|Year : 2017 | Volume
| Issue : 1 | Page : 34-39
Fragmented QRS complex in healthy adults: Prevalence, characteristics, mechanisms, and clinical implications
Ying Tian1, Ying Zhang2, Qian Yan1, Jun Mao3, Jianzeng Dong3, Changsheng Ma3, Xingpeng Liu1
1 Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100029, China
2 Department of Cardiology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
3 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
|Date of Web Publication||19-Jun-2017|
Heart Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020
Source of Support: None, Conflict of Interest: None
Background: Fragmented QRS (fQRS) complex on a 12-lead electrocardiogram (ECG) is reportedly associated with myocardial scar or fibrosis in patients with structural heart disease. In healthy persons, however, the prevalence, underlying mechanisms, and clinical implications of fQRS remain unknown. Methods: In this prospective study, the routine 12-lead resting ECGs of 1500 consecutive healthy adults (707 male, age [38 ± 12] years) were independently screened for fQRS by two ECG readers. fQRS was defined as ≥1 additional deflection or notching within the QRS complex, including the peak of the R-wave or the nadir of S-wave, in at least two continuous leads. Results: fQRS was identified in 76 participants (5.1%) in a mean of (2.3 ± 0.7) leads, most commonly inferior leads (86.8%, 66/76), followed by precordial leads (13.2%, 10/76). Longer QRS duration and left deviation of the frontal QRS axis of ≤30° were identified as independent predictors of fQRS. In addition, fQRS in the precordial leads covered the QRS transition lead (from R/S <1 to R/S >1) in all ten participants. Sixteen healthy volunteers who were found to have fQRS underwent late gadolinium enhancement–cardiac magnetic resonance scanning, which revealed no myocardial fibrosis, scar, or other abnormalities. Conclusions: fQRS is not rare in healthy adults. The underlying mechanisms of fQRS in healthy adults seem to be mainly related to left axis deviation (especially deviations ≤30°), rather than myocardial scar or fibrosis.
Keywords: Enhancement-cardiac magnetic resonance, fragmented QRS, healthy adult, prevalence
|How to cite this article:|
Tian Y, Zhang Y, Yan Q, Mao J, Dong J, Ma C, Liu X. Fragmented QRS complex in healthy adults: Prevalence, characteristics, mechanisms, and clinical implications. Int J Heart Rhythm 2017;2:34-9
|How to cite this URL:|
Tian Y, Zhang Y, Yan Q, Mao J, Dong J, Ma C, Liu X. Fragmented QRS complex in healthy adults: Prevalence, characteristics, mechanisms, and clinical implications. Int J Heart Rhythm [serial online] 2017 [cited 2019 Dec 10];2:34-9. Available from: http://www.ijhronline.org/text.asp?2017/2/1/34/208459
| Introduction|| |
Fragmented QRS complex (fQRS) on a routine 12-lead electrocardiogram (ECG) was first observed in patients with coronary artery disease. Since then, this ECG sign, a novel marker of ventricular depolarization abnormalities, has also been studied in patients with other heart diseases including arrhythmogenic right ventricular cardiomyopathy, nonischemic dilated cardiomyopathy, rheumatic valve disease, and Brugada syndrome. Most of these studies have suggested that the presence of fQRS on the 12-lead ECG is associated with increased risk of mortality and arrhythmic events in patients with structural heart disease (SHD).,,,,
The mechanisms of fQRS in patients with SHD remain speculative. Theoretically, nonparallel activation of the ventricles resulting from myocardial scar, fibrosis, or both could result in fQRS on the surface ECG. Like some other ECG markers of malignant ventricular arrhythmias such as the J wave, fQRS is not exclusive to patients with SHD. In fact, this ECG sign is frequently encountered in healthy persons. In this prospective study, we sought to investigate the prevalence, characteristics, potential mechanisms, and clinical implications of fQRS on a routine 12-lead ECG in a cohort of 1500 consecutive healthy persons.
| Methods|| |
Between November 2009 and July 2010, persons who underwent their annual medical examinations in Beijing Anzhen Hospital and Beijing Chao-Yang Hospital were screened. The inclusion criteria were as follows: age 18–65 years, no symptoms or history of any SHD, normal results on the medical interview, physical examination, blood and urine tests, chest radiography, and echocardiography, and no findings on the routine 12-lead ECG tracing suggestive of arrhythmia, pre-excitation syndrome, complete right or left bundle branch block, left posterior or anterior fascicular block, intraventricular conduction delay (QRS duration >120 ms), pacing artifacts, or significant repolarization abnormalities including Brugada ECG pattern and long- or short-QT syndrome.
