Improving Risk Assessment with Cardiac Testing in Peripheral Arterial Disease
Article Outline
Abstract
Purpose
The study’s objective was to evaluate the prognostic value of left ventricular ejection fraction and stress-induced ischemia during dobutamine stress echocardiography, in addition to ankle-brachial index measurements and clinical risk factors in patients with suspected or known peripheral arterial disease.
Methods
In 852 patients with suspected or known peripheral arterial disease (mean age 63 years, 70% male), the ankle-brachial index was measured, left ventricular ejection fraction was assessed, and all patients underwent additional stress testing. Endpoints were all-cause mortality and hard cardiac events (cardiac death or nonfatal myocardial infarction).
Results
During a mean follow-up of 7.6
±4.4 years, death occurred in 288 patients (34%), and hard cardiac events occurred in 216 patients (25%). Mean left ventricular ejection fraction was 50%±17%, and stress-induced ischemia was observed in 352 patients (41%). In multivariate analysis with adjustment for clinical risk factors and ankle-brachial index, each 5% decrease in left ventricular ejection fraction was associated with increased all-cause mortality (hazard ratio [HR] 1.05, 95% confidence interval [CI], 1.02-1.09) and hard events (HR 1.14, 95% CI, 1.08-1.21). Stress-induced ischemia also independently predicted all-cause mortality (HR 2.01, 95% CI, 1.38-2.79) and hard events (HR 2.06, 95% CI, 1.39-3.08). Left ventricular ejection fraction and stress-induced ischemia provided incremental prognostic information over clinical data and ankle-brachial index values (P <.001).
Conclusions
Left ventricular ejection fraction and stress-induced ischemia independently predict long-term outcome and improve prognostic risk assessment, in addition to ankle-brachial index and clinical risk factors in patients with suspected or known peripheral arterial disease.
Keywords: Ankle-brachial index, Coronary artery disease, Dobutamine stress echocardiography, Left ventricular dysfunction, Peripheral arterial disease, Prognosis
Lower extremity peripheral arterial disease is a manifestation of systemic atherosclerosis and has been recognized as a growing health burden worldwide.1 Prevalence rates up to 29% have been reported for peripheral arterial disease in the United States, depending on the age of the study cohort, the underlying atherosclerosis risk factor profile, and the presence of cardiovascular co-morbidities.2, 3, 4, 5, 6, 7 A high prevalence of left ventricular dysfunction among patients with symptomatic peripheral arterial disease has been observed.8 Moreover, coronary artery disease frequently co-exists with peripheral arterial disease because both conditions share the same atherosclerotic risk factors. More than half of patients who present with peripheral arterial disease may have evidence of coronary artery disease based on electrocardiography or medical history.1, 9, 10 The prognosis of patients with peripheral arterial disease is therefore characterized by a 2- to 6-fold increased risk of cardiovascular death.11, 12, 13, 14, 15, 16, 17
The American College of Cardiology/American Heart Association has emphasized in their guidelines for the management of patients with peripheral arterial disease the importance of identifying and treating underlying cardiovascular risk factors and obtaining ankle-brachial index data for prognostic risk stratification.1 Although the detection of coronary artery disease and left ventricular dysfunction in this particular patient population may be important because of the benefit from subsequent medical therapy or coronary intervention, evidence-based recommendations for cardiac assessment in literature are limited.
Dobutamine stress echocardiography is an accurate, safe, and widely used noninvasive imaging technique for the evaluation of coronary artery disease and risk assessment.18, 19 However, because ankle-brachial index data can risk stratify this population, it is not known whether stress testing can further provide prognostic information in addition to ankle-brachial index values. The purpose of this study was to determine the prognostic value of dobutamine stress echocardiography in addition to ankle-brachial index measurements and clinical risk factors in a large cohort of patients with suspected or known peripheral arterial disease.
