Atrial arrhythmias after cardiac resynchronization therapy: an inverse correlation with achieving 100% biventricular pacing and cardiac resynchronization therapy effectiveness

Cardiac resynchronization therapy (CRT) is an important device-based, non-pharmacological approach that has been shown to improve outcome in selected patients with chronic heart failure. 1 Large randomized trials have demonstrated that CRT improves left ventricular function and reduces morbidity and mortality. 2 Until recently, CRT has been indicated in patients with advanced heart failure, reduced left ventricular systolic function, evidence of electrical dyssynchrony, who receive optimal medical therapy and are in sinus rhythm (SR). 3 According to recent ESC recommendations, 4 patients with concomitant atrial fibrillation (AF), who constitute an important subgroup of patients treated with CRT for heart failure, have been considered as eligible to receive CRT, provided that the effects of the underlying arrhythmia are eliminated by atrio-ventricular junction (AVJ) ablation. The incidence of AF in patients with heart failure treated with CRT ranges from 20–25% for permanent AF to 35–40% for paroxysmal AF. 5 The AHA/ACC/HRS Guidelines 6 also support the use of CRT in patients with heart failure and AF, but do not emphasize the need for adequate rate control, although it has been demonstrated that suboptimal rate control could reduce the percentage of effective biventricular (BIV) pacing. 7 However, it is well known that a high burden of AF or atrial tachyarrhythmias (AT) may reduce the percentage of effective BIV pacing, thus reducing the efficacy of CRT. 7 The concepts of AF/AT burden and the percentage of effective BIV pacing are important in order to adequately evaluate the value of determining the AF/AT burden after CRT implantation and to select the best therapeutic strategy (drugs, device programming, or AVJ ablation) to overcome this problem. Leclercq et al . 8 demonstrated the importance of assessment of AF/AT burden in patients with SR implanted with a CRT device. Utilizing CRT device diagnostics, the authors were able to determine AF/AT burden during the first months after CRT. Using a simple clinical endpoint (improvement in NYHA class and hospitalizations), the authors have demonstrated that the efficacy of CRT was inversely related to the incidence of AF/AT during follow-up. The lessons learned from this multicentre study are that the incidence of AF/AT is not insignificant in this subset of patients and that non-responders to CRT have a significantly higher incidence of AF/AT compared with responders. As usual, at that point, a sort of ‘the chicken or the egg’ dilemma appears: what is the real primum movens ? Does the poor response to CRT directly relate to the AF/AT burden (that consequently reduces effective BIV pacing), or is AF/AT burden just a marker of more compromised dilated cardiomyopathy, less prone to respond to CRT? Given that baseline characteristics are comparable between patients with and without AF/AT, the paper supports the concept that AF/AT burden determines the high percentage of spontaneous ventricular rhythm and, therefore, significantly reduces the percentage of BIV pacing; the ultimate effect is a reduction of the therapeutic effect of CRT. The first paper which highlighted the importance of achieving 100% BIV pacing was published by our group in 2006. 7 We demonstrated that the percentage of BIV pacing as high as 88% (considered at that time ‘adequate’) in AF patients treated with negative chronotropic drugs did not result in the same effects on left ventricular reverse remodelling and functional capacity that were observed in AF patients treated with CRT and AVJ ablation. In the latter subset of patients (with 100% BIV pacing), the degree of reverse remodelling and improvement in functional capacity were significantly greater. This concept was reinforced by another multicentre study in nearly 1300 patients which demonstrated that AF patients undergoing CRT and treated with negative chronotropic drugs had significantly higher total and cardiac mortality rates compared with AF patients who had AVJ ablation. 5 These observations have recently been confirmed in a cohort of over 30 000 patients who participated in the US Latitude programme and in whom a decrease in the percentage of BIV pacing <92%, irrespective of the baseline rhythm, was associated with a significant increase in overall and cardiac mortality. 9 Similar results have recently been published by Koplan et al . 10 who reported increased 1-year cardiac and total mortality in 1800 patients with SR and the percentage of BIV pacing <92% compared with patients in whom 100% BIV capture was achieved. Among patients with the BIV percentage <92%, mortality rates were higher in patients who developed AF/AT during follow-up compared with those without atrial arrhythmias (due to a significant reduction in BIV pacing in the subset of patients with AT/AF). Leclercq et al.8 demonstrated a higher incidence of AF/AT in patients did not respond to CRT as defined by improvement in NYHA functional class. However, because of a small number of patients and a short follow-up period of 6 months, no correlation between AF/AT burden and ‘stronger’ endpoints, such as the degree of reverse remodelling or mortality rates, could be demonstrated. Nonetheless, this work is important because it emphasizes the usefulness of accurate evaluation of AT/AF burden, especially during the first months after CRT implant. Presently, different remote monitoring systems allow the accurate evaluation of the incidence of AF/AT burden and BIV pacing percentage. These two aspects are extremely important in determining the effectiveness of CRT and even more so for initiating or modifying pharmacological therapies. Remote monitoring may be useful for evaluating the day by day efficacy of different therapeutic schemes aimed at reducing AF/AT burden and, consequently, at increasing the percentage of BIV pacing. However, it should be acknowledged that in patients with heart failure the only available pharmacological therapy for rate or rhythm control in AF/AT is amiodarone, usually in combination with beta-blockers and/or digoxin. If this combination fails to achieve adequate rate control and the recommended percentage of BIV pacing, AVJ ablation should be considered. In fact, this is the only strategy that has been demonstrated to be effective in ensuring the target of 100% BIV pacing. The last point that needs to be made on the paper by Leclercq et al. concerns the choice of CRT-P device. This is a major limitation of this paper, a kind of ‘lost opportunity,’ particularly in light of AF/AT and the effectiveness of CRT. It is well known that the importance of AF/AT in determining inappropriate shocks in patients implanted with CRT-D devices, and how these inappropriate shocks may decrease the quality of life and outcome in these patients. 11 These data would have added a further value to this study. In conclusion, the relevant ‘take home’ message of the paper by Leclerq et al . 8 is that the burden of AF and other AT, if not appropriately managed, may have an important negative impact on the clinical benefit conferred by CRT in patients with heart failure. Monitoring of AF/AT is mandatory to precisely define AT/AF burden and, therefore, to articulate tailored therapeutic strategies. Remote monitoring could become important in evaluating AF/AT burden and the percentage of BIV pacing. More studies are necessary to further support recourse to more aggressive therapy and eventually better establish the role of AVJ ablation or modification in this clinical setting. Conflict of interest: none declared.