Automated Quantification of Abnormal QRS Peaks From High‐Resolution ECGs Predicts Late Ventricular Arrhythmias in Hypertrophic Cardiomyopathy: A 5‐Year Prospective Multicenter Study

Abstract

Background Patients with hypertrophic cardiomyopathy (HCM) are at risk of ventricular arrhythmia (VA) attributed to abnormal electrical activation arising from myocardial fibrosis and myocyte disarray. We sought to quantify intra‐QRS peaks (QRSp) in high‐resolution ECGs as a measure of abnormal activation to predict late VA in patients with HCM. Methods and Results Prospectively enrolled patients with HCM (n=143, age 53±14 years) with prophylactic implantable cardioverter‐defibrillators had 3‐minute, high‐resolution (1024 Hz), digital 12‐lead ECGs recorded during intrinsic rhythm. For each precordial lead, QRSp was defined as the total number of peaks detected in the QRS complex that deviated from a smoothing filtered version of the QRS. The VA end point was appropriate implantable cardioverter‐defibrillator therapy during 5‐year prospective follow‐up. After 5 years, 21 (16%) patients had VA. Patients who were VA positive had greater QRSp (6.0 [4.0–7.0] versus 4.0 [2.0–5.0]; P <0.01) and lower left ventricular ejection fraction (57±11 versus 62±9; P =0.038) compared with patients who were VA negative, but had similar established HCM risk metrics. Receiver operating characteristic analysis revealed that QRSp discriminated VA (area under the curve=0.76; P <0.001), with a QRSp ≥4 achieving 91% sensitivity and 39% specificity. The annual VA rate was greater in patients with QRSp ≥4 versus QRSp <4 (4.4% versus 0.98%; P =0.012). In multivariable Cox regression, age <50 years (hazard ratio [HR], 2.53; P =0.009) and QRSp (HR per QRS peak, 1.41; P =0.009) predicted VA after adjusting for established HCM risk metrics. In patients aged <50 years, the annual VA rate was 0.0% for QRSp <4 compared with 6.9% for QRSp ≥4 ( P =0.012). Conclusions QRSp predicted VA in patients with HCM who were eligible for an implantable cardioverter‐defibrillator after adjusting for established HCM risk metrics, such that each additional QRS peak increases VA risk by 40%. QRSp <4 was associated with a <1% annual VA risk in all patients, and no VA risk among those aged <50 years. This novel ECG metric may improve patient selection for prophylactic implantable cardioverter‐defibrillator therapy by identifying those with low VA risk. These findings require further validation in a lower risk HCM cohort. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02560844.

Predicting lethal ventricular arrhythmias in hypertrophic cardiomyopathy using electrophysiologic methods: Invasive EGM vs. non-invasive ECG analysis of fragmentation

“…In our study, QRSp was greater in HCM patients with extensive (>15%) LGE MRI than those without [4.0 (3.0–6.0) vs. 3.5 (2.0–4.0), P < 0.001]. 7 As such, non-invasive EP metrics of fragmentation in combination with LGE MRI may provide a more practical, robust approach to HCM risk stratification than paced EGM fragmentation, which should be the focus of future prospective studies.…”

“…We have recently developed a novel QRS fragmentation metric, known as QRS peak (QRSp), that quantifies low-amplitude intra-QRS peaks during sinus rhythm. 7 QRSp is quantified from the precordial leads of a 3-minute high-resolution 12-lead ECG after selective filtering and signal-averaging to maximize signal to noise ( Figure 1A ). In a prospective study of 134 HCM patients (mean age 52 ± 13 years, ESC risk score 4.6 ± 2.7) with prophylactic defibrillators and no history of VT/VF, maximum QRSp across the precordial leads was greater in patients with VT/VF than those without during the 5-year follow-up [6.0 (4.0–7.0) vs. 4.0 (2.0–5.0), P < 0.001].…”

Strain Imaging and Ventricular Arrhythmia

“…Given the constraints of LVEF and the varying pathophysiological mechanisms that may promote the development of VAs, several studies have evaluated the potential prognostic utility of other biomarkers in the context of VAs. These include electrocardiographic markers as well as findings from cardiac magnetic resonance imaging, computed tomography, radionuclide imaging, and novel echocardiographic techniques [8][9][10][11][12][13][14][15][16][17][18][19][20][21].…”

Ultra-High-Resolution Electrocardiography Enables Earlier Detection of Transmural and Subendocardial Myocardial Ischemia Compared to Conventional Electrocardiography

“…In particular, high-resolution ECG is focused on low-voltage (~1 µV) late potentials which follow the QRS complex [10]. Late potentials reflect mild disorders of intraventricular conduction, serving as an important tool for the prediction of arrhythmic events in special cohorts [11]. One more type of ECG is high-frequency QRS ECG, which has been proven to be instructive in patients with IHD due to an analysis of the high-frequency (≤300 Hz) component of cardiac electrical signal [12].…”