Evaluation of QRS dispersion and its association with tachyarrhythmia events in patients with implanted cardiac resynchronization therapy defibrillator device

© 2018 The Authors; Tabriz University of Medical Sciences This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Evaluation of QRS dispersion and its association with tachyarrhythmia events in patients with implanted cardiac resynchronization therapy defibrillator device

contraction (PVC), ventricular tachycardia (VT), left ventricular block, and atrial fibrillation (AF); and these arrhythmias are a predictor of sudden death. 5,6One of the noninvasive criteria that determines the risk of malignant arrhythmias in these patients is the change in the duration of the QRS wave in the 12-lead, simply called QRS dispersion. 7It is a rather novel predictor of mortality in HF patients and results from changes in the repolarization time of various myocardial sites. 8QRS dispersion indicates the instability of the myocardial electricity.It is simple and reproducible and can identify HF patients with high risk of sudden cardiac death. 9ifferent therapies are used for HF patients, which include medical treatment and cardiac resynchronization therapy defibrillator (CRT-D).CRT-D improves left ventricular function as well as hemodynamic and the quality of life in patients with severe HF by shortening the QRS duration.In addition, CRT-D may have a more effective impact on reducing arrhythmia risk in patients with more prolonged QRS duration.This might be due to its superior effects on reducing QRS duration in this set of patients. 10,11onsidering the importance of HF and the therapeutic methods used in these patients, this study aimed to investigate the association between dispersion of QRS and its relationship with arrhythmias in patients who are being treated with CRT.
In an analytical study, 45 patients were enrolled, who had undergone CRT-D implantation, at least six months before the study, in Shahid Madani University Hospital, Tabriz, Iran, during 2012-2015.All available sampling was included in the study.The convinient sampling method was used to select these patients.
Every patient with HF that had undergone CRT-D implantation at least six months before the study was included, and all of them had informed self-consent for participation in this investigation.On the other hand, every patient taking any antiarrhythmic drug, having an electrolyte imbalance, having no left ventricular lead, or being reluctant to participate in the study were excluded.
This study was in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.After approval of the Ethics Committee of Tabriz University of Medical Sciences and by considering the exclusion and inclusion criteria, and explaining the purpose of the study to the patients, 45 patients were included, and written informed consent was obtained from them.The basic information of the patients including age, sex, underlying illness, blood pressure, risk factors for heart disease, and kidney failure was gathered.
First, in the intrinsic mode of CRT-D, ECG was obtained from all patients.Other ECGs were obtained from the patients 3 min after setting the device on 50-LV (left ventricle), 30-LV, only RV (right ventricle), and simultaneous modes.Then arrhythmias were extracted from the CRT-D memory and QRS wavelengths were measured by the cardiocaliper software in all 12 leads of ECGs.It should be noted that in all patients, V-V was considered to be 0 ms as the default of device after CRT-D insertion.The study protocol has been depicted in figure 1.
All the patients were informed that their information would be kept confidential, and their personal information would not be mentioned anywhere.During the study, no additional diagnostic and therapeutic interventions were performed on patients, and the patients were referred to the Cardiology Clinic of Shahid Madani Hospital in Tabriz City only for periodical analyses after CRT insertion.No additional costs were imposed on the patients and their families.The study was supported by vice-chancellor of Tabriz University of Medical Sciences.The comparison of QRS dispersion was done in two levels as more or less than 40 ms based on the previous studies. 12,13he data were expressed as mean ± standard deviation (SD), frequency, and percentage.Chi-square test was applied to compare the qualitative variables; independent t-test and one-way ANOVA were used to examine and compare the quantitative variables.All analyses were performed using SPSS (version 22, IBM Corporation, Armonk, NY, USA), and P ≤ 0.05 was considered as statistically significant.
