The tricky choice of an ablation tool for atrial fibrillation: how delicate divergences can make the difference

This editorial refers to ‘Comparison of effects on coagulation and inflammatory markers using a duty-cycled bipolar and unipolar radiofrequency pulmonary vein ablation catheter vs. a cryoballoon catheter for pulmonary vein isolation’ by H. Malmborg et al., on page 798. Since the very first cardioversion in 19621 there has been a continuously hastening proliferation of therapeutic options for atrial fibrillation (AF), topped by the advent of catheter ablation. An impressive amount of literature has been published on this topic during the last decade. Currently, selecting the appropriate alternative for every patient among the plethora of available left atrial (LA) ablation strategies and devices might be puzzling. Efficacy and easiness of use play an important role in that choice, but safety must remain a central point. Collateral damage has repeatedly been an issue in the development of LA ablation techniques. Fortunately, conceptual and technical advances have allowed coming over some of them. Moving ablation targets away from the veins, for example, has dramatically reduced the rate of pulmonary vein stenosis after AF catheter ablation.2 Inflammatory responses and especially embolic events after LA ablation procedures remain matters of concern, and should be addressed by new technologies. Cryoenergy has long been thought to be ‘softer’ than radiofrequency (RF), particularly regarding the thromboembolic risk. Early bench research showed a higher thrombus formation and endothelial damage using RF.3 Later, a clinical study in AF patients also found a lower level of platelet activation using cryoenergy compared with RF.4 These two studies however were performed with a non-irrigated RF catheter and a focal cryoablation catheter, both tools are presently seldom used for AF catheter ablation. A first comparison study using current AF ablation devices failed to show any safety benefit of the cryoballon vs. conventional irrigated-tip RF catheters.5 In this issue of the Journal, Malmborg et al.6 complete the picture by comparing the cryoballoon with the phased-RF pulmonary vein ablation catheter (PVAC). Both devices are one-shot tools designed to perform pulmonary vein isolation. They are both mainly used in patients with paroxysmal AF, do only require one single trans-septal puncture, and are introduced through a 10-F or 12-F long sheath. All these similarities make these devices especially suited to compare the two energy sources. As in the previous study with irrigated-tip RF, Malmborg et al. did not find any significant difference in platelet or coagulation activation between PVAC and cryoballoon ablation. However, the ratio of endothelial damage and activation of the coagulation system to myocardial damage was higher using PVAC, suggesting that the prothrombotic effect of phased-RF when creating bigger lesions might be greater. An interesting aspect of the present study is the observation of low D-dimer levels and decreasing prothrombin levels throughout the procedure, showing a satisfactory anticoagulating effect of heparin despite subtherapeutic pre-procedural international normalized ratio levels (mean 1.5 ± 0.2) and relatively low activated clotting time levels during the procedure (268 ± 24 and 263 ± 26). Anyhow, not all embolic events after AF ablation are thromboembolic phenomena. Air or char embolism should also be bore in mind. Microbubbles produced by rashly introducing big devices through a long sheath or originated during phased-RF ablation through inadvertently overlapping electrodes can also be responsible for small cerebral lesions after an ablation procedure.7 No matter with which device, a carefully performed procedure paying attention at proper handling and flushing of a long sheath and a sufficient anticoagulation does also prevent embolic events. Lately, attention has also been drawn to inflammatory responses after LA ablation. They are responsible for pericardial and pleural effusion and also possibly for generalized oedema after AF catheter ablation. Inflammation plays a central role in the establishment of myocardial necrosis and has been linked to clinical outcomes after ablation. It might be a crucial difference between ablation tools and energies, as lesions undergo totally different pathophysiological processes during thermal and cryoinjury. With RF, myocardial tissue is mainly directly damaged by thermal denaturalization of proteins. This produces large but heterogeneous lesions. Cryolesions on the contrary are created in two phases. First, intracellular ice crystals formation yields to direct cell death; reforming of ice crystals into larger ones during thawing magnifies the effect. Hours later, coagulative necrosis takes place due to the capillary damage produced by extracellular ice. Finally, cells within the peripheral zone of the lesion undergo an enzymatic reaction cascade resulting in cellular apoptosis. All these result in a well-circumscribed fibrotic lesion. Whether these two processes induce the same kind and degree of inflammation remains unclear. In the present study by Malmborg et al. C-reactive protein (CRP) levels 24 h after ablation were comparable in both ablation forms. However, in the previous comparison between cryoballoon and irrigated-tip RF, CRP levels tended to be higher 48 h after RF.5 Inflammatory markers have finally been shown to keep on increasing beyond 48 h after ablation, a time horizon not explored by any of the published studies. Lastly, Malmborg et al. also attempt a comparison of lesion sizes through troponin I levels 6 and 24 h after ablation. In their study, troponin I levels were significantly higher after cryoballoon ablation than after PVAC. Previous studies comparing cryoballoon and irrigated-tip RF yielded completely different results: troponin levels have been reported to be either higher after RF,8 or similar with both techniques5 or even greater after cryoballoon.9 Lesion size assessment using 2–4 blood measurements of troponin levels harbours the clear limitation of displaying a continuous evolution using discrete samples at predefined time points. Moreover, the temporal evolution of myocardial necrosis markers after RF and cryoablation is expected to be different, maybe even bimodal for cryoenergy, making a comparison at discrete time points even more inaccurate. The real peak of troponin after either technique might be missed. Myocardial damage seems to be imperatively associated with a certain degree of platelet activation, endothelial disruption, and inflammatory response, no matter which energy is used to produce it. Notwithstanding, the amount of destructed myocardium and the size of the originated lesions have a great impact on the efficacy of AF ablation.10 Collateral damage is regrettably a hazard that we are not close to get rid of, but that we should strive to minimize. Conflict of interest: C.H.S. has received speaker fees from Biosense Webster and consulting fees from Endosense.