Clinical Data

Impulse Dynamics has successfully completed three major clinical studies, the results of which have been published in leading medical journals. The European studies have shown CCM therapy to be safe and effective in the treatment of heart failure patients. 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.

FIX-HF-5 Pivotal Trial (US) – a multi-center, randomized, unblinded study

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, CCM 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, CCM improved anaerobic threshold, peak VO2, MLWHFQ and NYHA by particularly large and 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.

 

FIX-CHF-4 (Europe) – a multi-center, randomized, double blind study

164 subjects with EF ≤35% and NYHA Class II (24%) or III (76%) symptoms received a CCM pulse generator (Optimizer III). Patients were randomly assigned to Group 1 (n=80, CCM treatment first 3 months, sham treatment for following 3 months) or Group 2 (n=84, sham treatment first 3 months, CCM 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. CCM 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, CCM signals were safe and improved exercise tolerance and quality of life with as little as 3-months of treatment.


Borggrefe et al., European Heart Journal, 2008 Apr;29(8):1019-28

 

Retrospective Studies Show Sustained Long Term Benefit of CCM Therapy

Multiple investigators initiated retrospective reports related to the long-term benefit of CCM 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 CCM 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 CCM was better than expected (p=0.022).


J. Kuschyk, et al. International Journal of Cardiology 2015 (183C): 76–81.

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 CCM 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 CCM was better than expected (p=0,007)

Observed Kaplan-Meier survival curve (blue) compared to point estimates of survival at 1 and 3 years provided per patient by the MAGGIC score.

J. Kuschyk, et al. International Journal of Cardiology 2015 (183C): 76–81.

Kaplan–Maier curve for the survival of CCM treated patients compared with the SHFM predicted survival based on the cohort’s baseline characteristics.

A. Kloppe et al. International Journal of Cardiology 209 (2016) 291–295)

The study of Liu M et al. (International Journal of Cardiology 206 (2016) 122–126) on 41 CHF patients (NYHA III) shows reduced all-cause mortality, cardiovascular mortality and hospitalization rate for patients with EV 25-40% in up to 96 months observation.

 


Kaplan-Maier analysis for all-cause mortality hosptializations and cardiovascular mortality.
Liu M et al. International Journal of Cardiology 206 (2016) 122–126