Author + information
- Elena Biagini, MD,
- Abdou Elhendy, MD, FACC,
- Arend F.L. Schinkel, MD,
- Jeroen J. Bax, MD,
- Rizzello Vittoria, MD,
- Ron T. van Domburg, PhD,
- Claudio Rapezzi, MD,
- Maarten L. Simoons, MD, FACC and
- Don Poldermans, MD⁎ ()
- ↵⁎Thoraxcenter Room Ba 300, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands
To the Editor:The incremental value of myocardial ischemia assessed by dobutamine stress echocardiography (DSE) for predicting cardiac events has been shown in various patient groups (1). The clinical utility of non-invasive stress testing has been mostly established among patients with intermediate pre-test probability of coronary artery disease (CAD). In patients with a low pre-test probability of CAD, exercise echocardiography was shown to provide limited prognostic information and was not routinely recommended (2). There are currently insufficient data to suggest a prognostic role of myocardial ischemia assessed by stress echocardiography in patients with typical angina who are determined to have a high pre-test probability of CAD. According to the Bayes theorem, a normal stress test result in these patients only modestly reduces the post-test probability of CAD. Therefore, it is not known whether patients with a high pre-test probability of CAD would be considered a low-risk population if they had a normal stress echocardiogram. We sought to assess the additional value of myocardial ischemia during DSE in predicting mortality and hard cardiac events in patients with angina and no history of CAD.
The study population consisted of consecutive patients with typical angina who were considered to have a high pre-test probability of CAD (>0.7) referred for DSE. This was considered in the presence of typical angina pectoris in women ≥50 years of age and in men ≥30 years of age, according to the published data (3). Patients were excluded if they had a previous myocardial infarction, myocardial revascularization, or significant coronary artery stenosis by angiography. Criteria were fulfilled in 329 patients. The protocol was approved by the Hospital Ethics Committee. Follow-up was successful in 327 patients (99%); 28 (8%) underwent early coronary revascularization (within 60 days after the DSE).
The DSE was performed and interpreted according to a standard protocol as previously reported (1). An abnormal test result was defined as resting wall motion abnormality or ischemia. Follow-up events were overall mortality and hard cardiac events (nonfatal myocardial infarction and cardiac death).
The mean age was 64 ± 10 years. There were 205 (63%) men. Thirty-six (11%) patients had a history of diabetes mellitus, 100 (31%) had hypertension, and 24 (7%) had a history of heart failure. The target heart rate was reached in 262 (80%) patients.
The DSE was normal in 125 (38%) patients. Fixed wall motion abnormalities were detected in 53 (16%) and ischemia was detected in 149 (46%) patients. During a mean follow-up of 6 ± 3.8 years, there were 89 (27%) deaths, of which 52 (16%) were attributed to cardiac causes. Twenty-one (6%) patients experienced nonfatal myocardial infarction. Twenty-five of 125 patients with a normal stress test result (20%) underwent revascularization, whereas 75 of 202 patients with an abnormal test result (37%) underwent revascularization (p = 0.002). Cox proportional hazards regression analysis for the end points of cardiac death, hard cardiac events, and all-cause mortality is presented in Table 1.The presence of myocardial ischemia was an independent predictor for all end points.
Kaplan-Meier survival curves for the end point cardiac death are presented in Figure 1.The annual cardiac death, all cause mortality, and hard cardiac event rates at 5 years were 1.5%, 2.6%, and 2.3% in patients with a normal test result and 3.6%, 5.5%, and 5.4% in patients with an abnormal DSE result, respectively.
An additional analysis was performed excluding patients with early revascularization. This analysis of 299 patients showed that myocardial ischemia was an independent predictor for cardiac death (risk ratio [RR], 2.7; confidence interval [CI], 1.2 to 5.7), all-cause mortality (RR, 2.3; CI, 1.4 to 3.8), and hard cardiac events (RR, 4.3; CI, 2.3 to 8.1).
In this study, DSE added independent prognostic information in patients with angina and a high pre-test probability of CAD. Patients with a normal DSE had a lower risk of death and hard cardiac events, whereas in patients with an abnormal DSE, the incidence of all events was substantially higher. The presence of myocardial ischemia was the strongest independent predictor for all end points and was associated with an increased risk of events after adjustment to clinical data.
The prevalence of CAD in patients who present with typical angina is expected to be approximately 90% for men and 70% for women (4). In this study, however, DSE was normal in 38% of the population. The results of our study indicate that patients with a normal DSE have a low event rate during intermediate to long-term follow-up, and therefore these patients, who represent a relatively large proportion of the study population, can be exempted from further (invasive) diagnostic evaluation unless a change in clinical status occurs.
Few studies evaluated the prognostic value of stress echocardiography in patients with a high pre-test probability of CAD. These studies used composite end points that include soft events such as unstable angina and revascularization (5,6), or were not powered enough to show an incremental value of myocardial ischemia alone (7). A recent study by Hachamovitch et al. (8) showed that myocardial perfusion imaging provided incremental prognostic information for predicting cardiac death in 1,270 patients with a high likelihood of CAD who underwent exercise or adenosine stress myocardial perfusion tomography.
Although patients were determined to have a high pre-test probability of CAD in our study, the annual hard cardiac event rate was moderate (4%). This can be explained by the exclusion of patients with previous myocardial infarction, unstable symptoms, and a history of CAD, which resulted in inclusion of a stable population with preserved left ventricular systolic function. Although this study excluded patients with cardiomyopathy, the possible existence of other cardiac conditions that may be associated with cardiac death without ischemia, such as cor pulmonale, may have been confounding. However, the incremental significance of myocardial ischemia was demonstrated despite this potential limitation.
We conclude that in patients with classic angina, determined to have a high pre-test probability of CAD, DSE yields independent prognostic information. A negative DSE is associated with a relatively low event rate for cardiac and all-cause mortality as well as for the combined end point of hard cardiac events. These findings have important clinical implications because these patients can be exempted from invasive studies if they have no change in clinical status. Myocardial ischemia during DSE is independently associated with an increased risk of death after adjustment for clinical data.
- American College of Cardiology Foundation
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