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Circulation. 2022;145:e895–e1032. DOI: 10.1161/CIR.0000000000001063 May 3, 2022 e945 CLINICAL STATEMENTS AND GUIDELINES 14. Extension of benefit to patients with narrow QRS has been attempted but has generally failed. In the RETHINQ (Cardiac Resynchronization Therapy in Patients with Heart Failure and Narrow QRS) trial, patients with QRS duration <130 ms were randomized to CRT or not.40 There was no benefit from CRT, but subgroup analysis showed there was a benefit with QRS durations between 120 and 130 ms. In the ECHO-CRT (Echocardiography Guided Cardiac Resynchronization Therapy) trial, patients with NYHA class III to IV HF, LVEF ≤35% and a QRS duration ≤130 ms, and mechanical dysynchrony on echocardiography underwent randomization to CRT.50 There was no benefit to CRT in this trial. And in the LESSER-EARTH (Evaluation of Resynchronization Therapy for Heart Failure) trial, patients with severe LV dysfunction and QRS <120 ms derived no benefit from CRT.51 The NARROW-CRT (Narrow QRS Ischemic Patients Treated With Cardiac Resynchronization Therapy) was the only trial that showed a benefit in a clinical composite score in patients with an indication for an ICD and QRS <120 ms.52 15. Subgroup analysis of the CRT trials has shown no benefit for those with LVEF ≤35%, non-LBBB 120 to 149, and NYHA class I-II HF.17,28–32 16. The 1-year survival is a standard inclusion for ICD and CRT trials.1–9,16–21 7.4.2. Other Implantable Electrical Interventions Autonomic nervous system modulation is intriguing as a treatment for HFrEF because of the heightened sympathetic response and decreased parasympathetic response in HF.1 Trials of device stimulation of the vagus nerve, spinal cord, and baroreceptors have had mixed responses.2 An implantable device that electrically stimulates the baroreceptors of the carotid artery has been approved by the FDA for the improvement of symptoms in patients with advanced HF who are unsuited for treatment with other HF devices including CRT. In a prospective, multicenter, RCT with a total of 408 patients with current or recent NYHA class III HF, LVEF ≤35%, baroreceptor stimulation was associated with improvements in QOL, exercise capacity, and NT-proBNP levels.3 To date, there are no mortality or hospitalization rates results available with this device. Although early trials of vagus nerve stimulation were positive, the largest and latest trial did not show a reduction in mortality and HF hospitalizations.4 Multisite LV pacing studies initially were promising.5,6 However, more recent data have not confirmed benefit, and the larger phase 2 trial was terminated early for low probability of benefit.7 His bundle and left bundle pacing are attractive because they use the intrinsic conduction system. In observational data, there does appear to be a benefit over RV pacing8; however, comparisons to CRT are limited.9,10 Cardiac contractility modulation (CCM), a device-based therapy that involves applying relatively high-voltage, long-duration electric signals to the RV septal wall during the absolute myocardial refractory period, has been associated with augmentation of LV contractile performance. CCM is FDA-approved for patients with NYHA class III with LVEF of 25% to 45% who are not candidates for CRT. Four RCTs have shown benefits in exercise capacity and QOL but, as of yet, no benefits in death or hospitalizations.11–14 Most patients in these trials were class III CHF.3 7.4.3 Revascularization for CAD Recommendation for Revascularization for CAD Referenced studies that support the recommendation are summarized in the Online Data Supplements. COR LOE Recommendation 1 B-R 1. In selected patients with HF, reduced EF (EF ≤35%), and suitable coronary anatomy, surgical revascularization plus GDMT is beneficial to improve symptoms, cardiovascular hospitalizations, and long-term all-cause mortality.1–8 Synopsis CAD is commonly associated with HF, necessitating revascularization in selected patients with angina or HF symptoms. Data from the STICH Trial showed that, compared with optimal medical management alone, CABG surgery plus GDMT did not reduce the primary endpoint of all-cause mortality at a median of 56 months; however, at 10 years’ follow-up, CABG+GDMT resulted in significant reductions in all-cause mortality, cardiovascular mortality, and death from any cause or cardiovascular hospitalization in patients with LVEF ≤35% and ischemic cardiomyopathy.7,8 Furthermore, a retrospective analysis showed significant reductions in first and recurrent all-cause, cardiovascular, and HF hospitalizations at 10 years in patients receiving CABG+ optimal medical therapy compared with optimal medical therapy alone.2 Similar benefits from percutaneous coronary intervention revascularization, in this cohort, have not yet been shown in an RCT, although the REVIVED-BCIS2 (Study of Efficacy and Safety of Percutaneous Coronary Intervention to Improve Survival in Heart Failure) trial, which compares percutaneous coronary intervention with medical therapy in a similar population, is ongoing.9 Recent data continue to show a benefit of CABG over percutaneous coronary intervention in patients with diabetes, CAD, and LV dysfunction and in patients with left main CAD and moderate or severe LV dysfunction.4,6,10 Figure 9 summarizes revascularization and additional device therapy recommendations. Recommendation-Specific Supportive Text 1. CABG has been shown to improve outcomes in patients with left main or left main equivalent Downloaded from http://ahajournals.org by on October 7, 2026