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May 3, 2022 Circulation. 2022;145:e895–e1032. DOI: 10.1161/CIR.0000000000001063 e944

CLINICAL STATEMENTS AND GUIDELINES

5.	 The economic value of CRT has been evaluated by 3 RCTs (COMPANION,22 MADIT-CRT,26 and REVERSE23), 2 model-based analyses,25,27 and 1 observational study.24 These analyses consistently found CRT increased survival and QOL in addition to increasing health care costs. However, the economic value of CRT likely varies as a result of the shown variation in treatment effect.26 Among populations with larger expected mortality reduction and improvement in QOL, such as patients with a LBBB with QRS duration >150 ms, the cost per QALY is <$60 000.22,26,27 Among other populations expected to have smaller treatment benefit, the economic value is more uncertain. However, a model-based analysis of patients with NYHA class I to II found the incremental cost-effectiveness ratio remained <$150 000 per QALY with even small reductions in all-cause mortality.27 Therefore, CRT likely provides at least intermediate value for patients with other guideline-indicated recommendations in which CRT is expected to reduce mortality. 6.	 Subgroup analysis of the previously mentioned trials has informed us of the predictors of benefit, including longer QRS duration, and LBBB versus non-LBBB.28 The most benefit was gained with wider QRS durations and with LBBB. This was true in COMPANION, CARE-HF, MADIT-CRT, REVERSE, and RAFT.17,29–32 A QRS duration >150 ms was also a predictor of response, and in those with non-LBBB, a prolonged PR predicted benefit in MADIT-CRT but not in REVERSE.33

7.	 Extension of benefit to those with LVEF between 35% and 50% has been seen. In the BLOCK-HF (Biventricular versus Right Ventricular Pacing in Heart Failure) trial, patients with NYHA class I to III HF, LVEF ≤50%, and atrioventricular block randomized to RV pacing or CRT, there was benefit to CRT in reduction in the primary outcome of death, urgent HF visit, or 15% increase in LV end systolic volume.34 8.	 In the previously mentioned CRT trials, there was some benefit for those with LBBB and QRS durations between 120 and 149, but not as much benefit as those with LBBB ≥150 ms.17,28–32 9.	 Several trials have included patients with AF. In the MUSTIC AF (Multisite Stimulation in Cardiomyopathies),44 RAFT,45 and the SPARE (Spanish Atrial Fibrillation and Resynchronization)46 trials, there were benefits in patients with AF, while in COMPANION,47 AF attenuated the benefit of CRT. In the PAVE (Post AV Nodal Ablation Evaluation) study, patients with NYHA class II to III, mean LVEF of 46%, and AF undergoing atrioventricular node ablation, CRT improved the 6-minute walk test and LVEF compared with those who were RV paced.35 10.	 In patients in whom there is an expected high burden of ventricular pacing, especially if >40%, CRT may be used to reduce mortality, reduce hospitalizations, and improve symptoms and QOL.35,48 11.	 Identification of specific arrhythmogenic genetic variants such as LMNA/C, desmosomal proteins, phospholamban, and Filamin-C carry implications for implantation of ICDs for primary prevention of sudden death even in patients who have LVEF >35%, or <3 months of GDMT. Most patients with LMNA/C cardiomyopathy will progress to cardiac transplantation, sometimes precipitated by refractory arrhythmias more than by pump failure.36–38,49 12.	 Subgroup analysis of the CRT RCTs has shown that patients with LVEFs ≤35%, non-LBBB, and QRS duration of 120 to 149 ms and NYHA class III to ambulatory class IV did not derive as much benefit as those with LBBB ≥120 ms.17,28–32 13.	 The MADIT-CRT trial included NYHA class I (and class II) patients with ischemic heart disease, LVEF ≤30%, and QRS >130 ms.39 Patients with nonischemic cardiomyopathy were enrolled if they had NYHA class II HF.

Figure 9. Additional Device Therapies. Colors correspond to COR in Table 2. Recommendations for additional nonpharmaceutical interventions that may be considered for patients with HF are shown. GDMT indicates guideline-directed medical therapy; HF, heart failure; HFH, heart failure hospitalization; HFrEF, heart failure with reduced ejection fraction; IV, intravenous; LVEF, left ventricular ejection fraction; LVESD, left ventricular end systolic dimension; MV, mitral valve; MR, mitral regurgitation; NP, natriuretic peptide; NSR, normal sinus rhythm; NYHA, New York Heart Association; and PASP, pulmonary artery systolic pressure.

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