Abstract
BACKGROUND: Microvolt QRS alternans (QRSA) on the surface electrocardiogram is a strong predictor of ventricular arrhythmia (VA) in patients with cardiomyopathy (CM); however, its intracardiac origin has not been defined. OBJECTIVE: This study aimed to assess the spatiotemporal features of intracardiac activation alternans (AA) in relation to body surface QRSA and VA. METHODS: Unipolar electrograms were recorded from the great cardiac vein (left ventricular epicardium) and the right ventricular endocardium in 10 patients with CM (age 59 ± 16 years; left ventricular ejection fraction 32% ± 9%). Unipolar AA and surface QRSA were quantified using the spectral method during consecutive atrial pacing at 75, 100, and 120 beats per minute. AA was simulated with a 1500-node heart model to assess the relationship with surface QRSA. Patients were followed for VA over 5 years. RESULTS: AA was more prevalent in the left ventricular epicardium than the right ventricular endocardium (25% vs 5% of recording electrodes; P = .01) and more prevalent in the late QRS than early QRS (92% vs 69%; P < .01). AA and QRSA were equally prevalent (62% vs 46%; P = .12) but AA had greater magnitude (43 [0-90] vs 0 [0-6] μV; P < .01). AA prevalence and magnitude increased with rate but had a lower heart rate onset than QRSA. Simulated activation time alternans of 2-5 ms in a 1 cm node produced surface QRSA of similar magnitude to patients with AA. Patients with AA at 75 beats per minute were more likely to have VA in follow-up (100% vs 0%; P = .048). CONCLUSION: AA exhibits substantial spatiotemporal heterogeneity in patients with CM and is dependent on heart rate. Surface microvolt QRSA is the noninvasive manifestation of intracardiac AA, which may explain its prognostic utility.