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...................................................................................................................... undergoing AVJ ablation.198,199,316318 Non-conventional CRT using HBP coronary sinus pacing (so-called ‘His-optimized CRT’) or left bundle branch area pacing, in comparison with conventional CRT, can achieve a narrower QRS with a ‘quasi-normal’ axis morphology, echocardiographic improvement of mechanical resynchronization indexes, and a better short-term clinical outcome.319321 In general, the potential benefit of HBP depends on the ability to achieve a narrow QRS complex that is similar to the native QRS complex, rather than on the LVEF. Widespread adoption of this technique relies upon further validation of its efficacy in large RCTs and improvements in lead design, delivery tools, and devices (see section 7).

6.4 Patients with conventional

pacemaker or implantable cardioverter defibrillator who need upgrade to cardiac resynchronization therapy Several studies have demonstrated the deleterious effect of chronic RV pacing with respect to an increased risk of HF symptoms or hospitalizations, which may be reduced by programming to maximize intrinsic conduction or prevented by CRT.148,183,190,324 Previously, the benefit of CRT upgrade had been investigated only by observational controlled trials and registries,325339 mainly comparing upgrade with de novo CRT; in early, small, observational pre- vs. post-CRT studies;340346 and in crossover trials,347350 providing only limited clinical outcome data.

Based on a recent meta-analysis of observational studies, mostly single-centre,351 echocardiographic and functional response as well as the risk of mortality or HF events was similar in patients after de novo vs. upgrade CRT; however, in previous subgroup analyses from large, randomized, prospective trials such as RAFT,37 morbidity or mortality benefit was not confirmed. Clinical outcomes are also influenced by the clinical characteristics of patients referred to CRT upgrade. Based on data from the European CRT Survey II,352 a high-volume registry, and clinical characteristics from previous studies,351 patients referred for a CRT upgrade differ from patients referred for de novo CRT implantation: they are older (even compared with those in RCTs), mainly male patients, and have more comorbidities such as AF, ischaemic heart disease, anaemia, and renal failure. On average, the number of upgrade procedures reaches 23% of total CRT implantations, 60% from a conventional device and 40% from an ICD352 in ESC countries, showing significant regional differences regarding the type of implanted device, such as CRT-P or CRT-D.352,353 Regarding procedure-related complications, several studies described a higher burden during upgrade procedures, ranging from 6.8% to 20.9% compared with de novo implantations.339,354 This was not confirmed in a recent analysis of registry data, where upgrades had similar complication rates to de novo implantations.352 Notably, 82% of these procedures were performed in high-volume centres. However, data on the long-term infection rates or lead revisions after CRT upgrade are scarce.354,355 The first prospective, randomized trial, the BUDAPEST CRT Upgrade study, is still ongoing, but may clarify these questions.356

Recommendations for cardiac resynchronization therapy in patients with persistent or permanent atrial fibrillation

Recommendations Classa Levelb

1) In patients with HF with permanent AF who are candidates for CRT: 1A) CRT should be considered for patients with HF and LVEF <_35% in NYHA class III or IV despite OMT if they are in AF and have intrinsic QRS >_130 ms, provided a strategy to ensure biventricular capture is in place, in order to improve symptoms and reduce morbidity and mortality.302,306,307,322 IIa C 1B) AVJ ablation should be added in the case of incomplete biventricular pacing (<9095%) due to conducted AF.297302 IIa B 2) In patients with symptomatic AF and an uncontrolled heart rate who are candidates for AVJ ablation (irrespective of QRS duration): 2A) CRT is recommended in patients with HFrEF.196,197,306,308 I B 2B) CRT rather than standard RV pacing should be considered in patients with HFmrEF. IIa C 2C) RV pacing should be considered in patients with HFpEF.188,196,323 IIa B 2D) CRT may be considered in patients with HFpEF. IIb C

AF = atrial fibrillation; AVJ = atrioventricular junction; CRT = cardiac resynchronization therapy; EF = ejection fraction; HF = heart failure; HFrEF = heart failure with reduced ejection fraction (<40%); HFmrEF = heart failure with mildly reduced ejection fraction (40- 49%); HFpEF = heart failure with preserved ejection fraction (>_50%) according to the 2021 ESC HF Guidelines;242 LVEF = left ventricular ejection fraction; NYHA = New York Heart Association; RV = right ventricular. aClass of recommendation. bLevel of evidence. Recommendation for upgrade from right ventricular pacing to cardiac resynchronization therapy

Recommendation Classa Levelb

Patients who have received a conventional pacemaker or an ICD and who subsequently develop symptomatic HF with LVEF <_35% despite OMT, and who have a significantc proportion of RV pacing, should be considered for upgrade to CRT.37,148,185,190,324352 IIa B

CRT = cardiac resynchronization therapy; HF = heart failure; ICD = implantable cardioverter-defibrillator; LVEF = left ventricular ejection fraction; OMT = optimal medical therapy; RV = right ventricular. aClass of recommendation. bLevel of evidence. cA limit of 20% RV pacing for considering interventions for pacing-induced HF is supported by observational data. However, there are no data to support that any percentage of RV pacing can be considered as defining a true limit below which RV pacing is safe and beyond which RV pacing is harmful. ESC 2021

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