Although PVCs used to be considered as mostly benign, long-term frequent PVCs may lead to PVC-CM in some patients [13], via pathogenic mechanisms possibly involving ventricular systolic dyssynchrony during PVCs, longer coupling intervals, and post-extrasystolic potentiation [14–17].
PVC-CM was first classified as an indication of catheter ablation by European Heart Rhythm Association/Heart Rhythm Society Expert Consensus on Catheter Ablation of Ventricular Arrhythmias in 2009 [18]. However, there is uncertainty about the exact diagnostic criteria for recognizing PVC-CM, so the diagnosis is mostly made retrospectively and by exclusion. It also remains controversial whether intervention is necessary in patients with frequent PVCs who are asymptomatic or have normal LVEF. In this study, we used 2D-STE and evaluated strain values to detect cardiac dysfunction in patients with frequent PVCs but without concomitant structural heart disease. It should be kept in mind that there are varying degrees of cardiac dysfunction even in patients without abnormal findings on conventional echocardiography. These patients manifest as having reduced global and regional strain values, uneven overall color of bull’s eye plots, disordered strain, less smooth curves, and significantly reduced wave amplitudes.
Myocardial strain can identify early stages of PVC-CM particularly in patients with preserved LVEF. Therefore, strain imaging has emerged as a critical adjunct in the assessment of systolic function, especially in patients whom LV function is expected to deteriorate progressively [19].
Recent studies reported that LV-GLS values were significantly decreased in patients with frequent PVCs and preserved LVEF [19–21]. Studies evaluating the effects of RF ablation on LV-GLS in patients with preserved LVEF are limited. In a recent study, Koca et al. reported that RF ablation increased LV longitudinal strain values [22]. Again, Uhm et al. showed the positive effect of RF ablation on RV-GLS in patients with frequent PVCs originating from RVOT [23]. Recent article also demonstrated impaired LV-GLS in the sinus rhythm beat preceding PVC. This finding suggests that perturbations in cellular physiological processes such as excitation-contraction coupling (autonomic or calcium handling) may play a role in the generation of frequent PVCs [24]. In our study, similar to the result of the above mentioned study, we found that there was a significant increase in LV-GLS value after RF ablation in patients with normal LVEF. This improvement was statistically significant in group 1 patients whose LV-GLS values were >-16 before ablation. In group 2 patients whose LV-GLS values were within the normal range a slight improvement trend was observed, especially in patients whose values are close to the reference value, which did not reach statistical significance. A larger study sample is necessary to determine the exact reference values.
In this study our aim was to evaluate differences between the patients according to their LVGLS values demonstrated by the 2D-STE before ablation. As a result, there were no remarkable differences in the clinical, electrocardiographic, and common echocardiographic parameters between the two groups. On the other hand, the group with impaired LV-GLS values (group 1) showed significantly lower PVC E wave flow and PVC SV with higher post-PVC E wave flow and post-PVC SV values. As a result, PVC E flow/ Post-PVC E flow and PVC SV / Post-PVC SV rates were significantly lower in group 1 than in group 2.
The mechanism of PVC-CM is not clear. There is general agreement that the higher the number of PVC per day, the greater the risk of developing cardiomyopathy [25]. In our study, number of PVCs per day was higher in group 1 but the difference was not statistically significant (p = 0.089). Besides PVC burden, some other risks factors for progression to cardiomyopathy have been identified, but there are inconsistencies between different studies. Patient characteristics such as increasing age [26], high body mass index [27], and male gender [28] were found to be related with PVC-CM. In our study, there were no significant difference between the groups in terms of these patient characteristics. A longer exposure to frequent PVCs increases the risk of subsequent cardiomyopathy [4]. Although group 1 had a longer history of PVC in our study, the difference did not reach statistical significance (p = 0.054). Some electrocardiogram (ECG) characteristics (more than one PVC morphology, presence of nonsustained VT) may promote cardiomyopathy [3]. In our study, patients with this ECG characteristics were excluded from the study. Another indicator of PVC-induced cardiomyopathy is a greater QRS width of the PVCs [3]. In our study, there was no difference in PVC width between the groups. Longer coupling interval [15], and presence of interpolation [29] were associated with PVC-induced cardiomyopathy due to mechanisms such as dyssynchrony and ventriculo-atrial dissociation. Similarly, we found that the PVCs coupling interval time was higher in group 1 patients.
Some PVCs do not create sufficient ejection volume or pressure for aortic valve opening and detectable aortic pressure (mechanical systole), leading to a concealed mechanical bradycardia. In our study, PVCs in group 2 were more efficient in ejecting into the aorta than PVCs in group 1, resulting in less concealed mechanical bradycardia. Frequent mechanically inefficient PVCs lead to sustained concealed mechanical bradycardia, decreased cardiac output [30] and increased LV diastolic pressures, volume overload, LV dilation, and LV systolic dysfunction. Furthermore, repeated lack of arterial pulse can be responsible for neurovegetative imbalance through baroreceptor reflex mechanism [31, 32], which may detoriate myocardial function over time. In our study, patients with impaired LV-GLS (group 1) have significantly lower PVC E wave flow and PVC SV values which supports the above mentioned mechanisms.
Some authors consider postextrasystolic potentiation (PEP) as a mechanism for PVC-CM. PEP significantly increases myocardial oxygen consumption [33–34], and when frequent this increased energy consumption may cause systolic dysfunction. However, this hypothesis has never been investigated. In our study, patients with impaired LV-GLS had a significantly higher post-PVC E wave flow and post-PVC SV values. Although we indicated a significant correlation between poor hemodynamic performance of PVCs and the presence of impaired LV-GLS, it is difficult to conclude with the results of this study that inefficient PVCs cause cardiomyopathy. Definitive conclusions cannot be drawn from this study, and only prospective studies can resolve this issue.
4.1. Limitations
Interpretation of the findings of this study is limited due to several factors. The study had a limited sample size, this precluded the definition of PVC-induced cardiomyopathy predictors and strain value cutoffs to determine the need for intervention including radiofrequency ablation. We were unable to examine variables that would have been useful in identifying subclinical left ventricular dysfunction in patients with normal ejection fraction, such as BNP levels, the Kansas City Cardiomyopathy Questionnaire, and the 6-minute walk distance. Long-term follow-up is needed to verify the results of the present study and to assess cardiac function recovery in patients with frequent PVCs undergoing clinical intervention. 2D-STE requires high-quality images, comparison of experimental results is restricted because parameters vary between different echocardiography devices and software workstations used for analysis. However, interobserver and intraobserver variability in strain values is good and consistent with previous studies. Future studies conducted with large sample size is necessary to determine the exact reference values.