Two-Parameter Noninvasive Assessment Identifies High-Risk MI Patients


CALGARY, Alberta, Dec. 4 -- Assessing autonomic tone and electrical substrate in patients with low ejection fraction doubled the likelihood of identifying MI patients at risk for serious events, results of a multicenter trial demonstrated. The combined assessment, performed more than eight weeks post-MI, identified 52% of patients with an increased risk of cardiac death or cardiac arrest, Derek Exner, M.D., of the University of Calgary, and colleagues reported in the Dec. 11 issue the Journal of the American College of Cardiology.
Action Points --->
Explain to interested patients that this study suggests that combining two widely available tests with a measure of heart function can identify patients at high risk for arrhythmic events after myocardial infarction.
In contrast, conventional approaches to risk assessment identify about a quarter of high-risk patients, Dr. Exner said in an interview.
"We found that a relatively simple testing protocol that included assessment of [left ventricular ejection fraction], a 24-hour ambulatory ECG monitor, and a low-level exercise test beyond eight weeks after MI readily identified the majority of patients destined to suffer serious events," the authors stated. "Similar results were obtained with assessment of LVEF and a 24-hour high-resolution Holter."
"This simple, easy-to-implement screening strategy has significant clinical appeal," they added. "However, this approach, particularly Holter-based [T-wave alternans] assessment, requires validation."
Despite advances in post-MI risk stratification, reliable identification of patients at risk of serious events has remained elusive, the authors noted. Noninvasive measures of autonomic tone and cardiac electrical substrate have demonstrated limited sensitivity when used alone.
Combining measures of autonomic tone and electrical substrate might improve risk assessment, they theorized, but the strategy had not been examined in the era of contemporary post-MI management.
So investigators at six Canadian hospitals evaluated the utility of combined post-MI assessment of autonomic tone and electrical substrate in the Risk Estimation Following Infarction, Noninvasive Evaluation (REFINE) trial. The study involved 322 patients who had an LVEF <40% in the first 48 hours after MI or <50% beyond 48 hours.
Patients underwent assessments at two to four weeks post-MI and then again at 10 to 14 weeks. The assessment included a submaximal exercise test to assess repolarization alternans (TWA) and a 20- to 30-minute high-resolution digital ECG evaluation, from which signal-averaged QRS width and Holter TWA were measured.
The patients also underwent baroreflex sensitivity testing, heart rate variability assessment, and evaluation of heart rate turbulence.
All patients had LVEF assessment by echocardiography, contrast ventriculography, or radionuclide ventriculography one week post-MI. LVEF assessment was repeated eight to 10 weeks post-MI, using radionuclide ventriculography.
Altered heart rate turbulence was defined by abnormalities in onset or slope. The exercise T-wave alternans result was categorized as non-negative versus negative on the basis of standard criteria.
The primary outcome was cardiac death or resuscitated cardiac arrest. Secondary outcomes consisted of all-cause mortality and fatal or nonfatal cardiac arrest. Patients were followed for a median of 47 months.
Ejection fraction increased significantly from 40% within the first week post-MI to 47% after eight weeks (P<0.001). Noninvasive assessment within two to four weeks of MI did not reliably identify high-risk patients.
However, the 20% of patients with impaired heart rate turbulence, abnormal exercise T-wave alternans, and LVEF <50% beyond eight weeks had a 30% primary outcome rate, compared with 5% in the remaining 80% of patients (P<0.00001).
The combination of impaired heart rate turbulence, abnormal exercise T-wave alternans, and LVEF <50% at 8+ weeks had a 23% positive and 95% negative accuracy for the primary outcome (95% CI for both: 17% to 26% and 93% to 97%, respectively). Similar results were observed for secondary outcomes.
In an accompanying editorial, Peter Sleight, M.D., of the University of Oxford, noted that REFINE involved a highly selected patient population (322 of 5,700 screened) and had a low event rate (24 serious arrhythmic events). Additionally, as noted by Dr. Exner and colleagues, only 20% of patients had the most predictive combination of parameters.
Despite the study's shortcomings, REFINE showed that a "combination of an autonomic measure with a measure of cardiac vulnerability to arrhythmia [TWA], in a higher-risk population with impaired LV function, gave better prognostic discrimination than either measure alone," Dr. Sleight commented.
"The finding that these tests were better long-term predictors when measured after the acute phase after MI is also important, because most risk stratification is performed in the acute (and unstable) phase," Dr. Sleight added.
The authors pointed out that "this was not a randomized trial, and our results are subject to both known and unknown factors."
Support for the study was provided by the Canadian Institutes of Health Research, the Alberta Heritage Foundation for Medical Research, Cambridge Heart Inc., and GE Healthcare Technologies.
Dr. Exner is a clinician scientist for the Canadian Institutes of Health Research and a scholar of the Alberta Heritage Foundation for Medical Research.
Dr. Sleight made no financial disclosures.
Primary source: Journal of the American College of CardiologySource reference:Exner DV, et al "Noninvasive risk assessment early after myocardial infarction: the REFINE study" J Am Coll Cardiol 2007; 50: 2275-2284. Additional source: Journal of the American College of CardiologySource reference: Sleight P, “New methods for risk stratification in patients after myocardial infarction: autonomic control and substrate sensitivity” J Am Coll Cardiol 2007; 50: 2291-2293