Speckle Tracking Versus Conventional Echocardiography in Patients with Symptomatic Premature Ventricular Contractions

Background: Frequent premature ventricular complexes [PVCs] are linked to the left ventricular [LV] dysfunction. Early diagnosis is crucial for the proper treatment. Aim of the Work: This study aimed to prove the superiority of modern diagnostic modalities as speckle tracking over the conventional echocardiography in the detection of subtle left ventricular dysfunction in symptomatic PVCs. Patients and Methods: This study included 40 patients with frequent PVCs and 20 healthy subjects, as a comparison group. The myocardium strain in the circumferential [CS], radial [R] and longitudinal [L] directions were evaluated using conventional echocardiography and speckle tracking imaging. Result: The study included 21 male and 39 females with age ranging between 22 and 56 years in the study group and between 22 and 57 years in the control group. In the case group, PVCs were more frequent [18.73 ± 7.15]. The two groups have normal resting conventional echocardiography with no evidence of structural heart or systemic disease. In the study group, 25 patients have PVCs arising from the right ventricle [RV] [62.5%] and 15 patients have PVCs arising from the LV [37.5%]. There was no significant correlation between PVCs origin and LV global longitudinal strain [GLS], radial strain [RS] and circumferential strain [CS] [p value= 0.285, 0.380 and 0.401] respectively. There was a significant inverse correlation between the total number of PVCs [PVC burden] and LV ejection fraction [EF], GLS, RS, and CS [p value <0.001]. Conclusion: The study concluded that speckle tracking echocardiography is an important and valuable tool for early identification of impairment in the LV function in patients with frequent PVCs earlier than conventional echocardiogram.


INTRODUCTION
Premature ventricular contractions [PVCs] are one of the common types of arrhythmias with estimated prevalence of 6% of patients aged between 45 and 65 years old, which may lead to disturbing and potentially debilitating symptoms [e.g., chest pain, palpitation, presyncope, syncope, and heart failure]. PVCs may produce several hemodynamic effects especially on LVEF [1] . The concept of PVCsstimulated cardiomyopathy was suggested after improvement of the left ventricular [LV] systolic function in patients complained of idiopathic dilated cardiomyopathy by pharmacological suppression of PVCs [2] . Also, in cases with frequent PVCs, there was progressive worsening of LV function as measured by LVEF during follow-up [3] . Bogun et al. [5] found a reduction of LVEF in 37% of 60 patients with idiopathic PVCs greater than 10 per hour. Patients with decreased LVEF tend to have a higher burden of PVCs [4] .
The assessment of LVEF is usually achieved by conventional echocardiography or by newly introduced speckle tracking strain imaging. Previous studies in the last five year reported the ability of speckle tracking to identify subtle changes in the heart ventricles [5] . The speckle tracking echocardiography is a quantitative ultrasound modality, used for accurate assessment of myocardial function by analysis of the speckle motions registered by the routine two-dimensional sonograms. The advantages of speckle-tracking based on its non-Doppler and angleindependency. In addition, it provides an objective quantification of myocardial deformation and LV systolic and diastolic dynamics. Additionally, it calculates strain and the strain rate offline after a satisfactory image acquisition [6,7] .
Speckle tracking imaging permits assessment of multidirectional LV strain in radial [RS], circumferential [CS] and longitudinal [LS] directions, and RV longitudinal strain, regardless of the angle [angle-independent] [5] .
Yao et al. [8] included 30 patients with PVCs, and concluded that speckle tracking imaging could be useful in the detection of changes in ventricular function in the PVC setting before conventional echocardiogram.

THE AIM OF THE WORK
The current study aimed to prove the superiority of modern techniques of echocardiography as speckletracking and strain and strain rate over conventional echocardiography in early detection of subtle LV systolic dysfunction in patients with symptomatic PVCs. Included subjects were submitted to through clinical examination and history taking for the assessment of symptoms due to PVC [palpitation, syncope, chest pain and exertional or resting dyspnea] and their duration. New York Heart Association [NYHA] functional class was assessed for all patients. A detailed medical history was obtained from all patients. Routine laboratory analysis including renal function tests and serum electrolytes, complete blood picture, liver function tests and thyroid profile were obtained for all patients. Resting 12-Lead ECG was performed to detect morphology and origin of PVCs, evidence of myocardial infarction, evidence of another arrhythmia. Forty-eight hours Holter monitoring was done to all patients for confirmation of the presence of frequent PVCs, exclusion of the presence of other tachyarrhythmia and calculation of PVC burden. The %PVC was calculated as the following: 100 [number of PVC/numbers of total heart beats per 48 hours].

