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............................................................................................................................................................................. population with HF, and HFrEF is less prevalent among individuals aged 70 years or older. The prognosis of HF varies according to the defined population. In contemporary clinical trials of HFrEF, 1-year mortality rates of 6% are seen, whereas in large registry-based surveys, 1-year mortality rates exceed 20% in patients recently hospitalized for HF, but are closer to 6% in those recruited with stable outpatient HF.243 The concept of CRT is based on the fact that in patients with HF and LV systolic dysfunction, high-grade intraventricular conduction delays are frequently observed, with a prevalence of QRS duration >120 ms in 2550% of patients and of LBBB in 1527% of cases. Moreover, in such patients, AV dyssynchrony is also often present with prolonged PR on the surface ECG in up to 52% of cases.244246 These electrical abnormalities may result in AV, interventricular, and intra-LV mechanical dyssynchrony.247,248

Recommendations for CRT are based on the results of the major RCTs of CRT, most of which have been restricted to the 60% of HFrEF patients who are in SR. CRT is recommended (in addition to guideline-directed medical therapy) in only defined subsets of the HF patient population, the majority being symptomatic HF patients in SR with a reduced LVEF and a QRS duration >_130 ms. Other smaller groups that may be considered for CRT include New York Heart Association (NYHA) class III or IV HF patients in AF with a reduced LVEF and a QRS duration >_130 ms, provided a strategy to ensure biventricular capture is in place or the patient is expected to return to SR, and occasionally as an upgrade from a conventional pacemaker or an ICD in HFrEF patients who develop worsening HF with a high rate of ventricular pacing. A recent survey in the USA, which derived a nationally representative estimate of the entire US population of hospitalized patients, found that over a 10-year period (20032012), there were an estimated 378 247 CRT-D implantations, representing 40 000 per year, or roughly 135 per million per year.249 In Europe, previous estimates have reported that 400 patients per million population per year might be suitable for CRT. This was based on an estimated prevalence of 35% for LVEF <_35% in a representative HF population, of which 41% of patients were estimated to have a QRS duration >_120 ms. The change to a higher threshold of QRS duration of 130 ms will reduce these estimates modestly.250,251 In Sweden, a recent survey of 12 807 HFrEF patients showed that 7% had received CRT and 69% had no indication for CRT, but 24% had an indication and had not received CRT. These data highlight the underuse of CRT.252,253 Finally, the Task Force stresses the point that the decision to implant CRT requires a shared decision-making with the patient.

6.2 Indication for cardiac

resynchronization therapy: patients in sinus rhythm CRT improves cardiac function, symptoms, and well-being, and reduces morbidity and mortality in an appropriately selected group of HF patients. CRT also improves quality-adjusted life-years among patients with moderate to severe HF. The beneficial effects of CRT have been extensively proven in patients with NYHA class II, III, and IV.37,39,40,254266 In contrast, there is rather limited evidence of CRT benefit in patients with NYHA functional class I and ischaemic cardiomyopathy.40,265 In the Multicenter Automatic Defibrillator Implantation with Cardiac Resynchronization Therapy (MADIT- CRT) study,265 a total of 265 (7.8%) of 1820 patients were class I and had an ischaemic cardiomyopathy. At 7-year follow-up, the subgroup of patients with LBBB, NYHA functional class I, and ischaemic cardiomyopathy showed a non-significant trend towards lower risk of death from any cause [relative risk 0.66, 95% confidence interval (CI) 0.301.42; P = 0.29]. Therefore, present CRT recommendations are applicable to all patients in NYHA functional class IIIV of any aetiology.

The MUltisite STimulation In Cardiomyopathies (MUSTIC),256,257 Multicenter Insync RAndomized Clinical Evaluation (MIRACLE), PAcing THerapies in Congestive Heart Failure (PATH-CHF) I and II,58,254,255,259 COmparison of Medical therapy, PAcing aNd defibrillatION (COMPANION),260 and CArdiac REsynchronization in Heart Failure (CARE-HF)39,261 trials compared the effect of CRT vs. guideline-directed medical therapy in NYHA functional class III or IV; in contrast, most recent trials have compared CRT-D with ICD on top of best medical therapy in NYHA functional class II.37,40,262266 Few studies have compared CRT-pacemaker (CRT-P) with conventional pacing.190,267,268 Most studies of CRT have specified that LVEF should be <_35%, but MADIT-CRT40 and the Resynchronization Defibrillation for Ambulatory Heart Failure Trial (RAFT)37 considered an LVEF <_30%, and the REsynchronization reVErses Remodelling in Systolic left vEntricular dysfunction (REVERSE) trial262 specified <_40%. Relatively few patients with an LVEF of 3540% have been randomized, but an individual participant data meta-analysis suggests no diminution of the effect of CRT in this group.33 Not all patients respond favourably to CRT. Several characteristics predict reduction in ventricular volume (reverse remodelling) and improvement in morbidity and mortality. QRS width predicts CRT response and was the inclusion criterion in all randomized trials (for ECG criteria for LBBB and RBBB, see Supplementary Table 1). QRS morphology has been related to a beneficial response to CRT. Several studies have shown that patients with LBBB morphology are more likely to respond favourably, whereas there is less certainty about patients with non-LBBB morphology. Sipahi et al.269,270 performed a meta-analysis in which they examined 33 clinical trials investigating the effect of QRS morphology on CRT, but only four (COMPANION, CARE-HF, MADIT-CRT, and RAFT) included outcomes according to QRS morphology. When they evaluated the effect of CRT on composite adverse clinical events in 3349 patients with LBBB at baseline, they observed a 36% reduction in risk with the use of CRT (relative risk 0.64, 95% CI 0.520.77; P < 0.00001). However, such benefit was not observed in patients with non-LBBB conduction abnormalities (relative risk 0.97, 95% CI 0.821.15; P < 0.75). When the analysis was limited to trials without ICD (CARE-HF and COMPANION), the benefit of CRT was still observed only in patients with LBBB (P < 0.000001). In a meta-analysis excluding COMPANION and MADIT-CRT, LBBB was not found to be a predictor of mortality, in contrast to QRS duration.266 In a recent large meta-analysis of five RCTs (COMPANION, CARE-HF, MADIT-CRT, RAFT, and REVERSE) including 6523 participants (1766 with non- LBBB QRS morphology), CRT was not associated with a reduction in death and/or HF hospitalization in patients with non-LBBB QRS morphology (HR 0.99, 95% CI 0.82- 1.2).271 As patients have been aggregated in the non-LBBB category in nearly all studies and post-hoc analyses on the beneficial effect of QRS morphology in CRT, it is not possible to provide a separate recommendation for CRT in patients presenting with diffuse intraventricular conduction disturbance and Downloaded from academic.oup.com/eurheartj/article/42/35/3427/6358547 by guest on 07 October 2026