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ScienceDirect Journal of Electrocardiology 47 (2014) 677 – 683 www.jecgonline.com
Regional myocardial dysfunction assessed by two-dimensional speckle tracking echocardiography in systemic sclerosis patients with fragmented QRS complexes Kursat Tigen, MD, a Murat Sunbul, MD, a,⁎ Gulsen Ozen, MD, b Erdal Durmus, MD, a Tarik Kivrak, MD, a Altug Cincin, MD, a Beste Ozben, MD, a Halil Atas, MD, a Haner Direskeneli, MD, b Yelda Basaran, MD a a b
Marmara University Faculty of Medicine, Department of Cardiology, Istanbul, Turkey Marmara University Faculty of Medicine, Department of Rheumatology, Istanbul, Turkey
Abstract
Background: The aim of the study was to explore the relation between regional myocardial dysfunction and fragmented QRS (fQRS) complexes in systemic sclerosis (SSc). Methods: Fifty-three SSc patients and 26 controls were included. All subjects underwent speckle tracking echocardiography for evaluation of left ventricular (LV) function and ECG to check for fQRS complexes. Results: SSc patients had significantly lower LV global longitudinal, radial and circumferential strain and twist compared to controls. Thirteen SSc patients had fQRS (DII, DIII, aVF leads in eleven patients and V1 to V5 leads in two patients) and they had significantly lower global longitudinal and circumferencial strain compared to SSc patients with normal QRS. The SSc patients with fQRS in DII, DIII, and aVF leads had impaired longitudinal strain and delay in time to peak longitudinal strain in inferior LV segments compared to those with normal QRS. Conclusion: fQRS is associated with lower strain measures in SSc patients indicating impairment in LV function. © 2014 Elsevier Inc. All rights reserved.
Keywords:
Fragmented QRS; Speckle tracking echocardiography; Systemic sclerosis
Introduction Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular dysfunction and excessive fibrosis involving the skin and visceral organs [1]. Cardiac manifestations are common in SSc, with an estimated clinical prevalence of 15%–35% and when clinically evident, are often associated with mortality [2,3]. However, in the majority of SSc patients, cardiac manifestations may remain subclinical [4–6]. Thus, monitoring of myocardial involvement represents an important aspect of the disease management [7]. Two-dimensional (2D) speckle-tracking echocardiography (STE) has been proposed as a sensitive method for the evaluation of myocardial involvement in SSc patients [8,9]. Spethmann et al. [10] showed that left ventricular (LV) deformation analysis by STE was a sensitive method to detect early LV systolic impairment ⁎ Corresponding author at: Fevzi Cakmak Mahallesi, Mimar Sinan Caddesi, No: 41, Ustkaynarca, Pendik, İstanbul, Turkey. E-mail address: [email protected] http://dx.doi.org/10.1016/j.jelectrocard.2014.07.008 0022-0736/© 2014 Elsevier Inc. All rights reserved.
primarily in the basal segments in patients with SSc having preserved LV ejection fraction (EF). Cardiac involvement in SSc does not only involve the myocardium but also the conduction system [11]. Ventricular late potentials were proposed to be used as an early index of myocardial fibrosis in SSc [12]. Morelli et al. [13] explored the role of late ventricular potentials in detecting early myocardial involvement in SSc patients and reported that signal averaged electrocardiography (ECG) was a sensitive and inexpensive technique in the clinical assessment and follow up of patients with SSc. While fragmented QRS (fQRS) is shown to be associated with regional myocardial damage and increased cardiovascular morbidity and mortality in patients with coronary artery disease [14,15], the association between fQRS and regional myocardial dysfunction has not been studied in SSc patients. The aim of this study was to evaluate deformation analyses derived from 2D STE for early detection of LV regional myocardial dysfunction in patients with SSc and to explore a relation between myocardial function and fQRS complexes present in surface ECG of SSc patients.
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Materials and methods The investigation complies with the principles outlined in the Declaration of Helsinki. The study was approved by the Local Ethics Committee and all participants gave written informed consent before participating. Sixty-two consecutive patients with SSc who were followed by the Department of Rheumatology were enrolled to the study. The diagnosis of SSc was based on the American Rheumatism Association criteria [16]. After the exclusion of the patients with coronary artery disease, valvular heart disease, cardiomyopathy, arrhythmias or conduction disorders, LV systolic dysfunction (LV EF b 55%), and diabetes mellitus, peripheral arterial disease, and chronic obstructive pulmonary disease, the remaining 53 SSc patients were included in the study. Twenty-six healthy subjects were included into the study as control group. Standard echocardiography and 2D speckle tracking echocardiography All patients underwent a complete echocardiographic study with a commercially available echocardiography device (Vivid 7, GE Vingmed Ultrasound AS, Horten, Norway) by a single experienced cardiologist. Data acquisition was performed with a 3.5-MHz transducer at a depth of 16 cm in the parasternal and apical views (standard parasternal shortaxis from midventricular level, apical long-axis, two-chamber and four-chamber images). Standard M-mode, 2D and color coded TDI images were obtained during breath hold, stored in cine loop format from 3 consecutive beats and transferred to a workstation for further offline analysis (EchoPAC 6.1; GE Vingmed Ultrasound AS). Gain settings, filters, and pulse repetitive frequency were adjusted to optimize color saturation, and a color Doppler frame scanning rate of 100–140 Hz was used for color TDI images. Cardiac dimensions were measured according to the guidelines of the American Society of Echocardiography and LV EF was calculated by biplane Simpson's method [17]. Multidirectional analysis of LV strain (in the radial, circumferential, and longitudinal directions) was performed using 2D speckle-tracking imaging as previously described [18,19]. All of the images were recorded with a frame rate of at least 30 frames per seconds to allow for reliable operation of the software (EchoPac 6.1). The speckles, natural acoustic markers equally distributed within the myocardium, can be detected and tracked on the standard grayscale 2D images. Myocardial strain can be calculated by measuring the change of the position of the speckles within a myocardial segment along the cardiac cycle. The assessment of global radial strain (GRS) and global circumferential strain (GCS) was performed by applying 2D speckle-tracking imaging to the parasternal short-axis views of the LV. The midventricular short-axis of the LV was divided into six segments, and the values of GRS and GCS were derived from the average of the six segmental peak systolic strain values. The assessment of longitudinal peak systolic strain was performed by applying 2D speckle-tracking imaging to the apical twoand four-chamber views of the LV. The LV was divided into six segments in each apical view. The values of global
