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J Am Coll Cardiol, 2008; 51:1910-1911, doi:10.1016/j.jacc.2008.02.037
© 2008 by the American College of Cardiology Foundation
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CORRESPONDENCE: LETTER TO THE EDITOR

Reply

Derek V. Exner, MD, MPH* on behalf of the REFINE Investigators

* Libin Cardiovascular Institute of Alberta, 3330 Hospital Drive NW; Room G208, Calgary, Alberta, Canada T2N 4N1 (Email: exner{at}ucalgary.ca).


We thank Drs. Goyal and Punnam for their interest in our study (1). The prevalence and prognostic significance of nonsustained ventricular tachycardia (NSVT) was evaluated in the REFINE (Risk Estimation Following Infarction, Noninvasive Evaluation) study, but these data were not included, owing to space limitations. At 10 to 14 weeks after the index myocardial infarction (MI), 95 of the 322 patients (30%) had 1 or more NSVT episodes lasting at least 5 beats. The prevalence of NSVT did not differ among patients who suffered the primary outcome of cardiac death or nonfatal cardiac arrest (p = 0.3) versus patients who did not. Also, NSVT was not associated with a significantly higher risk of the primary outcome (hazard ratio [HR] 1.8, 95% confidence interval [CI] 0.8 to 3.8; p = 0.1). Importantly, the association between Holter-assessed impaired heart rate turbulence plus abnormal repolarization alternans with an increased risk of the primary outcome (HR 5.0, 95% CI 2.3 to 10.7; p < 0.0001) was not altered when NSVT was adjusted for (HR 4.9, 95% CI 2.3 to 10.6; p < 0.0001).

Antiarrhythmic drug use was uncommon in the REFINE study; 6 patients (2%) received amiodarone and 3 (1%) received sotalol. Antiarrhythmic drug use was similar in patients who did versus did not suffer the primary outcome (p = 0.2) and was not associated with an increased risk of the primary outcome (HR 1.6, 95% CI 0.2 to 12.5; p = 0.6). As with NSVT, the association of impaired heart rate turbulence plus abnormal repolarization alternans with an increased risk of the primary outcome was not altered when antiarrhythmic drug usage was adjusted for (HR 5.4, 95% CI 2.3 to 12.6; p < 0.0001).

We did not evaluate distal embolization in the REFINE study, because we sought to assess markers of long-term risk. Multiple studies have shown that distal embolization impacts short-term 30- to 60-day risk of adverse clinical outcomes and not long-term 4-year risk (2,3). The strong association between impaired heart rate turbulence plus abnormal repolarization alternans with an increased risk of the primary outcome was not altered when change in ejection fraction over the initial 2 months after MI, a surrogate of successful reperfusion, was adjusted for (HR 5.1, 95% CI 2.2 to 11.9; p < 0.0001).

In conclusion, the concerns of Drs. Goyal and Punnam do not detract from our findings. As clearly demonstrated (1), the combination of impaired heart rate turbulence plus abnormal repolarization alternans assessed in the nonacute post-MI period reliably predicts the long-term risk of serious outcomes. Thus, we believe these markers are the right indicators.


    References
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 References
 
1. Exner D, Kavanagh K, Slawnych M, et al. Noninvasive risk assessment early after a myocardial infarction. the REFINE study. J Am Coll Cardiol 2007;50:2275-2284.[Abstract/Free Full Text]

2. Izgi A, Kirma C, Tanalp AC, et al. Predictors and clinical significance of angiographically detected distal embolization after primary percutaneous coronary interventions Coron Artery Dis 2007;18:443-449.[CrossRef][Web of Science][Medline]

3. Blankenship JC, Haldis T, Feit F, et al. Angiographic adverse events, creatine kinase-MB elevation, and ischemic end points complicating percutaneous coronary intervention (a REPLACE-2 substudy) Am J Cardiol 2006;97:1591-1596.[CrossRef][Web of Science][Medline]


Related Article

Noninvasive Risk Assessment Early After a Myocardial Infarction: Are We Looking at the Right Indicators?
Sandeep Goyal and Sujeeth R. Punnam
J. Am. Coll. Cardiol. 2008 51: 1910. [Full Text] [PDF]




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