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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
Libin Cardiovascular Institute of Alberta, University of Calgary
Why Do We Need Risk Stratification Tools? fatal cardiac arrest. Non-invasive testing of patients in the acute and
Sudden death accounts for between 300,000 and 500,000 deaths non-acute early post-MI periods was performed, since significant left
each year in North America.
1
Patients with a history of myocardial ventricular remodelling typically occurs during the 12 weeks after MI.
13
infarction (MI) have a four-fold higher risk of sudden death than The non-invasive assessments included state-of-the art measures of
those without such a history. Most sudden deaths in ambulatory autonomic tone (heart-rate turbulence, heart-rate variability,
populations result from life-threatening ventricular arrhythmias baroreflex sensitivity) and electrical substrate (T-wave alternans, signal-
that lead to a cardiac arrest.
2
Since survival from an out-of-hospital averaged electrocardiogram [ECG]). Most patients in the REFINE study
cardiac arrest is typically poor,
1
identifying patients prior to its (75%) underwent revascularisation in the initial post-MI period. The
development is essential. majority of patients also received aggressive medical therapy
throughout follow-up, with 80% receiving beta blockers, angiotensin-
While the implantable cardioverter–defibrillator (ICD) effectively converting enzyme (ACE) inhibitors or angiotensin receptor blockers,
treats life-threatening ventricular arrhythmias, our current approach antiplatelet agents and statins at three years of follow-up.
of identifying patients who may benefit from a prophylactic ICD (by
identifying a low ejection fraction [EF]) is hampered by poor sensitivity When Should We Test Post-myocardial Infarction and
and specificity.
3,4
Multiple non-invasive markers have been developed Which Tests Are Best?
to identify patients at risk of a cardiac arrest. These tools can be Testing in the non-acute phase provided more reliable information on
categorised broadly as either assessing autonomic tone or evaluating risk of all of the non-invasive parameters than compared with testing
underlying electrical substrate. While individual markers of impaired in the initial four weeks post-MI. This was not surprising, as significant
autonomic tone identify patients at risk, when used as single measures improvements in EF were observed over the initial eight to 10 weeks
they are hampered by poor sensitivity.
5–7
These markers of impaired post-MI. In fact, the average relative improvement in EF was 18% (see
autonomic tone typically identify a three- to five-fold higher risk of Table 1). The REFINE study also demonstrated that autonomic
serious events after MI, but fewer than one-third of at-risk patients are measures obtained from a 24-hour ambulatory ECG recording or
identified. Markers of electrical substrate have focused on beat-to- Holter monitor provided similar information to more complex testing.
beat changes in cardiac repolarisation or T-wave alternans.
8–11
Similar results were also observed for T-wave alternans measured using
an exercise treadmill protocol and T-wave alternans measured by a
While these techniques have merit, individually they are hampered by Holter monitor immediately after a submaximal exercise test. Thus,
low positive accuracy
8
or poor sensitivity.
10,11
Thus, methods that reliable non-invasive test results were achieved using a single, relatively
identify most patients at risk of a cardiac arrest and provide reasonable simple testing approach.
positive accuracy are required. Studies conducted prior to the
contemporary era of aggressive post-MI care suggest that combining What Is the Optimal Combination of Parameters?
measures of autonomic tone with electrical substrate may aid in Combining markers of autonomic tone with measures of electrical
patient identification.
12
However, there are no contemporary data to substrate better identified patients at risk of serious outcomes than
support this concept. Recent refinements assessing autonomic tone
5–7
and electrical substrate
8–11
have provided the opportunity to validate
Derek V Exner is an Associate Professor in the Libin
this concept in patients receiving optimal post-MI management.
Cardiovascular Institute of Alberta at the University of
Calgary, and Medical Director of the Tachyarrhythmia and
Heart Failure Device Program in the Calgary Health Region.
Optimal Risk Assessment After Myocardial Infarction
He is a heart rhythm specialist and clinical trials expert. His
The Risk Estimation Following Infarction Non-invasive Evaluation clinical work and research focus on device therapy for
(REFINE) study was designed with two main goals:
3
to determine when
patients with heart failure and the non-invasive
identification of people at risk of serious cardiac
non-invasive test results provide the most reliable information on
arrhythmias. Dr Exner’s research is supported by the
future risk, and to derive an optimal combination of non-invasive
Canadian Institutes of Health Research, the Alberta Heritage Foundation for Medical
parameters to identify patients at risk of serious outcomes. A group of
Research, the Heart and Stroke Foundation of Alberta and a number of industry partners. He
has authored or co-authored more than 150 articles, book chapters and abstracts, including
322 patients underwent a battery of non-invasive assessments in the
publications in leading medical journals such as the New England Journal of Medicine, the
acute (two to four weeks) and non-acute (10 to 14 weeks) periods
Journal of the American Medical Association, Circulation and the Journal of the American
College of Cardiology related to device therapy and heart failure.
after MI to determine the best time to assess risk. A typical post-MI
population was enrolled (see Table 1). During an average follow-up of
E: exner@ucalgary.ca
four years, 30 patients died and 24 patients suffered a fatal or near-
© TOUCH BRIEFINGS 2008 21
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