longitudinal strain (GLS) were derived from the average of the six segmental peak systolic longitudinal strain values. For the measurement of timing, the onset of the aortic valve closure was used as the reference point which was estimated automatically by the software and adjusted by the user if needed. Time to peak longitudinal systolic strain was quantified and displayed automatically by the software as previously described [20]. A recent study [21] demonstrated LV peak systolic longitudinal strain value of 18.6% ± 0.1% as the average of nearly 250 volunteers without evidence of cardiovascular disease. We used this value as a cut-off point to indicate patients with reduced LV peak systolic longitudinal strain. LV ‘twist’ was defined as the net difference of LV peak systolic ‘rotation’ between basal (clockwise) and apical (counterclockwise) short axis planes. The value was expressed in ‘°’. ‘Untwist’ was expressed as a diastolic angular motion of the LV, opposite to twist. ‘Untwisting rate’ [°/s] was defined as the peak twist rate during early diastole. For the left atrial (LA) speckle tracking analysis, LA-focused images in apical four-chamber view were obtained. A minimum frame rate of 40 frames per second was required for the reliable operation of this program. For two dimensional speckle tracking strain analysis, a line was manually drawn along the LA endocardial border of the apical four chamber view after contraction, when the LA was at its minimum volume, using the point-and-click approach as previously described [18]. The software then automatically generated additional lines near the atrial epicardium and mid-myocardial line, with the narrowest region of interest (ROI). The ROI then included the entire LA myocardial wall, and a click feature increased or decreased the widths between endocardial and epicardial line for thicker or thinner walls, respectively. The software generated strain curves for each atrial segment. The value of peak early and late diastolic longitudinal strain were determined as left atrial reservoir (LA Res) and conduit (LA Con) function. Electrocardiographic analysis The resting 12-lead ECG (0.5 Hz to 150 Hz, 25 mm/s, 10 mm/mV) was analyzed by two independent clinicians who were blinded to echocardiographic data. There was a 97.5% concordance for ECG signs. In case of disagreement, the final diagnosis was achieved by mutual agreement. The fQRS included various RSR′ patterns and was defined by the presence of an additional R wave (R′), notching in the nadir of the S wave, notching of the R wave, or the presence of more than one R′ (fragmentation) in two contiguous leads corresponding to a major myocardial segment. The presence of fQRS in two or more contiguous V1 to V5 leads corresponded to anterior myocardial segments, the presence of two or more fQRS in leads DI, aVL and V5, V6 corresponded to the lateral myocardial segments, and the presence of two or more fQRS in leads DII, DIII and aVF corresponded to the inferior myocardial segments. Statistical analysis Statistical analyses were performed using SPSS 20.0 statistical package for Windows. Continuous data were
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expressed as mean ± standard deviation while categorical data were presented as number of patients. Chi-square test was used for comparison of categorical variables. Kruskal Wallis test or Mann–Whitney U test were used to compare nonparametric continuous variables. Post hoc analysis was performed by Bonferroni test. A value of p b 0.05 was considered statistically significant. Reproducibility For the assessment of intraobserver variability, the analyses were repeated twice by the same observer one day later. For the interobserver variability assessment, a second independent observer repeated the analyses. Intraobserver variability was calculated by the average difference between the 10 measurements realized. Interobserver variability was calculated as the absolute difference divided by the average of the two observations for all parameters. The intraobserver and interobserver variabilities were 6.4% and 7.2%, respectively in our study.
Results The study included 53 SSc patients (F/M: 47:6, mean age: 49.1 ± 11.5 years) and 26 healthy controls (F/M: 22:4, mean age: 42.8 ± 11.7 years). There were not any statistically significant differences in sex and age distribution between the patients and controls (p = 0.722 and p = 0.058). The characteristics and clinical data of SSc patients are shown in Table 1. SSc patients were divided into two groups according to the presence of fQRS in surface ECG. Thirteen SSc patients (24.5%) had fQRS in two or more contiguous leads in the surface ECG and were included in the fQRS patients group. Two of these patients had fQRS in V1 to V5 leads (one patient had fQRS in 4 leads and one patient had fQRS in 3 leads) while the remaining 11 patients had fQRS in DII, DIII, and aVF leads (two patients had fQRS in 3 leads and nine patients had fQRS in 2 leads). Mean number of fQRS leads was 2.4 ± 0.7 in fQRS patient group. Seven patients had fQRS in single lead (five patients in DII, DIII, and aVF leads and two patients in V1 to V5 leads) and thirty-three patients had no fQRS. These forty patients constituted the SSc patient group with normal QRS. There were no fQRS complexes in control subjects. There were also no significant differences in terms of other ECG characteristics such as Q waves, QRS duration, and ST-T changes between the SSc patients with fQRS and those without fQRS (Table 2). The conventional echocardiographic parameters of the SSc patients and controls are listed in Table 3. There were no significant differences in conventional echocardiographic parameters between the SSc patients and controls (Table 3). Deformation analyses of the patients and controls derived from 2D STE are presented in Table 4. SSc patients had significantly lower LV GLS, LV GRS, LV GCS and LV twist compared to controls. Additionally, SSc patients with fQRS had significantly lower LV GLS and LV GCS compared to SSc patients with normal QRS complexes although there were not any significant differences in their conventional echocardiographic measures. Although the
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number of the patients with reduced LV strain was higher in patients with fQRS, the difference did not reach statistical significance. Four SSc patients with fQRS (30.8%) had LV GLS b 18.5% while only 3 SSc patients with normal QRS (7.5%) had LV GLS b 18.5% (p = 0.053). LA reservoir and conduit functions were similar among the groups. We explored a relation between characteristics of SSc patients and deformation parameters. There was only a weak correlation between LV GLS and modified Rodnan skin thickness score in SSc patients (r = − 0.279, p = 0.043). We compared the regional myocardial strain measures of the SSc patients with fQRS in DII, DIII, and aVF leads. SSc patients with fQRS in DII, DIII, and aVF leads demonstrated significantly impaired longitudinal strain values and delay in time to peak longitudinal strain in the inferior LV segments (Fig. 1). Fig. 2 demonstrates the difference in the longitudinal strain values in the inferior LV segments between SSc patients with fQRS complexes and SSc patients with normal QRS complexes (− 20.2% ± 1.7% vs − 22.9% ± 3.3%, p = 0.015). Fig. 3 demonstrates the difference in the delay in time to peak longitudinal strain in the inferior LV segments between SSc patients with fQRS and SSc patients with normal QRS complexes (54.5 ± 35.8 ms vs 4.4 ± 8.1 ms, p b 0.001).