The study protocol was approved by the Institutional Ethics Committee. Each patient gave written informed consent before the study.
Definition of fragmented QRS
The resting 12-lead ECG (filter range, 0.15–100 Hz; AC filter, 50 Hz, 25 mm/s, 10 mm/mV) was independently analyzed by two ECG readers. In cases of disagreement between the two readers, the final diagnosis was made by an experienced electrophysiology physician (XP Liu). As described in the literature, the fQRS complex was defined as the presence of an additional R-wave (R') or notching at the peak of the R-wave or in the nadir of S-wave, or the presence of >1 R' (fragmentation) in at least two contiguous leads, corresponding to a major coronary artery territory [Figure 1]. Typical incomplete right bundle branch block was excluded from the definition of fQRS.
|Figure 1: An example of a 12-lead electrocardiogram showing fragmented QRS complex (red arrows) over inferior leads (III, aVF).|
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Characteristics of fragmented QRS
In participants with fQRS, the distribution of fQRS on the 12-lead ECG was located as inferior leads (lead II, III, or aVF), anterior leads (V1-V4), lateral leads (V5, V6), high lateral leads (I, aVL), and various combinations between any of two regions. The number of leads showing fQRS and the number of notches within the fQRS complexes were calculated for all participants. Heart rate, RR interval, PR interval, frontal QRS axis, and precordial R/S transition were also recorded for later testing as potential predictors of fQRS.
Substrate of fragmented QRS: A cardiovascular magnetic resonance study
The first twenty participants who have fQRS were asked to undergo late gadolinium enhancement–cardiac magnetic resonance (LGE-CMR) scanning. Three patients declined, and the examination was aborted in 1 because of claustrophobia, so complete LGE-CMR data were collected from 16 participants (10 male, aged [43 ± 12] years).
The LGE-CMR scans were performed with a 3.0-T CMR system (MAGNETOM Verio 3T, Siemens, Erlangen, Germany). Steady-state free precession of cine images was used to quantify left ventricular (LV) function (short-axis stack, slice thickness of 6 mm) and myocardial mass according to standard criteria. Late gadolinium enhancement was assessed with segmented inversion-recovery fast gradient-echo imaging 10 min after 0.1 mmol/kg gadolinium-diethylenetriamine pentaacetic acid was administered. The extent of late gadolinium enhancement was quantified by planimetric assessment of all short-axis slices for total volume (the sum of the areas measured, in grams) and as a proportion of the total LV mass (the percentage of LGE). LGE was defined as two standard deviations (SDs) above the mean signal intensity of the distant myocardium. CMR image analysis was performed by a single experienced investigator. LV ejection fraction, LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV mass were also measured in these 16 participants.
At the end of 2011, 2012, and 2013, telephone calls were made to all participants with fQRS to collect follow-up data. These data included information regarding death, syncope, and newly diagnosed SHD.
Continuous variables were expressed as mean ± SD and categorical variables as frequencies and percentages. Baseline clinical characteristics and demographic data were compared between fQRS and non-fQRS participants. Dichotomous variables were examined using Chi-square tests or Fisher's exact test as appropriate for categorical data, and continuous data were examined with Student's t-test. Only significant covariates were included in the multivariable logistic regression analysis that was performed to determine the association of the fQRS complex with clinical and ECG parameters. The 95% confidence intervals of the hazard ratio were reported for all of the significant predictors. For all tests, a P< 0.05 was considered statistically significant. All tests were two-tailed. All statistical analyses were performed with SPSS (Statistical Package for Social Sciences) version 18.0 (SPSS Inc., Chicago, IL, USA).
| Results|| |
Prevalence and characteristics of fragmented QRS in healthy persons
The concordance for the ECG reading between the two readers was 98.7%. Of 1500 (1000 from Anzhen Hospital and 500 from Chao-Yang Hospital) healthy adults [Table 1], 76 (5.1%) had fQRS on a resting 12-lead ECG. The mean number of leads that recorded fQRS in these 76 participants was 2.3 ± 0.7 (range, 2–4). fQRS was detected in inferior leads in 66 participants (66/76, 86.8%) and in anterior leads (lead V2 and lead V3) in 10 participants (10/76, 13.2%). The fQRS was characterized by an additional R-wave (R') in 44 leads (25.6%) or notching at the peak of the R-wave or in the nadir of the S-wave in 128 leads (74.4%).
