Frequent premature ventricular contractions (PVCs) cause left ventricular (LV) dysfunction, and may even result in a form of cardiomyopathy known as premature ventricular contraction-induced cardiomyopathy (PVC-CM).1,2 The incidence of PVC-CM is approximately 7%, but this is likely to be a significant underestimation, since it was also reported to be as high as 30% in patients referred for catheter ablation.3,4 Although radiofrequency (RF) ablation and antiarrhythmic drugs are accepted strategies to reverse LV dysfunction due to PVCs,5,6 the minimum burden, origin (LV, RV, outflow, endocardial, epicardial), duration and coupling interval of PVCs required to impair LV function are unknown.7,8

In daily practice, PVC-CM is determined by the measurement of left ventricular ejection fraction (LVEF) using two-dimensional (2D) transthoracic echocardiography (TTE). Measuring LVEF enables detection of cardiomyopathy only in later stages, therefore, attempts have been made to find new imaging methods to detect PVC-CM at an earlier stage. Frequent PVCs may cause the development of cardiomyopathy, if only a significant portion of the myocardium has been affected over time.7,8 Myocardial strain can identify early stages of PVC-CM especially in patients with preserved LVEF.9 Therefore, strain imaging has emerged as a critical adjunct in the assessment of systolic function, particularly in patients whose LVEF is expected to worsen in the future.10

The present study evaluated subtle and early forms of PVC-induced ventricular impairment in patients without any structural heart disease by using global longitudinal strain, which might be useful for early detection and risk stratification of cardiac dysfunction. In this study, we also evaluated changes in LV-GLS values after ablation as an indicator of regression in left ventricular dysfunction and various parameters showing the hemodynamic results of PVCs.

Thirty-six symptomatic patients (16 females, age 50.3±9.7 years) were enrolled into the study. All patients used at least one antiarrhythmic drug before ablation (beta-blocker, calcium channel blocker, amiodarone, propafenone, sotalol). In the 24-hour outpatient Holter recordings obtained after the ablation procedure, it was observed that success (>80% decrease of PVC burden compared to baseline) was achieved in all patients.

The mean LV-GLS value before ablation was 17.3±3.7. This value was observed as 20.5±2.6 after ablation and the difference was statistically significant (p<0.01). Based on the existing literature17 where normal LV-GLS ranged from −15.9% to −22.1%, patients were categorized into two groups in the form of those having LV-LGS value >−16% and ≤−16%. In Group 1, whose LV-GLS values were >−16%, it was observed that the mean LV-GLS value improved significantly after ablation (−12.6±2.0 vs. −18.3±1.9, p<0.01). Although there was a trend toward improvement after ablation in Group 2, whose LV-GLS values were within the normal range, this trend did not reach statistical significance (18.9±2.1 vs. 20.6±1.8, p=0.06). After ablation, there were no significant changes in any of the common transthoracic echocardiographic parameters listed in Table 3. There were no significant differences in age, sex, body mass index, serum creatinine levels, hematocrit levels, and the prevalence of major comorbidities including diabetes, hypertension and smoking between groups. Although PVC history in years was longer in Group 1, the difference did not reach statistical significance (p=0.054) (Table 1).

The sites of PVC origins in patients who underwent successful ablation were as follows: right ventricular outflow tract (RVOT) 19 (52.7%), left ventricular outflow tract (LVOT) 9 (25%), Parahisian 2 (5.5%), papillary muscles 2 (5.5%), aortomitral continuity (AMC) 2 (5.5%), mitral valve 1 (2.7%), tricuspid valve 1 (2.7%). Mean procedure time was 138±53 minutes, fluoroscopy time was 19±34 minutes, and RF ablation time was 7±5 minutes (p=NS, between groups).

Comparison of ECG and 24-hour Holter recordings data between groups showed that PVCs coupling interval time was found to be significantly longer in Group 1 (Table 2). Total PVCs and PVCs burden were higher in Group 1 but the difference was not statistically significant. Other parameters were also found to be similar between groups (Table 2).

LVDd, LVEF, left atrial diameter, E/A ratio, E′ wave, E/E′ in Group 1 did not differ from Group 2 (Table 3). All patients with LV hypertrophy were excluded, so there was no difference in LV mass index between the groups. No patients had moderate or severe mitral regurgitation. While there was no difference in sinus E wave flow between groups (20.0±2.8 vs. 20.3±3.2, p=0.55), PVC E wave flow was lower in Group 1 than in Group 2 (7.6±2.8 vs. 13.6±3.4, p=0.02). Post-PVC E wave flow in Group 1 was higher in comparison to Group 2 (27.7±4.3 vs. 19.8±3.5, p=0.04). Similarly, while there was no difference in sinus SV between groups (74.2±7.7 vs. 77.7±10.7, p=0.12), PVC SV was lower in Group 1 than in Group 2 (17.6±5.8 vs. 35.2±6.9, p=0.02), and post PVC SV was higher in Group 1 in comparison to Group 2 (94.9±4.6 vs. 79.1±8.2, p=0.03). E wave flow and SV values at the time of PVC and post-extra systolic sinus beat were proportioned between the two groups. PVC E flow/post-PVC E flow and PVC SV/post-PVC SV were both significantly lower in Group 1 than in Group 2 (Table 3).

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 in the absence of concomitant structural heart disease. It should be remembered that there are varying degrees of cardiac dysfunction even in patients without abnormal findings on conventional echocardiography. These patients present with reduced global and regional strain values, uneven overall color of bull's-eye plots, disordered strain, fewer 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 whose 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 Uhm et al. showed the positive effect of RF ablation on RV-GLS in patients with frequent PVCs originating from RVOT.23 A recent article also demonstrated impaired LV-GLS in the sinus rhythm beat preceding PVC. This finding suggests that disturbances 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 abovementioned study, we found that there was a significant increase in LV-GLS after RF ablation in patients with normal LVEF. This improvement was statistically significant in Group 1 patients whose LV-GLS was >−16 before ablation. In Group 2 patients, whose LV-GLS values were within the normal range, there was a slight trend toward improvement, especially in patients whose values were close to the reference; it did not, however, achieve statistical significance. A larger study sample is needed to determine the exact reference values.

In this study our aim was to evaluate differences between patients according to their LV-GLS 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) had 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, the 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 in studies. Patient characteristics such as increasing age,26 high body mass index,27 and male gender28 were found to be related to PVC-CM. In our study, there were no significant difference in patient characteristics between the groups. 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 non-sustained 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 interpolation29 were associated with PVC-induced cardiomyopathy due to mechanisms such as dyssynchrony and atrioventricular dissociation. Similarly, we found that the PVC 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 output30 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 worsen myocardial function over time. In our study, patients with impaired LV-GLS (Group 1) had significantly lower PVC E wave flow and PVC SV values, which supports the abovementioned mechanisms.

Some authors consider post-extrasystolic 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 from 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.

In symptomatic patients with frequent PVCs and normal LVEF, we observed significant improvement in LV-GLS following successful ablation. Patients with impaired LV-GLS more often displayed non-ejecting PVCs and PEP compared to patients with normal LV-GLS. Lower PVC E wave flow, PVC SV and higher post-PVC E wave flow, post-PVC SV values were observed in patients with impaired LV-GLS. Further studies are required to determine these associations.

All authors contributed to: (1) conception and design, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, and (3) final approval of the version to be published.

The study was performed in compliance with the principles outlined in the Declaration of Helsinki and approved by the ethics committee of TC. Atlas University.

The authors received no financial support for the research, authorship, and/or publication of this article.

The authors have no conflicts of interest to declare.