute myocardial infarction: significance of right ventricular infarction.

Five patients with acute myocardial infarction had ventricular fibrillation as a complication of indicated temporary pacing. All five patients had evidence of right ventricular infarction (three patients with postmortem confirmation). The presence of right ventricular infarction seems to be a contributing mechanism involved in the induction of ventricular fibrillation during temporary pacing for bradyarrhythmia complicating acute myocardial infarction.

Left and right ventricular function in inferior acute myocardial infarction and significance of advanced atrioventricular block.

Of 139 consecutive patients with a first inferior acute myocardial infarction, 26 (19%) had advanced atrioventricular (AV) block and 113 (81%) did not. All were evaluated by 2-dimensional echocardiography (2-D echo) and radionuclide angiography. Patients with advanced AV block had lower radionuclide left ventricular (LV) ejection fraction (51 +/- 10 vs 58 +/- 11%, p less than 0.01), higher LV wall motion score on 2-D echo (5.6 +/- 2.6 vs 3.1 +/- 2.7, p less than 0.001), lower radionuclide right ventricular (RV) ejection fraction (32 +/- 15 vs 39 +/- 16%, p less than 0.001) and higher RV wall motion score on 2-D echo (3.4 +/- 1.7 vs 1.5 +/- 2, p less than 0.002) than did patients without AV block. The incidence rate of RV dysfunction was higher in patients with advanced AV block (78 vs 40%, p less than 0.02), and the mortality rate was also higher (although not significantly) in patients with advanced AV block (15 vs 6%). In conclusion, patients with inferior acute myocardial infarction and advanced AV block have larger infarct sizes (as seen on radionuclide angiography and 2-D echo) and lower RV and LV function than patients without AV block. This finding may explain the higher mortality rate observed in this group.

Relation between evolutionary ST segment and T-wave direction and electrocardiographic prediction of mycardial infarct size and left ventricular function among patients with anterior wall Q-wave acute myocardial infarction who received reperfusion therapy.

In the prethrombolytic era it was found that infarct size and left ventricular ejection fraction could be predicted using the Selvester QRS score. We evaluated whether infarct size and left ventricular ejection fraction could be predicted by the predischarge QRS score in patients who had received reperfusion therapy and whether considering the configuration of the ST segments and T waves would increase the accuracy of these predictions. We evaluated 51 patients with first anterior wall myocardial infarction who had received reperfusion therapy and predischarge resting technetium-99m-sestamibi scan. The electrocardiograms recorded on the same day of the scan were analyzed for the QRS score and were divided into 3 groups: A, isoelectric ST and negative T waves; B, ST elevation (> or =0.1 mV) and negative T waves; and C, ST elevation (> or =0.1 mV) and positive T waves. Groups A, B, and C included 12, 23, and 16 patients, respectively. The myocardial perfusion defect extent increased from groups A to C (median 21%, 37%, and 43.5% in groups A, B, and C, respectively; p = 0.023). Similarly, left ventricular ejection fraction decreased (44%, 38%, and 34%, respectively; p = 0.042) from groups A to C. Overall, the correlation between the QRS score and the myocardial perfusion defect extent (rho 0.249; p = 0.08) and ejection fraction (rho -0.229; p = 0.11) was poor. A statistically significant correlation between myocardial perfusion defect size and QRS score was found only in group A (rho 0.599, p = 0.04). Among patients with anterior myocardial infarction who received reperfusion therapy, the predischarge QRS score was predictive of infarct size only in those in whom ST elevation resolved completely. In patients with residual ST elevation there was no correlation between QRS score and infarct size.

The impact of right ventricular infarction on the prevalence of ventricular arrhythmias during acute inferior myocardial infarction.

To determine the impact of RV infarction on the prevalence and complexity of ventricular arrhythmias during inferior AMI, 57 patients with no prior MI were studied by 24-hour Holter monitoring on the first and tenth days of AMI. Based on radionuclear studies, patients were allocated into two groups: (1) group A, 21 patients (37 percent) with normal RVEF (greater than or equal to 40 percent); and (2) group B, 36 patients (63 percent) with depressed RVEF (less than 40 percent). There were no significant differences between the groups regarding age and LVEF. Values of RVEF were 47 +/- 6 percent and 31 +/- 6 percent, respectively (p less than 0.05). The RVEF had no influence on the prevalence and complexity of early and late arrhythmias. Stratification of patients in group B into two subgroups based on the extent of RV dysfunction did not reveal any differences in the occurrence of all forms of ectopy (when both groups were matched to group A). Therefore, patients with inferior AMI, with or without RV infarction, have a similar prevalence of arrhythmias. Ventricular ectopic beats may be related to the severity and spread of LV involvement, rather than to RV dysfunction.

