What Is The Prognostic Significance Of A Normal Myocardial Perfusion Scan?

2003. Determinants of risk and its temporal variation in patients with normal stress myocardial perfusion scans: What is the warranty period of a normal scan? Hachamovitch R, Hayes S, Friedman JD, Cohen I, Shaw LJ, Germano G, Berman DS. J Am Coll Cardiol. 2003 Apr 16;41(8):1329-40. UCLA and the Atlanta Cardiovascular Research Institute. Link to the full study in PDF format.

  • 7,376 consecutive patients with normal exercise or adenosine MPS.
  • Excluded patients: (1) Patients with valvular heart disease or primary cardiomyopathy, (2) patients who underwent SPECT within 90 days after percutaneous transluminal coronary angioplasty (PTCA). Also: Patients with previous MI or revascularization were considered to have known CAD, but they were NOT excluded from the study (N = 1280).
  • Among those not known to have CAD, pre-test probability of CAD was 0.22 ± 0.41.
  • Among those known to have CAD, pre-test probability of ischemia was 0.38 ± 0.35.
  • Follow-up: 22 ± 6 months, follow-up 96% complete.
  • For the entire cohort, annualized risk of  “hard” events (= death or non-fatal myocardial infarction) = 0.6% per year (1/167 per year). This breaks down further to 0.34% per year risk of death (1/294 per year) and 0.26% per year risk of non-fatal MI (1/385 per year).
  • [The annualized risk of “hard” events (=death or non-fatal myocardial infarction) for the 7,376 with normal myocardial perfusion scans was 1/6 that of the 8,091 patients with abnormal myocardial perfusion scans (who were eliminated from the study).]
  • Among the 7,376 patients in the study, predictors of higher risk for hard events included the following: (1) Known history of CAD; (2) Need for adenosine stress instead of treadmill stress; (3) Male gender; (4) Achievement of <80% of age-predicted maximum heart rate in those undergoing treadmill stress; (5) Age; (6) Diabetes mellitus, especially in women.
  • Among the 1280 patients with known coronary artery disease with normal myocardial perfusion scans, risk of hard events was higher in the second year of follow-up than in the first year of follow-up. This trend was not seen in those with no known coronary artery disease.
  • The highest risk subgroups had a maximal event rate of 1.4% to 1.8%/year. That is, a 1% per year risk of death (1/100 per year) and a 0.8% per year risk on non-fatal MI (1/125 per year). It is understood that when this highest risk subset is removed from the analysis, the remaining patients will have a substantially lower risk than when the highest risk subset is included.

 

2007. The Prognostic Value of Normal Exercise Myocardial Perfusion Imaging and Exercise Echocardiography: A Meta-Analysis. Louise D. Metz, MD, Mary Beattie, MD, Robert Hom, MD, Rita F. Redberg, MD, MSc, Deborah Grady, MD, MPH and Kirsten E. Fleischmann, MD, MPH. J Am Coll Cardiol, 2007; 49:227-237. NYU and UCSF. Link to the Abstract.

  • Only patients who underwent exercise (not pharmacologic stress) were included in the meta-analysis.
  • 8008 patients were included in the meta-analysis.
  • The negative predictive value (NPV) for MI and cardiac death was 98.8% (95% confidence interval [CI] 98.5 to 99.0) over 36 months of follow-up for MPI, and 98.4% (95% CI 97.9 to 98.9) over 33 months for echocardiography.
  • The corresponding annualized event rates were 0.45% per year for MPI (total death + MI risk = 1/222 per year) and 0.54% per year for echocardiography (total death + MI risk = 1/185 per year). [Comment: These annualized event rates are slightly lower than those found in the Hachamovitch study which is discussed above. This is exactly the expected pattern, since inability to undergo exercise stress was a potent risk factor for death or MI in the Hachamovitch study.]
  • These annualized event rates are both similar to a normal age-matched population, who carry a rate of  <1% per year. Thus, both noninvasive imaging modalities accurately identify low-risk patients.

 

2007. Clinical Outcomes After Both Coronary Calcium Scanning and Exercise Myocardial Perfusion Scintigraphy. Alan R, Berman DS, et al. J Am Coll Cardiol 2007 49: 1352-1361. Link to the Abstract.

  •  We assessed the frequency of cardiac death and myocardial infarction over a mean follow-up of 32 ±16 months in 1,153 patients undergoing both CAC scanning and MPS. Results were compared with those from a referent cohort of 9,308 patients who had earlier undergone MPS only.

  • The frequency of myocardial ischemia rose with increasing CAC scores (p < 0.001), but ischemia was present in only 64 patients. Among the 1,089 nonischemic patients, of which only 3 (0.3%) underwent early revascularization, the annualized cardiac event rate was <1% in all CAC subgroups, including those with CAC scores >1,000. Among patients with nonischemic MPS studies, high CAC scores do not confer an increased risk for cardiac events.

  • Thus, although patients with high CAC scores may be considered for intensive medical therapy to prevent future coronary artery disease events, a normal MPS study in such patients suggests no need for more aggressive interventions.



 2007. Long-Term Prognosis Associated With Coronary Calcification: Observations From a Registry of 25,253 Patients. Matthew J. Budoff, MD, Daniel S. Berman, MD, et al. J Am Coll Cardiol, 2007; 49:1860-1870.
Link to the Abstract.