Discussion In the present study, we demonstrated that SSc patients can exhibit subtle LV systolic dysfunction, as assessed by 2D speckle tracking strain analysis, despite having a normal LVEF and normal LV dimensions. More importantly, some of the SSc patients with fQRS complexes on the surface ECG had significantly lower mean LV global longitudinal and circumferential strains compared to those with normal QRS complexes. Those patients with relatively lower strain values may be considered to have impaired LV systolic function. On the other hand, our results showed that some of the patients with fQRS complexes had similar strain measures compared to patients without fQRS. The relatively small difference in strain values noted between the two groups could be explained by the fact that most of the SSc patients in our study were asymptomatic and had a relatively preserved functional capacity, suggestive of mild and subclinical
Table 1 Patient characteristics and clinical data of SSc patients. Age (years) Gender (Male—n) Body mass index (kg/m2) Limited/diffuse cutaneous Ssc (n) Time since diagnosis (years) Time since onset of Raynaud phenomenon (years) Modified Rodnan skin thickness score Active diseasea, n (%) Erythrocyte sedimentation rate (mm) C-reactive protein (mg/dl)
49.1 ± 11.5 6 (11.3%) 25.6 ± 3.6 30/23 7.4 ± 5.8 10.9 ± 7.9 15.1 ± 7.2 14 (26.4) 29.7 ± 16.6 6.2 ± 5.8
Data are presented as mean ± standard deviation or number of patient. SSc: systemic sclerosis. a Active disease is defined as the European Scleroderma Study Group activity index score of higher than 3.
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cardiovascular involvement. Therefore, it is not adequate to draw a definite conclusion that fQRS is associated with impaired LV systolic function in SSc patients. However, our study arises the possibility of such association and verification of our results is needed with larger sample size. Cardiac involvement in patients with SSc has been characterized mainly by the presence of an elevated systolic pulmonary artery pressure and LV diastolic dysfunction while the results of recent studies using tissue Doppler imaging or 2D STE have also suggested impairment in myocardial systolic deformation despite preserved LVEF and LV dimensions [22–25]. Similar to our study, Yiu et al. [9] assessed the presence of myocardial dysfunction in SSc patients using STE and found that both LV GLS and GCS were significantly impaired in SSc patients compared to healthy controls. The exact mechanism underlying LV systolic dysfunction is not known. There is a significant amount of myocardial fibrosis in SSc patients. These structural alterations, mainly caused by repeated focal ischemia due to abnormal vasoreactivity, may be responsible for the myocardial dysfunction. In the present study, we found significant impairment of longitudinal and circumferential strains, but not of radial strain. Since subendocardial longitudinal fibers are mainly responsible for longitudinal deformation and midmyocardial circumferential fibers are responsible for radial and circumferential shortening, our findings suggest that subendocardial layer is affected earlier than midmyocardial layer. Extensive fibrosis in the midmyocardium and/ or transmural myocardial damage may cause prominent impairment in radial deformation. However, scleroderma is associated with patchy fibrosis, which is not extensive and does not always involve the midmyocardial layer. This might also be a reason why our patients did not have impairment in radial deformation. Fragmentation of QRS is present in certain leads, which is a reflection of prominent fibrosis in the associated myocardial regions. As certain myocardial segments are affected, this may not cause a significant decrease in the mean GRS measures as whole myocardial regions are included in the measurement of GRS. Similarly, in patients with fQRS, GLS measures were lower in the myocardial regions associated with fQRS. However, we did not measure GRS in these specific myocardial regions. We believe that similar results may be obtained if GRS is studied specifically in the regions associated with fQRS and this should be confirmed with further studies with larger samples.
Table 2 Comparison of ECG parameters between SSc patients with fQRS and normal QRS.
Abnormal T wave (n) Abnormal Q wave (n) ST depression (n) Early repolarization (n) QRS duration (ms)
fQRS (n = 13)
Normal QRS (n = 40)
p
2 1 0 1 84.7 ± 7.7
2 0 0 0 83.7 ± 8.4
0.218 0.565 1 0.565 0.547
Data are presented as mean ± standard deviation or number of patients. SSc: systemic sclerosis; fQRS: fragmented QRS; ECG: electrocardiography.
Table 3 Comparison of conventional echocardiographic parameters between SSc patients and controls.
LAD (mm) LVEDD (mm) LVESD (mm) IVS (mm) PW (mm) EF (%) LAA (cm2) RAA (cm2) E velocity (m/s) e′ (cm/s) E/e′ sPAP (mm Hg)
SSc patients with fQRS (n = 13)
SSc patients with normal QRS (n = 40)
Control groups (n = 26)
p
32.8 43.7 27.5 10.0 9.8 66.2 14.7 12.5 0.76 11.7 7.3 26.1
32.1 43.9 27.8 9.4 9.2 65.5 14.3 12.6 0.78 10.0 7.0 27.6
31.5 43.8 27.0 9.6 9.2 65.9 13.9 11.9 0.83 10.8 8.0 26.7
0.576 0.970 0.570 0.243 0.180 0.613 0.485 0.579 0.073 0.303 0.050 0.826
± ± ± ± ± ± ± ± ± ± ± ±
3.1 3.8 3.8 1.1 0.9 5.4 2.1 1.9 0.15 2.3 2.9 7.2
± ± ± ± ± ± ± ± ± ± ± ±
5.4 4.7 3.7 1.4 1.2 4.8 3.4 3.3 0.17 2.5 2.4 7.8
± ± ± ± ± ± ± ± ± ± ± ±
3.2 2.9 2.5 1.3 1.2 3.8 1.7 1.3 0.11 1.7 2.0 3.7
Data are presented as mean ± standard deviation. SSc: systemic sclerosis; fQRS: fragmented QRS; LAD: left atrial diameter; LVEDD: left ventricular end diastolic diameter; LVESD: left ventricular end systolic diameter; IVS: interventricular septum; PW: posterior wall; EF: ejection fraction; LAA: left atrial area; RAA: right atrial area; sPAP: systolic pulmonary arterial pressure.