Significance of the magnitude of a QS wave deflection in evaluating the uninvolved muscle in anterior wall myocardial infarction.

The significance of dynamic changes of the QS wave magnitude, as demonstrated in the precordial leads, within the natural evolution of acute anterior wall myocardial infarction (AAMI) was assessed in 25 patients within two weeks of their admission to the intensive cardiac care unit. Two sets of tests, including 12-lead electrocardiogram and a full radionuclear study, were performed in two time periods: (1) within the first 48 hours of admission; and (2) between the 12th and 15th day after admission. Comparison and correlation between the electrocardiographic data, QS waves in leads V2 and V3 and in V1 to V6 (sigma QV2-3 and sigma QV1-6), and radionuclear regional ejection fractions of the noninfarcted posterior muscle (inferior, infero-apical, and posterolateral regions and posterior index) were done. Significant linear correlations were demonstrated between the electrocardiographic variant differences in percentages (sigma QV2-3 and sigma QV1-6) and the radionuclear variant differences, especially the posterolateral and the infero-apical regions, as well as the posterior radionuclear index (r between 0.5 and 0.75; p less than 0.01). In addition, almost all of the patients who showed deepening of QS waves in the precordial leads also showed an increase in regional ejection fractions in uninvolved myocardium, and vice versa. It is concluded that the dynamic changes of the QS wave magnitude in the precordial leads within the evolution of acute anterior myocardial infarction well reflect the changes of the posterior noninfarcted muscle contraction and therefore offers a simple, inexpensive, and indirect electrocardiographic method for evaluating changes in contraction patterns of noninfarcted myocardium.

A simplified QRS scoring system for the estimation of the severity of acute inferior wall myocardial infarction.

Electrocardiographic assessment of the R/Q wave ratio (lead 2) of patients with a first acute inferior wall myocardial infarction (IWMI) offers important indirect quantitative information regarding the severity and extent of the myocardial damage. Eighty-eight consecutive patients with IWMI were investigated by echocardiography and radionuclear angiography. After measuring the R/Q ratio in lead 2 during the ST-wave stabilized stage of myocardial infarction, patients were separated into three groups--group 1 with an R/Q ratio greater than 2; group 2 with an R/Q ratio between 1 to 2; and group 3 with an R/Q ratio less than 1. Utilizing the information thus gathered from the electrocardiogram (ECG) offers a simple and efficient method for early prognosis which merits further investigation.

The effect of lovastatin on early restenosis.

The effect of lovastatin given before percutaneous coronary angioplasty (PTCA) on early restenosis was investigated in men with mild to moderate hypercholesterolemia. Thirty-four hypercholesterolemic patients (serum LDL cholesterol 130-200 mg/dL) undergoing their first PTCA completed a 6-month prospective, double-blind, placebo-controlled trial. Eighteen received lovastatin 20 mg/day (Lo group) and 16 placebo (P1 group), beginning 10 to 21 days before PTCA. All underwent a thallium-201 quantitative exercise test 5 to 7 days after PTCA. Endpoints for restenosis were either 50% narrowing of the dilated artery on coronary angiography, performed in symptomatic patients or, in asymptomatic patients, the appearance of newly developed reversible filling defects in the vascular territory of the dilated artery on a second thallium scan done 6 months after PTCA. The hypocholesterolemic change observed in the Lo group was not accompanied by a reduction in early restenosis risk. The authors conclude that effective hypocholesterolemic therapy before PTCA does not affect early restenosis rate in men with mild to moderate hypercholesterolemia.

Effect of dipyridamole on myocardial perfusion and function using technetium-99m MIBI.

Myocardial perfusion imaging with dipyridamole is an accepted method for diagnosing coronary artery disease. However, the simultaneous effect of dipyridamole on perfusion and function in the detection of coronary artery disease has not been studied extensively. The aim of this study was to investigate this effect using technetium-99m methoxy isobutyl isonitrile (Tc-MIBI) imaging. Twenty-eight patients with proven coronary artery disease participated in a 2-day protocol (rest and then 0.56 mg/kg dipyridamole i.v.) using Tc-MIBI for first-pass radionuclide ventriculography followed by SPECT imaging. Fifteen patients (54%) demonstrated a decrease in left ventricular ejection fraction from rest to dipyridamole and/or wall motion abnormality, while 21 patients (75%) showed abnormal perfusion by dipyridamole MIBI SPECT imaging. Concordance between perfusion and function was 65%. Correlation for one-, two- and three-vessel disease (coronary angiography) to perfusion versus function were: 54% vs. 38%, 80% vs. 60% and 80% vs. 80%, respectively. Left ventricular dysfunction using dipyridamole was noted in patients with multivessel disease, and with multi-reversible perfusion filling defects. We conclude that dipyridamole in combination with Tc-MIBI for assessment of perfusion and function serves as a valuable tool to identify patients with multivessel disease and a high amount of myocardium at risk.