Methods
The study population consisted of consecutive patients referred for evaluation of peripheral arterial disease at the outpatient vascular clinic of the Erasmus Medical Center (MC), Rotterdam, the Netherlands between January 1990 and January 2005. The Erasmus MC is a metropolitan university hospital in the southwestern area of the Netherlands, serving a population of approximately 3 million and acting as a tertiary referral center for approximately 30 affiliated hospitals. Patients with suspected peripheral arterial disease had a typical history of intermittent claudication or other symptoms of chronic arterial insufficiency, including ulceration of the foot, hair loss, or reduced capillary refill. Patients with known peripheral arterial disease had a resting ankle-brachial index ≤0.90. Dobutamine stress echocardiography was performed to assess the presence and extent of concomitant coronary artery disease. Specific indications for stress echocardiography included typical or atypical chest pain, assessment for coronary artery revascularization, and (presurgical) prognostic risk stratification. The hospital’s Medical Ethical Committee approved the study protocol. Patients who fulfilled inclusion criteria agreed on participation in the study. Based on hospital records and personal interviews at the time of the visit, a medical history was recorded, and data were prospectively entered into a computerized database. Diabetes mellitus was recorded if patients presented with a fasting glucose level of ≥7.0 mmol/L or in those who required insulin treatment. Hypertension was recorded if patients presented with a blood pressure ≥140/90 mm Hg or if patients received antihypertensive drugs. Hypercholesterolemia was recorded if patients presented with a plasma cholesterol level ≥5.5 mmol/L or if patients were taking lipid-lowering agents. Patients were considered to have renal dysfunction if they presented with a serum creatinine level ≥2.0 mg/dL (177 μmol/L) or if they required dialysis. Cigarette smoking included only current smoking. Patients were assessed for cardiac medication use and a baseline 12-lead electrocardiography was obtained.
Ankle-Brachial Index Measurement
Systolic blood pressures in the right and left brachial artery, right and left dorsalis pedis artery, and right and left posterior tibial artery were measured by trained technicians using a Doppler ultrasonic instrument with an 8-MHz vascular probe (Imexdop CT+ Vascular Doppler, Miami Medical, Glen Allen, Virginia). The ankle-brachial index in the right and left leg was calculated by dividing the right and the left ankle pressure by the brachial pressure. The higher of the 2 brachial blood pressures was used if a discrepancy in systolic blood pressure was present. Again, the higher of the dorsalis pedis and posterior tibial artery pressure was used when a discrepancy in systolic blood pressure between the 2 arteries was measured. The ankle-brachial index was measured after the participants had been resting in the supine position for at least 10 minutes. Of the ankle-brachial index values obtained in each leg, the lower was used in all analysis. Inter- and intraobserver agreement for the ankle-brachial index was 97% and 98%, respectively. We considered patients with values greater than 1.50 to have calcified atherosclerosis. These patients were excluded from the study.
Dobutamine Stress Echocardiography
The dobutamine stress echocardiography was performed as previously described.20, 21 Patients underwent a resting 2-dimensional echocardiographic examination. Left ventricular end-diastolic and end-systolic volumes were obtained from the apical 4- and 2-chamber views by using the Simpson’s rule formula, from which the ejection fraction was calculated. Dobutamine hydrochloride was then administered intravenously by infusion pump, starting at 10 μg/kg/min for 3 minutes, and increased by 10 μg/kg/min every 3 minutes to a maximum of 40 μg/kg/min. The dobutamine infusion was stopped if a target heart rate was achieved (85% of a theoretic maximal heart rate). If the target heart rate was not achieved and patients had no symptoms or signs of ischemia, atropine sulphate (starting with 0.25 mg, increased to a cumulative maximum of 2.0 mg) was given intravenously. Patients were excluded from the study if the test was prematurely terminated because of: symptomatic decrease in systolic blood pressure >40 mm Hg from the resting value, or a systolic blood pressure <100 mm Hg; blood pressure >240/140 mm Hg; occurrence of cardiac arrhythmias; intolerable adverse effects from dobutamine or atropine; and poor echocardiographic images. Off-line assessment of echocardiographic images was performed by 2 experienced investigators without knowledge of the patient’s clinical data. From 1990 to 1993, a 14-segment 4-point ordinal scale was used. After 1993, a 16-segment 5-point score was used.21, 22, 23 Stress-induced myocardial ischemia was considered if new wall motion abnormalities occurred (ie, if wall motion in any segment worsened by ≥1 grade(s) during the test, with the exception of akinesis becoming dyskinesis). The extent and location of ischemia were evaluated, and a wall-motion score index (total score divided by the number of segments scored) was calculated, both at rest and during peak stress. When there was disagreement between the 2 assessors, a third investigator viewed the images and a majority decision was reached.