Fragmentation of QRS complexes is shown to be associated with intraventricular systolic dyssynchrony and subendocardial fibrosis in nonischemic cardiomyopathy patients [26,27]. Patients with fQRS have ischemia and fibrosis in subendocardial area [28]. Coronary artery disease or previous myocardial infarction is associated with fQRS complexes on ECG and lower strain measures in infarct related LV segments due to regional or transmural fibrosis. Yan et al. [29] showed that the fQRS complex was associated with subclinical global and regional LV dysfunctions in patients with coronary artery disease with preserved LV EF and it predicted adverse cardiac events in these patients. In our study, 13 SSc patients had fQRS complexes and LV GLS and GCS were modestly, but significantly, impaired in these patients as compared to those with normal QRS complexes. Strain measures were reduced in our SSc patients especially in those with fQRS complexes although we excluded coronary artery disease in this patient group. This might be related with the presence of patchy fibrosis in related LV segments due to overproduction of abnormal collagen in SSc patients. The extent of fibrosis is associated with poor prognosis in SSc [30,31]. Thus the presence of fQRS may indicate not only subtle LV systolic dysfunction but also poor prognosis in SSc patients. In addition, both LV GLS and GCS have been recently shown to be associated with functional capacity and ventricular arrhythmias [9]. Early assessment of LV dysfunction by echocardiography and presence of fQRS may be used as a prognostic marker in these patients. Verification of fibrosis by late gadolinium enhancement cardiac magnetic resonance imaging might strengthen our findings. Our study has important clinical implications. We showed that SSc patients had subclinical myocardial dysfunction assessed by 2D STE while conventional echocardiographic measures were normal. Additionally, we detected fQRS complexes in SSc patients and these patients had significantly
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Table 4 Comparison of left ventricular and left atrial strain parameters between SSc patients and controls. S (%)
GLS GRS GCS Twist Untwist LA-Res LA-Con
SSc patients with fQRS (n = 13)
SSc patients with normal QRS (n = 40)
Control groups (n = 26)
p
−19.6 41.6 − 15.2 18.9 − 126.5 33.4 14.7
− 21.6 37.9 − 18.8 16.4 − 134.5 34.4 14.3
− 25.8 47.7 − 25.2 31.8 − 134.5 38.1 13.7
b0.001⁎,⁎⁎,⁎⁎⁎ 0.022⁎⁎⁎ b0.001⁎,⁎⁎,⁎⁎⁎ b0.001⁎⁎,⁎⁎⁎ 0.726 0.335 0.811
± ± ± ± ± ± ±
2.1 18.3 5.1 5.5 45.4 9.1 6.8
± ± ± ± ± ± ±
2.1 17.5 4.9 8.8 44.2 10.3 3.9
± ± ± ± ± ± ±
2.7 7.0 3.3 9.4 29.5 10.1 3.3
Data are presented as mean ± standard deviation. SSc: systemic sclerosis; fQRS: fragmented QRS; GLS: global longitudinal strain; GRS: global radial strain; GCS: global circumferencial strain; LA-Res: left atrial reservoir; LA-Con: left atrial conduit. ⁎ Post hoc analysis: p b 0.05 between SSc patients with fQRS and SSc patients with normal QRS. ⁎⁎ Post hoc analysis: p b 0.05 between SSc patients with fQRS and controls. ⁎⁎⁎ Post hoc analysis: p b 0.05 between SSc patients with normal QRS and controls.
lower LV GLS and GCS when compared to SSc patients with normal QRS complexes. To the best of our knowledge, this is the first study in the literature to evaluate regional myocardial
function with 2D STE in SSc patients with fQRS complexes in surface ECG. Our results have suggested that surface ECG might be useful for early detection of myocardial involvement
Fig. 1. (A) Surface electrocardiography showing fragmented QRS complexes in DII, DIII, and aVF leads. (B) Peak systolic strain values of cardiac segments in a patient with fragmented QRS in DII, DIII, and aVF leads. (C) Time to peak longitudinal strain of cardiac segments in that patient with fragmented QRS in DII, DIII, and aVF leads.
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in SSc patient and would rather be performed in every SSc patient suspected from myocardial dysfunction. Study limitations The major limitation of our study was the small sample size. A larger sample size might give more convincing and significant results in comparison to strain values between fQRS and normal QRS groups. LV strain values were higher in our study group when compared to elegant papers in literature [21,32,33]. We included relatively more female patients and the patients in our study were relatively younger compared to those studies. Younger age and female sex are associated with higher longitudinal and radial strain levels and this might explain the discrepancy between our strain values and others. Although the study had a prospective design, we did not gather data regarding prognosis of the patients. Thus, we could not explore a relation between adverse cardiac events and decreased myocardial strain parameters or fQRS complexes in these patients. We did not perform cardiac magnetic resonance imaging which can accurately show extend of the fibrosis and myocardial dysfunction in these patients. We did not evaluate the inner and outer radial strain of LV wall separately. Inner radial strain might be more impaired in patient with fQRS due to subendocardial fibrosis. Further prospective long-term largescale studies are necessary to determine the outcome and the best approach to treatment of such abnormalities.
Fig. 3. Systemic sclerosis patients with fragmented QRS in DII, DIII, and aVF leads had significantly higher the delay in time to peak longitudinal strain in the inferior LV segments compared to those with normal QRS complexes. Data are presented mean ± standard deviation.
SSc. However, a simple cheap ECG may also give idea about cardiac involvement in SSc and should be included in cardiovascular evaluation of these patients. Funding sources None.
Conclusion Patients with SSc may have subtle LV systolic dysfunction, which can be successfully assessed by 2D STE. Importantly, some SSc patients may have fQRS complexes in surface ECG and these patients have lower LV global longitudinal and circumferential strain measures. The use of novel imaging techniques such as 2D STE may improve risk stratification and monitoring of the cardiovascular involvement in patients with
Conflict of interest None to declare. Acknowledgments None. References
Fig. 2. Systemic sclerosis patients with fragmented QRS in DII, DIII, and aVF leads had significantly lower longitudinal strain values in the inferior LV segments compared to those with normal QRS complexes. Data are presented mean ± standard deviation.
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syndromes by assessing global longitudinal strain. Heart Vessels 2014;29(3):300–7. Marwick TH, Leano RL, Brown J, Sun JP, Hoffmann R, Lysyansky P, et al. Myocardial strain measurement with 2-dimensional speckle-tracking echocardiography: definition of normal range. JACC Cardiovasc Imaging 2009;2(1):80–4. Meune C, Avouac J, Wahbi K, Cabanes L, Wipff J, Mouthon L, et al. Cardiac involvement in systemic sclerosis assessed by tissue-Doppler echocardiography during routine care: a controlled study of 100 consecutive patients. Arthritis Rheum 2008;58(6):1803–9. Kepez A, Akdogan A, Sade LE, Deniz A, Kalyoncu U, Karadag O, et al. Detection of subclinical involvement in systemic sclerosis by echocardiographic strain imaging. Echocardiography 2008;25(2): 191–7. Mele D, Censi S, La Corte R, Merli E, Lo Monaco A, Locaputo A, et al. Abnormalities of left ventricular function in asymptomatic patients with systemic sclerosis using Doppler measures of myocardial strain. J Am Soc Echocardiogr 2008;21(11):1257–64. D'Andrea A, Stisi S, Bellissimo S, Vigorito F, Scotto di Uccio F, Tozzi N, et al. Early impairment of myocardial function in systemic sclerosis: non-invasive assessment by Doppler myocardial and strain rate imaging. Eur J Echocardiogr 2005;6(6):407–18. Basaran Y, Tigen K, Karaahmet T, Isiklar I, Cevik C, Gurel E, et al. Fragmented QRS complexes are associated with cardiac fibrosis and significant intraventricular systolic dyssynchrony in nonischemic dilated cardiomyopathy patients with a narrow QRS interval. Echocardiography 2011;28(1):62–8. Tigen K, Karaahmet T, Gurel E, Cevik C, Nugent K, Pala S, et al. The utility of fragmented QRS complexes to predict significant intraventricular dyssynchrony in nonischemic dilated cardiomyopathy patients with a narrow QRS interval. Can J Cardiol 2009;25(9):517–22. Kocaman SA, Çetin M, Kırış T, Erdoğan T, Çanga A, Durakoğlugil E, et al. The importance of fragmented QRS complexes in prediction of myocardial infarction and reperfusion parameters in patients undergoing primary percutaneous coronary intervention. Turk Kardiyol Dern Ars 2012;40(3):213–22. Yan GH, Wang M, Yiu KH, Lau CP, Zhi G, Lee SW, et al. Subclinical left ventricular dysfunction revealed by circumferential 2D strain imaging in patients with coronary artery disease and fragmented QRS complex. Heart Rhythm 2012;9(6):928–35. Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med 2009;360(19):1989–2003. Janssen NM, Karnad DR, Guntupalli KK. Rheumatologic diseases in the intensive care unit: epidemiology, clinical approach, management, and outcome. Crit Care Clin 2002;18(4):729–48. Dalen H, Thorstensen A, Aase SA, Ingul CB, Torp H, Vatten LJ, et al. Segmental and global longitudinal strain and strain rate based on echocardiography of 1266 healthy individuals: the HUNT study in Norway. Eur Journal Echocardiogr 2010;11(2):176–83. Hurlburt HM, Aurigemma GP, Hill JC, Narayanan A, Gaasch WH, Vinch CS, et al. Direct ultrasound measurement of longitudinal, circumferential, and radial strain using 2-dimensional strain imaging in normal adults. Echocardiography 2007;24(7):723–31.
