Catheter ablation of premature ventricular contractions with multiple morphologies in tachycardia-induced cardiomyopathy: all or nothing?

This editorial refers to ‘Best ablation strategy in patients with premature ventricular contractions with multiple morphology: a single-centre experience’ by S. Mohanty et al., https://doi.org/10.1093/europace/euad038.

Tachycardia-induced cardiomyopathy by ventricular arrhythmias such as premature ventricular contractions (PVCs) is a well-recognized cause of heart failure today.¹ Since the first description of a case of tachycardia-induced cardiomyopathy in 1913 in a patient with so-called ‘auricular fibrillation’,² there has been huge progress in the understanding of underlying pathology, diagnosis, and treatment of the disease. Tachycardia-induced cardiomyopathy related to high PVC burden has been described the first time in the 1990s.³ It can occur either as pure tachycardia-induced cardiomyopathy or as deterioration of left ventricular (LV) function in the presence of structural heart disease. There is an increasing performance of catheter ablation as a potentially curative therapy for patients suffering from PVC. Premature ventricular contraction reduction is attempted either as a symptomatic therapy or as a prognostic intervention in patients with deterioration of LV function associated to high PVC burden. The Current European Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death give a class I recommendation for catheter ablation in patients with PVC-induced tachycardia-induced cardiomyopathy or aggravated LV dysfunction associated with a high PVC burden.⁴ Importantly, this recommendation is only given in patients with monomorphic or predominantly monomorphic PVC.⁵ The guideline statement is based on earlier studies that found reduced success of catheter ablation as well as lower likelihood of recovery of LV function after PVC ablation in patients with multiform PVC.⁵ Based on guideline recommendations, catheter ablation has been widely adopted across European countries in routine clinical management of patients suffering from PVCs.⁶ Nevertheless, PVC ablation procedures can be challenging with a need for high operator experience and elaborate tools and techniques.^7,8

In the current issue of EP Europace, Mohanty et al.⁹ present a single-centre experience on catheter ablation of PVC with multiple origins in patients with reduced LV ejection fraction (LVEF). A relatively large cohort of 171 patients with a PVC burden above 10% and two or more PVC morphologies were analysed. In this study, the authors aimed at analysing the effects of catheter ablation targeting all PVC morphologies instead of targeting only the dominant morphology. Interestingly, the authors found that 2 years after catheter ablation of all PVC morphologies during the index procedure, patients experienced persistent elimination of all PVCs or reduction of PVC burden below 5% in 84% of the cases. Patients who underwent catheter ablation of the dominant PVC morphology presented significantly lower success rates with only 43.4% of the patients experiencing complete PVC elimination or PVC burden reduction below 5%. In a large number of patients (87.6%), repeat catheter ablation was performed. In the majority of patients, repeat ablation was performed due to rising frequencies of previously non-predominant PVC. During repeat ablation, all PVC morphologies were targeted. At 5-year follow-up after the repeat ablation, high success rates with 91% of the patients being free of any PVC or presenting with a PVC burden below 5% were observed. In patients with failed ablation of all PVC morphologies at repeat ablation, PVC burden reduction was significantly lower than in patients with complete ablation of all PVC foci. Notably, LVEF improved significantly in patients with successful index ablation, while a reduction of LVEF could be observed in patients with persistent high PVC burden. Normalization of LVEF above 50% was observed in 10.9% of the patients who remained free of PVC at follow-up. Despite two cases of groin hematoma, no relevant major complications were observed.

Mohanty et al. have to be congratulated for their analysis of a patient cohort in which a systematic clinical study is accompanied by many difficulties. Based on the present data, the authors raise the important question: when should multiple PVC morphologies be ablated? Many electrophysiologists focus on catheter ablation of a predominant morphology in patients with multiple PVC origins as success rates of catheter ablation are known to be reduced in patients with multifocal PVCs.¹ Multiform PVC may represent an electrocardiogram (ECG) correlate of different PVC foci in some patients, while it may only be a correlate of different myocardial exit sites of singular PVC foci in other individuals. Misinterpretation of fused beats and incorrectly placed ECG leads are possible explanation as well. A clear distinction of these phenotypes can sometimes be challenging, and precise diagnosis requires careful ECG interpretation by treating physicians. To give a clear recommendation to patients with multiform PVCs to undergo catheter ablation or not, the likelihood of successful PVC suppression should be taken into account. In the current study, encouragingly high success rates of catheter ablation targeting all PVC morphologies with very low complication rates at the same time were observed. Nevertheless, the patient collective that has been studied remains a very heterogenous group of individuals. There are typical localizations of multiform PVC origins that represent very challenging sites in terms of PVC ablation such as LV papillary muscles and the LV summit area. Patients with PVCs from these areas might differ substantially from other patients with multiform right ventricular outflow tract (RVOT) PVCs. Additionally, patients with two PVC morphologies may differ substantially from patients with multiple morphologies regarding pathophysiological mechanisms and success of catheter ablation. There are also distinct aetiologies of PVCs and tachycardia induced cardiomyopathy like the genetically caused multifocal ectopic Purkinje-related PVCs that might be more amenable for systemic medical antiarrhythmic therapy than for catheter ablation.¹⁰ In the current study, the vast majority of patients suffered from two to three different PVC morphologies.⁹ The exact success rates for patients with four or more PVC morphologies are not described by the authors, but we can assume that PVC recurrence might be a frequent issue in these patients. A remaining question is if ablation should target all PVCs directly in an initial ablation procedure or if this should be performed only when a high PVC burden persists because the previously non-dominant PVC morphologies become more frequent. There is also a need for clearer target values for post-procedural PVC burdens that should be aimed at. A major strength of the present study is that all patients included in this analysis were suffering from PVC-induced cardiomyopathy and an average follow-up of 5 years including echocardiographic examination was performed. Furthermore, all patients were followed up including 12-lead Holter ECG that significantly increases follow-up quality. The effects of successful PVC suppression of all PVC morphologies on LVEF recovery were significant.

However, the present study shows several limitations. The study represents a single-centre non-randomized experience that is based on ablation of clinically challenging PVC foci in a highly experienced electrophysiological centre. Observed success rates therefore may not be generally applicable to other centres. The ablation approach in the initial PVC ablation procedure was not standardized resulting in attempted ablation of only dominant morphologies in the majority of patients and attempted ablation of all morphologies in about 11%. Furthermore, the cut-off value of PVC burdens below 5% for procedural success was randomly defined by the authors and makes the presented results harder to compare to pre-existing data. Unfortunately, the study population did not undergo routine cardiac magnetic resonance imaging that would have characterized the population better regarding fibrotic substrate and potentially underlying structural heart disease. It should also be clearly stated that the present data cannot be applied to heart failure patients with multifocal PVCs without any predominant morphology.

The authors however contributed with the present study significantly to the understanding of the potential role of catheter ablation targeting multiple PVC origins in patients with reduced LVEF and presented promising results in terms of treating PVC-induced cardiomyopathy. Future studies with a randomized trial design are warranted to confirm these encouraging preliminary findings. Until these studies become available, catheter ablation of multifocal PVCs should be considered as a treatment approach after careful assessment of benefits and risks for each individual patient.

Funding

No funding was received.

Author notes

The opinions expressed in this article are not necessarily those of the Editors of Europace or of the European Society of Cardiology.

Conflict of interest: P.S. is an advisory board member of Abbott, Biosense Webster, Boston Scientific and Medtronic.