Follow-up
During follow-up, study endpoints were all-cause mortality and hard cardiac events (cardiac death or nonfatal myocardial infarction). Survival status was obtained by approaching the referring physician or the municipal civil registries. Clinical information was obtained by outpatients visits, mailed questionnaires, telephone interviews, and reviewing hospital records. Nonfatal myocardial infarction was diagnosed when at least 2 of the following were present: elevated cardiac enzyme levels (CK level >190 U/L and CK-MB >14 U/L, or CK-MB fraction >10% of total CK, or cardiac troponin T >0.1 ng/mL), development of typical electrocardiographic changes (new Q waves >1 mm or >30 ms), and typical symptoms of angina pectoris. Death certificates and autopsy reports were reviewed, and general practitioners were approached to ascertain the cause of death. Cardiac death was defined as death caused by acute myocardial infarction, cardiac arrhythmias, or congestive heart failure. Sudden unexpected death in previously stable patients was considered cardiac death.
Statistical Analysis
Continuous data were compared using the Student’s t test or analysis of variance techniques when appropriate. Categorical data were compared using the chi-squared test. A final set of independent predictors of left ventricular ejection fraction <35% and stress-induced myocardial ischemia was obtained by multivariate analysis with stepwise deletion of the least significant variable. The Kaplan-Meier method with the log-rank test was used to assess differences in survival between different groups of patients. Univariate and multivariate Cox hazard regression analysis was used to evaluate the prognostic value of dobutamine stress echocardiography, ankle-brachial index, and baseline clinical variables. The incremental value of dobutamine stress test results over clinical variables and ankle-brachial index values in the prediction of events was determined according to 3 models. In the first model, clinical variables, baseline electrocardiography, and ankle-brachial index values were entered. In the second and third model, left ventricular ejection fraction and stress-induced ischemia, respectively, were added to the first model. Tests for heterogeneity were used to reveal a possible interaction between dobutamine stress echocardiography and ankle-brachial index values. For all tests, a P-value <.05 (2-sided) was considered significant. Analysis was performed using SPSS-11.0 statistical software (SPSS Inc., Chicago, Ill).
Results
A total of 944 patients were referred for ankle-brachial index measurement and dobutamine stress echocardiography. A total of 30 patients (3%) were excluded because of ankle-brachial index values >1.50, and 62 patients (7%) were excluded due to termination of the stress test before an ischemic endpoint (cardiac arrhythmia in 8 patients, hypotension in 14, chills and intolerable adverse effects in 11, and poor echocardiographic images in 29 patients). The remaining 852 patients were considered for follow-up and constituted our study population (Table 1). Follow-up was successful in all. Mean age was 63 years, and 598 patients (70%) were male. Mean ankle-brachial index was 0.72±0.24, and 621 patients (73%) had an ankle-brachial index ≤0.90. During dobutamine stress echocardiography, no fatal complications occurred. Mean left ventricular ejection fraction was 50%±17%, and 105 patients (12%) had an ejection fraction <35%. A total of 122 patients (14%) had an ejection fraction <40%. Rest wall motion abnormalities were observed in 469 patients (55%). Ischemia (new wall motion abnormalities) was detected in 352 patients (41%). In the patients who presented with left ventricular ejection fraction <35%, stress-induced ischemia occurred in 79 patients (75%, 9% of the total study population). In the current patient cohort, the prevalence rate of coronary artery disease by medical history alone (angina pectoris or history of myocardial infarction) was 47% and when combined with dobutamine stress echocardiography, 70%. Variables independently associated with left ventricular ejection fraction <0.35% included male sex, history coronary artery disease, history of heart failure, diabetes, renal failure, and hypercholesterolemia. Variables independently associated with stress-induced myocardial ischemia included age, low ankle-brachial index values, and ischemic baseline electrocardiogram (Table 2).