The mean age of the patients was 65.66 ± 11.37 years.33 (73.3%) patients were male, and 12 (26.7%)patients were female.The results revealed that 36 (80.0%) patients had ischemic cardiomyopathy, and 9 (20.0%)patients had non-ischemic cardiomyopathy.It was found that 41 (91.1%) patients had left bundle branch block (LBBB), and 4 (8.9%)patients had right bundle branch block (RBBB).Additionally, 40 (88.9%)patients had sinus rhythm, and 5 (11.1%) patients had AF rhythm.Table 1 represents the prevalence of risk factors and underlying diseases in patients.Table 2 shows the mean of QRS duration in the tested leads and its comparison to the simultaneous and intrinsic modes.Based on the results of this table, it was found that CRT-D implantation resulted in a significant decrease in the QRS duration in all leads.Moreover, because the default was based on V-V = 0 in the simultaneous mode, it was revealed that QRS dispersion increased in comparison to the intrinsic mode (P < 0.001).
In addition, it was found that 36 (80.0%) patients experienced VT/ventricular fibrillation (VF) arrhythmias, 18 of which had sustained VT/VF.The following tables (Tables 3 and 4) compare the QRS duration in all the 12 leads in the patients with or without VT/VF (non-Sustained or sustained) in the intrinsic and simultaneous modes.
According to these tables, there was a significant difference in QRS duration in the pre-cordial and limb leads between patients with total VT/VF and no arrhythmia (P = 0.004 and P = 0.040, respectively).This means that patients with a more extended QRS duration had fewer arrhythmias or, in the other words, CRT-D effect on decreasing arrhythmias is more evident in patients who previously had wider QRS.
Moreover, it was revealed that mean QRS duration in the intrinsic mode had a higher association with arrhythmic events than max QRS duration (Table 5).
The following table (Table 6) compares the mean duration of QRS among patients with or without VT/VF (non-sustained or sustained) in the various modes of the CRT-D device.
The results also showed that QRS dispersion in the intrinsic mode was significantly lower than the other modes of the CRT-D device (P < 0.001), as shown in table 7.
Table 8 represents the frequency and comparison of QRS dispersion and its relation to arrhythmia incidence among patients with sustained or non-sustained VT/VF in various modes of CRT-D device.
Based on the current guidelines, CRT-D was indicated for patients who were on medical treatment and had moderate to severe HF, individuals with left ventricular ejection fraction of 35% or less, or patients with QRS duration of more than 120 ms. 5 In many patients with HF, the duration of QRS was less than 120 ms, 14 and thus CRT-D is not recommended; however, electrocardiographic studies indicated that 50% of these patients had dyssynchrony evidence, and therefore can benefit from CRT-D implantation. 15,160][21] On the other hand, measurements of interlead changes in QRS duration during a twelve-lead ECG, which is called QRS dispersion, is a non-invasive simple method for detecting regional differences in the relaxation time of contracted ventricle. 22,24This study was conducted to provide a hypothesis regarding the probable relationship between QRS duration changes in patients with or without arrhythmias after CRT-D implantation.
In the present study, 45 HF patients with CRT-D implantation were studied.During the study, the QRS dispersion was evaluated in different functioning modes of the device, and its association with arrhythmic events was investigated.Based on the results of the study, the mean duration of QRS in the simultaneous mode was significantly lower than that of the intrinsic mode (indicating the function of the device).However, there was no significant difference between different modes of CRT-D related to the association of QRS dispersion and arrhythmia events (VF/VT).Besides, according to the results of this study, the effect of CRT-D on decreasing arrhythmias was more prominent in patients with wider QRS wave.The results of this study showed that there was no significant difference in QT dispersion between patients with low and high risk of arrhythmias. 25On the other hand, Peters et al. showed that QT dispersion in the QRS complexes of pre-cordial leads is a non-invasive predictor for frequent arrhythmias in this group of patients. 26urrini et al. also studied the importance of ECG findings such as QRS dispersion in estimating the risk of sudden cardiac death in patients with ARVC.During the study, patients were divided into four groups: 1) 20 patients with sudden death from the disease; 2) 20 patients living with the disease; 3) 20 patients with ARVC with PVCs ≤ 3; and 4) 20 subjects as the control group.Based on the findings of this study, the QRS-QT dispersion was higher in the first group than that of the second and third groups.Moreover, they found that QRS dispersion (40 ms) is a strong and non-dependent predictor of sudden death in ARVC patients. 27However, in the present study, there was no significant association between QRS dispersion (≥ 40 ms) and arrhythmogenic events.These controversies can be due to the choice of the patients, the underlying conditions and the status of the LV of the patients.