  • The frequency of CAC scores was 44%, 14%, 20%, 13%, 6%, and 4% for scores of 0, 1 to 10, 11 to 100, 101 to 400, 401 to 1,000, and >1,000, respectively.

  • During a mean follow-up of 6.8 ± 3 years, the death rate was 2% (510 deaths). The CAC was an independent predictor of mortality in a multivariable model controlling for age, gender, ethnicity, and cardiac risk factors (model chi-square = 2,017, p < 0.0001).

  • The addition of CAC to traditional risk factors increased the concordance index significantly (0.61 for risk factors vs. 0.81 for the CAC score, p < 0.0001). Risk-adjusted relative risk ratios for CAC were 2.2-, 4.5-, 6.4-, 9.2-, 10.4-, and 12.5-fold for scores of 11 to 100, 101 to 299, 300 to 399, 400 to 699, 700 to 999, and >1,000, respectively (p < 0.0001), when compared with a score of 0.

  • Ten-year survival (after adjustment for risk factors, including age) was 99.4% for a CAC score of 0 and worsened to 87.8% for a score of >1,000 (p < 0.0001).

     

2007. Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography (ACCURACY). Min J., et al. In press.

  • 64-slice CT coronary angiography was carried out in a real-world group of 232 unselected chest-pain patients referred for invasive coronary angiography from 16 sites. No patients were excluded due to high coronary artery calcification score, body mass index or vessel size. All patients underwent CT coronary angiography and invasive coronary angiography. Findings: Positive predictive value of the test was mediocre (33% to 62%), but negative predictive value was superb (97% to 99%). However, less than 15% of study patients had obstructive coronary artery disease (Comment: Is this referral pattern widespread?) and this low incidence of disease substantially influenced outcomes. Clearly, this study needs to be repeated in a larger and more varied patient group, but it appears to provide guidance for the moment. The arrival of even better CT scanners will doubtless render this study obsolete in the near future. Click here to read the news report.

     

2008. Assessment of Coronary Artery Disease in Los Angeles Firefighters. In press.

  • L.A. firefighters have routine treadmill stress tests to screen for coronary artery disease. In this study, about 6000 treadmill tests were performed. Of these, 495 treadmill tests (about 8%) were abnormal or equivocal. Coronary calcium scoring was performed, with the result that 281 subjects (57% of the questionable ETT's) had a Calcium Score of 0 and no further testing was done. 81 subjects (16% of the questionable ETT's) had a Calcium Score of 1 to 9, and were given lifestyle/medication counseling. 133 subjects (27% of the questionable ETT's) had a Calcium score of 10 or above and were sent for CT angiography. Among these 133 subjects, 93 (70% of the "high-risk" group) had no significant coronary artery disease by CTA, and 40 subject (30% of the "high-risk" group) had significant coronary artery disease. Thus, 40/~6000 (about 1/150) ETT's resulted in discovery of significant coronary artery disease. Those cleared to go back to work had no negative outcomes over the three-year follow-up period. Use of this screening paradigm resulted in minimal time off work for those with abnormal/equivocal ETT, with subsequent marked cost savings. Click here to read a lengthy (but error-plagued) press report of this study.


     

2009. Achieving an Exercise Workload of >10 Metabolic Equivalents Predicts a Very Low Risk of Inducible Ischemia. Does Myocardial Perfusion Imaging Have a Role? Bourque JM, Beller GA et al.        J Am Coll Cardiol 2009;54:538–45. (University of Virginia)

  • Objectives We sought to identify prospectively the prevalence of significant ischemia (>=10% of the left ventricle [LV]) on exercise single-photon emission computed tomography (SPECT) imaging relative to workload achieved in consecutive patients referred for myocardial perfusion imaging (MPI).
    Background High exercise capacity is a strong predictor of a good prognosis, and the role of MPI in patients achieving high workloads is questionable.
    Methods Prospective analysis was performed on 1,056 consecutive patients who underwent quantitative exercise gated 99mTc-SPECT MPI, of whom 974 attained >=85% of their maximum age-predicted heart rate. These patients were further divided on the basis of attained exercise workload (<7, 7 to 9, or >=10 metabolic equivalents [METs] [=the end of Bruce Stage 3 or longer]) and were compared for exercise test and imaging outcomes, particularly the prevalence of >=10% LV ischemia. Individuals reaching >=10 METs but <85% maximum age-predicted heart rate were also assessed.
    Results Of these 974 subjects, 473 (48.6%) achieved >=10 METs. This subgroup had a very low prevalence of significant ischemia (2 of 473, 0.4%). Those attaining <7 METs had an 18-fold higher prevalence (7.1%, p <0.001). Of the 430 patients reaching >=10 METs without exercise ST-segment depression, none had >=10% LV ischemia. In contrast, the prevalence of >=10% LV ischemia was highest in the patients achieving <10 METs with ST-segment depression (14 of 70, 19.4%).
    Conclusions In this referral cohort of patients with an intermediate-to-high clinical risk of coronary artery disease, achieving >=10 METs with no ischemic ST-segment depression was associated with a 0% prevalence of significant ischemia. Elimination of MPI in such patients, who represented 31% (430 of 1,396) of all patients undergoing exercise SPECT in this laboratory, could provide substantial cost-savings.

    [For a superb editorial overview of the subject of stress testing and detection of myocardial ischemia, click here.]