Table 1. Baseline Characteristics According to Groups Defined by Ankle-Brachial Index Values and Dobutamine Stress Echocardiography
| Characteristic | DSE with No Ischemia, Normal ABI (n=154) | DSE with No Ischemia, Abnormal ABI (n=346) | DSE with Ischemia, Normal ABI (n=77) | DSE with Ischemia, Abnormal ABI (n=275) | P-Value |
|---|---|---|---|---|---|
| Demographics | |||||
| Age (years) (±SD) | 59±12 | 63±11 | 62±12 | 65.±11 | <.001 |
| Male sex | 61.0 | 74.0 | 68.8 | 70.9 | .027 |
| Angina | 20.8 | 27.5 | 29.9 | 19.3 | .046 |
| Previous myocardial infarction | 23.4 | 41.6 | 31.2 | 34.5 | .001 |
| Previous CABG | 13.6 | 19.4 | 22.1 | 14.2 | .13 |
| Previous PTCA | 1.3 | 6.1 | 2.6 | 2.9 | .041 |
| Known CAD (summary variable) | 35.7 | 55.8 | 46.8 | 45.1 | <.001 |
| History of congestive heart failure | 8.4 | 8.1 | 3.9 | 6.5 | .53 |
| History of stroke or TIA | 3.2 | 9.0 | 7.8 | 5.8 | .11 |
| Diabetes mellitus | 12.3 | 17.3 | 18.2 | 15.3 | .50 |
| Hypercholesterolemia | 22.7 | 20.5 | 27.3 | 16.0 | .11 |
| Hypertension | 27.9 | 41.3 | 20.8 | 37.5 | <.001 |
| Cigarette smoking | 28.6 | 37.9 | 29.9 | 26.2 | .013 |
| Renal failure | 3.9 | 4.0 | 1.3 | 6.2 | .26 |
| Abnormal electrocardiography | 31.8 | 47.7 | 45.5 | 45.1 | .01 |
| Q waves | 19.5 | 28.9 | 24.7 | 26.5 | .17 |
| ST segment changes | 1.9 | 2.3 | 6.5 | 5.8 | .042 |
| Medications | |||||
| Aspirin | 13.0 | 24.9 | 16.9 | 22.2 | .018 |
| ACE-inhibitor | 22.7 | 28.0 | 22.1 | 24.4 | .48 |
| Beta-blocker | 28.6 | 28.9 | 27.3 | 22.9 | .37 |
| Calcium channel blocker | 20.1 | 30.3 | 24.7 | 25.5 | .11 |
| Digoxin | 4.4 | 7.2 | 6.5 | 5.5 | .65 |
| Diuretic | 8.4 | 15.0 | 14.3 | 13.5 | .25 |
| Nitrate | 23.4 | 26.6 | 22.1 | 23.6 | .74 |
| Statin | 23.4 | 20.5 | 27.3 | 16.0 | .094 |
| Ankle-brachial index | 1.02±0.07 | 0.62±0.17 | 1.01±0.06 | 0.60±0.20 | <.001 |
| Rest wall motion abnormalities | 37.0 | 47.7 | 35.1 | 37.8 | .022 |
| Left ventricular ejection fraction | 53±16 | 51±17 | 49±18 | 47±17 | .12 |
Table 2. Variables Independently Associated with Left Ventricular Ejection Fraction <0.35% and Stress-induced Myocardial Ischemia During Dobutamine Stress Echocardiography Identified by Stepwise Multivariate Analysis
| Characteristic | Odds Ratio (95% CI) Left Ventricular Ejection Fraction <0.35% (n=105)⁎ | Odds Ratio (95% CI) for Stress-induced Myocardial Ischemia During DSE (n=352)† |
|---|---|---|
| Male sex | 2.08(1.25-3.49) | |
| Coronary artery disease | 4.07(2.60-6.36) | |
| History of heart failure | 3.48(1.75-6.91) | |
| Diabetes mellitus | 2.48(1.49-4.12) | |
| Renal failure | 3.54(1.27-9.88) | |
| Hypercholesterolemia | 1.84(1.14-2.97) | |
| Ankle-brachial index (per 0.10 decrease) | 1.06(1.01-1.13) | |
| Age (per year increase) | 1.02(1.00-1.03) | |
| Ischemic baseline electrocardiogram | 1.48(1.10-2.01) |
⁎C-statistic: 0.76. |
†C-statistic: 0.60. |
Prognostic Value of Dobutamine Stress Echocardiography
