P1597QT rate dependence in risk stratification for sudden death in hypertrophic cardiomyopathy

Abstract

Background: Risk stratification for sudden death (SD) in hypertrophic cardiomyopathy (HCM) is mainly based on evaluation of simple parameters like syncope, maximal wall thickness and the presence of non-sustained VT. QT rate dependence has been proposed as a marker of increased susceptibility to ventricular arrhythmias and sudden death, however this was only evaluated in small cohorts. Purpose(s): Evaluate whether QT rate dependence is altered in HCM patients compared to controls and whether it plays any role in risk stratification for sudden death. Method(s): We retrospectively analysed our hypertrophic cardiomyopathy database to identify patients with HCM, mutation positive phenotype negative individuals (HCMG+) and mutation negative family members of HCM patients with known mutation (HCM-G-). Patients were selected if 24 hour holter recording was performed. Linear regression of 24 hour QT-RR data plots were calculated resulting in a formula (QT = alpha x RR + beta) where alpha denotes the QT-RR slope or QT rate dependence. We first compared QT rate dependence during 24 hour, daytime, nighttime and circadian variation (difference between daytime and nighttime QT-RR slope) between the 3 groups. Secondly, we assessed whether these holter parameters have any added value in risk stratification for the composite endpoint of SD, cardiac arrest, sustained VT or ICD shock using binary logistic regression (enter method). Variables with P value <0.1 in the univariable model were entered into the multivariable model. Conventional risk markers that were included in the analysis were MWT, unexplained syncope, family history of SD, maximal left ventricular outflow tract obstruction (LVOTO) and nsVT. Result(s): We included 231 HCM patients, 18 HCM-G+ patients and 21 HCM-G- individuals. QT rate dependence during daytime was higher in HCM patients (0.179+/-0.057; P=0.04) compared to HCM-G+ patients (0.157+/-0.043) and HCM-G- individuals (0.154+/-0.045). There was no difference regarding 24 hour and nighttime QT rate dependence and its circadian variation. The composite endpoint occurred in 18 HCM patients either at baseline or during a mean follow-up of 104+/-87 months. Patients who reached the composite endpoint had loss of the circadian variation of the QT rate dependence (-0.0123+/-0.154, P=0.74), while patients who did not reach the composite endpoint retained this variation (0.019+/-0.055, P<0.001). In the univariable model, family history of SD, presence of nsVT and nighttime QT rate dependence were significant predictors of the composite endpoint. However, family history of SD was the only independent predictor (OR 3.27; 1.12-9.59). Conclusion(s): There was no difference between QT rate dependence in HCM patients and controls, apart from increased slopes during daytime. Loss of circadian variation was observed in patients with HCM who reach the composite endpoint. However in a multivariable model, only familial history of SD was a predictor of events.