Safety, Performance, and Efficacy of Cardiac Contractility Modulation Delivered by the 2-Lead Optimizer Smart System

Abstract

Background: Prior studies of cardiac contractility modulation (CCM) employed a 3-lead Optimizer system. A new 2-lead system eliminated the need for an atrial lead. This study tested the safety and effectiveness of this 2-lead system compared with the 3-lead system. Methods: Patients with New York Heart Association III/IVa symptoms despite medical therapy, left ventricular ejection fraction 25% to 45%, and not eligible for cardiac resynchronization therapy could participate. All subjects received an Optimizer 2-lead implant. The primary end point was the estimated difference in the change of peak VO 2 from baseline to 24 weeks between FIX-HF-5C2 (2-lead system) subjects relative to control subjects from the prior FIX-HF-5C (3-lead system) study. Changes in New York Heart Association were a secondary end point. The primary safety end point was a comparison of device-related adverse events between FIX-HF-5C2 and FIX-HF-5C subjects. Results: Sixty subjects, 88% male, 66±9 years old with left ventricular ejection fraction 34±6% were included. Baseline characteristics were similar between FIX-HF-5C and FIX-HF-5C2 subjects except that 15% of FIX-HF-5C2 subjects had permanent atrial fibrillation versus 0% in FIX-HF-5C. CCM delivery did not differ significantly between 2- and 3-lead systems (19 892±3472 versus 19 583±4998 CCM signals/day, CI of difference [−1228 to 1847]). The change of peak VO 2 from baseline to 24 weeks was 1.72 (95% Bayesian credible interval, 1.02–2.42) mL/kg per minute greater in the 2-lead device group versus controls. 83.1% of 2-lead subjects compared with 42.7% of controls experienced ≥1 class New York Heart Association improvement ( P <0.001). There were decreased Optimizer-related adverse events with the 2-lead system compared with the 3-lead system (0% versus 8%; P =0.03). Conclusions: The 2-lead system effectively delivers comparable amount of CCM signals (including in subjects with atrial fibrillation) as the 3-lead system, is equally safe and improves peak VO 2 and New York Heart Association. Device-related adverse effects are less with the 2-lead system. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03339310

A comprehensive individual patient data meta‐analysis of the effects of cardiac contractility modulation on functional capacity and heart failure‐related quality of life

“…The four deaths in the control group included two deaths due to cardiac pump failure (on Days 4 and 36), one death following a VT ablation procedure (on Day 70), and pulmonary complications of a non‐cardiac procedure (on Day 117) 29 . In the FIX‐HF‐5C2, 32 no deaths were reported during the 24 week study period in the 2‐lead OPTIMIZER subjects; in contrast, there were four deaths in the FIX‐HF‐5C control subjects during the same period of follow‐up.…”

How many patients with heart failure are eligible for cardiac contractility modulation therapy?

“…This study excluded patients with atrial fibrillation and patients with preserved EF in line with the current indications for CCM therapy 4 . There is some evidence that CCM therapy may be beneficial in AF patients which is delivered by the newer two lead system which does not require an atrial lead 24 . However, the efficacy of CCM in AF patients has not been confirmed by randomised clinical trials, although there are ongoing studies investigating these cohort of patients 25,26 .…”

Clinical effects of cardiac contractility modulation in heart failure with mildly reduced systolic function

“…In this subgroup analysis of efficacy and safety, data were obtained from patients with baseline LVEF ≥ 40% from the FIX‐HF‐5, FIX‐HF‐5C, and FIX‐HF‐5C2 studies 1,2 . The primary efficacy analyses in all three studies were performed at 6 months following study inclusion.…”

“…In all studies, serious adverse events, hospitalizations, and mortality were adjudicated by an independent Events Adjudication Committee as detailed previously. [1][2][3]…”

“…Recently, increased attention has been devoted to describing the characteristics and outcomes in patients with heart failure in the setting of mildly reduced LVEF (40% < LVEF < 50%) for which there are no approved therapies. At the same time, additional data concerning CCM effects in patients with LVEF ≥ 40% have become available 1,2 …”