During a mean follow-up of 7.6±4.4 years, death occurred in 288 patients (34%) and hard cardiac events in 216 patients (25%; cardiac death in 145 patients and nonfatal myocardial infarction in 71). Kaplan Meier curves stratified according to ankle-brachial index and dobutamine stress echocardiography demonstrated that in patients with an ankle-brachial index ≤0.90, those with stress-induced ischemia had a decreased survival (annual mortality rate of 5.7%), compared with patients without ischemia (annual mortality rate of 3.2%, P <.001), and compared with patients without ischemia and ankle-brachial index >0.90 (annual mortality rate of 2.5%, P <.001) (Figure). Comparable results were obtained for the endpoint of hard events (Figure). In univariate analysis, left ventricular ejection fraction and stress-induced ischemia were significantly associated with adverse outcome (Table 3, Table 4). In multivariate analysis, left ventricular ejection fraction and stress-induced ischemia independently predicted all-cause mortality and hard cardiac events, and provided significant incremental prognostic information over clinical data and ankle-brachial index values (P <.001) (Table 3, Table 4). In a similar model including clinical baseline characteristics, electrocardiography, ankle-brachial index values, and left ventricular ejection fraction, a higher number of ischemic segments was also significantly associated with mortality (HR per ischemic segment: 1.06, 95% CI, 1.01-1.12, P=.01) and hard cardiac events (HR per ischemic segment: 1.08, 95% CI, 1.02-1.14, P=.006).
Figure.
Kaplan Meier curves in patient with suspected and known peripheral arterial disease stratified according to stress-induced myocardial ischemia (DSE+) and ankle-brachial index values ≤0.90 (ABI+).
Table 3. Univariate and Multivariate Predictors of All-cause Mortality
| Univariate HR (95% CI) | Multivariate | |||
|---|---|---|---|---|
| Characteristic | Model 1 HR (95% CI) | Model 2 HR (95% CI) | Model 3 HR (95% CI) | |
| Clinical characteristics | ||||
| Age (per year increase) | 1.06(1.04-1.07) | 1.05(1.03-1.07) | 1.04(1.02-1.06) | 1.04(1.02-1.06) |
| Male sex | 1.38(1.05-1.80) | 1.26(0.95-1.66) | 1.21(0.84-1.73) | 1.25(0.60-2.57) |
| Previous myocardial infarction | 1.53(1.21-1.93) | 1.32(0.99-1.69) | 1.15(0.82-1.62) | 1.08(0.57-2.04) |
| Congestive heart failure | 2.35(1.64-3.37) | 1.87(1.22-2.88) | 1.60(0.99-2.41) | 1.25(0.48-3.24) |
| History of stroke or TIA | 1.52(1.01-2.29) | 1.17(0.77-1.78) | 1.15(0.72-1.84) | 1.48(0.49-4.52) |
| Diabetes mellitus | 1.40(1.03-1.90) | 1.49(1.09-2.05) | 1.31(0.87-1.95) | 1.05(0.50-2.05) |
| Hypercholesterolemia | 0.76(0.55-1.05) | 0.94(0.67-1.31) | 0.90(0.61-1.34) | 0.96(0.46-2.03) |
| Hypertension | 1.09(0.86-1.39) | 1.01(0.78-1.27) | 0.98(0.72-1.33) | 1.04(0.56-1.94) |
| Cigarette smoking | 1.22(0.96-1.55) | 1.25(0.98-1.60) | 1.19(0.88-1.61) | 1.49(0.81-2.75) |
| Renal failure | 4.59(3.12-6.76) | 3.16(1.80-5.55) | 2.86(1.63-5.01) | 2.63(1.50-4.62) |