Isolated mid-anterior myocardial infarction: a special electrocardiographic sub-type of acute myocardial infarction consisting of ST-elevation in non-consecutive leads and two different morphologic types of ST-depression.

UNLABELLED: We describe eight patients with a distinct electrocardiographic pattern of anterior wall myocardial infarction characterized by three main features: (1) a pattern of 'transmural ischemia' (ST-elevation with positive T-wave) in non-consecutive leads: a VL and V2, and two different types of ST-depression; (2) a pattern of 'true reciprocal changes' (ST-depression and negative T-wave) in III and a VF; (3) a pattern of 'sub-endocardial ischemia' (ST-depression with positive T-wave) in V4-5, while ST in V3 was either isoelectric or depressed. We characterize the electrocardiographic features and correlate them with the echocardiographic, radionuclide, and angiographic data. All patients admitted to the coronary care unit from January 1990 to April 1992 with evolving acute myocardial infarction were evaluated prospectively. Patients whose admission electrocardiogram met the description above were included. The electrocardiographic evolution, echocardiographic, Technetium MIBI tomography, and coronary angiography are described. Of 471 patients with acute anterior wall myocardial infarction, admitted to the coronary care unit during the study period, eight patients met the inclusion criteria (1.7% of acute anterior wall myocardial infarction). Echocardiographic studies revealed mid-anterior hypokinesis in two patients, anterior and apical hypokinesis in one, and no wall motion abnormality in four patients. Technetium MIBI tomography, done in five patients, was consistent with mid-anterior or midanterolateral infarction without involvement of the septum or apex. Coronary angiography, performed in seven patients, demonstrated significant obstruction of the first diagonal branch in all of the patients. In four patients, the diagonal occlusion was the only significant coronary lesion in the left coronary artery. CONCLUSION: Most of the anterior myocardial infarctions also involve the septal and apical regions. Anterior wall myocardial infarctions limited to the mid-anterior or mid-anterolateral wall, without apical or septal wall involvement are relatively rare. This study describes a special electrocardiographic form of anterior wall acute myocardial infarction. This distinct electrocardiographic pattern represents true mid-anterior wall myocardial infarction, caused by occlusion of a first diagonal branch of the left anterior descending coronary artery. The septal and apical regions are not involved because the blood supply via the left anterior descending artery is not interrupted.

Short- and long-term dobutamine treatment in chronic ischemic heart failure.

This study was undertaken in order to characterize the short-term (1 hour) and long-term (72 hours) effect of dobutamine on hemodynamic and regional ejection fraction parameters measured by radionuclear angiography in patients with chronic congestive heart failure due to coronary artery disease. Baseline hemodynamic and radionuclear parameters were measured and then intravenous dobutamine (8.5 mu/kg/min) was administered. The above parameters were determined again after 1 hour and 72 hours of continuous dobutamine administration. Sixty minutes (short-term) after dobutamine administration heart rate and cardiac index increased significantly (p less than 0.001 for both) and peripheral resistance decreased concomitantly (p less than 0.005). Global left ventricular ejection fraction (LVEF) as measured by multigated equilibrium nuclear angiography (MUGA) increased from 21.8 +/- 10.6% to 25 +/- 13.5 (p less than 0.02). Count-based mean regional ejection fraction in the septal, inferoapical, posterolateral (45 degrees left anterior oblique view) and inferior apical and anterolateral (30 degree right anterior oblique gated first pass) regions increased also. At 72 hours (long-term) after continuous dobutamine infusion, heart rate and cardiac index were still significantly higher and peripheral resistance lower than in the control study. However, global and count-based regional ejection fraction decreased to control values in the right anterior oblique view (first-pass analysis) and the left anterior oblique view (MUGA). Global LVEF measured in the right anterior oblique view by first-pass technique was significantly higher than control in the long-term study (23 +/- 9.7 vs. 27.8 +/- 2.4; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Increased adhesiveness of peripheral blood leukocytes corresponds to the appearance of expansion following anterior wall myocardial infarction.