ScienceDirect Journal of Electrocardiology 47 (2014) 677 – 683 www.jecgonline.com
Regional myocardial dysfunction assessed by two-dimensional speckle tracking echocardiography in systemic sclerosis patients with fragmented QRS complexes Kursat Tigen, MD, a Murat Sunbul, MD, a,⁎ Gulsen Ozen, MD, b Erdal Durmus, MD, a Tarik Kivrak, MD, a Altug Cincin, MD, a Beste Ozben, MD, a Halil Atas, MD, a Haner Direskeneli, MD, b Yelda Basaran, MD a a b
Marmara University Faculty of Medicine, Department of Cardiology, Istanbul, Turkey Marmara University Faculty of Medicine, Department of Rheumatology, Istanbul, Turkey
Abstract
Background: The aim of the study was to explore the relation between regional myocardial dysfunction and fragmented QRS (fQRS) complexes in systemic sclerosis (SSc). Methods: Fifty-three SSc patients and 26 controls were included. All subjects underwent speckle tracking echocardiography for evaluation of left ventricular (LV) function and ECG to check for fQRS complexes. Results: SSc patients had significantly lower LV global longitudinal, radial and circumferential strain and twist compared to controls. Thirteen SSc patients had fQRS (DII, DIII, aVF leads in eleven patients and V1 to V5 leads in two patients) and they had significantly lower global longitudinal and circumferencial strain compared to SSc patients with normal QRS. The SSc patients with fQRS in DII, DIII, and aVF leads had impaired longitudinal strain and delay in time to peak longitudinal strain in inferior LV segments compared to those with normal QRS. Conclusion: fQRS is associated with lower strain measures in SSc patients indicating impairment in LV function. © 2014 Elsevier Inc. All rights reserved.
Keywords:
Fragmented QRS; Speckle tracking echocardiography; Systemic sclerosis
Introduction Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular dysfunction and excessive fibrosis involving the skin and visceral organs [1]. Cardiac manifestations are common in SSc, with an estimated clinical prevalence of 15%–35% and when clinically evident, are often associated with mortality [2,3]. However, in the majority of SSc patients, cardiac manifestations may remain subclinical [4–6]. Thus, monitoring of myocardial involvement represents an important aspect of the disease management [7]. Two-dimensional (2D) speckle-tracking echocardiography (STE) has been proposed as a sensitive method for the evaluation of myocardial involvement in SSc patients [8,9]. Spethmann et al. [10] showed that left ventricular (LV) deformation analysis by STE was a sensitive method to detect early LV systolic impairment ⁎ Corresponding author at: Fevzi Cakmak Mahallesi, Mimar Sinan Caddesi, No: 41, Ustkaynarca, Pendik, İstanbul, Turkey. E-mail address: [email protected] http://dx.doi.org/10.1016/j.jelectrocard.2014.07.008 0022-0736/© 2014 Elsevier Inc. All rights reserved.
primarily in the basal segments in patients with SSc having preserved LV ejection fraction (EF). Cardiac involvement in SSc does not only involve the myocardium but also the conduction system [11]. Ventricular late potentials were proposed to be used as an early index of myocardial fibrosis in SSc [12]. Morelli et al. [13] explored the role of late ventricular potentials in detecting early myocardial involvement in SSc patients and reported that signal averaged electrocardiography (ECG) was a sensitive and inexpensive technique in the clinical assessment and follow up of patients with SSc. While fragmented QRS (fQRS) is shown to be associated with regional myocardial damage and increased cardiovascular morbidity and mortality in patients with coronary artery disease [14,15], the association between fQRS and regional myocardial dysfunction has not been studied in SSc patients. The aim of this study was to evaluate deformation analyses derived from 2D STE for early detection of LV regional myocardial dysfunction in patients with SSc and to explore a relation between myocardial function and fQRS complexes present in surface ECG of SSc patients.
