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.......................................................................................................................................................................... Patients with Chronic Heart Failure (RESET-CRT; ClinicalTrials.gov Identifier NCT03494933).

In conclusion, prospective randomized trials are lacking, and available data are insufficient to firmly prove a superiority of CRT-D over CRT-P. However, it is important to consider that CRT trials in mild HF almost exclusively included patients with an ICD,37,40,262 and that survival benefit of CRT without an ICD is uncertain in this particular group. Furthermore, observational data point towards significant survival benefits by CRT-D over CRT-P in patients with ischaemic cardiomyopathy, while no clear benefit has been shown in those with non-ischaemic cardiomyopathy. Further predictive power concerning the risk of ventricular arrhythmia may be derived by contrast-enhanced CMR-guided scar characterization.379,380 When discussing the choice between CRT-D and CRT-P, it is particularly important to consider general predictors of ICD effectiveness such as age and comorbidities associated with a mortality risk that competes with sudden arrhythmic death. Thus, the addition of ICD to CRT should be considered, especially in younger patients with a good survival prognosis, ischaemic aetiology, and a favourable comorbidity profile or presence of myocardial fibrosis (Figure 10). Moreover, the benefit of the ICD is governed by the balance between the risk of SCD and the risk of death from other causes, as well as comorbidities. Generally, the rate of sudden arrhythmic death in primary prevention appears to be declining (1%/ year). Owing to the complexity of the matter and the lack of clear evidence, it is particularly important that the choice between CRT-P and CRT-D is guided by a process of shared decision-making between patients and clinicians, taking into account both medical facts and patient values.

6.7 Factors influencing the efficacy of

cardiac resynchronization therapy: role of imaging techniques The role of cardiac imaging in selecting HF patients for CRT has been evaluated mostly in observational analyses. Cardiac dyssynchrony,384386 myocardial scar,387,388 and site of latest activation of the LV in relation to the LV lead position389,390 have been associated with response to CRT. LVEF is the only parameter included in the guidelines for the selection of patients for CRT and is key to define the type of HF (<40%, HFrEF; 4049%, HFmrEF; and >_50%, HFpEF).242 Echocardiography is the imaging technique of first choice for the assessment of LVEF. However, when intravenous contrast is not available and the acoustic window does not allow accurate assessment of LVEF, CMR or nuclear imaging should be considered.242 Strain imaging (based on echocardiography or CMR) to quantify LV systolic function has shown incremental prognostic value in HF, and allows assessment of LV mechanical dyssynchrony.384,391393 CMR with LGE techniques (which show the presence of myocardial scar tissue) provide the best resolution to differentiate ischaemic cardiomyopathy and non-ischaemic cardiomyopathy.394 The location (posterolateral) and extent (transmural vs. non-transmural and percentage of LV mass) of LGE on CMR or with nuclear techniques has been associated with the benefit from CRT.380,387,395,396 Severe mitral regurgitation,397 lack of significant electromechanical LV dyssynchrony,384,385,392 and RV systolic dysfunction398 have been associated with less improvement in clinical symptoms and reduced survival after CRT. Several imaging techniques have been tested to assess LV mechanical dyssynchrony, but most measures of LV dyssynchrony have not been tested in randomized trials including patients with HFrEF and wide QRS.399 The presence of septal flash and apical rocking,400 time differences based on radial strain and patterns of regional longitudinal strain,384,392,401403

non-invasive and invasive ECG mapping,385,404 and vector-cardiography405 have been proposed as novel techniques to predict response to CRT. Furthermore, LV myocardial work assessed with speckletracking echocardiography has been associated with survival in CRT recipients.406 Coronary sinus venography is commonly performed to detect a suitable coronary vein in which to deploy an LV lead. Randomized trials have not systematically demonstrated that the guidance of LV lead implantation based on imaging (assessing myocardial scar or site of latest activation) is superior to standard practice.389,390,407,408 Initial experience on using artificial intelligence to combine clinical, electrical, and imaging parameters to define phenotypes of patients that will benefit from CRT is promising, but more data are needed.409 Significant (moderate to severe and severe) secondary mitral regurgitation is frequent among candidates for CRT and has been shown to affect long-term survival as well as response to therapy.406,410 CRT can improve mitral regurgitation in as many as 40% of patients.406 However, in 60% of patients, significant mitral regurgitation is not corrected and, at long-term follow-up, progression of the underlying disease may lead to further deterioration of mitral valve function and poor prognosis. Transcatheter edge-to-edge mitral valve repair has been demonstrated to improve the response to CRT in registries.411414 However, results from recent RCTs including patients with symptomatic severe secondary mitral regurgitation despite guideline-directed medical therapy (including CRT when indicated) have not consistently shown a benefit from transcatheter edge-to-edge mitral valve repair.415,416 Therefore, selection of patients for CRT based on imaging is limited to the measurement of LVEF, whereas the assessment of other factors such as extent of myocardial scar, presence of mitral

Recommendations for adding a defibrillator with cardiac resynchronization therapy

Recommendations Classa Levelb

In patients who are candidates for an ICD and who have CRT indication, implantation of a CRT-D is recommended.260,369,370,381 I A In patients who are candidates for CRT, implantation of a CRT-D should be considered after individual risk assessment and using shared decision-making.382,383 IIa B

CRT = cardiac resynchronization therapy; CRT-D = defibrillator with cardiac resynchronization therapy; ICD = implantable cardioverter-defibrillator. aClass of recommendation. bLevel of evidence. ESC 2021 Downloaded from academic.oup.com/eurheartj/article/42/35/3427/6358547 by guest on 07 October 2026