The appearance of increased leukocyte adhesiveness/aggregation as an inflammatory marker in the peripheral blood of patients with anterior wall myocardial infarction was monitored. Of the 26 patients included in the study, 7 had infarct expansion as shown by an enlargement of left ventricular end-diastolic volume. The percent of aggregated leukocytes in the peripheral blood of patients with expansion (29.7 +/- 15.5%) was significantly higher (p = 0.01) than that obtained from patients with no expansion (18.5 +/- 6.8%). The lack of significant differences in peak creatine kinase concentrations between patients with and without expansion suggests that infarct size is not necessarily the main determinant for the appearance of expansion; an increased inflammatory reaction could be a contributory factor.

Predictive value of dobutamine radionuclide ventriculography in detection of functional improvement after acute anterior wall infarction and thrombolytic therapy.

BACKGROUND: Prolonged postischemic ventricular dysfunction (stunned myocardium) may prevent the assessment of myocardial salvage early after thrombolysis. Dobutamine in conjunction with radionuclide ventriculography has been proposed for the early assessment of myocardial viability and prediction of functional recovery. HYPOTHESIS: This study was designed to investigate the effects of low-dose dobutamine infusion on early global and regional function of reperfused myocardium after acute anterior wall myocardial infarction (MI). In particular, our purpose was to examine whether this response can predict late recovery of left ventricular function and correlate with the reperfused status (patency of infarct-related artery). METHODS: In all, 29 consecutive patients with first uncomplicated anterior wall MI, and who had received thrombolytic therapy, underwent radionuclide ventriculography at rest and 2 min after each dose increment of dobutamine infusion (5-15 micrograms/kg/min) on the third day after the infarction, at discharge, and at 3 months' follow-up. Global and regional ejection fraction were calculated at each stage. Four patients with complications were dropped from the study. A significant response to dobutamine was defined as an increase of at least > or = 7% in global or regional ejection fraction at the infarct zones. RESULTS: Of the 25 patients, 18 (72%) fulfilled these criteria. Of these, 10 patients (56%) had a significant improvement in global or regional ejection fraction at discharge and 13 patients (72%) at 3-month follow-up. The overall sensitivity of the dobutamine test in predicting left ventricular improvement was 100% at discharge and 93% at 3-month follow-up. However, the positive and negative predictive values were 56 and 100% at discharge and 72 and 86%, respectively, at 3-month follow-up. CONCLUSION: Low-dose dobutamine radionuclide ventriculography is a safe and useful test for assessing myocardial viability and may predict late functional improvement in patients with anterior wall MI.

The utility and potential cost-effectiveness of stress myocardial perfusion thallium SPECT imaging in hospitalized patients with chest pain and normal or non-diagnostic electrocardiogram.

BACKGROUND: The evaluation of hospitalized patients with chest pain and non-diagnostic electrocardiogram is problematic and the optimal cost-effective strategy for their management controversial. OBJECTIVES: To determine the utility of myocardial perfusion imaging with thallium-201 for predicting outcome of hospitalized patients with chest pain and a normal or non-diagnostic ECG. METHODS: On pain cessation, 109 hospitalized patients, age 61 +/- 14 years (mean +/- SD), with chest pain and non-diagnostic ECG underwent stress myocardial perfusion SPECT imaging with thallium-201. Costs related to their management were calculated. The occurrence of non-fatal myocardial infarction or cardiac death was recorded at 12 +/- 5 months follow-up. RESULTS: A normal SPECT was found in 84 patients (77%). During one year follow-up, only 1 (1.2%) compared to 7 (28%) cardiac events (6 myocardial infarctions, 1 cardiac death) occurred in patients with normal versus abnormal scans respectively (P < 0.0001). Negative predictive value and accuracy of the method were 99% and 83% respectively. Multivariate regression analysis identified an abnormal SPECT as the only independent predictor of adverse cardiac event (P = 0.0016). Total cost from admission until discharge was 11,193 vs. 31,079 shekels (P < 0.0001) for normal and abnormal scan. Considering its high negative predictive value, shortening the hospital stay from admission until scan performance to 2 days would result in considerably reduced management costs (from NIS 11,193 to 7,243) per patient. CONCLUSION: Stress SPECT applied to hospitalized patients with chest pain and a normal or non-diagnostic ECG is safe, highly accurate and potentially cost effective in distinguishing between low and high risk patients.