Fragmented QRS (fQRS) is a readily available finding on the electrocardiogram (ECG) which can be easily used in clinical practice. It is typically defined as notching in the R or S waves in the absence of bundle branch block or as an additional RSR’ pattern in the original QRS wave (with a duration of <120 ms). fQRS develops as a result of heterogeneous electrical activation caused by disrupted ventricular depolarization. It is an electrocardiographic marker of myocardial fibrosis or scar tissue and has been associated with worse prognosis.1,2 Additionally, fQRS has been associated with increased sudden cardiac death in patients with idiopathic dilated cardiomyopathy and heart failure.3,4

Epicardial adipose tissue (EAT) is the visceral fat depot covering the heart5 and can be measured with several imaging techniques including echocardiography, cardiac magnetic resonance imaging, or multidetector computed tomography.6 EAT thickness and volume have been associated with the severity and extent of atherosclerotic coronary artery disease.7–11 Increased EAT thickness is also strongly associated with increased cardiovascular disease, visceral obesity, subclinical atherosclerosis at multiple locations, and the metabolic syndrome,12–16 and is a useful parameter in predicting adverse cardiovascular events.17,18

Two-dimensional (2D) speckle tracking echocardiography (STE) enables detailed assessment of myocardial function, both systolic and diastolic, and is particularly useful for assessment of subclinical left ventricular (LV) dysfunction in patients with normal LV ejection fraction (LVEF) on conventional echocardiography.19,20

The aim of this study was to measure EAT and to assess LV systolic and diastolic function with STE in a healthy population classified according to the presence of fQRS.

In this prospective case-control study, the initial study population consisted of 185 healthy fQRS(+) individuals (with fQRS) on the ECG from a routine screening examination, and a control group of 128 healthy age- and gender-matched fQRS(-) individuals (without fQRS). All of the participants were non-smokers and they were not taking any medication for acute or chronic disease. Five participants were excluded due to imaging problems. All of the 308 participants included in the study had normal sinus rhythm on ECG and echocardiographic images were of adequate quality. The study was approved by the local ethics committee and all participants were informed about the study and their consent was obtained. The following characteristics were recorded for each participant: age, gender, body mass index (BMI) and heart rate, and measurements were taken of 12-hour fasting blood glucose, triglycerides, total cholesterol, high-density (HDL) and low-density lipoprotein (LDL) cholesterol, and creatinine. Standard 12-lead ECGs were taken. Imaging studies were performed of all patients to obtain data from conventional echocardiography, tissue Doppler and STE.

The baseline clinical and laboratory characteristics of the QRS(+) and QRS(-) groups are presented in Table 1. There were no statistically significant differences between the two groups in terms of age, gender, BMI, systolic or diastolic blood pressure, heart rate, family history, fasting glucose, total cholesterol, LDL-C, HDL-C or triglycerides, hematocrit, or hemoglobin (p>0.05).

LAD, LVEDD and LVESD, LVEF, IVST, PWT, and LAVmax were similar between the two groups; however, LAVmin and EAT were greater and GLS was significantly decreased in fQRS(+) individuals. The conventional Doppler parameters of diastolic function – E wave, deceleration time, and isovolumetric relaxation time (IVRT) – were similar between the two groups, but the E/A ratio was lower and the A wave was significantly greater in fQRS(+) individuals (Table 2).

EAT thickness was found to be significantly increased in fQRS(+) individuals (Table 2). When Spearman rank correlation analysis was performed between EAT and baseline demographic, clinical and laboratory parameters, EAT was found to be positively correlated with BMI (r=0.195, p=0.009), LVEF (r=0.147, p=0.048), IVRT (r=0.171, p=0.022), and number of fQRS on the ECG (r=0.498, p=0.022) in fQRS(+) individuals (Table 3).

On multiple logistic regression analysis, EAT was found to be related to increased age (β=0.002, 95% confidence interval [CI]: 0.001-0.004, p=0.008), number of leads with fQRS on the ECG (β=0.040, 95% CI: 0.030-0.051, p<0.001), and presence of fragmented QRS (β=0.205, 95% CI: 0.142-0.268, p<0.001) (Table 4).

The present study demonstrated that EAT thickness was significantly increased in the group with fQRS on the admission ECG compared with the control group. To the best of our knowledge, this is the first evidence of this association.

On multivariate analysis, the presence of fQRS was found to be a significant independent predictor of increased EAT thickness after adjustment for other risk parameters. In the present study, we also found for the first time that GLS in healthy individuals with fQRS is lower than in those without fQRS.

fQRS is a simple, inexpensive and readily available noninvasive ECG parameter that can be easily identified by clinicians. In patients with dilated cardiomyopathy, coronary artery disease or heart failure, fQRS indicates myocardial scarring and fibrosis. The prevalence of fQRS in healthy individuals is 7.2%, but it is seen at a higher rate in diseases such as ST-elevation myocardial infarction (21.9%), chronic renal failure (60%), cardiac sarcoidosis (75%), and metabolic syndrome (26.1%).24–27 The finding of fQRS is more frequent in those with myocardial damage.

It has been proposed that EAT influences the development of coronary atherosclerosis owing to its endocrine and paracrine activity, by secreting anti-inflammatory and proinflammatory cytokines and chemokines.28–30 EAT is associated with various forms of atherosclerosis, including the presence and severity of coronary artery disease,7 as well as coronary artery ectasia,31 slow coronary flow,32 metabolic syndrome and diabetes.33 In the current study of a healthy population, EAT thickness in the fQRS(+) group was greater than in the fQRS(-) group. This finding may be related to the development of more extensive fibrosis in the myocardial tissue of these individuals due to the increased release of inflammatory cytokines and chemokines from the thicker EAT. Detailed studies should be performed using magnetic resonance imaging to show the extent of fibrosis in healthy fQRS(+) individuals to better understand the underlying cause of this ECG finding.

The use of more sensitive echocardiographic methods may enable the detection of subclinical LV systolic dysfunction. 2D STE is a quantitative technique to assess myocardial function by analyzing the movement of speckles on 2D gray-scale ultrasound images of the myocardium. It is not user- or angle-dependent and STE parameters are not affected by cardiac motion. STE also provides information on segmental function.34 Previous studies35–39 have shown that it is a useful method for early detection of LV dysfunction in patients with systemic disease. In the current study, GLS in the fQRS(+) group was lower than in the fQRS(-) group. As mentioned above, these findings showing subclinical myocardial dysfunction in fQRS(+) individuals may be also related to the presence of more extensive fibrosis, which disrupts myocardial function, in these individuals. Thus, we can speculate that increased EAT thickness may lead to the development of more extensive fibrosis and hence myocardial dysfunction, which may be demonstrated by the presence of fQRS in 12-lead ECGs in healthy individuals.

Several limitations in our study should be noted. First, the sample size was relatively small. Second, we measured EAT thickness by means of echocardiography, rather than the more precise computed tomography. Third, we did not perform coronary angiography to identify coronary artery disease, which was excluded based on history, electrocardiography, echocardiography (wall motion abnormalities), and exercise stress tests or myocardial single-photon emission computed tomography. Finally, we did not demonstrate the presence of cardiac fibrosis histopathologically or with other imaging modalities.

The presence of fQRS on the admission ECG is associated with increased EAT thickness and with pronounced subclinical LV systolic and diastolic dysfunction in this healthy population. Further studies with larger patient groups are needed to clarify the exact pathophysiological mechanisms underlying these findings in healthy populations.

The authors have no conflicts of interest to declare.