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............................................................................................................................................................................. 6.3 Patients in atrial fibrillation This section considers indications for CRT in patients with permanent AF or persistent AF unsuitable for AF ablation or after unsuccessful AF ablation. AF ablation has been reported to improve LVEF and reduce the HF hospitalization rate in selected patients. In particular, AF ablation is recommended for reversing LV dysfunction in AF patients when tachycardia-induced cardiomyopathy is highly probable, regardless of symptoms.296 Therefore, CRT should be considered in those patients with persistent AF and HFrEF when AF ablation cannot be performed or is declined by the patient. With regard to indications for rate control therapy and in particular to AVJ ablation, refer to the ESC Guidelines for the management of AF.296

6.3.1 Patients with atrial fibrillation and heart failure who are candidates for cardiac resynchronization therapy A major determinant of the success of CRT is the effective delivery of biventricular pacing. A particular aspect of AF patients is that AF rhythm with fast ventricular rate and irregularity may interfere with adequate biventricular pacing delivery. AF may reduce the rate of effective biventricular capture by creating spontaneous, fusion, or pseudo-fusion beats. A high rate of biventricular pacing is not reached in two-thirds of patients with persistent or permanent AF.297 Data from large registries show that AF patients undergoing CRT have an increased risk of mortality even after adjusting for several clinical variables.297299 In most AF patients with intact AV conduction, an adequate biventricular pacing delivery can be achieved only by means of AVJ ablation.300302 A substudy of the RAFT trial300 was unable to show benefit of CRT without AVJ ablation with regard to the combined endpoint of death or hospitalization for HF; notably, only 47% of the patients had a biventricular capture >90%. The decision to perform AVJ ablation is still a matter of debate, but most studies have shown improvements in LV function, functional capacity, exercise capacity, and survival (with the same magnitude as in patients with SR).301 Gasparini et al.302 compared total mortality of 443 AF patients who received AVJ ablation (n = 443) and of 895 AF patients who received rate-slowing drugs with the mortality of 6046 patients who were in SR. The long-term survival after CRT among patients with AF and AVJ ablation was similar to that observed among patients in SR (HR 0.93); the mortality was higher for AF patients treated with rate-slowing drugs (HR 1.52). The most common ratecontrolling drugs used in AF are beta-blockers; although safe even in the context of AF and HFrEF, they do not necessarily have the same benefit as in patients with SR303 and the benefitrisk ratio is influenced by other cardiovascular comorbidities.304,305 In a systematic review and meta-analysis,306 AVJ ablation, compared with no AVJ ablation, reduced mortality by 37% and reduced the rate of nonresponse by 59% in patients with biventricular pacing <90%, but showed no benefit in those with >_90% biventricular pacing. Similarly, Tolosana et al. observed the same rate of responders (defined as >_10% decrease in end-systolic volume) in AF patients who received AVJ ablation or rate-slowing drugs and patients in SR who had adequate biventricular pacing (97, 94, and 97%, respectively).307 Importantly, AVJ ablation did not improve survival for patients in AF treated with CRT compared with those treated with rate-slowing drugs when an adequate biventricular pacing was achieved either with ablation (97%) or with drugs (94%).308 In conclusion, despite the weak evidence due to lack of large, randomized trials, the prevailing opinion of experts is in favour of the usefulness of CRT in patients with permanent AF and NYHA class III and IV with the same indications as for patients in SR, provided that AVJ ablation is added in those patients with incomplete (<90 - 95%) biventricular capture due to AF (Figure 9). However, there are other causes for incomplete biventricular pacing such as frequent premature ventricular beats, which may need to be treated (with drugs or ablation) before considering AVJ ablation. Importantly, evaluation of the biventricular pacing percentage is mainly given by the percentage of biventricular pacing using device memory, which does not reflect exactly the rate of effective biventricular capture. Holter monitoring may help to assess the real biventricular capture percentage.309,310 A new algorithm has been developed that can continuously assess the effective biventricular pacing.311

For patients with permanent AF, there are no data supporting the difference in the magnitude of response to CRT according to the QRS morphology or a QRS duration cut-off of 150 ms. It is important to remember that limited data are available for patients in NYHA class II.

6.3.2 Patients with uncontrolled heart rate who are candidates for atrioventricular junction ablation (irrespective of QRS duration) AVJ ablation should be considered to control heart rate in patients unresponsive or intolerant to intensive rate and rhythm control therapy, or who are ineligible for AF ablation, accepting that these patients will become pacemaker dependent.296 In particular, AVJ ablation combined with CRT may be preferred to AF ablation in severely symptomatic patients with permanent AF and at least one hospitalization for HF.296 AVJ ablation and permanent pacing from the RV apex provides highly efficient rate control and regularization of the ventricular response in AF, and improves symptoms in selected patients.192 A large study with a propensity score-matched control group194 showed a 53% reduction in total mortality in patients who underwent AVJ ablation compared with those treated with pharmacological rate control therapy. A class IIa indication is provided in the 2020 ESC Guidelines on AF.296 The downside of RV pacing, however, is that it induces LV dyssynchrony in 50% of patients,312 and that this may lead to worsening of HF symptoms in a minority. In the majority of patients, AVJ ablation improves LVEF even with RV apical (RVA) pacing due to amelioration of tachycardia-induced LV dysfunction, which commonly exists in these patients. CRT may prevent RV pacing-induced LV dyssynchrony. The multicentre, randomized, prospective Ablate and Pace in Atrial Fibrillation (APAF) trial313 included 186 patients in whom a CRT or RV pacing device was implanted, followed by AVJ ablation. During a median follow-up of 20 months, CRT significantly reduced by 63% the primary composite endpoint of death due to HF, hospitalization due to HF, or worsening of HF. The beneficial effects of CRT were similar in patients with an EF <_35%, NYHA class >_III, and QRS width >_120 ms, and in other patients with EF>35% or NYHA class < III or narrow QRS. Compared with the RV pacing group, responders increased from 63% to 83% (P 1⁄4 0.003).314 A meta-analysis of 696 patients from five trials showed a 62% reduction in Downloaded from academic.oup.com/eurheartj/article/42/35/3427/6358547 by guest on 07 October 2026