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Materials and methods The investigation complies with the principles outlined in the Declaration of Helsinki. The study was approved by the Local Ethics Committee and all participants gave written informed consent before participating. Sixty-two consecutive patients with SSc who were followed by the Department of Rheumatology were enrolled to the study. The diagnosis of SSc was based on the American Rheumatism Association criteria [16]. After the exclusion of the patients with coronary artery disease, valvular heart disease, cardiomyopathy, arrhythmias or conduction disorders, LV systolic dysfunction (LV EF b 55%), and diabetes mellitus, peripheral arterial disease, and chronic obstructive pulmonary disease, the remaining 53 SSc patients were included in the study. Twenty-six healthy subjects were included into the study as control group. Standard echocardiography and 2D speckle tracking echocardiography All patients underwent a complete echocardiographic study with a commercially available echocardiography device (Vivid 7, GE Vingmed Ultrasound AS, Horten, Norway) by a single experienced cardiologist. Data acquisition was performed with a 3.5-MHz transducer at a depth of 16 cm in the parasternal and apical views (standard parasternal shortaxis from midventricular level, apical long-axis, two-chamber and four-chamber images). Standard M-mode, 2D and color coded TDI images were obtained during breath hold, stored in cine loop format from 3 consecutive beats and transferred to a workstation for further offline analysis (EchoPAC 6.1; GE Vingmed Ultrasound AS). Gain settings, filters, and pulse repetitive frequency were adjusted to optimize color saturation, and a color Doppler frame scanning rate of 100–140 Hz was used for color TDI images. Cardiac dimensions were measured according to the guidelines of the American Society of Echocardiography and LV EF was calculated by biplane Simpson's method [17]. Multidirectional analysis of LV strain (in the radial, circumferential, and longitudinal directions) was performed using 2D speckle-tracking imaging as previously described [18,19]. All of the images were recorded with a frame rate of at least 30 frames per seconds to allow for reliable operation of the software (EchoPac 6.1). The speckles, natural acoustic markers equally distributed within the myocardium, can be detected and tracked on the standard grayscale 2D images. Myocardial strain can be calculated by measuring the change of the position of the speckles within a myocardial segment along the cardiac cycle. The assessment of global radial strain (GRS) and global circumferential strain (GCS) was performed by applying 2D speckle-tracking imaging to the parasternal short-axis views of the LV. The midventricular short-axis of the LV was divided into six segments, and the values of GRS and GCS were derived from the average of the six segmental peak systolic strain values. The assessment of longitudinal peak systolic strain was performed by applying 2D speckle-tracking imaging to the apical twoand four-chamber views of the LV. The LV was divided into six segments in each apical view. The values of global
longitudinal strain (GLS) were derived from the average of the six segmental peak systolic longitudinal strain values. For the measurement of timing, the onset of the aortic valve closure was used as the reference point which was estimated automatically by the software and adjusted by the user if needed. Time to peak longitudinal systolic strain was quantified and displayed automatically by the software as previously described [20]. A recent study [21] demonstrated LV peak systolic longitudinal strain value of 18.6% ± 0.1% as the average of nearly 250 volunteers without evidence of cardiovascular disease. We used this value as a cut-off point to indicate patients with reduced LV peak systolic longitudinal strain. LV ‘twist’ was defined as the net difference of LV peak systolic ‘rotation’ between basal (clockwise) and apical (counterclockwise) short axis planes. The value was expressed in ‘°’. ‘Untwist’ was expressed as a diastolic angular motion of the LV, opposite to twist. ‘Untwisting rate’ [°/s] was defined as the peak twist rate during early diastole. For the left atrial (LA) speckle tracking analysis, LA-focused images in apical four-chamber view were obtained. A minimum frame rate of 40 frames per second was required for the reliable operation of this program. For two dimensional speckle tracking strain analysis, a line was manually drawn along the LA endocardial border of the apical four chamber view after contraction, when the LA was at its minimum volume, using the point-and-click approach as previously described [18]. The software then automatically generated additional lines near the atrial epicardium and mid-myocardial line, with the narrowest region of interest (ROI). The ROI then included the entire LA myocardial wall, and a click feature increased or decreased the widths between endocardial and epicardial line for thicker or thinner walls, respectively. The software generated strain curves for each atrial segment. The value of peak early and late diastolic longitudinal strain were determined as left atrial reservoir (LA Res) and conduit (LA Con) function. Electrocardiographic analysis The resting 12-lead ECG (0.5 Hz to 150 Hz, 25 mm/s, 10 mm/mV) was analyzed by two independent clinicians who were blinded to echocardiographic data. There was a 97.5% concordance for ECG signs. In case of disagreement, the final diagnosis was achieved by mutual agreement. The fQRS included various RSR′ patterns and was defined by the presence of an additional R wave (R′), notching in the nadir of the S wave, notching of the R wave, or the presence of more than one R′ (fragmentation) in two contiguous leads corresponding to a major myocardial segment. The presence of fQRS in two or more contiguous V1 to V5 leads corresponded to anterior myocardial segments, the presence of two or more fQRS in leads DI, aVL and V5, V6 corresponded to the lateral myocardial segments, and the presence of two or more fQRS in leads DII, DIII and aVF corresponded to the inferior myocardial segments. Statistical analysis Statistical analyses were performed using SPSS 20.0 statistical package for Windows. Continuous data were
K. Tigen et al. / Journal of Electrocardiology 47 (2014) 677–683
expressed as mean ± standard deviation while categorical data were presented as number of patients. Chi-square test was used for comparison of categorical variables. Kruskal Wallis test or Mann–Whitney U test were used to compare nonparametric continuous variables. Post hoc analysis was performed by Bonferroni test. A value of p b 0.05 was considered statistically significant. Reproducibility For the assessment of intraobserver variability, the analyses were repeated twice by the same observer one day later. For the interobserver variability assessment, a second independent observer repeated the analyses. Intraobserver variability was calculated by the average difference between the 10 measurements realized. Interobserver variability was calculated as the absolute difference divided by the average of the two observations for all parameters. The intraobserver and interobserver variabilities were 6.4% and 7.2%, respectively in our study.
Results The study included 53 SSc patients (F/M: 47:6, mean age: 49.1 ± 11.5 years) and 26 healthy controls (F/M: 22:4, mean age: 42.8 ± 11.7 years). There were not any statistically significant differences in sex and age distribution between the patients and controls (p = 0.722 and p = 0.058). The characteristics and clinical data of SSc patients are shown in Table 1. SSc patients were divided into two groups according to the presence of fQRS in surface ECG. Thirteen SSc patients (24.5%) had fQRS in two or more contiguous leads in the surface ECG and were included in the fQRS patients group. Two of these patients had fQRS in V1 to V5 leads (one patient had fQRS in 4 leads and one patient had fQRS in 3 leads) while the remaining 11 patients had fQRS in DII, DIII, and aVF leads (two patients had fQRS in 3 leads and nine patients had fQRS in 2 leads). Mean number of fQRS leads was 2.4 ± 0.7 in fQRS patient group. Seven patients had fQRS in single lead (five patients in DII, DIII, and aVF leads and two patients in V1 to V5 leads) and thirty-three patients had no fQRS. These forty patients constituted the SSc patient group with normal QRS. There were no fQRS complexes in control subjects. There were also no significant differences in terms of other ECG characteristics such as Q waves, QRS duration, and ST-T changes between the SSc patients with fQRS and those without fQRS (Table 2). The conventional echocardiographic parameters of the SSc patients and controls are listed in Table 3. There were no significant differences in conventional echocardiographic parameters between the SSc patients and controls (Table 3). Deformation analyses of the patients and controls derived from 2D STE are presented in Table 4. SSc patients had significantly lower LV GLS, LV GRS, LV GCS and LV twist compared to controls. Additionally, SSc patients with fQRS had significantly lower LV GLS and LV GCS compared to SSc patients with normal QRS complexes although there were not any significant differences in their conventional echocardiographic measures. Although the
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number of the patients with reduced LV strain was higher in patients with fQRS, the difference did not reach statistical significance. Four SSc patients with fQRS (30.8%) had LV GLS b 18.5% while only 3 SSc patients with normal QRS (7.5%) had LV GLS b 18.5% (p = 0.053). LA reservoir and conduit functions were similar among the groups. We explored a relation between characteristics of SSc patients and deformation parameters. There was only a weak correlation between LV GLS and modified Rodnan skin thickness score in SSc patients (r = − 0.279, p = 0.043). We compared the regional myocardial strain measures of the SSc patients with fQRS in DII, DIII, and aVF leads. SSc patients with fQRS in DII, DIII, and aVF leads demonstrated significantly impaired longitudinal strain values and delay in time to peak longitudinal strain in the inferior LV segments (Fig. 1). Fig. 2 demonstrates the difference in the longitudinal strain values in the inferior LV segments between SSc patients with fQRS complexes and SSc patients with normal QRS complexes (− 20.2% ± 1.7% vs − 22.9% ± 3.3%, p = 0.015). Fig. 3 demonstrates the difference in the delay in time to peak longitudinal strain in the inferior LV segments between SSc patients with fQRS and SSc patients with normal QRS complexes (54.5 ± 35.8 ms vs 4.4 ± 8.1 ms, p b 0.001).
