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

Background— Most studies examining the relationship between ventricular tachycardia (VT) after acute coronary syndrome and sudden cardiac death (SCD) were performed before widespread use of reperfusion, revascularization, or contemporary medical therapy and were limited to ST-elevation myocardial infarction. The incidence and prognostic implications of VT in patients with non–ST-elevation acute coronary syndrome receiving contemporary care have not been examined. Methods and Results— The Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndrome–Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) trial randomized 6560 patients hospitalized with a non–ST-elevation acute coronary syndrome to ranolazine or placebo in addition to standard therapy. Continuous ECG recording was performed for the first 7 days after randomization and evaluated in a blinded core laboratory. SCD (n=121) was assessed over a median follow-up of 1 year. A total of 6345 patients (97%) had continuous ECG recordings evaluable for analysis. Compared with patients with no VT (n=2764), there was no increased risk of SCD in patients with only ventricular triplets (n=1978, 31.2%) (1.4% versus 1.2%); however, the risk of SCD was significantly greater in patients with VT lasting 4 to 7 beats (n=1172, 18.5%) (SCD, 2.9%; adjusted hazard ratio, 2.3; P<0.001) and in patients with VT lasting at least 8 beats (n=431, 6.8%) (SCD, 4.3%; adjusted hazard ratio, 2.8; P=0.001). This effect was independent of baseline characteristics and ejection fraction. VT occurring within the first 48 hours after admission was not associated with SCD. Conclusion— Nonsustained VT is common after admission for non–ST-elevation acute coronary syndrome, and even short episodes of VT lasting 4 to 7 beats are independently associated with the risk of SCD over the subsequent year. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00099788.

[1]  A. Skene,et al.  Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. , 2007, JAMA.

[2]  Pekka Raatikainen,et al.  Prediction of sudden cardiac death after myocardial infarction in the beta-blocking era. , 2003, Journal of the American College of Cardiology.

[3]  L. Wallentin,et al.  Analytical and clinical evaluation of the Bayer ADVIA Centaur automated B-type natriuretic peptide assay in patients with heart failure: a multisite study. , 2004, Clinical chemistry.

[4]  M. Pencina,et al.  Evaluating the added predictive ability of a new marker: From area under the ROC curve to reclassification and beyond , 2008, Statistics in medicine.

[5]  R. Califf,et al.  Sustained Ventricular Arrhythmias Among Patients With Acute Coronary Syndromes With No ST-Segment Elevation: Incidence, Predictors, and Outcomes , 2002, Circulation.

[6]  S. Hohnloser,et al.  Prevalence, characteristics and prognostic value during long-term follow-up of nonsustained ventricular tachycardia after myocardial infarction in the thrombolytic era. , 1999, Journal of the American College of Cardiology.

[7]  R. Califf,et al.  Prognostic value of serial B-type natriuretic peptide testing during follow-up of patients with unstable coronary artery disease. , 2005, JAMA.

[8]  J. Shryock,et al.  An increase of late sodium current induces delayed afterdepolarizations and sustained triggered activity in atrial myocytes. , 2008, American journal of physiology. Heart and circulatory physiology.

[9]  Barry J Maron,et al.  American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society Scientific Statement on Noninvasive Risk Stratification Techniques for Identifying Patients at Risk for Sudden Cardiac Death. A scientific statement from the American Heart Association Council on Clinical Cardi , 2008, Journal of the American College of Cardiology.

[10]  J. Manson,et al.  Blood levels of long-chain n-3 fatty acids and the risk of sudden death. , 2002, The New England journal of medicine.

[11]  P. Armstrong,et al.  Incidence of and outcomes associated with ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention. , 2009, JAMA.

[12]  S. Solomon,et al.  Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. , 2005, The New England journal of medicine.

[13]  A. Skene,et al.  Evaluation of a novel anti-ischemic agent in acute coronary syndromes: design and rationale for the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation acute coronary syndromes (MERLIN)-TIMI 36 trial. , 2006, American heart journal.

[14]  J. Shryock,et al.  Antagonism by Ranolazine of the Pro-Arrhythmic Effects of Increasing Late INa in Guinea Pig Ventricular Myocytes , 2004, Journal of cardiovascular pharmacology.

[15]  A. Habets,et al.  Defibrillator implantation early after myocardial infarction. , 2009, The New England journal of medicine.

[16]  Eric Fain,et al.  Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. , 2004, The New England journal of medicine.

[17]  L. Tavazzi,et al.  Prevalence and Prognostic Significance of Ventricular Arrhythmias After Acute Myocardial Infarction in the Fibrinolytic Era GISSI‐2 Results , 1993, Circulation.

[18]  Andrew C. Zygmunt,et al.  Electrophysiological Effects of Ranolazine, a Novel Antianginal Agent With Antiarrhythmic Properties , 2004, Circulation.

[19]  Demosthenes G Katritsis,et al.  Nonsustained ventricular tachycardia: where do we stand? , 2004, European heart journal.

[20]  R. Passman,et al.  Implantable cardioverter-defibrillator therapy after acute myocardial infarction: the results are not shocking. , 2009, Journal of the American College of Cardiology.

[21]  H. Huikuri,et al.  Prediction of sudden cardiac death after acute myocardial infarction: role of Holter monitoring in the modern treatment era. , 2005, European heart journal.

[22]  L E Hinkle,et al.  Clinical Classification of Cardiac Deaths , 1982, Circulation.

[23]  K. Patton The riddle of nonsustained ventricular tachycardia and sudden cardiac death: are we approaching a solution? , 2010, Circulation.

[24]  A. Camm,et al.  Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT , 1997, The Lancet.

[25]  A. Kadish,et al.  Nonsustained ventricular tachycardia in the setting of acute myocardial infarction: tachycardia characteristics and their prognostic implications. , 1998, Circulation.

[26]  A J Camm,et al.  Baroreflex Sensitivity and Heart Rate Variability in the Identification of Patients at Risk for Life-Threatening Arrhythmias: Implications for Clinical Trials , 2001, Circulation.

[27]  J. Fleiss,et al.  Prevalence, characteristics and significance of ventricular tachycardia detected by 24-hour continuous electrocardiographic recordings in the late hospital phase of acute myocardial infarction. , 1986, The American journal of cardiology.

[28]  M. Pfisterer,et al.  Effect of antiarrhythmic therapy on mortality in survivors of myocardial infarction with asymptomatic complex ventricular arrhythmias: Basel Antiarrhythmic Study of Infarct Survival (BASIS) , 1990, Journal of the American College of Cardiology.

[29]  S. Solomon,et al.  Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. , 2005, The New England journal of medicine.

[30]  Dan M. Roden,et al.  ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines , 2006 .