PATIENTS AND METHODS
Patients underwent transthoracic echocardiography at admission using Philips IE 33, using the X 5-1 phased array sector probe [frequency range 1.5-4.3 MHz]. Images were attained when patients were in the left lateral position at the end of expiration according to the guidelines of the American Society of Echocardiography [8] and attached to a single lead ECG. All standard measurements were gained in the parasternal long-and short-axis, apical four-chamber, twochamber and apical long axis views. LV-EF, LV-ESV and LV-EDV were calculated using the modified Simpson's rule by outlining the endocardial border at the end-diastole and end-systole in the 2-chamber and four-chamber views. End-diastolic frame was recognized as the frame after closure of mitral valve or the frame in largest cardiac dimension in the cardiac cycle. End-systolic frame was defined as the frame before the opening of the mitral valve or the smallest cardiac dimension in the cardiac cycle [8] .
Speckle tracking echocardiography [STE] was done for all subjects [case and control] as follow: We acquired the images using the same probe for conventional echocardiography of the Philips IE33. Digital loops with three successive cardiac cycles were acquired from apical four chambers, apical long-axis, apical two chambers and short axis at basal, mid and apical levels. Frame rates had to be > 40 frames/second. The views had identical depth, sector width, and frame rates. We analyzed the digitally stored clips offline using commercial imaging analysis software. Speckle tracking application was started and image was opened, automatically the software showed the end-systolic frame of the cardiac cycle. In this frame, endocardial border was manually traced from its beginning to its end, then the myocardium was divided by the software into six segments with generation of segmental and global longitudinal strain, velocity and displacement curves. Clinical, Holter and echocardiographic parameters were recorded and a descriptive analysis was completed and the data were collected, verified and coded.
Statistical analysis: All quantitative variables were presented in the form of their arithmetic mean and standard deviation provided that, they were normally distributed. On the other side, categorical data were presented as frequency and percentages. Chi-square or student "t" tests were used to assess the association in categorical data and difference between two means, respectively. P-value < 0.05 was set as the margin of significance. Pearson's correlation coefficient was calculated to estimate correlation between parameters and all analysis process had been completed

DISCUSSION
PVCs are the most common arrhythmia seen by the physician and may be considered a normal finding in healthy subjects, and reported in 6% of patients aged between 45 and 65 years [9] .
Although they are always benign, in observational studies, they may be associated with a higher risk of complications [e.g., malignant arrhythmias, and sudden cardiac death] in otherwise healthy subjects [10,11] .
So, attention of researchers is paid for early recognition of LV dysfunction in patients with frequent PVCs for improvement of morbidity and mortality. The aim of this study was to prove the superiority of modern techniques of echocardiography as speckle tracking and strain and strain rate over conventional echocardiography in early detection of subtle LV systolic dysfunction in patients with symptomatic PVCs.
In the current work, there was female sex predominance [65.0%]. The reason for a higher prevalence of women can be explained by the fact that the study population was limited to the patients with PVCs associated symptoms as females are more symptomatizing and this finding coincides Results of the current study revealed that, there was no statistically significant differences between patients with PVCs originating from right when compared to left ventricle regarding LVEF, LV-GLS and LV-CS. Myocardial strain was reduced in all directions to a similar extent in patients with LV or RV origin.
These findings are comparable to Wijnmaalen et al. [12] and Del Carpio Munoz et al. [13] , regarding PVCs origin and their effect on LV systolic function. These finding coincides with Niwano et al. [4] , Wijnmaalen et al. [12] , and Del Carpio Munoz et al. [13] finding regarding the correlation between PVC burden and LV function.
Several published studies showed that the frequency of PVCs correlates with the extent of LV dysfunction and ventricular dilation at the time of first clinical complaints. Patients with reduced LVEF had a higher PVC burden than subjects with normal function of the LV. However, there are no clear-cut points that clearly differentiate or predict when cardiomyopathy is unavoidable [14,15] . However, Niwano and coworkers [4] used a 20.000 PVCs over 24 hours, as a cutoff point to outline the high-frequency group.
Kanei et al. [16] , on the other side, used a cutoff point of 10.000 PVCs per day.
Other studies demarcated "frequent" PVCs as > 10% of total beats rather than an absolute number of PVCs [17] ; yet in some patients, a high burden of PVC may not affect the function of the LV, whereas PVC-induced cardiomyopathy can be detected in patients with low PVC burden [18] The benign course in cases with high PVC burden is not fully understood, although one third or more of those cases could develop cardiomyopathy. One potential explanation is that, the assessment of PVC burden by Holter monitoring for 48 hours may be inadequate and could misinterpret the PVC burden [16] .
Baman et al. [18] suggested that, 24% PVC burden or more, yield a sensitivity of 79.0%, specificity of 78.0% for differentiating LV function [preserved versus impaired]. However, patients with frequent PVCs usually had a preserved ejection fraction of the left ventricle as reported by different researchers [3,4,17,19] . Therefore, the PVC burden is not the only contributing or responsible factor to impaired LV systolic function, irrespective of its significance [17] .
Regarding 2D speckle tracking variables of global function, there was a significant difference as regard LV-GLS and CS between cases and controls. Global values of LV were significantly lower in the PVC group than in the control subjects, whereas LV function evaluated by traditional echocardiographic methods were normal. This shows that, PVCs may stimulate early LV dysfunction, which not recognized by the traditional 2D echocardiography.
This result is in accordance with Wijnmaalen et al. [12] and Yao et al. [8] .
The assessment of multidirectional strain with 2D speckle tracking aids the recognition of the functional deviations by exploring the myocardium mechanical properties and constitutes a more sensitive instrument to recognize the subtle ventricular dysfunction in contrast to traditional 2D echocardiography [20] .
Results of the current work are in line with Ling et al. [21] who reported non-significant differences in baseline echocardiographic variables between cases and controls. However, strain assessed variables [GLS, CS, RS] and individual segment strain was significantly reduced in the PVC group than the control group and there were strong correlations with left ventricular function assessed by left ventricular ejection fraction.

Study Limitations:
First, the study included a small number of patients. Second, the severity of symptomatic PVC was not evaluated and diastolic dysfunction was not correlated with PVC and speckle tracking parameters. Finally, the effects of various drugs such as beta-blockers and ACE inhibitors were not evaluated.

Conclusion:
The study concluded that speckle tracking echocardiography is an important and valuable tool for early detection of impairment in LV function in patients with frequent PVCs earlier than conventional echocardiogram.

Financial and Non-financial Relationships and Activities of Interest
None to be declared