Medicare Advantage

The Optimizer Smart System and Mini System (Impulse Dynamics) received US Food and Drug Administration (FDA) premarket approvals in 2019 and 2021, respectively. The devices are indicated to “improve 6 minute hall walk, quality of life, and functional status of NYHA Class III heart failure patients who remain symptomatic despite guideline directed medical therapy, are not indicated for Cardiac Resynchronization Therapy (CRT), and have a left ventricular ejection fraction ranging from 25% to 45%." The original indication included a normal sinus rhythm necessity, but this was removed in 2021.

The systems provide cardiac contractility modulation (CCM) therapy via nonexcitatory pulses to the right ventricle of the heart. The pulses occur during the absolute refractory period (when the heart is unable to contract again), thus considered "nonexcitatory." Under normal circumstances, the device should be charged once per week and can provide 20 years of service. The therapy consists of scheduled pulses for 5 hours per 24-hour period, with no clear endpoint (e.g., 1-year use, 10-year use).

There are proposed short- and long-term mechanisms of action. In the short term, calcium plays a crucial role in the contraction of the heart muscle. As calcium binds to the troponin complex, myosin heads are able to bind to actin, leading to contraction. In a healthy heart, intracellular calcium is regulated by L-type calcium channels (intake calcium from extracellular space) and the sarcoplasmic reticulum (intracellular complex that intakes and releases calcium). In an individual with heart failure, calcium regulation may be distorted, leading to improper contractions. It is thought that the CCM therapy nonexcitatory pulses increase the calcium intake by L-type calcium channels and release of calcium stored in the sarcoplasmic reticulum (followed by reuptake causing relaxation). In the long-term, it is possible that reverse remodeling of the proteins involved in the calcium regulation complex may occur.

REVIEW OF EVIDENCE 

Borggrefe et al. (2008) conducted a prospective, double-blind, randomized crossover study of 164 individuals with heart failure, recruited between 2002 and 2005. Inclusion criteria included, but is not limited to, New York Heart Association (NYHA) class II-IV, and ejection fraction less than 35%. Individuals with atrial fibrillation were excluded. The participants were divided into two groups: Group 1 (n = 80) and Group 2 (n =84). Participants in Group 1 had their OPTIMIZER Smart System turned on for the first 12 weeks, then turned off for the final 12 weeks. Group 2 underwent the opposite (off then on). At 12 weeks, there was no difference in peak oxygen between the groups. In the subsequent 12 weeks, there was a significant difference in peak oxygen between the groups, primarily driven by a decrease below baseline in the control group at the time (Group 1). The Minnesota Living with Heart Failure Questionnaire significantly improved with active treatment, although neither of these statistically significant results are clinically meaningful. Regarding secondary endpoints, the 6-minute walk test followed similar results as the peak oxygen endpoint, and the NYHA class improved in both groups at 24 weeks.

Kadish et al. (2011) conducted a prospective randomized controlled trial (RCT) of 428 individuals diagnosed with heart failure, recruited between 2005 and 2007. Inclusion criteria included, but was not limited to, an ejection fraction less than 35%, NYHA class III-IV, normal sinus rhythm, implantable cardioverter defibrillator, and QRS less than 130 ms. Individuals with permanent atrial fibrillation were excluded. The control arm (n = 213) was subject to optimal medical therapy; the intervention arm (n = 215) was subject to optimal medical therapy and the OPTIMIZER Smart System. The primary effectiveness endpoint of a difference in number of “responders" (>20% increase in ventilatory anaerobic threshold) at 24 weeks of treatment was not met. The primary safety endpoint of a noninferior composite all-cause mortality and all-cause hospitalization at 50 weeks was met. Other quality of life and clinical outcomes that were not studied in a primary manner produced mixed results. Interestingly, peak oxygen was significantly different (although not clinically) between the groups, primarily driven by a decrease in the control group. A subgroup analysis of individuals with NYHA III and ejection fraction greater than 25% revealed that these individuals may be more likely to “respond" to the intervention. This finding focused on the study population of the subsequent clinical trial.

Abraham et al. (2018) conducted a prospective RCT of 160 new individuals diagnosed with heart failure, combined with the subgroup from the previous trial totaling 198 controls (optimal medical therapy) and 191 interventions (optimal medical therapy and OPTIMIZER Smart System). The added subgroup was 70% downweighted when utilized (some analyses did not utilize this additional subgroup). Inclusion criteria included, but was not limited to, an ejection fraction between 25% and 45%, NYHA III-IV, implantable cardioverter defibrillator (where appropriate), and QRS less than 130 ms. Individuals with permanent atrial fibrillation were excluded. Notably, normal sinus rhythm was not an inclusion criterion, and the ejection fraction criterion changed from the previous trial. The primary effectiveness endpoint of difference in peak volume oxygen at 24 weeks of treatment was met (which included the subgroup from the previous trial). The primary safety endpoint of complication-free participants (>70% complication-free) at 24 weeks was met. Other quality of life and clinical outcome differences were statistically significant, although not all were clinically meaningful changes. Overall survival was not statistically significantly different.

Wiegn et al. (2020) conducted a prospective, single arm (compared to 67 controls of 2018 study) trial of 59 individuals diagnosed with heart failure. Inclusion criteria included, but was not limited to, an ejection fraction between 25% and 45%, NYHA III-IV, and implantable cardioverter defibrillator (where appropriate). Importantly, individuals with atrial fibrillation were not excluded (n = 9) and the OPTIMIZER Smart System with two leads (instead of three) was used. Peak oxygen was significantly greater in the treatment arm compared to the control arm at 24 weeks (statistical significance, not clinical meaningful; wide, overlapping confidence intervals). The complication rate was minimal and somewhat decreased compared to three-lead systems.

Following this study, the FDA removed the “normal sinus rhythm" from the labeled indication and the two-lead system was approved.

Additional study types with long-term follow up (>6 months) suggest that all-cause mortality and hospitalization rates may be lower compared to controls or models (i.e., Seattle Heart Failure Model, Meta-Analysis Global Group in Chronic Heart Failure).

There are several meta-analyses of RCTs, but these do not provide increased insight into the effectiveness or safety of the OPTIMIZER Smart System; rather they reinforce the findings of the RCTs already summarized.

There are no clinical practice guidelines that support CCM. The recent (2025) appropriate use document from the American College of Cardiology, American Heart Association, and others provides the following statements:

• “CCM has emerged as a promising treatment for patients with chronic HF with reduced EF who are not indicated for CRT."
• “The full effect of CCM on HF morbidity and mortality requires further investigation."
• “The lack of differentiation of AUC recommendations according to HF class as well as the paucity of U.S. or European guideline recommendations likely reflect the strength of evidence related to hard clinical outcomes, such as HF hospitalization and mortality. Studies evaluating longer-term clinical outcomes and impact of CCM on reverse remodeling in larger cohorts are needed."

As such, the appropriate use document only provides “may be appropriate" recommendations (scores of 4–5; “appropriate" requires scores of 7–​9).