Spatiotemporal heterogeneity of activation alternans in cardiomyopathy: Implications for risk stratification with microvolt QRS alternans

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.