Cardiac outcomes with submaximal normal stress echocardiography: a meta-analysis

Objectives: The aim of the study was to evaluate the risk of cardiac events in patients with normal stress echocardiography (SE) who attained maximal age-predicted heart rate (APHR) compared with those who did not in the setting of both normal and abnormal SE.

Background: SE is an important tool in the risk stratification and prognosis of patients with known or suspected coronary artery disease (CAD). The prognostic value of a normal but submaximal SE (<85% of maximal APHR) is conflicting.

Methods: PubMed, EMBASE, and CENTRAL were searched from 1980 to September 2011 for SE studies reporting cardiac outcomes in patients with known or suspected CAD stratified by achieved APHR. Both hard events (cardiac death and myocardial infarction) and total cardiac events (revascularization procedures in addition to hard events) were analyzed separately. Data on all-cause mortality were obtained when available.

Results: Fourteen studies with 11,542 patients followed up for a mean duration of 32 months fulfilled the inclusion criteria. In 8 studies with 4,577 patients, the risk of hard events with normal SE (both exercise and dobutamine) was 70% higher in patients who achieved submaximal compared with those with maximal APHR (annualized event rate 2.08% vs. 0.77%; p=0.0008; 95% confidence interval [CI]: 1.25 to 2.31). In 7 studies with 5,798 patients, the risk of total cardiac events with normal SE (both exercise and dobutamine) was 127% higher in patients who achieved submaximal compared with those with maximal APHR (annualized event rate 1.87% vs. 1.02%; p<0.0001; 95% CI: 1.54 to 3.34). The risk of total cardiac events was 278% higher in patients with abnormal SE with submaximal APHR compared with those with normal SE with submaximal APHR (p<0.0001; 95% CI: 2.81 to 5.08). There was a trend toward increased all-cause mortality in patients with normal SE with submaximal compared with maximal APHR (relative risk: 1.36; p=0.15; 95% CI: 0.89 to 2.09).

Conclusions: Patients with submaximal APHR in the setting of normal SE have a higher risk of cardiovascular events than those who attained maximal stress test. Thus, the results of submaximal APHR in the setting of normal SE should be taken into consideration for more accurate risk stratification and prognosis.