| Ischemic baseline electrocardiogram | 1.45(1.13-1.85) | 1.64(1.21-2.22) | 1.50(1.10-2.04) | 1.48(1.08-2.01) |
| ABI (per 0.10 decrease) | 1.14(1.09-1.20) | 1.06(1.01-1.12) | 1.05(1.01-1.11) | 1.05(1.01-1.11) |
| Stress test results | — | |||
| LVEF (per 5% decrease) | 1.07(1.03-1.11) | 1.06(1.02-1.11) | 1.05(1.02-1.09) | |
| Angina pectoris during test | 0.98(0.65-1.48) | — | 1.01(0.47-1.89) | |
| ST changes during test | 1.26(0.89-1.79) | 1.05(0.67-2.01) | ||
| New wall motion abnormalities | 2.20(1.57-3.08) | 2.01(1.38-2.79) | ||
| Global χ2 | 78 | 85 | 102 | |
| Incremental value | P=.01 | P <.001 | ||
Table 4. Univariate and Multivariate Predictors of the Composite Endpoint of Cardiac Death or Non-fatal Myocardial Infarction
| Characteristic | Univariate HR (95% CI) | Multivariate | ||
|---|---|---|---|---|
| Model 1 HR (95% CI) | Model 2 HR (95% CI) | Model 3 HR (95% CI) | ||
| Clinical characteristics | ||||
| Age (per year increase) | 1.03(1.02-1.04) | 1.03(1.01-1.05) | 1.03(1.00-1.05) | 1.03(1.00-1.05) |
| Male sex | 1.46(1.07-2.01) | 1.24(0.89-1.71) | 1.09(0.71-1.68) | 0.67(0.29-1.55) |
| Previous myocardial infarction | 2.04(1.56-2.67) | 1.51(0.97-2.37) | 1.32(0.79-2.23) | 1.37(0.60-3.10) |
| History of heart failure | 2.41(1.58-3.66) | 1.99(1.20-3.30) | 1.70(0.95-3.45) | 1.31(0.46-3.78) |
| History of stroke or TIA | 1.17(0.68-2.02) | 1.05(0.55-1.95) | 1.00(0.42-2.01) | 1.03(0.40-2.15) |
| Diabetes mellitus | 2.02(1.46-2.79) | 1.63(1.08-2.47) | 1.52(1.03-2.20) | 1.73(0.77-3.92) |
| Hypercholesterolemia | 1.37(1.01-1.88) | 1.38(0.99-1.94) | 1.25(0.84-1.88) | 0.95(0.43-2.11) |
| Hypertension | 1.32(1.00-1.71) | 1.08(0.81-1.44) | 1.11(0.77-1.59) | 1.64(0.81-3.32) |
| Cigarette smoking | 0.97(0.73-1.30) | 1.02(0.76-1.38) | 1.06(0.73-1.53) | 1.03(0.50-2.13) |
| Renal failure | 5.40(3.45-8.45) | 3.21(1.60-6.46) | 2.87(1.43-5.78) | 2.92(1.45-5.90) |
| Ischemic baseline electrocardiogram | 1.71(1.30-2.25) | 1.65(1.16-2.33) | 1.45(0.95-2.57) | 1.40(0.80-2.97) |
| ABI(per 0.10 decrease) | 1.15(1.08-1.21) | 1.07(1.00-1.13) | 1.03(0.98-1.10) | 1.03(0.97-1.11) |
| Stress test results | — | |||
| LVEF (per 5% decrease) | 1.17(1.13-1.25) | 1.15(1.09-1.22) | 1.14(1.08-1.21) | |
| Angina pectoris during test | 0.87(0.53-1.41) | — | 1.13(0.46-2.76) | |
| ST changes during test | 1.42(0.96-2.11) | 1.76(0.74-4.19) | ||
| New wall motion abnormalities | 2.34(1.58-3.47) | 2.06(1.39-3.08) | ||
| Global χ2 | 53 | 80 | 93 | |
| Incremental value | P <.001 | P <.001 | ||
Tests for heterogeneity revealed no evidence for a differential effect of dobutamine stress echocardiography results among patients with different ankle-brachial index values (all interaction terms: P >.05), indicating that decreased left ventricular ejection fraction and an ischemic stress test predicted the risk of death and hard cardiac events across the entire spectrum of ankle-brachial index values.
