Cardiac Contractility Modulation (CCM) Therapy

Number: 0930

Policy

Aetna considers cardiac contractility modulation (CCM) therapy, administered by Impulse Dynamics’ Optimizer system, experimental and investigational because the effectiveness of this approach has not been established.

See also: CPB 0585 - Cardioverter-Defibrillators and CPB 0610 - Biventricular Pacing (Cardiac Resynchronization Therapy)/Combination Resynchronization-Defibrillation Devices for Congestive Heart Failure.

Background

Impulse Dynamics offers cardiac contractility modulation (CCM) therapy to treat adults with moderate-to-severe “chronic” heart failure that is symptomatic despite optimal medical therapy.  CCM delivers non-excitatory electrical signals to the right side of the intraventricular septum during the absolute refractory period of the ventricular contraction, and does not trigger a new action potential.  CCM signals are delivered by Impulse Dynamics’ Optimizer system (i.e., Optimizer IVs), which is an implantable pulse generator.  This device is implanted in a minimally-invasive procedure under local anesthesia, typically in the right pectoral region.  CCM has been evaluated in patients with heart failure with reduced ejection fraction (HFrEF) in New York Heart Association (NYHA) Classes II to IV with normal QRS duration (less than 120 ms).  In contrast to a pacemaker or a defibrillator, the system is designed to modulate the strength of contraction of the heart muscle rather than the rhythm.  CCM therapy is delivered at regular intervals throughout the day.  The "common patient profile" for this therapy is NYHA II to III, normal QRS, EF greater than 20 %, peak VO≥ 10 ml/kg/min, and ventricular ectopies or bigeminies less than 10,000 per day (Impulse Dynamics, 2018).

Some individuals may also require and implantable cardioverter-defibrillator (ICD) device, or already have one implanted.  The Optimizer IVs is designed to work in parallel with any ICD device and generally does not cause any interruption of ICD function.  The Optimizer IVs is contraindicated for patients with permanent or long-standing persistent atrial fibrillation or flutter, mechanical tricuspid valve, no venous access, and device programmed to 100 % VVI pacing (Impulse Dynamics, 2018).

Kadish et al (2011) conducted a randomized controlled prospective study (FIX-HF-5) to evaluate the safety and efficacy of CCM in advanced HF.  A total of 428 adults with NYHA class III or IV, narrow QRS (defined as less than 130 msec duration) and EF less than or equal to 35 % were randomly assigned to receive optimal medical therapy (OMT) plus CCM (n = 215), or OMT alone (n = 213).  The primary efficacy endpoint, required by the U.S. FDA, was the change from baseline in the ventilatory anaerobic threshold (VAT) measured on CPX.  Secondary efficacy endpoints were peak Vo2 (pVo2), and quality of life (QOL) assessed by the Minnesota Living with Heart Failure Questionnaire (MLWHFQ) at 6 months.  The primary safety endpoint was a test of non-inferiority between groups at 12 months for the composite of all-cause mortality and hospitalizations through 50 weeks.  While VAT did not improve at 6 months, CCM significantly improved pVo2 (p = 0.024) and MLWHFQ (p < 0.0001), respectively, over OMT; 48 % of OMT and 52 % of CCM patients experienced a safety endpoint, which satisfied the non-inferiority criterion (p = 0.03).  Post-hoc, hypothesis-generating analysis identified a subgroup (characterized by baseline greater than or equal to 25 and NYHA class III symptoms) in which all parameters were improved by CCM.  The authors concluded that further study is required to clarify the roll of CCM therapy in refractory HF. 

