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Disease Risk Management
Non-invasive Risk Stratification Early After a Myocardial Infarction—
The Risk Estimation Following Infarction Non-invasive Evaluation (REFINE) Study
a report by
Derek V Exner, MD, MPH, FRCPC
Libin Cardiovascular Institute of Alberta, University of Calgary
Why Do We Need Risk Stratification Tools? contemporary data to support this concept. Recent refinements assessing
Sudden death accounts for between 300,000 and 500,000 deaths each autonomic tone
5–7
and electrical substrate
8–11
have provided the opportunity
year in North America.
1
Patients with a history of myocardial infarction (MI) to validate this concept in patients receiving optimal post-MI management.
have a four-fold higher risk for sudden death than those without such a
history. Most sudden deaths in ambulatory populations result from life- Optimal Risk Assessment After Myocardial Infarction
threatening ventricular arrhythmias that lead to a cardiac arrest.
2
Since The Risk Estimation Following Infarction Non-invasive Evaluation (REFINE) study
survival from an out-of-hospital cardiac arrest is typically poor,
1
identifying was designed with two main goals:
3
to determine when non-invasive test
patients prior to its development is essential. results provide the most reliable information on future risk, and to derive an
optimal combination of non-invasive parameters to identify patients at risk for
While the implantable cardioverter–defibrillator (ICD) effectively treats life- serious outcomes. A group of 322 patients underwent a battery of non-
threatening ventricular arrhythmias, our current approach of identifying invasive assessments in the acute (two to four weeks) and non-acute (10 to 14
patients who may benefit from a prophylactic ICD (by identifying a low weeks) periods after MI to determine the best time to assess risk. A typical
ejection fraction [EF]) is hampered by poor sensitivity and specificity.
3,4
post-MI population was enrolled (see Table 1). During an average follow-up of
Multiple non-invasive markers have been developed to identify patients at four years, 30 patients died and 24 patients suffered a fatal or near-fatal
risk for a cardiac arrest. These tools can be categorized broadly as either cardiac arrest. Non-invasive testing of patients in the acute and non-acute early
assessing autonomic tone or evaluating underlying electrical substrate. post-MI periods was performed, since significant left ventricular remodeling
While individual markers of impaired autonomic tone identify patients at typically occurs during the 12 weeks after MI.
13
The non-invasive assessments
risk, when used as single measures they are hampered by poor sensitivity.
5–7
included state-of-the art measures of autonomic tone (heart-rate turbulence,
These markers of impaired autonomic tone typically identify a three- to five- heart-rate variability, baroreflex sensitivity) and electrical substrate (T-wave
fold higher risk for serious events after MI, but fewer than one-third of alternans, signal-averaged electrocardiogram [ECG]). Most patients in the
at-risk patients are identified. Markers of electrical substrate have focused REFINE study (75%) underwent revascularization in the initial post-MI period.
on beat-to-beat changes in cardiac repolarization or T-wave alternans.
8–11
The majority of patients also received aggressive medical therapy throughout
follow-up, with 80% receiving beta blockers, angiotensin-converting enzyme
While these techniques have merit, individually they are hampered by low (ACE) inhibitors or angiotensin receptor blockers, antiplatelet agents, and
positive accuracy
8
or poor sensitivity.
10,11
Thus, methods that identify most statins at three years of follow-up.
patients at risk for a cardiac arrest and provide reasonable positive accuracy
are required. Studies conducted prior to the contemporary era of aggressive When Should We Test Post-myocardial Infarction and
post-MI care suggest that combining measures of autonomic tone with Which Tests Are Best?
electrical substrate may aid in patient identification.
12
However, there are no Testing in the non-acute phase provided more reliable information on risk for
all of the non-invasive parameters compared with testing in the initial four
weeks post-MI. This was not surprising, as significant improvements in EF were
Derek V Exner, MD, MPH, FRCPC, is an Associate Professor in
the Libin Cardiovascular Institute of Alberta at the University of
observed over the initial eight to 10 weeks post-MI. In fact, the average relative
Calgary, and Medical Director of the Tachyarrhythmia and Heart improvement in EF was 18% (see Table 1). The REFINE study also demonstrated
Failure Device Program in the Calgary Health Region. He is a
that autonomic measures obtained from a 24-hour ambulatory ECG recording
heart rhythm specialist and clinical trials expert. His clinical
work and research focus on device therapy for patients with
or Holter monitor provided similar information to more complex testing. Similar
heart failure and the non-invasive identification of people at risk results were also observed for T-wave alternans measured using an exercise
for serious cardiac arrhythmias. Dr Exner’s research is supported
treadmill protocol and T-wave alternans measured by a Holter monitor
by the Canadian Institutes of Health Research, the Alberta
Heritage Foundation for Medical Research, the Heart and Stroke Foundation of Alberta, and a
immediately after a submaximal exercise test. Thus, reliable non-invasive test
number of industry partners. He has authored or co-authored more than 150 articles, book results were achieved using a single, relatively simple testing approach.
chapters, and abstracts, including publications in leading medical journals such as the New
England Journal of Medicine, the Journal of the American Medical Association, Circulation, and the
Journal of the American College of Cardiology related to device therapy and heart failure.
What Is the Optimal Combination of Parameters?
Combining markers of autonomic tone with measures of electrical substrate
E: exner@ucalgary.ca
better identified patients at risk for serious outcomes than any of the tests
alone. Depending on the combination of parameters used, a six- to eight-fold
10 © TOUCH BRIEFINGS 2008
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