Compared with the healthy persons without fQRS, those with fQRS were older [(42 ± 12) years vs. (37 ± 12) years, P= 0.003], were more commonly men (68.4% vs. 46%, P= 0.002), and had a longer RR interval [(864 ± 108) ms vs. (830 ± 102) ms, P= 0.005], a longer PR interval [(147 ± 18) ms vs. (141 ± 18) ms, P= 0.003], a longer QRS width [(92 ± 8) ms vs. (86 ± 11) ms, P< 0.001], a similar QTc interval [(403 ± 19) ms vs. (402 ± 19) ms, P= 0.679], and a more left deviation of the frontal QRS axis [(54 ± 28) degrees vs. (28 ± 31) degrees, P< 0.001]. A similar pattern of relative differences was seen when these parameters were compared between the non-fQRS group and the 66 participants with fQRS in inferior leads [Table 1].
There were 450 participants with QRS duration more than 92 ms among 1424 normal participants who had no fQRS. The frontal QRS axis of these participants was 53 ± 27 degree, which was no difference with other 974 participants who QRS duration <92 ms (The frontal QRS axis 55 ± 28, P= 0.228). On the contrary, participants with QRS duration more than 92 ms in the fQRS group had a more left deviation (19 ± 20) compare with these 450 participants (P < 0.001).
A multivariable logistic regression analysis that included gender, age, RR interval, and PR interval revealed smaller frontal QRS axis and longer QRS duration as independently associated with fQRS (P < 0.001; odds ratio [OR] 0.097; 95% confidence interval [CI] 0.970–0.984 and P= 0.005; OR 7.485; 95% CI 2.212–8.195, respectively) [Table 2]. A subgroup analysis of participants with different frontal QRS axis revealed a significant relationship between fQRS in the inferior wall and frontal axis. As shown in [Figure 2], the smaller the frontal axis, the higher the prevalence of fQRS in inferior leads was.
|Table 2: Multivariate logistic regression analysis of potential predictors of fragmented QRS|
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|Figure 2: The relation between the prevalence of fragmented QRS in inferior leads and frontal QRS axis. Greater frontal axis was associated with a higher prevalence of fragmented QRS in inferior leads. fQRS: Fragmented QRS.|
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Over the 3 years of follow-up, no patient died and no participants were reported to have syncope, newly diagnosed SHD.
Cardiovascular magnetic resonance
LGE-CMR imaging was performed in 16 healthy individuals with fQRS, whose baseline clinical characteristics did not differ significantly from those of the other participants with fQRS [Table 3]. In all 16 participants, CMR revealed normal cardiac structure and function. Mean LVEDV, LVESV, and LV mass were 104 ± 2 3 ml, 43 ± 13 ml, and 70 ± 15 g, respectively, and the mean indexed LVEDV, LVESV, and LV mass were 58 ± 11 ml, 24 ± 7 ml, and 39 ± 6 g/m 2 of body surface area, respectively [Table 3]. Cine imaging sequences did not reveal any focal wall thinning or wall-motion abnormalities, and LAG-CMR did not reveal any enhancement in the wall of the heart [Figure 3].
|Table 3: Baseline data from the magnetic response Imaging and nonmagnetic response imaging groups|
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|Figure 3: An electrocardiogram (a) and late gadolinium enhancement–cardiac magnetic resonance scans (b and c) from a healthy 36-year-old man with fragmented QRS. (a) Fragmented QRS was observed in leads III and aVF (red arrows). (b) There were no morphologic abnormalities within the ventricles. (c) There was no delayed enhancement after gadolinium injection.|
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| Discussion|| |
This study has two main findings. First, fQRS was not a rare ECG finding in healthy adults, having a prevalence of 5.1%, and appearing mostly in inferior leads. Second, fQRS was associated with difference frontal QRS axis or QRS transition in precordial leads, suggesting that these factors, and not myocardial scar or fibrosis, were the underlying mechanisms of fQRS among our participants.
fQRS has been studied as a predictor of potential malignant cardiac events in patients with coronary heart disease and Brugada syndrome. However, there were not sufficient data to draw conclusions about fQRS in healthy adults. Yuce et al. studied fQRS in 193 adult patients with mitral stenosis and in 97 age- and gender-matched healthy persons. As in our study, the prevalence of fQRS among the healthy persons was approximately 5%; thus, the subgroup of healthy persons with fQRS was too small (n = 5) to allow a meaningful study of the characteristics and mechanisms of fQRS in healthy adults.