Abraham et al (2015) designed a confirmatory study (the FIX-HF-5C) to prospectively confirm the efficacy of CCM originally identified in the FIX-HF-5 study of patients with EF 25 % to 45 %.  This Impulse Dynamics FIX-HF-5C study is an ongoing, prospective, multi-center, randomized, parallel-controlled trial that evaluated the safety and efficacy of CCM signals delivered by the implantable Optimizer System (specifically the Optimizer IVs) in patients with NYHA class III and IV HF and an EF 25 to 45 %.  A total of 160 adult subjects were recruited and have been randomly assigned to either the Optimizer IVs plus OMT, or to a control group receiving OMT alone.  One of the exclusion criteria included QRS duration greater than or equal to 130 msec duration.  Based on difficulties encountered in reliably quantifying VAT, the relatively large number of studies in which VAT could not be quantified, and the statistical inefficiency and arbitrary nature of thresholds employed in a “responders” analysis of a continuous variable in the FIX-HF-5 study, the primary efficacy endpoint was changed to compare changes in peak VO2 between the treatment and control groups. This study was registered in ClinicalTrials.gov with an estimated completion date of March 2019 (NCT01381172).

Muller et al (2017) evaluated clinical effects of long-term CCM in subjects with HF caused by left ventricular systolic dysfunction.  Out of 143 subjects from 24 sites, 106 with HFrEF completed the 24 month follow-up which was recorded via a clinical registry.  Recordings included NYHA class, MLWHFQ score, 6-min walk test (6MWT) distance, left ventricular ejection fraction (LVEF), and peak VO2 at baseline and 6 month intervals as clinically indicated.  Serious adverse events, and all cause as well as cardiovascular mortality were recorded.  Data are presented stratified by LVEF (all subjects, LVEF less than 35 %, LVEF greater than or equal to 35 %).  The investigators found that baseline parameters were similar among LVEF groups. NYHA and MLWHFQ improved in all 3 groups at each time-point.  LVEF in the entire cohort improved 2.5, 2.9, 5.0, and 4.9 % at 6, 12, 18, and 24 months, respectively.  Insufficient numbers of subjects had follow-up data for 6MWT or peak VO2 assessment, precluding comparative analysis.  Serious adverse events (n = 193) were observed in 91 subjects and similarly distributed between groups with LVEF less than 35 % and LVEF greater than or equal to 35 %, and similar to other device trials for HF; 18 deaths (7 cardiovascularly related) over 2 years.  Overall survival at 2 years was 86.4 % (95 % confidence intervals [CI]: 79.3 to 91.2 %).  The investigators concluded that in patients with HFrEF and persistent symptoms despite GDMT, CCM provided sustained improvement in both cardiac function and QOL.  The benefit was present not only in subjects with baseline LVEF less than 35 %, but also in those with LVEF greater than or equal to 35 %.  These data suggested that CCM may be beneficial in select patients with HF, narrow QRS, and symptoms despite OMT.  Limitations of the study included: lack of a control group, improvement in NYHA, MLWHFQ, and LVEF could have resulted from the increased use of pharmacological treatment of HF in these patients, and registry follow-up testing was performed based on clinical need, which may have limited the number of patients available with outcomes data related to LVEF and exercise tolerance including 6MWT, and peak VO2.

The Optimizer system has been launched in Europe; however, is limited to investigational use only in the United States (Impulse Dynamics, 2018).