Several studies have pointed to improved cardiac function and increased ejection fraction with the CRT-D implantation.Thus, it is likely to be effective in reducing arrhythmias by improving the function of the LV and reducing its size. 21,28In addition, based on the results of this study, it was found that mean QRS association with arrhythmic events in the intrinsic mode was higher than that of max QRS duration.Because max QRS duration is considered as an indication for CRT-D implantation, it can be stated that QRS mean is probably a better indication for CRT-D implantation.However, this should be considered in the future studies.
Additionally, Anastasiou-Nana et al. examined the usefulness of QRS dispersion in the prognosis of patients with congestive HF.During the study, 104 patients with HF (ejection fraction ≤ 35%) who did not take any anti-arrhythmic drugs were studied.During the 20-month period of the study, 13 non-sudden and 10 sudden cardiac deaths occurred.They showed that the average length of QRS in the dead patients was significantly more than that of the other patients.The study revealed that QRS dispersion is an independent predictor of non-sudden cardiac death, and in general, mortality rate in people with a QRS dispersion ≥ 46 ms, is 3.9 folds higher than other individuals. 29n another study, Kearney et al. assessed 553 patients with congestive HF and sudden cardiac death.They found that high cardiothoracic ratio, high QRS dispersion, high corrected QT dispersion, and VT are predictors of sudden cardiac death in these patients. 30In a study by Tsagalou et al. the relationship between QT and QRS dispersion and mortality in patients with congestive HF was evaluated.During the 20-month period of follow-up, 13 non-sudden and 10 sudden cardiac death occurred.They showed that QT and QRS dispersion was higher in these individuals than survivors indicating that QRS dispersion is an independent risk factor that predicts sudden cardiac deaths in HF patients. 31ntil now, all studies that have demonstrated the effect of QRS dispersion on the incidence of arrhythmic events have been performed before CRT-D implantation.One of the novelties of this study was that by implantation of CRT-D, the effect of QRS dispersion on patients with severe HF, who were highly susceptible to sudden death due to the arrhythmias, was evaluated.
This study had some limitations which may affect its results.First, the effects of changes in the ejection fraction and LV size on the arrhythmic events in HF patients could not be assessed.Therefore, the effects of QRS dispersion on these events should also be evaluated independently of these parameters.Second, the sample size was small, and thus studies with larger sample size are of top priority in this regard.
In conclusion, it was found that CRT-D implantation in HF patients significantly reduced the QRS duration and increased QRS dispersion.However, this increase in the QRS dispersion was not associated with an increase in the incidence of cardiac arrhythmias.Moreover, it was found that using mean QRS duration before CRT-D implantation is more related to arrhythmic events than max QRS duration.Further studies are necessary in this field for better decision making.This study was approved by the Regional Medical Ethics Committee of Tabriz University of Medical Sciences under the number 93.3-6.7.

Table 1 .
The prevalence of risk factors and underlying illnesses in patients

Table 3 .
The comparison of mean QRS duration (ms) based on ventricular tachycardia/ ventricular fibrillation (VT/VF) in the intrinsic mode

Table 8 .
The frequency and comparison of QRS dispersion (more or less than 40 ms) and its relation to arrhythmia incidence among patients with sustained or non-sustained ventricular tachycardia/ventricular fibrillation (VT/VF) in various modes of cardiac resynchronization therapy defibrillator (CRT-D) device .This paper is based on Nasrin Khaky's specialty dissertation (93/3-6/7) submitted to the School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.Authors have no conflict of interest.