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............................................................................................................................................................................. morphology often have wider QRS durations, and there is a current debate about whether QRS durations or QRS morphology is the main predictor of a beneficial response to CRT. Evidence from two IPD meta-analyses indicates that after accounting for QRS duration, there is little evidence to suggest that QRS morphology or aetiology of disease influence the effect of CRT on morbidity or mortality.211,220 In addition, none of the landmark trials selected patients for inclusion according to QRS morphology, sex, or ischaemic aetiology, nor were they powered for subgroup analyses.

The Echo-CRT trial222,223 and an IPD meta-analysis213 suggest possible harm from CRT when QRS duration is <130 ms, thus implantation of CRT is not recommended if QRS duration is <130 ms. If a patient is scheduled to receive an ICD and is in SR, with a LBBB, CRT-D should be considered if the QRS is between 130 and 149 ms and is recommended if QRS is >_150 ms. However, clinical practice varies widely among countries and if the primary reason for implanting CRT is for the relief of symptoms, then the clinician should choose CRT-P or CRT-D, whichever they consider appropriate. The only randomized trial to compare CRT-P and CRT-D210 did not demonstrate a difference in morbidity or mortality between these technologies (although the trial was not powered to show such a difference). Furthermore, in the DANISH study in patients with NICM where 58% of patients received CRT there was no suggestion from subgroup analysis that CRT-P was inferior to CRT-D.166,167 When LVEF is reduced, RV pacing may exacerbate cardiac dyssynchrony. This can be prevented by CRT, which might improve patient outcomes.216218,231 However, a difference in outcome was not observed between CRT and RV pacing in a subgroup analysis of RAFT.212 On balance, CRT rather than RV pacing is recommended for patients with HFrEF regardless of NYHA class who have an indication for ventricular pacing in order to reduce morbidity, although no clear effect on mortality was observed. Patients with HFrEF who have received a conventional pacemaker or an ICD and subsequently develop worsening HF with a high proportion of RV pacing, despite OMT, should be considered for ‘upgrading’ to CRT. Only two small trials have compared pharmacological therapy alone vs. CRT in patients with AF, with conflicting results. Several studies have indicated that CRT is superior to RV pacing in patients undergoing atrio-ventricular (AV) node ablation.217,218,231 However, AF is not an indication to carry out AV node ablation in patients with CRT except in a few cases when ventricular rate remains persistently high despite attempts at pharmacological rate control. A subgroup analysis of patients with AF from the RAFT study found no benefit from CRT-D compared with ICD, although less than half of patients had >90% biventricular capture.219 In view of the paucity of evidence for the efficacy of CRT in patients with AF, it may be an option in selected patients—particularly those with a QRS >_150 ms—ensuring a proportion of biventricular pacing as high as possible. Observational studies report that when biventricular capture is <98%, the prognosis of patients with CRT declines.218,232 Whether this association reflects a loss of resynchronization (which might be remedied by device programming), poor placement of the LV lead, or greater difficulty in pacing severely diseased myocardium is uncertain. This observation has not been confirmed in any randomized trial. Early studies suggested that imaging tests for dyssynchrony were not of value in selecting patients for CRT.233 However, a recent study has suggested that two novel markers of dyssynchrony (apical rocking and septal flash) are associated with a response to CRT, but these have not been tested as selection criteria or as prespecified subgroups in a randomized trial.234 Patients with extensive myocardial scar will have less improvement in LV function with CRT, but this is true of any treatment for HFrEF and does not reliably predict less clinical benefit. Pacing thresholds are higher in scarred myocardium and, if possible, lead placement should avoid such regions.235,236

Although patients with extensive scarring have an intrinsically worse prognosis, there is little evidence that they obtain less prognostic benefit from CRT.211 The value of trying to optimize AV intervals or interventricular delay intervals (VV intervals) after implantation using echo- or electrocardiographic criteria or BP response is uncertain but may be considered for patients who have had a disappointing response to CRT.237,238 Other options to consider to optimize response to CRT are covered in a recently published practical article.239 Following CRT implantation, a review of diuretic therapy is advised as a reduction in dose or its discontinuation may be required. In addition, CRT implantation may afford an opportunity to further optimize MT for HFrEF.240 The reader is directed to guidelines on pacing and CRT for recommendations on device implantation procedures.240a

6.3 Devices under evaluation

Cardiac contractility modulation (CCM) has been evaluated in patients with NYHA class IIIIV HF, with an LVEF >_25% to <_45% and QRS duration <130 ms, and was associated with a small improvement in exercise tolerance and QOL.241,242 Technologies that involve modification of the activity of the autonomic nervous system, e.g. baroreflex activation therapy,243,244 have also been shown to offer a modest improvement in effort capacity and QOL. However, currently, the evidence is considered insufficient to support specific guideline recommendations for a reduction in mortality or hospitalization for these and a variety of other implantable electrical therapeutic technologies (see also Gaps in Evidence in section 16).

7 Heart failure with mildly

reduced ejection fraction

7.1 The diagnosis of heart failure with

mildly reduced ejection fraction The diagnosis of HFmrEF requires the presence of symptoms and/or signs of HF, and a mildly reduced EF (4149%) The presence of elevated NPs (BNP >_35 pg/mL or NT-proBNP >_125 pg/mL) and other evidence of structural heart disease [e.g. increased left atrial (LA) size, LVH or echocardiographic measures of LV filling] make the diagnosis more likely but are not mandatory for diagnosis if there is certainty regarding the measurement of LVEF. An algorithm for the diagnosis of HFmrEF is depicted in Figure 1. For the investigation of the underlying aetiology, please refer to Table 5 (which refers to investigations regardless of LVEF). Downloaded from academic.oup.com/eurheartj/article/42/36/3599/6358045 by guest on 07 October 2026