Abraham and colleagues (2018) sought to confirm a subgroup analysis of the prior FIX-HF-5 (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure) study showing that CCM improved exercise tolerance (ET) and QOL in patients with EFs between 25 % and 45 %.  A total of 160 patients with NYHA functional class III or IV symptoms, QRS duration of less than 130 ms, and EF of greater than or equal to 25 % and less than or equal to 45 % were randomized to continued medical therapy (control, n = 86) or CCM (treatment, n = 74, unblinded) for 24 weeks.  Peak Vo2 (primary end-point), Minnesota Living With Heart Failure questionnaire, NYHA functional class, and 6-min hall walk were measured at baseline and at 12 and 24 weeks.  Bayesian repeated measures linear modeling was used for the primary end-point analysis with 30 % borrowing from the FIX-HF-5 subgroup.  Safety was assessed by the percentage of patients free of device-related adverse events (AEs) with a pre-specified lower bound of 70 %.  The difference in peak Vo2 between groups was 0.84 (95 % Bayesian CI: 0.123 to 1.552) ml O2/kg/min, satisfying the primary end-point.  Minnesota Living With Heart Failure questionnaire (p < 0.001), NYHA functional class (p < 0.001), and 6-min hall walk (p = 0.02) were all better in the treatment versus control group.  There were 7 device-related events, yielding a lower bound of 80 % of patients free of events, satisfying the primary safety end-point.  The composite of cardiovascular death and HF hospitalizations was reduced from 10.8 % to 2.9 % (p = 0.048).  The authors concluded that CCM was safe, improved exercise tolerance and QOL in the specified group of HF patients, and led to fewer HF hospitalizations.  Moreover, these researchers stated that future research is needed to examine the impact of CCM on mortality in the current target population.  Furthermore, because CCM works through a mechanism completely different than cardiac resynchronization (CRT), future research can examine the impact of CCM in patients with prolonged QRS duration in addition to CRT, in particular in CRT non-responders.

The authors stated that short-term follow-up duration (24 weeks) and small sample size (n = 74 in the CCM group) were the 2 main drawbacks of this trial.  The short-term follow-up duration limited the ability to evaluate the long-term effects of CCM on mortality and hospitalizations.  Although a double-blinded trial design employing an implanted, non-activated control group as used in some device trials (including the prior feasibility study of the OPTIMIZER [5]) was initially considered, this was deemed unfeasible as detailed in the description of the original FIX-HF-5 study.  Accordingly, given the unblinded nature of the study, several measures were taken to minimize placebo effect and investigator bias.  Cardiopulmonary exercise tests were performed according to rigorous protocols with significant oversight of a core laboratory.  Test results were read blinded, with specific criteria applied to exclude tests that were not performed properly and resulted in inadequate tests.  Patients were required to perform 2 tests on separate days at each time-point to ensure that maximal efforts were achieved.

Kuschyk and colleagues (2019) noted that a significant proportion of patients receiving cardiac resynchronization therapy (CRT) are non-responders.  In a multi-center, open-label, treatment-only, feasibility study, these researchers evaluated the efficacy of CCM in subjects with reduced LVEF who, despite CRT, continued to experience clinically significant symptoms.  This was a trial of 17 CRT non-responders who received CCM therapy.  Changes in NYHA class, EF, MLWHFQ score, and exercise tolerance (6 minute walk test [6MWT] and pVo2) were analyzed over 6 months. Mortality and hospitalization rates were determined.  Patients (82 % men) were 69.4 ± 9.6 years of age with baseline EF = 22.8 ± 6.5 %.  Among primary end-points, peak VO2 increased 1.1 ± 1.6 ml/kg/min (p = 0.03) and MLWHFQ improved (-16 ± 16 points; p < 0.01).  Mean NYHA class improved (-0.33 ± 0.49; p = 0.02), 6MWT increased (52 ± 60 m; p < 0.01), while EF trended up (2.9 ± 5.8 %; p = 0.08) at 6 months.  During the 6-month follow-up period, there were 18 hospitalizations in 9 subjects and 2 patients died.  The authors concluded that patients with HF and reduced EF who remained moderately to severely symptomatic despite use of CRT, may benefit from CCM therapy with improvement in QOL and exercise tolerance.  These researchers stated that a larger prospective study in this population is needed.

