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Introduction: Based on recently published randomized controlled trials, cardiac contractility modulation (CCM) seems to be an effective device-based therapeutic option in symptomatic chronic heart failure (HF) (CHF). The aim of the current study was to estimate what proportion of patients with CHF and left ventricular ejection fraction (LVEF) <50% could be eligible for CCM based on the inclusion criteria of the FIX-HF-5C trial. Methods: Consecutive patients referred and followed up at our HF clinic due to HF with reduced or mid-range LVEF were retrospectively assessed. After a treatment optimization period of 3–6 months, the inclusion criteria of the FIX-HF-5C trial (New York Heart Association (NYHA) class III/IV, 25% ≤ LVEF ≤45%, QRS <130 ms, and sinus rhythm) were applied to determine the number of patients eligible for CCM. Results: Of the 640 patients who were involved, the proportion of highly symptomatic patients in NYHA class III/IV decreased from 77.0% (n = 493) at baseline to 18.6% (n = 119) after the treatment optimization period (p < 0.001). Mean LVEF increased significantly from 29.0 ± 7.9% to 36.3 ± 9.9% (p < 0.001), while the proportion of patients with 25% ≤ LVEF ≤45% increased from 69.7% (n = 446) to 73.3% (n = 469) (p < 0.001). QRS duration was below 130 ms in 63.1% of patients, while 30.0% of patients had persistent or permanent atrial fibrillation. We found that the eligibility criteria for CCM therapy based on the FIX-HF-5C study were fulfilled for 23.0% (n = 147) of patients at baseline and 5.2% (n = 33) after treatment optimization. Conclusion: This single-center cohort study showed that 5% of patients with CHF and impaired LVEF immediately after treatment optimization fulfilled the inclusion criteria of the FIX-HF-5C study and would be candidates for CCM. [ABSTRACT FROM AUTHOR]