Microvolt T-Wave Alternans with Exercise in Pediatrics and Congenital Heart Disease: Limitations and Predictive Value MARK E. ALEXANDER, FRANK CECCHIN, KATHIE P. HUANG, and CHARLES I. BERUL From the Arrhythmia Service, Department of Cardiology, Children’s Hospital, and the Department of Pediatrics, Harvard Medical School, Boston, Massachusetts Background: Microvolt t-wave alternans (TWA) in early exercise is a noninvasive marker of life- threatening ventricular arrhythmia in some adult cardiac populations. The incidence and potential sig- nificance of sustained TWA in pediatric and congenital heart disease (CHD) populations has not been well defined. Methods: TWA treadmill exercise studies in pediatric patients with CHD, myopathy, potential myocar- dial ischemia, syncope, or history of cardiac arrest were analyzed. Tests were categorized as abnormal for sustained TWA with onset heart rate <130 beats/min with specific analyses for lower onset heart rates. Patient characteristics were analyzed as possible correlates of TWA. Results: Over 2 years, 318 consecutive TWA exercise studies were performed in 304 patients (60% male, median 14 years, 6–41) for indications of syncope, cardiac arrest, possible ventricular arrhythmia, or evaluation of functional myocardial perfusion. Underlying conditions included apparently normal hearts (45%), CHD (16%), cardiomyopathy (11%), coronary anomalies (11%), electrical myopathy (9%), and transplant (8%). Abnormal TWA was seen in 24 (7%, onset HR 106 ± 18) and included 19 at high clinical risk for serious events including 3 with cardiac arrest. By multivariate analysis sustained TWA was associated with cardiac arrest, ventricular arrhythmias, and a clinical classification of high risk. Conclusions: TWA is associated with pediatric and CHD diagnoses at high risk of serious events and may contribute, with other diagnostic tools, to management choices. While the absence of TWA has rel- atively high negative predictive value, it does not completely exclude the potential for serious sustained ventricular arrhythmias. A more robust noninvasive marker for risk stratification in these populations is required. (PACE 2006; 29:733–741) t-wave alternans, ventricular arrhythmias, congenital heart disease, pediatrics, exercise testing Introduction Evaluating risk for life-threatening ventricular arrhythmias represents a challenge. For the adult with recent myocardial infarction and depressed ventricular function, the 2-year risk of cardiac ar- rest approaches 20%. This is sufficiently high that ICD therapy is used as primary prevention in se- lected patients. 1 Further, with the high volume of patients and relatively concentrated risk, multiple tools have proven to be useful in predicting risk. The annual risks are notably lower in the hetero- geneous patient populations cared for in pediatric cardiology practices. Therefore, precise tools are Dr. Huang was supported by an American Academy of Pedi- atrics fellowship for clinical research and was a medical stu- dent at Stanford Medical School, Palo Alto, CA. This work was supported by the Boston Children’s Heart Foun- dation. Address for reprints: Mark E. Alexander, M.D., Arrhythmia Ser- vice, Department of Cardiology, Children’s Hospital, Boston, 300 Longwood Avenue, Boston, MA 02115. Fax: 617-739-9058; e-mail: mark.alexander@cardio.chboston.org Received April 4, 2006; revised April 19, 2006; accepted April 23, 2006. not readily available to accurately stratify patients with worrisome symptoms or arrhythmias in these groups. Microvolt t-wave alternans (TWA) is a predic- tive tool in relatively high-risk adult populations. Specifically, the observation of significant TWA with an onset HR of ≤110 beats/min during bi- cycle exercise is associated with inducible VT on programmed stimulation, spontaneous VT during follow-up, and appropriate ICD discharge. Within a high-risk adult ischemic heart disease popula- tion, the absence of TWA is associated with a low incidence of appropriate ICD use. 2 Data in the pe- diatric and congenital heart disease (CHD) popu- lations are limited. Using bicycle exercise in pe- diatric volunteers without apparent heart disease, 9% had significant TWA with a median onset heart rate of 138 beats/min and only 1% of subjects with an onset heart rate <130 beats/min. 3 In asymp- tomatic subjects with favorable repairs of tetralogy of Fallot, 14% had significant and sustained TWA at a lower onset HR and 42% of those with TWA had an onset HR of <120 beats/min. The presence of TWA did not correlate with any outcome vari- able or hemodynamic finding. 4 C 2006, The Authors. Journal compilation C 2006, Blackwell Publishing, Inc. PACE, Vol. 29 July 2006 733