Mann and Abraham (2019) stated that despite advances in medical therapy, HFrEF is still a leading cause of mortality, hospitalizations, and healthcare costs.  These researchers described 2 novel, implantable devices for the treatment of patients with HFrEF: CCM and baroreflex activation therapy (BAT), and summarized literature regarding these devices from the last 5 years.  CCM improved QOL and functional capacity as indexed by the MLWHFQ score, 6MHWT distance, NYHA functional class, pVo2, HF hospitalizations, and mortality.  BAT improved MLWHFQ, 6MWT distance, NYHA functional class, and HF hospitalizations.  Both devices have been shown to be safe.  CCM and BAT have been shown to be safe and effective treatment modalities for HFrEF.  The authors concluded that CCM has been approved for use in Europe and has been implanted in thousands of patients; BAT has also been approved in Europe and continues to show promise in treating patients with HFrEF who fail OMT.  These investigators noted that at present, both therapies are considered investigational in the United States.

Tint and associates (2019) noted that HF is a major cause of morbidity and mortality throughout the world. Despite substantial progress in its prevention and treatment, mortality rates remain high.  Device therapy for HF mainly includes CRT and the use of an ICD.  Recently, however, a new device therapy – CCM – became available.  These researchers presented a first case-series of patients with different clinical patterns of HFrEF, supported with the newest generation of CCM devices.  A total of 5 patients with a LVEF of less than or equal to 35 % and a NYHA class of greater than or equal to III were supported with CCM OPTIMIZER SMART IPGCCMX10 at the authors’ clinic.  Subjects had a median age of 67 ± 8.03 years (47 to 80) and were all men (4 with ischemic etiology dilated cardiomyopathy).  In 2 cases, CCM was added on top of CRT (non-responders), and, in 1 patient, CCM was delivered during persistent atrial fibrillation (AF).  After 6 months of follow-up, the LVEF increased from 25.4 ± 6.8 % to 27 ± 9 %, and the 6MWT distance increased from 310 ± 65.1 m to 466 ± 23.6 m.  One patient died 47 days after device implantation.  The authors concluded that CCM therapy provided with the new model OPTIMIZER SMART IPG CCMX10 was safe, feasible, and applicable to a wide range of patients with HF.  These researchers stated that further trials are needed to determine the magnitude of the effect of CCM provided by the new OPTIMIZER SMART IPG CCMX10 on HF in patients with AF or who fail CRT.

The authors stated that this study had several drawbacks.  This was a case-series study involving only a limited number of patients (n = 5), with a relatively short follow-up (6 months), without a randomized control group.  It should be noted, however, that, even in previously published trials and studies, the number of patients enrolled was quite small and much lower compared to studies focusing on CRT and/or ICD therapy.  

Mando and colleagues (2019) carried out an updated meta-analysis of the randomized clinical trials (RCTs) to examine the safety and efficacy of CCM therapy.  These investigators conducted a systematic review and meta-analysis of RCTs between January 2001 and June 2018.  Outcomes of interest were peak VO2, 6-Minute Walk Distance (6MWD), MLHFQ, HF hospitalizations, cardiac arrhythmias, pacemaker/ICD malfunctioning, all-cause hospitalizations, and mortality.  Data were expressed as standardized mean difference (SMD) or odds ratio (OR).  A total of 4 RCTs including 801 patients (CCM; n = 394) were available for analysis.  The mean age was 59.63 ± 0.84 years, mean EF was 29.14 ± 1.22 %, and mean QRS duration was 106.23 ± 1.65 msec.  Mean follow-up duration was 6 months.  CCM was associated with improved MLWHFQ (SMD -0.69, p = 0.0008).  There were no differences in HF hospitalizations (OR 0.76, p = 0.12), 6MWD (SMD 0.67, p = 0.10), arrhythmias (OR 1.40, p = 0.14), pacemaker/ICD malfunction/sensing defect (OR 2.23, p = 0.06), all-cause hospitalizations (OR 0.73, p = 0.33), or all-cause mortality (OR 1.04, p = 0.92) between the CCM and non-CCM groups.  The authors concluded that short-term treatment with CCM may improve MLFHQ without significant difference in 6MWD, arrhythmic events, HF hospitalizations, all-cause hospitalizations, and all-cause mortality.  There is a trend towards increased pacemaker/ICD device malfunction.  These researchers stated that larger RCTs might be needed to determine if the CCM therapy will be beneficial with longer follow-up.

