Antitachycardia pacing for termination of ventricular tachyarrhythmias: should we use it?

This editorial refers to ‘Clinical course and prognostic relevance of antitachycardia pacing-terminated ventricular tachyarrhythmias in implantable cardioverter-defibrillator patients’ by T. Kleemann et al., on page 1068–1075. The first implantable cardioverter-defibrillator (ICD) device was developed by Drs Michel Mirowski and Morty Mower, and successfully implanted in a human being at John Hopkins Hospital in February 1980.1 The device only had the capability of defibrillation, required thoracotomy, and due to the size and weight of the device (225 g), the battery had to be implanted abdominally. Since then, major advances in the design, implantation technique, and capabilities of the device have been implemented, including transvenous lead implantation, subcutaneous device placement, and the addition of overdrive pacing, also known as antitachycardia pacing (ATP), for termination of ventricular tachycardia.2 Today, through numerous randomized trials, the survival benefit of both primary and secondary prevention ICD implantation has irrevocably been established.3,4 However, even though the device provides a clear survival benefit, there is evidence that unnecessary ICD therapy might contribute to increased mortality and morbidity.5–8 For appropriate ICD therapy, this is mainly due to the deleterious effects of the malignant rhythm on the myocardium, but some studies also suggest that the shock itself, may contribute to myocardial damage and hence worse prognosis irrespective of the underlying rhythm.7,8 Furthermore, from a patient perspective, there are psychological issues as well as evidence of reduced quality-of-life in relation to ICD shocks that need to be taken into account.9,10 Therefore, it is imperative that the number of ICD shocks is kept at a minimum. In this context, ATP therapy provides a valuable component. Antitachycardia pacing was originally incorporated into the device as a tool for treating haemodynamically stable, slower rate ventricular tachyarrhythmias (VTAs) without adding discomfort to the patient. The effectiveness of ATP in successfully terminating slower rate VTAs has been widely substantiated, with reported success rates up to 96%.2,11 The PAIN-FREE (Pacing Fast Ventricular Tachycardia Reduces Shock Therapies) trial further demonstrated an 89% effectiveness of ATP in terminating fast VTAs with rates up to 250 b.p.m. and thereby reducing the risk of shock delivery.11 Therefore, ATP is most often programmed as first-line therapy, especially for ventricular tachycardia.12 However, whether ATP therapy also has an adverse effect on the myocardium and outcome remains controversial. In this issue of the Journal, Kleemann et al.13 report an impressive and elegantly performed study, evaluating the prognostic significance of ATP-terminated VTA episodes in a single-centre cohort of 1398 consecutively included primary and secondary prevention ICD patients. Patients received ICD in 1992–2008 and followed for a median of 6 years. Ventricular tachyarrhythmia episodes treated by ICD occurred in 54% of all patients, of which 74% were successfully terminated by ATP and 26% by an ICD shock. The authors found that both shock-terminated and ATP-terminated VTA episodes were associated with significantly increased mortality risk compared with no ICD therapy. The authors should be complimented on organizing the study, with a large number of patients, long follow-up with 17 827 adjudicated VTA episodes, and only 4% of patients lost to follow-up. However, with an inclusion period stretching from 1992 to 2008, different programming strategies over time and advances in both rhythm detection software of the devices and pharmacological treatment are a significant challenge and may have affected the results. It is interesting that according to Kaplan–Meier survival analysis, appropriate shocks were associated with a higher mortality risk than appropriate ATP. However, the authors do not provide an adjusted relative risk that makes it difficult to assess the reliability of these results. One explanation for higher risk in the ICD shock group could be that ATP was more often reserved for slower rate rhythms than ICD shocks,8 and thus the difference in risk merely represents a surrogate marker for a more compromised myocardial substrate in patients who receive ICD shocks, as opposed to those who received ATP only. Another explanation could be that ICD shocks in the presence of already vulnerable myocardium further compromises the myocardium and thereby increases risk of death. There are several issues the paper does not provide information on, which could have potential interest. In the aftermath of MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial to Reduce Inappropriate Therapy)5 and ADVANCE-III (Avoid DeliVering TherApies for Non-sustained Arrhythmias in ICD PatiEnts),14 one must assume that currently, clinicians are more ‘conservative’ in the programming of the therapy zones, with a detection threshold of ∼190–200 b.p.m. as well as a longer detection time before therapy. The study by Kleemann et al. does not include ATP for rhythms >200 b.p.m. The current clinical applicability of the results is thereby somewhat limited, as they cannot be extrapolated to higher rate VTAs. Inappropriate ICD therapies were not systematically adjudicated, and therefore the authors did not include this variable in analysis. This lack of information is disappointing, as it could have served several purposes. First, inappropriate therapies most often occur because of atrial arrhythmias, which have been associated with increased mortality, and could potentially have affected the results. Secondly, the impact of inappropriate ATP on mortality could have shown whether the increased risk associated with appropriate ATP was due to the effect of the malignant rhythm or if the ATP itself actively contributed to the increased mortality. Likewise, information regarding monitored VTA episodes could have shed some light on this. The authors did not provide much discussion regarding the reason for increased mortality risk associated with appropriate ATP. They do state, however, that it is not likely that ATP causes myocardial deterioration. Even though a cause-and-effect relationship is difficult to prove, it would have been interesting to carry out analysis on inappropriate ATP and monitored VTAs in order to better understand the relationship between ATP and mortality. As the authors point out, it is perplexing why this study has found an association between appropriate ATP and increased mortality, when so many other studies have failed to show this.6–8,11 However, longer follow-up and differences in patient selection, with 75% secondary prevention ICD implantations may explain this discrepancy. Our group have not been able to establish an association between appropriate ATP and increased mortality in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial—Cardiac Resynchronization Therapy)8 or MADIT-RIT6 trial. However, inappropriate ATP has been shown to be associated with increased mortality even when appropriate ATP was not, suggesting that ATP does not actively contribute to increased mortality.6,8 However, there is a small possibility that repeated unsuccessful inappropriate ATP in an otherwise compromised myocardium may cause further myocardial damage adding to the increased mortality risk. The results of this study emphasize the importance of conservative programming of the devices with therapy detection starting at minimum 200 b.p.m., possibly also with longer detection time, as shown to be effective in MADIT-RIT and ADVANCE-III. In view of the adverse prognosis of VTA even when treated with ATP, aggressive treatment of heart failure, systolic dysfunction, and ischaemia with appropriate measures (medications, revascularization, resynchronization pacing, and/or ablation) in an effort to reduce the chance of first or recurrent VTA seems logical. Previous studies have confirmed a significant and clinically relevant effect of ATP for termination of ventricular rhythms >200 b.p.m.11 Therefore, programming of ATP still has a substantial role in diminishing the number of shocks. Conflict of interest: A.-C.R. has received minor research grant from Biotronic (<10 000 USD) and travel support from Medtronic (<10 000 USD). J.P.D. has received research grants to Duke University from Biosense-Webster, Medtronic, Boston Scientific, and Gilead (all are >10 000 USD), has received honoraria for lectures, advisory board, or consultation from ARCA Biopharma, Biosense-Webster, Biotronik, Boston Scientific, Cardiofocus, Gilead, Medtronic, Orexigen, St Jude, and Vytronus (all are <10 000 USD), and has received fellowship support to Duke University provided by Biosense-Webster, Boston Scientific Medtronic, and St Jude (all are >10 000 USD).