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Non-invasive Risk Stratification Early After a Myocardial Infarction—The REFINE Study
increased risk for cardiac arrest was observed for patients who were
Table 1: Risk Estimation Following Infarction Non-invasive
categorized as having abnormal test results (see Figure 1). Compared with prior
Evaluation (REFINE) Study Patient Characteristics
studies using one parameter, the combination of parameters in the REFINE
study yielded substantially higher sensitivity. While previous studies have
Characteristic Value
demonstrated sensitivities of <30%, the REFINE approach doubled this.
Median age (years) 62
Male (%) 85
Importantly, the combination of parameters identified in the REFINE study also
History of multiple myocardial infarctions (%) 23
resulted in high positive accuracy (21%), meaning that a patient identified as
History of diabetes (%) 22
at risk for a cardiac arrest had a greater than one in five chance of developing
History of hypertension (%) 45
a cardiac arrest in follow-up. These results indicate that a simple combination
Index MI
of non-invasive tests appears to provide powerful and reliable risk prediction.
Q-wave (%) 68
Anterior location (%) 62
Should Non-invasive Tests Be Used to Predict Implantable Revascularization after myocardial infarction (%) 75
Cardioverter–Defibrillator Efficacy in 2008?
Initial ejection fraction (median) 0.40
The results of the REFINE study suggest that patients most likely to benefit from
Ejection fraction eight to 10 weeks after myocardial infraction (median) 0.47
an ICD can be identified using a combination of non-invasive parameters. Of
Medications
those tested, heart-rate turbulence and T-wave alternans performed best.
Antiplatelet agent (%) 99
Beta blocker (%) 91
Despite these very positive results, there is insufficient evidence to use these
Statin (%) 87
tests to decide whether any given patient should receive a prophylactic ICD. For
ACE inhibitor or angiotensin blocker (%) 90
example, it was previously thought that an abnormal signal-averaged ECG
MI = myocardial infarction; ACE = angiotensin-converting enzyme.
reliably predicted patients at risk for a cardiac arrest. However, the Coronary
Artery Bypass Graft (CABG)-Patch trial showed no benefit of prophylactic ICD Figure 1: Prediction of Fatal or Non-fatal Cardiac Arrest
therapy in patients with a low EF and an abnormal signal-averaged ECG
undergoing cardiac bypass surgery.
14
Likewise, abnormal heart rate variability 40
was also thought to identify post-MI patients at risk for a cardiac arrest.
However, the Defibrillator in Acute Myocardial Infarction Trial (DINAMIT)
Sensitivity = 58%
Abnormal
demonstrated no benefit of prophylactic ICD therapy for patients with a low 30
Positive accuracy = 21%
test results
EF and an abnormal heart-rate variability measured early after MI.
15
Finally, in
Risk ratio = 7.8
the recently reported Microvolt T-wave Alternans Testing for Risk Stratification
of Post-MI Patients (MASTERS) I study, exercise T-wave alternans failed to 20
predict a higher risk for sudden death or life-saving ICD therapies in a group of
p<0.0001
patients with low EF values undergoing prophylactic ICD therapy.
16
10
Thus, while the combination of non-invasive tools identified in the REFINE
Normal
study appears to predict which patients will versus will not benefit from
test results
prophylactic ICD therapy, there is currently insufficient evidence to make 0
clinical decisions based on these test results. Prospective trials are required 0 12345
to prove that these tests do predict which patients are likely to benefit from Follow-up (years)
prophylactic ICD therapy. Two large studies specifically addressing the utility
The risk for cardiac arrest was almost eight-fold higher in the 17% of patients with an
of the combination of parameters shown to be useful in the REFINE
ejection fraction <0.50 plus impaired heart rate turbulence and abnormal T-wave alternans
study are expected to commence in the next six to 12 months. Until these
assessed by a Holter (abnormal test results) versus the remaining 83% of patients with normal
test results. Moreover, this combination of tests identified the majority of patients at risk
data are available it is premature to use any of these non-invasive tests to
(58% sensitivity), and patients identified as being at risk had a greater than one in five chance
guide ICD therapy.
of a cardiac arrest during follow-up.
reduce mortality post-MI should be prescribed. These medications include
Should the REFINE Study Results Affect Patient Management? beta blockers, antiplatelet agents, statins, ACE inhibitors, angiotensin
The ability of heart-rate turbulence and T-wave alternans to predict a high receptor blockers, and aldosterone antagonists. Patients should also be
or low risk for serious outcomes after MI has clinical implications. The four assessed for residual ischemia and treated as per current standards.
out of five post-MI patients with normal test results can be reassured, as Whether prophylactic ICD therapy can further reduce mortality in patients
they are at very low risk for problems (see Figure 1). In contrast, the one in with impaired heart rate turbulence and abnormal T-wave alternans is
five higher-risk patients need to be closely monitored. Therapies proved to unknown, but will be answered by upcoming trials. ■
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3. Exner DV, et al., J Am Coll Cardiol, 2007;50(24):2275–84. 9. Myles RC, et al., Circulation, 2007;116(25):2984–91. 15. Hohnloser SH, et al., N Eng J Med, 2004;351(24):2481–2488.
4. Germano JJ, et al., Am J Cardiol, 2006;97(8):1255–61. 10. Nieminen T, et al., Eur Heart J, 2007;28(19):2332–7. 16. Chow T, et al., J Am Coll Cardiol, 2007;49(1):50–58.
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