Wiegn and associates (2020) noted that prior studies of CCM employed a 3-lead Optimizer system.  A new 2-lead system eliminated the need for an atrial lead.  These investigators examined the safety and effectiveness of this 2-lead system compared with the 3-lead system.  Patients with NYHA III/IVa symptoms despite medical therapy, LVEF 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 VO2 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 NYHA classification were a secondary end-point.  The primary safety end-point was a comparison of device-related adverse events (AEs) between FIX-HF-5C2 and FIX-HF-5C subjects.  A total of 60 subjects, 88 % men, 66 ± 9 years old with LVEF of 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 AF versus 0 % in FIX-HF-5C.  CCM delivery did not differ significantly between 2- and 3-lead systems (19,892 ± 3,472 versus 19,583 ± 4,998 CCM signals/day, CI of difference: -1,228 to 1,847).  The change of peak VO2 from baseline to 24 weeks was 1.72 (95 % Bayesian CI: 1.02 to 2.42) ml/kg/min greater in the 2-lead device group versus controls. 83.1 % of 2-lead subjects compared with 42.7 % of controls experienced greater than or equal to 1 class NYHA improvement (p < 0.001).  There were decreased Optimizer-related AEs with the 2-lead system compared with the 3-lead system (0 % versus 8 %; p = 0.03).  The authors concluded that the 2-lead system effectively delivered comparable amount of CCM signals (including in subjects with AF) as the 3-lead system, was equally safe and improved peak VO2 and NYHA.  Device-related adverse effects were less with the 2-lead system.

The authors stated that the major drawback of this study was that it was a non-randomized, unblinded study with a relatively small number of patients (n = 60) that used a historical control group from the prior FIX-HF-5C study.  The 2 studies were reasonably contemporaneous, having been completed less than 2 years of each other.  The only significant difference in background medical therapy was a slightly greater use of valsartan / sacubitril in the current study (15 % versus 4 %) due to its introduction into clinical practice toward the completion of enrollment into the FIX-HF-5C study.  Furthermore, there were some imbalances in baseline characteristics between the prospective treatment and retrospective control groups; however, frequentist mixed modeling of the results by sequential addition of baseline characteristics showing differences between groups showed little impact of these differences on the results.  Regarding unblinding, this aspect was similar to the prior FIX-HF-5C study, so these investigators considered it unlikely that it would have influenced the comparisons made between the 2 studies.

Campbell and co-workers (2020) stated that CCM by the Optimizer Smart device is an innovative intracardiac device-based therapy that has been recently received FDA approval for the treatment of patients with chronic HF (CHF), LVEF between 25 and 45 %, QRS of less than 130 ms who remain symptomatic despite optimal medical therapy.  Clinical trials demonstrated that CCM therapy is safe and effective in reducing HF hospitalization and improving HF symptoms, QOL and functional performance.  This novel device-based therapeutic offered benefits to patients who do not otherwise qualify for cardiac resynchronization therapy.  CCM expands the indication beyond the traditional LVEF cut-off of 35 % to a newer group including patients who fall in midrange LVEF group, up to 45 %.  The authors noted that CCM is a novel, innovative, device-based therapy for HF recently approved by the FDA in March 2019.  Based on the most recent randomized clinical trials, CCM could benefit patients with symptomatic HF despite optimized medical therapy with normal sinus rhythm and QRS less than 130 s.  The significance of CCM is that it provides additional device-based therapeutic benefits to patients who do not otherwise qualify for CRT (narrow QRS).  CCM also expands the indication beyond the traditional LVEF cut-off of 35 % to a newer group including patients who fall in mid-range LVEF group, up to 45 %.  More importantly, these studies were conducted in era before extensive use of sacubitril/valsartan and ivabradine.  These researchers stated that further prospective trials that address mortality in a prospective randomized fashion on background of current medical therapies are needed to confirm survival benefits.

