Elsevier

Heart Rhythm

Volume 11, Issue 8, August 2014, Pages 1433-1440
Heart Rhythm

Fragmented QRS as a candidate marker for high-risk assessment in hypertrophic cardiomyopathy

https://doi.org/10.1016/j.hrthm.2014.05.002Get rights and content

Background

The relationship between a fragmented QRS complex (fQRS) on 12-lead ECG and fatal arrhythmic events in hypertrophic cardiomyopathy (HCM) remains unclear.

Objective

The purpose of this study was to investigate whether fQRS is associated with ventricular arrhythmic events (VAEs) in HCM patients.

Methods

Of an initial cohort of 273 patients (57% male, mean age 55 years) diagnosed with HCM, 167 patients were included and divided into 2 groups: those with fQRS (n = 67) and those without fQRS (n = 100). fQRS was defined as notching of the R or S wave in 2 contiguous leads. VAEs were defined as nonsustained or sustained ventricular tachycardia (VT) or sudden cardiac death (SCD). Major arrhythmic events (MAEs) were sustained VT or SCD.

Results

During mean follow-up of 6.3 years, univariate analysis showed that fQRS was significantly associated with increased VAEs (unadjusted hazard ratio [HR] 6.17, 95% confidence interval [CI] 2.46–15.49, P < .001) and MAEs (unadjusted HR 5.12, 95% CI 1.38–19.01, P = .014). Multivariate analysis revealed that fQRS was a strong independent predictor of VAEs (adjusted HR 6.28, 95% CI 2.49–15.84, P < .001) and MAEs (adjusted HR 6.04, 95% CI 1.49–24.39, P = .011). fQRS in the inferior leads was most closely related to MAEs compared to fQRS in other myocardial territories, and its inclusion in a risk calculator for mortality in HCM patients increased the positive predictive value from 8% to 25% in low-risk patients.

Conclusion

Presence of an fQRS may be a good candidate marker for prediction of VAE in patients with HCM.

Introduction

A fragmented QRS complex (fQRS), defined as unexpected deviations in the QRS complex on 12-lead ECG, has recently been identified as an independent prognostic marker for sudden death.1, 2 An fQRS reflects regional conduction delay due to disorganized myocardial tissue or scar, which, in turn, provides an anatomic substrate by which ventricular arrhythmias may be generated.3, 4, 5, 6 An fQRS has been shown to predict fatal arrhythmic events such as ventricular tachycardia (VT) and ventricular fibrillation (VF) in patients with acute myocardial infarction, dilated cardiomyopathy, Brugada syndrome, and arrhythmogenic right ventricular dysplasia.7, 8, 9 However, little is known about the association of an fQRS complex and occurrence of ventricular tachyarrhythmias in patients with hypertrophic cardiomyopathy (HCM).

Risk stratification of sudden cardiac death (SCD) in patients with HCM is paramount when selecting patients for implantable cardioverter-defibrillator (ICD) placement. Selection of HCM patients to receive an ICD is guided by conventional risk factors such as family history of SCD, unexplained syncope, left ventricular (LV) wall thickness >30 mm, hypotension during exercise, and nonsustained or sustained VT.10 Almost 50% of HCM patients have 1 or more risk factors for SCD, yet the annual mortality rate of SCD in clinically identified HCM patients is only approximately 1%, demonstrating that use of conventional risk factors suffers from a low positive predictive value (PPV) when attempting to identify those HCM patients who will go on to experience SCD. Most patients with HCM who undergo screening are at relatively low risk, so the decision for primary prevention is made according to individual clinical situation.11 Here, clinicians must weigh the benefits of preventing SCD against the risks of unnecessary ICD placement. We hypothesized that fQRS would provide an additional marker to predict arrhythmic events in patients with HCM. Accordingly, we examined patients with HCM and investigated the presence of fQRS (as a surrogate marker of regional conduction delay) to ventricular arrhythmic events (VAEs), defined as nonsustained or sustained VT, and SCD. We then investigated whether fQRS can also predict major arrhythmic events (MAEs), defined as sustained VT and SCD.

Section snippets

Study population

Between February 2001 and April 2007, the records of 273 patients diagnosed with HCM via echocardiography were reviewed. All patients underwent routine clinical examination, 2-dimensional echocardiography, and standard 12-lead ECG. HCM was diagnosed if there was unexplained LV hypertrophy associated with nondilated ventricular chambers in the absence of other cardiac or systemic disease capable of producing maximal LV wall thickness ≥15 mm.2 Exclusion criteria included reduced LV function

Baseline characteristics between non-fQRS and fQRS groups

Baseline characteristics were similar between the fQRS and non-fQRS groups with respect to age, gender, family history of SCD, previous syncope, and echocardiographic parameters (Table 1). No statistical difference was observed between fQRS and non-fQRS patients with regard to resting heart rate and ECG parameters, including PR interval, QRS duration, and presence of ST inversion/depression or early repolarization. (P >.05 for all).

Distribution of fQRS and arrhythmic events

Representative examples of fQRS in 2 patients are shown in

Discussion

In this study population, an fQRS on 12-lead ECG (1) was strongly associated with VAEs and MAEs in patients with HCM; and (2) was predictive of future development of VAEs, including SCD, during long-term follow-up. Interestingly, an fQRS in the inferior leads was much more predictive of fatal arrhythmic events than that occurring in any other myocardial territory. Most importantly, the addition of fQRS in inferior leads to traditional markers used to assess the risk of SCD in HCM patients

Conclusion

In the current study, the presence of an fQRS, and especially an fQRS in the inferior leads, was significantly associated with a higher risk of fatal ventricular arrhythmia events in HCM patients. Our findings may provide an important additional clinical tool to more precisely risk stratify HCM patients eligible for primary prevention ICDs.

References (35)

Cited by (45)

  • J Waves for Predicting Cardiac Events in Hypertrophic Cardiomyopathy

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    The intraventricular conduction delay in HCM is also known to initiate notching of the QRS complex (fragmented QRS complex) (21). We and others (22,23) reported that the presence of fragmented QRS complexes, defined as the presence of an additional R-wave (R′), notching in the nadir of the S-wave, or the presence of >1 R′ on the 12-lead ECG, was associated with either heart failure with hospitalization or arrhythmic events in patients with HCM. We also showed, using late gadolinium enhancement in CMR, that fragmented QRS complexes can be markers of myocardial fibrosis in patients with HCM (24).

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    The study established that fQRS is significantly associated with ventricular arrhythmias and major arrhythmic events (unadjusted HR = 6.17, 95% CI 2.46–15.49, p < 0.001 and unadjusted HR 5.12, 95% CI 1.38–19.01, p = 0.014 respectively). fQRS was also identified to be an independent predictor of VA and major arrhythmic events in HCM (adjusted HR 6.28, 95% CI 2.49–15.84, p < 0.001 and adjusted HR 6.04, 95% CI 1.49–24.39, p = 0.011 respectively) [51]. As mentioned in the previous sections, fQRS is a marker of myocardial scar.

  • Sudden death related cardiomyopathies - Hypertrophic cardiomyopathy

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    Both presence of LGE and the extent of LGE have been shown to be associated with increased risk of sudden death, however this has yet to be validated in large prospective studies, therefore the predictive value remains indeterminant.40,41 Additional risk factors have been reported, including: extracellular volume on CMR,42 high T2-weighted signal intensity,43 Global longitudinal strain,44 left atrial volume,43 fragmented QRS patterns,45 J waves,45 and LV mechanical dispersion.46 Beta-blockers are first-line treatment for symptomatic patients; this is thought to be a class effect and there are little data to support use of individual beta-blockers.

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