Discussion In the present study, we demonstrated that SSc patients can exhibit subtle LV systolic dysfunction, as assessed by 2D speckle tracking strain analysis, despite having a normal LVEF and normal LV dimensions. More importantly, some of the SSc patients with fQRS complexes on the surface ECG had significantly lower mean LV global longitudinal and circumferential strains compared to those with normal QRS complexes. Those patients with relatively lower strain values may be considered to have impaired LV systolic function. On the other hand, our results showed that some of the patients with fQRS complexes had similar strain measures compared to patients without fQRS. The relatively small difference in strain values noted between the two groups could be explained by the fact that most of the SSc patients in our study were asymptomatic and had a relatively preserved functional capacity, suggestive of mild and subclinical
Table 1 Patient characteristics and clinical data of SSc patients. Age (years) Gender (Male—n) Body mass index (kg/m2) Limited/diffuse cutaneous Ssc (n) Time since diagnosis (years) Time since onset of Raynaud phenomenon (years) Modified Rodnan skin thickness score Active diseasea, n (%) Erythrocyte sedimentation rate (mm) C-reactive protein (mg/dl)
49.1 ± 11.5 6 (11.3%) 25.6 ± 3.6 30/23 7.4 ± 5.8 10.9 ± 7.9 15.1 ± 7.2 14 (26.4) 29.7 ± 16.6 6.2 ± 5.8
Data are presented as mean ± standard deviation or number of patient. SSc: systemic sclerosis. a Active disease is defined as the European Scleroderma Study Group activity index score of higher than 3.
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cardiovascular involvement. Therefore, it is not adequate to draw a definite conclusion that fQRS is associated with impaired LV systolic function in SSc patients. However, our study arises the possibility of such association and verification of our results is needed with larger sample size. Cardiac involvement in patients with SSc has been characterized mainly by the presence of an elevated systolic pulmonary artery pressure and LV diastolic dysfunction while the results of recent studies using tissue Doppler imaging or 2D STE have also suggested impairment in myocardial systolic deformation despite preserved LVEF and LV dimensions [22–25]. Similar to our study, Yiu et al. [9] assessed the presence of myocardial dysfunction in SSc patients using STE and found that both LV GLS and GCS were significantly impaired in SSc patients compared to healthy controls. The exact mechanism underlying LV systolic dysfunction is not known. There is a significant amount of myocardial fibrosis in SSc patients. These structural alterations, mainly caused by repeated focal ischemia due to abnormal vasoreactivity, may be responsible for the myocardial dysfunction. In the present study, we found significant impairment of longitudinal and circumferential strains, but not of radial strain. Since subendocardial longitudinal fibers are mainly responsible for longitudinal deformation and midmyocardial circumferential fibers are responsible for radial and circumferential shortening, our findings suggest that subendocardial layer is affected earlier than midmyocardial layer. Extensive fibrosis in the midmyocardium and/ or transmural myocardial damage may cause prominent impairment in radial deformation. However, scleroderma is associated with patchy fibrosis, which is not extensive and does not always involve the midmyocardial layer. This might also be a reason why our patients did not have impairment in radial deformation. Fragmentation of QRS is present in certain leads, which is a reflection of prominent fibrosis in the associated myocardial regions. As certain myocardial segments are affected, this may not cause a significant decrease in the mean GRS measures as whole myocardial regions are included in the measurement of GRS. Similarly, in patients with fQRS, GLS measures were lower in the myocardial regions associated with fQRS. However, we did not measure GRS in these specific myocardial regions. We believe that similar results may be obtained if GRS is studied specifically in the regions associated with fQRS and this should be confirmed with further studies with larger samples.
Table 2 Comparison of ECG parameters between SSc patients with fQRS and normal QRS.
Abnormal T wave (n) Abnormal Q wave (n) ST depression (n) Early repolarization (n) QRS duration (ms)
fQRS (n = 13)
Normal QRS (n = 40)
p
2 1 0 1 84.7 ± 7.7
2 0 0 0 83.7 ± 8.4
0.218 0.565 1 0.565 0.547
Data are presented as mean ± standard deviation or number of patients. SSc: systemic sclerosis; fQRS: fragmented QRS; ECG: electrocardiography.
Table 3 Comparison of conventional echocardiographic parameters between SSc patients and controls.
LAD (mm) LVEDD (mm) LVESD (mm) IVS (mm) PW (mm) EF (%) LAA (cm2) RAA (cm2) E velocity (m/s) e′ (cm/s) E/e′ sPAP (mm Hg)
SSc patients with fQRS (n = 13)
SSc patients with normal QRS (n = 40)
Control groups (n = 26)
p
32.8 43.7 27.5 10.0 9.8 66.2 14.7 12.5 0.76 11.7 7.3 26.1
32.1 43.9 27.8 9.4 9.2 65.5 14.3 12.6 0.78 10.0 7.0 27.6
31.5 43.8 27.0 9.6 9.2 65.9 13.9 11.9 0.83 10.8 8.0 26.7
0.576 0.970 0.570 0.243 0.180 0.613 0.485 0.579 0.073 0.303 0.050 0.826
± ± ± ± ± ± ± ± ± ± ± ±
3.1 3.8 3.8 1.1 0.9 5.4 2.1 1.9 0.15 2.3 2.9 7.2
± ± ± ± ± ± ± ± ± ± ± ±
5.4 4.7 3.7 1.4 1.2 4.8 3.4 3.3 0.17 2.5 2.4 7.8
± ± ± ± ± ± ± ± ± ± ± ±
3.2 2.9 2.5 1.3 1.2 3.8 1.7 1.3 0.11 1.7 2.0 3.7
Data are presented as mean ± standard deviation. SSc: systemic sclerosis; fQRS: fragmented QRS; LAD: left atrial diameter; LVEDD: left ventricular end diastolic diameter; LVESD: left ventricular end systolic diameter; IVS: interventricular septum; PW: posterior wall; EF: ejection fraction; LAA: left atrial area; RAA: right atrial area; sPAP: systolic pulmonary arterial pressure.
