Impulse Dynamics has successfully completed three major clinical studies, the results of which have been published in leading medical journals. The European studies suggest that the Cardiac Contractility Modulation therapy is safe and performs as intended in the treatment of heart failure patients. Safety and effectiveness of the Optimizer system is still under study in the US. The Optimizer® system, in its previous versions, has been implanted in over 3,000 patients to date, and has accumulated over 10 years of follow up data. Randomized clinical trials show improved patient performance and quality of life.
This study included 428 patients with NYHA Class III or IV symptoms and EF ≤35% who were randomized to receive either an Optimizer® III System implant plus Optimal Medical Management (OMM, n=215) or OMM alone (n=213). The primary safety endpoint was a comparison between groups of the composite of all-cause mortality and all-cause hospitalization (in a non-inferiority analysis) through one year of treatment; this endpoint was reached.
In the overall population, Cardiac Contractility Modulation improved peak VO2, quality of life (indexed by MLWHFQ) and NYHA but not anaerobic threshold (the study’s primary endpoint). Furthermore, in a pre-specified subgroup analysis consisting of about 50% of the overall population characterized by baseline EF ≥25% and NYHA III symptoms, the therapy improved anaerobic threshold, peak VO2, MLWHFQ and NYHA by statistically significant amounts (Figure below).
Presented as late breaking clinical trial at American College of Cardiology annual meeting, March 2008, in Chicago.
See also Kadish et al., American Heart Journal 2011,161:329-337.
164 subjects with EF ≤35% and NYHA Class II (24%) or III (76%) symptoms received a Cardiac Contractility Modulation pulse generator (Optimizer® III). Patients were randomly assigned to Group 1 (n=80, Cardiac Contractility Modulation treatment first 3 months, sham treatment for following 3 months) or Group 2 (n=84, sham treatment first 3 months, Cardiac Contractility Modulation treatment for consecutive 3 months). Data from therapy ON periods were pooled between the groups and data from therapy OFF periods were pooled between groups. Cardiac Contractility Modulation increased peak VO2 by 0.52±1.39 ml/kg/min (p=0.03) and improved Minnesota Living with Heart Failure Questionnaire (MLWHFQ) by -3 units (p=0.03)(Figure below). Overall, in patients with chronic heart failure and left ventricular dysfunction, Cardiac Contractility Modulation signals improved exercise tolerance and quality of life with as little as 3-months of treatment.
Multiple investigators initiated retrospective reports related to the long-term benefit of the therapy. A study on 81 CHF patients (J. Kuschyk, et al. International Journal of Cardiology 2015 (183C)) (NYHA II-IV, reduced EF) showed significant improvement by Cardiac Contractility Modulation during a mean follow-up period of 34 months (ranging 6-123 months). The cohort had significant long-term improvement in left ventricular size and function, quality of life, NYHA class, peak VO2 and decreased levels of NT-proBNP. Nearly 75 % of the patients had an improvement of at least one NYHA class even after long-term follow-up. Importantly, compared with the per patient mortality risk score (calculated by the MAGGIC model), the long-term results indicated that long-term survival with Cardiac Contractility Modulation was better than expected (p=0.022).
Another study of 68 CHF patients (A. Kloppe et al. International Journal of Cardiology 209 (2016) 291–295) (NYHA II-III, narrow QRS) treated by Cardiac Contractility Modulation during a mean follow-up period of 4,5 years (up to 10 years) showed that compared with the per patient mortality risk score (calculated by the SHFM), the survival with Cardiac Contractility Modulation was better than expected (p=0,007)
The study by Liu M et al. (International Journal of Cardiology 206 (2016) 122–126) on 41 CHF patients (NYHA III) reported reduced all-cause mortality, cardiovascular mortality and hospitalization rate for patients with EV 25-40% in up to 96 months of observation.
Kaplan-Maier analysis for all-cause mortality hospitalizations and cardiovascular mortality.
Liu M et al. International Journal of Cardiology 206 (2016) 122–126