Differential pacing from two sites to diagnose risk of ventricular arrhythmia and death

Background QRS abnormalities may not be apparent in sinus rhythm in electrically stable cardiomyopathy patients who can have quiescent but highly arrhythmogenic substrate. Here, we test the hypothesis that differential changes in QRS construction during right‐ventricular apex pacing (RVP) as opposed to atrial pacing (AP) will identify latent substrate for ventricular arrhythmias (VA) and death. Methods Forty patients with cardiomyopathy free of VA underwent baseline 114‐electrode body‐surface electrocardiogram during AP (100 beats per minute [bpm]) and RVP (100 and 120 bpm). The filtered‐averaged QRS at each electrode was deconstructed into individual intra‐QRS and post‐QRS ventricular myopotentials (V MP ). The primary outcome was VA or death. Prognostic accuracy of V MP was validated using V1 to V6 leads in another prospective cohort of 44‐cardiomyopathy patients. Results Twenty‐six patients were eligible for initial analysis. After 5 ± 2 years of follow‐up, eight (31%) patients had VA (VA Pos ) while rest were uneventful (VA Neg ). During AP 100 , VA Pos patients expressed more V MP than VA Neg patients (16 ± 1 vs 12 ± 1, P = 0.02). RVP 100 and RVP 120 in VA Pos patients introduced an additional 5.5 ± 0.5 and 6.0 ± 0.5 V MP ( P < 0.0001 vs AP 100 ). The relative change with RVP 120 versus AP 100 in VA Neg patients exceeded VA Pos patients by 1.2 ± 0.5 V MP ( P = 0.03). Increment in V MP count of <8 in lead‐V5 with RVP 120 compared to AP 100 best predicted VA (area under curve 0.81, P = 0.01). In the validation cohort, primary outcome occurred in 13 (33%) patients. Native QRS features and AP 100 alone failed to predict primary outcome. Patients with increment in V MP count of <8 in lead‐V5 with RVP 120 versus AP 100 had 7.9‐fold increased risk of primary outcome (95% confidence interval 1.01, 61.61; P = 0.049). Conclusion Cardiomyopathy patients at risk of VA or death perturb the QRS less than low‐risk patients with differential pacing. This functional response may be useful to identify arrhythmogenic substrate.