Compared with those without fQRS on a routine 12-lead ECG, we found that the participants with fQRS were older and more often male. As an earlier study showed, aging has important effects on the cardiac conductive system. In addition, the functional nature of fQRS in our healthy persons had four distinctive characteristics. First, most of the fQRS axes were detected in inferior leads, which were usually perpendicular to the frontal QRS axis in these participants. Second, fQRS detected in the precordial leads always included the leads presented QRS transition. Third, LGE-CMR scanning did not find any evidence of myocardial abnormalities in patients with fQRS. Fourth, there were no adverse cardiac events during the 3-year follow-up period in the participants with fQRS.
It has been speculated that fQRS on a routine 12-lead ECG results from the heterogeneous activation of the ventricles due to myocardial scar, ischemia, or fibrosis.,, However, Morita et al. showed that fQRS can also result from a conduction abnormality in the absence of SHD. In an experimental model of Brugada syndrome, they found local conduction delay in the epicardium secondary to changing of timing of pacing reproduced similar fQRS in the transmural ECG.
In the present study, we found that the QRS duration is independently associated with fQRS. However, such slight depolarization changes on surface ECG cannot be interpreted as proof that there are slight myocardial abnormalities in these participants. The “gold standard” for the diagnosis of small myocardial abnormalities is endomyocardial biopsy, but obviously, the invasiveness of this technique limits its applicability, especially in healthy persons. Recently, advances in CMR have enabled noninvasive detection and quantification of myocardial abnormalities with the LGE technique.,,, The extent of LGE regions has been associated with clinical markers of sudden death and progression to heart failure.
Our findings suggest that myocardial abnormalities are not a plausible mechanism of fQRS in healthy persons because contrast enhancement was not detected in any of the 16 volunteers in either the early perfusion phase or the delayed phase. Therefore, some other mechanism must have caused the fQRS in our healthy persons.
By multivariable regression, we found that fQRS was independently associated with QRS axis deviation. Of the fQRS recorded in inferior leads, 68% was detected in participants with a frontal QRS axis of <30°, indicating that fQRS in inferior leads is associated with left deviation of the frontal QRS axis. Frontal QRS axis is also associated with age. It was reported that left QRS axis deviation was found in 45.7% of centenarians. In addition, the fact that all precordial fQRS spanned the QRS wave transition leads (usually, V2/V3) suggest that fQRS is correlated with horizontal QRS axis. According to electrocardiovector theory, in the depolarization process, the depolarization wavefront could be detected twice by the leads that are perpendicular to the frontal axis plane, thereby forming an additional R-wave. Actually, because the frontal axis in most healthy persons was approximately 60°, fQRS could be recorded only in lead III. Thus, although fQRS could be said to have occurred in these participants, it did not meet our criteria for fQRS (because it was not detected in ≥2 contiguous leads) as shown in [Figure 4].
|Figure 4: Isolated fragmented QRS in lead III (red arrows). Because this participant's frontal axis was nearly zero, two R waves occurred in the inferior leads, which were perpendicular to it. The frontal QRS axis of this healthy person was approximately 60°, and although fragmented QRS was recorded in lead III (perpendicular to the 60° frontal axis), it did not satisfy the other criterion for fragmented QRS (i.e., detection by at least two contiguous leads).|
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This study has a few noteworthy limitations. First, although we followed up the participants with fQRS for 3 years and found no adverse cardiac events, even longer follow-up might be necessary to definitively rule out the possibility that fQRS is a cardiac risk factor in healthy persons. Second, we could not rule out the possibility that fQRS in seemingly healthy persons is related to very small pathological myocardial changes that cannot be detected by LGE-CMR scanning. Theoretically, however, the prognostic importance of such slight myocardial abnormalities should be minimal. Third, we might have more accurately defined the characteristics of fQRS in healthy adults if our study had included another group that comprised patients with fQRS secondary to SHD. Nonetheless, our study revealed much about the functional nature of fQRS in healthy adults by showing that the chief sign of benign fQRS is its relationship with frontal QRS axis and precordial QRS transition. Finally, MRI scan was performed in only 16 volunteers, rather than all participants with fQRS; therefore, we cannot exclude the possibilities of myocardial scar/fibrosis in another sixty participants.
| Conclusion|| |
In healthy persons, fQRS on routine 12-lead ECG appears to be a normal variant with a prevalence of approximately 5%. The distribution of fQRS in healthy adults is predominantly in inferior leads and is associated with left deviation of the frontal QRS axis or QRS transition in precordial leads, rather than myocardial scar or fibrosis.
Financial support and sponsorship
This work was supported in part by three grants from the National Natural Science Foundation of China (No. 81070146 to Xingpeng Liu, No. 81100125 and No. 81470023 to Ying Tian) and a grant from the Capital Health Research and Development of Special Projects (No. 2011-2003-04 to Xingpeng Liu).
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]
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