Predictive Value of NSVT in Non-ST Elevation Acute Coronary Syndromes
Abstract & Commentary
By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco receives grant/research support from St. Jude Medical, Astellas, and Novartis, is a consultant for Medtronic and Sanofi-Aventis, and is a speaker for St. Jude Medical and Boston Scientific
Source: Scirica BM, et al. Relationship between nonsustained ventricular tachycardia after non-ST elevation acute coronary syndrome and sudden cardiac death. Observations from the metabolic efficiency with ranolazine for less ischemia in non-ST-elevation acute coronary syndrome – Thrombolysis in Myocardial Infarction 36 (MERLIN TIMI-36) randomized controlled trial. Circulation. 2010;122:455-462.
Merlin-timi 36 tested the hypothesis that ranolazine, a recently approved anti-anginal agent, would benefit patients with non-ST-elevation acute coronary syndrome (NSTEACS). Favorable trends that did not reach statistical significance were noted in the main study report (Circulation. 2007;116:1647-1652). Since ranolazine has effects on both late sodium currents and potassium currents, MERLIN was designed to carefully measure spontaneous arrhythmias during the initial phases of treatment. In this report, Scirica and colleagues report on the frequency, prognostic significance, and response to ranolazine of nonsustained ventricular tachycardia (NSVT) in patients with NSTEACS.
In MERLIN-TIMI 36, 6,560 patients hospitalized with NSTEACS were randomized within the first 48 hours of hospital admission to either placebo or ranolazine in addition to standard medical and interventional therapy. Continuous ambulatory ECG recordings were obtained during the first seven days of treatment. NSVT was defined as three consecutive ventricular beats at a rate above 100 beats per minute. These runs were then further categorized by length into three groups: 3 beats only, 4-7 beats, and > 7 beats. Deaths were reviewed by a clinical-events committee and sudden cardiac deaths (SCD) were classified by standard criteria. Brain natriuretic peptide (BNP) and left ventricular ejection fraction (LVEF) values were available in most, but not all, patients. Hazard ratios for SCD are reported without adjustment, with adjustment for clinical variables (TIMI risk score, prior myocardial infarction, prior heart failure, creatinine clearance, and revascularization) during index hospitalization and, when data were available, for LVEF and admission BNP.
NSVT was common in these patients, with 3,581 patients (56.4%) having one or more VT episodes during the seven days of monitoring. Slightly more than half of these (1,978 patients) had only episodes of 3 beats duration. However, there were 1,172 patients (18.4%) with 4-7 beat episodes and 431 patients (6.8%) with at least one episode of 8 or more beats. In the entire study, there were 121 sudden cardiac deaths (1.8%).There was no difference in the sudden death rates between those with no VT and those with VT of only 3 beats duration (1.2% vs. 1.4%). However, the adjusted hazard ratio was increased for both the VT of 4-7 beats group (HR = 2.3) and the VT of 8 or more beats group (HR = 2.8). As expected, clinical variables also predicted SCD, but the findings of NSVT of 4-7 beats and 8 or more beats remained independent predictors. NSVT of any duration, detected only during the first 48 hours after hospitalization, did not carry prognostic significance, and only NSVT, found after 48 hours, predicted SCD. Ranolazine decreased the frequency of NSVT and patients with NSVT on ranolazine had less SCD risk than NSVT patients on placebo.
The authors conclude that NSVT is common in patients with NSTEACS, and the finding of NSVT episodes of > 4 beats after the first 48 hours of hospitalization predicts an increased risk for sudden death.
Commentary
NSVT has been recognized as a risk factor in post myocardial infarction patients for many years. However, the original observational studies included mostly patients with ST elevation infarctions and preceded the widespread use of early revascularization, ACE inhibitors, beta adrenergic blockers, and other newer therapies. In this paper, Scirica and colleagues show that NSVT still is associated with an increased risk for sudden death in patients with NSTEACS, most of whom had relatively well-preserved ventricular function. However, even though the hazard ratios are above 2, the absolute risk is still fairly low being only 5.4% in patients with NSVT of 8 or more beats who were not on ranolazine. This makes detection of NSVT interesting on a population basis, but of limited value in individual patients. In any case, few NSTEACS patients are monitored continuously for seven days, and the data here are not impressive enough to make us change our practices to do so.
The effects of ranolazine are of interest. Ranolazine blocks both the late-inward sodium current and the repolarizing potassium current IKr in the ventricle. MERLIN-TIMI 36 was conducted, at least in part, as a safety trial to make sure that ranolazine was not proarrhythmic. In contrast, the potentially antiarrhythmic effects of late sodium channel blockade seem to outweigh any adverse effects from effects on potassium channels. Larger studies will be needed to see if this is a clinically valuable drug for the purpose of preventing SCD.
Finally, we must remember NSVT is just one more factor that can help identify the high-risk patient. We learned long ago in the Cardiac Arrhythmia Suppression Trial that trying to suppress NVST with a traditional antiarrhythmic drug may be deleterious. The data shown here should just reinforce our efforts to provide optimal medical therapy and revascularization when possible to all our NSTEACS patients, with particular attention to those with NSVT.
Merlin-timi 36 tested the hypothesis that ranolazine, a recently approved anti-anginal agent, would benefit patients with non-ST-elevation acute coronary syndrome (NSTEACS).You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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