Fragmentation of QRS complexes is shown to be associated with intraventricular systolic dyssynchrony and subendocardial fibrosis in nonischemic cardiomyopathy patients [26,27]. Patients with fQRS have ischemia and fibrosis in subendocardial area [28]. Coronary artery disease or previous myocardial infarction is associated with fQRS complexes on ECG and lower strain measures in infarct related LV segments due to regional or transmural fibrosis. Yan et al. [29] showed that the fQRS complex was associated with subclinical global and regional LV dysfunctions in patients with coronary artery disease with preserved LV EF and it predicted adverse cardiac events in these patients. In our study, 13 SSc patients had fQRS complexes and LV GLS and GCS were modestly, but significantly, impaired in these patients as compared to those with normal QRS complexes. Strain measures were reduced in our SSc patients especially in those with fQRS complexes although we excluded coronary artery disease in this patient group. This might be related with the presence of patchy fibrosis in related LV segments due to overproduction of abnormal collagen in SSc patients. The extent of fibrosis is associated with poor prognosis in SSc [30,31]. Thus the presence of fQRS may indicate not only subtle LV systolic dysfunction but also poor prognosis in SSc patients. In addition, both LV GLS and GCS have been recently shown to be associated with functional capacity and ventricular arrhythmias [9]. Early assessment of LV dysfunction by echocardiography and presence of fQRS may be used as a prognostic marker in these patients. Verification of fibrosis by late gadolinium enhancement cardiac magnetic resonance imaging might strengthen our findings. Our study has important clinical implications. We showed that SSc patients had subclinical myocardial dysfunction assessed by 2D STE while conventional echocardiographic measures were normal. Additionally, we detected fQRS complexes in SSc patients and these patients had significantly
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Table 4 Comparison of left ventricular and left atrial strain parameters between SSc patients and controls. S (%)
GLS GRS GCS Twist Untwist LA-Res LA-Con
SSc patients with fQRS (n = 13)
SSc patients with normal QRS (n = 40)
Control groups (n = 26)
p
−19.6 41.6 − 15.2 18.9 − 126.5 33.4 14.7
− 21.6 37.9 − 18.8 16.4 − 134.5 34.4 14.3
− 25.8 47.7 − 25.2 31.8 − 134.5 38.1 13.7
b0.001⁎,⁎⁎,⁎⁎⁎ 0.022⁎⁎⁎ b0.001⁎,⁎⁎,⁎⁎⁎ b0.001⁎⁎,⁎⁎⁎ 0.726 0.335 0.811
± ± ± ± ± ± ±
2.1 18.3 5.1 5.5 45.4 9.1 6.8
± ± ± ± ± ± ±
2.1 17.5 4.9 8.8 44.2 10.3 3.9
± ± ± ± ± ± ±
2.7 7.0 3.3 9.4 29.5 10.1 3.3
Data are presented as mean ± standard deviation. SSc: systemic sclerosis; fQRS: fragmented QRS; GLS: global longitudinal strain; GRS: global radial strain; GCS: global circumferencial strain; LA-Res: left atrial reservoir; LA-Con: left atrial conduit. ⁎ Post hoc analysis: p b 0.05 between SSc patients with fQRS and SSc patients with normal QRS. ⁎⁎ Post hoc analysis: p b 0.05 between SSc patients with fQRS and controls. ⁎⁎⁎ Post hoc analysis: p b 0.05 between SSc patients with normal QRS and controls.
lower LV GLS and GCS when compared to SSc patients with normal QRS complexes. To the best of our knowledge, this is the first study in the literature to evaluate regional myocardial
function with 2D STE in SSc patients with fQRS complexes in surface ECG. Our results have suggested that surface ECG might be useful for early detection of myocardial involvement
Fig. 1. (A) Surface electrocardiography showing fragmented QRS complexes in DII, DIII, and aVF leads. (B) Peak systolic strain values of cardiac segments in a patient with fragmented QRS in DII, DIII, and aVF leads. (C) Time to peak longitudinal strain of cardiac segments in that patient with fragmented QRS in DII, DIII, and aVF leads.
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in SSc patient and would rather be performed in every SSc patient suspected from myocardial dysfunction. Study limitations The major limitation of our study was the small sample size. A larger sample size might give more convincing and significant results in comparison to strain values between fQRS and normal QRS groups. LV strain values were higher in our study group when compared to elegant papers in literature [21,32,33]. We included relatively more female patients and the patients in our study were relatively younger compared to those studies. Younger age and female sex are associated with higher longitudinal and radial strain levels and this might explain the discrepancy between our strain values and others. Although the study had a prospective design, we did not gather data regarding prognosis of the patients. Thus, we could not explore a relation between adverse cardiac events and decreased myocardial strain parameters or fQRS complexes in these patients. We did not perform cardiac magnetic resonance imaging which can accurately show extend of the fibrosis and myocardial dysfunction in these patients. We did not evaluate the inner and outer radial strain of LV wall separately. Inner radial strain might be more impaired in patient with fQRS due to subendocardial fibrosis. Further prospective long-term largescale studies are necessary to determine the outcome and the best approach to treatment of such abnormalities.
Fig. 3. Systemic sclerosis patients with fragmented QRS in DII, DIII, and aVF leads had significantly higher the delay in time to peak longitudinal strain in the inferior LV segments compared to those with normal QRS complexes. Data are presented mean ± standard deviation.
SSc. However, a simple cheap ECG may also give idea about cardiac involvement in SSc and should be included in cardiovascular evaluation of these patients. Funding sources None.
Conclusion Patients with SSc may have subtle LV systolic dysfunction, which can be successfully assessed by 2D STE. Importantly, some SSc patients may have fQRS complexes in surface ECG and these patients have lower LV global longitudinal and circumferential strain measures. The use of novel imaging techniques such as 2D STE may improve risk stratification and monitoring of the cardiovascular involvement in patients with
Conflict of interest None to declare. Acknowledgments None. References
Fig. 2. Systemic sclerosis patients with fragmented QRS in DII, DIII, and aVF leads had significantly lower longitudinal strain values in the inferior LV segments compared to those with normal QRS complexes. Data are presented mean ± standard deviation.
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