Microvolt QRS Alternans in Hypertrophic Cardiomyopathy: A Novel Risk Marker of Late Ventricular Arrhythmias

Background Unlike T‐wave alternans (TWA), the relation between QRS alternans (QRSA) and ventricular arrhythmia (VA) risk has not been evaluated in hypertrophic cardiomyopathy (HCM). We assessed microvolt QRSA/TWA in relation to HCM risk factors and late VA outcomes in HCM. Methods and Results Prospectively enrolled patients with HCM (n=130) with prophylactic implantable cardioverter‐defibrillators underwent digital 12‐lead ECG recordings during ventricular pacing (100–120 beats/min). QRSA/TWA was quantified using the spectral method. Patients were categorized as QRSA+ and/or TWA+ if sustained alternans was present in ≥2 precordial leads. The VA end point was appropriate implantable cardioverter‐defibrillator therapy over 5 years of follow‐up. QRSA+ and TWA+ occurred together in 28% of patients and alone in 7% and 7% of patients, respectively. QRSA magnitude increased with pacing rate (1.9±0.6 versus 6.2±2.0 µV; P =0.006). Left ventricular thickness was greater in QRSA+ than in QRSA− patients (22±7 versus 20±6 mm; P =0.035). Over 5 years follow‐up, 17% of patients had VA. The annual VA rate was greater in QRSA+ versus QRSA− patients (5.8% versus 2.0%; P =0.006), with the QRSA+/TWA− subgroup having the greatest rate (13.3% versus 2.6%; P <0.001). In those with <2 risk factors, QRSA− patients had a low annual VA rate compared QRSA+ patients (0.58% versus 7.1%; P =0.001). Separate Cox models revealed QRSA+ (hazard ratio [HR], 2.9 [95% CI, 1.2–7.0]; P =0.019) and QRSA+/TWA− (HR, 7.9 [95% CI, 2.9–21.7]; P <0.001) as the most significant VA predictors. TWA and HCM risk factors did not predict VA. Conclusions In HCM, microvolt QRSA is a novel, rate‐dependent phenomenon that can exist without TWA and is associated with greater left ventricular thickness. QRSA increases VA risk 3‐fold in all patients, whereas the absence of QRSA confers low VA risk in patients with <2 risk factors. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02560844.