Discussion
Atherosclerosis has a common systemic pathogenesis and simultaneously affects multiple vascular beds.24 Prevalence rates up to 75% of concomitant coronary artery disease in peripheral arterial disease have been published in literature, based on coronary angiography or clinical history.9, 10 The current results demonstrate that coronary artery disease, cerebrovascular disease, and renal disease were remarkably high in our study population, with prevalence rates of 70%, 7%, and 5%, respectively. In addition, 12% of the current study population presented with left ventricular ejection fraction <35%. The high risk of death and the impaired health-related quality of life in patients with peripheral arterial disease poses a significant health burden worldwide.25 In the current study, death occurred in 34% and hard cardiac events occurred in 25% during a mean follow-up of 7.6 years, reflecting the significant adverse consequences of peripheral arterial disease. It is well established that low ankle-brachial index values predict overall and cardiovascular mortality, and that ankle-brachial index measurements can be used for prognostic risk stratification.26 The current study demonstrated supportive results and showed that each decrease in ankle-brachial index of 0.10 was associated with a 6% and 7% increased risk of all-cause mortality and hard cardiac events, respectively, independent of clinical risk factors and baseline electrocardiography.
Current Recommendations
The prognostic value of dobutamine stress echocardiography has previously been demonstrated in patients with suspected or known coronary artery disease.27 A major finding in our study is that dobutamine stress echocardiography improves risk stratification in patients with suspected or known peripheral arterial disease, in addition to ankle-brachial index values and clinical risk factors. Each 5% decrease in left ventricular ejection fraction was associated with a 5% and 14% increased risk of all-cause mortality and hard cardiac events, respectively. Stress-induced new wall motion abnormalities during dobutamine stress echocardiography were associated with a 2.0-fold and 2.1-fold increased risk, respectively. Furthermore, the extent of ischemia also was significantly associated with adverse outcome. The American College of Cardiology/American Heart Association has provided useful evidence-based guidelines regarding the management of patients with peripheral arterial disease and accentuate the frequent coexistence of coronary artery disease in these patients. Because of the paucity of published data, recommendations for cardiac risk assessment are limited. An improvement in the detection of (sub) clinical coronary artery disease and identification of those at increased risk for adverse events appears essential in order to obtain reductions in morbidity and mortality. The implication of dobutamine stress echocardiography in the work-up of patients with suspected or known peripheral arterial disease should therefore be considered.
When Should Dobutamine Stress Echocardiography Be Performed?
Although dobutamine stress echocardiography is a safe and accurate noninvasive procedure, the question remains whether all patients should undergo routine screening with this technique. This will probably depend on the availability of dobutamine stress echocardiography in the clinical practice, the presence and local expertise of assessing and scoring echocardiographic images, and the consideration of costs versus benefit. The current results demonstrate that male patients with coronary artery disease, history of heart failure, diabetes, renal failure, and hypercholesterolemia were more likely to present with left ventricular dysfunction. A subgroup of patients with advanced age, lower ankle-brachial index values, and ischemic baseline electrocardiography were more likely to have stress-induced myocardial ischemia. Of note, lower ankle-brachial index values were directly associated with the severity of new wall motion abnormalities during dobutamine stress echocardiography. A limitation that should be addressed is that our study cohort consisted of patients referred to a tertiary referral center with specific indications for stress echocardiography, and that it may not reflect “real-world” patients with peripheral arterial disease. Furthermore, it remains to be elucidated whether other noninvasive modalities, such as exercise electrocardiographic testing and myocardial perfusion imaging are superior to dobutamine stress echocardiography for prognostic cardiac risk assessment in patients with suspected or known peripheral arterial disease. Exercise electrocardiography may not be suitable as test of screening for coronary artery disease, because patients with peripheral arterial disease often have limited exercise capacity and often present with baseline electrocardiographic abnormalities.
Conclusion
The current results reveal that decreased left ventricular ejection fraction and stress-induced myocardial ischemia during dobutamine stress echocardiography independently predict long-term outcome and improve prognostic risk assessment in addition to ankle-brachial index and clinical risk factors in patients with suspected or known peripheral arterial disease. The use of dobutamine stress echocardiography makes it possible to detect left ventricular dysfunction and coronary artery disease in an early stage, to identify patients at increased risk for future adverse events, and therefore to implement adequate preventive interventions.
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PII: S0002-9343(06)00892-8
doi:10.1016/j.amjmed.2006.06.041
© 2007 Elsevier Inc. All rights reserved.