Giallauria and associates (2020) performed a comprehensive individual patient data meta-analysis of all non-confounded prospective RCTs of CCM versus control that have measured functional capacity and/or QOL questionnaires in patients with HF.  The Cochrane Central Register of Controlled Trials, Medline, and Embase were searched in January 2020 to identify eligible RCTs.  These researchers also asked the sole manufacturer of the device for their list of known trials.  Primary outcomes of interest were peak VO2, 6MWD, and QOL measured by MLWHFQ, and all data were received as individual patient and individual time point data-points; MDs and 95 % CIs were calculated for continuous data using a fixed-effects model.  A total of 5 trials were identified, 4 randomized studies enrolling 801 subjects for all end-points of interest, and for peak VO2 alone (n = 60), there was an additional single arm non-randomized trial (FIX-HF-5C2) with a prospective comparison of its 24 week peak VO2 data compared with the control group of the FIX-HF-5C control patients.  Pooled analysis showed that, compared with control, CCM significantly improved peak VO2 (MD +0.93, 95 % CI: 0.56 to 1.30 ml/kg/min, p < 0.00001), 6MWD (MD +17.97, 95 % CI: 5.48 to 30.46 m, p = 0.005), and QOL measured by MLWHFQ (MD -7.85, 95 % CI: -10.76 to -4.94, p < 0.00001).  As a sensitivity analysis, these investigators excluded the FIX-HF-5C2 trial (only relevant for peak VO2), and the result was similar (MD +0.65, 95 % CI: 0.21 to 1.08 mL/kg/min, p = 0.004).  The authors concluded that this meta‐analysis showed statistically significant and clinically worthwhile beneficial effects of CCM in improving functional capacity, exercise tolerance, and QOL in HF patients.  Moreover, these researchers stated that larger, well‐conducted RCTs using a parallel double‐blind design are needed to examine the effect of CCM on major mortality and morbidity outcomes before CCM can be widely recommended as an effective therapeutic option for HF patients.  However, in those in whom conventional interventions are failing or contraindicated, these results suggested that worthwhile benefits could be expected.  Studies in less compromised HF patients are also encouraged in order to explore a wider application of CCM in all stages of HF.

The authors stated that this meta-analysis had several drawbacks.  Study cohorts are relatively young and predominantly male, thus, future data would be needed in older individuals and in more women.  Patients with permanent AF were initially excluded because the original 3‐lead OPTIMIZER device required detection of an appropriately timed P wave as part of a safety algorithm that ensures CCM signals are never delivered during the vulnerable period where they might trigger an arrhythmia.  New algorithms have been developed to overcome this issue, and the FIX‐HF‐5C2 study included 9 patients with AF.  Furthermore, the 2‐lead system has been available and used in patients with AF in European Union for 10 years although, as of now, specific reports of the effects of CCM in patients with AF have not been completed.  In addition, although no formal statistical heterogeneity was observed, the studies analyzed differed in study design limiting the ability to define representative results across different patient subgroups.

Matta and co-workers (2020) stated that CCM is a therapeutic option for patients suffering symptomatic CHF with reduced LVEF who are not eligible for cardiac resynchronization.  Data on mid-term follow-up were limited to small observational studies.  In a pilot study, these researchers examined the impact of CCM on QOL, symptoms, exercise tolerance and left ventricular function in patients with CHF and moderate-to-severe left ventricular systolic dysfunction.  Patients suffering CHF with LVEF of less  than 45% and NYHA class of greater than II despite optimal medical therapy, underwent CCM implantation.  Enrolled patients underwent baseline and 3-, 6- and 12-months evaluation with ECG, echocardiogram, clinical assessment, 6MWD and MLWHFQ.  A total of 10 patients underwent CCM implantation.  All subjects were actively treated with the optimal pharmacological therapy as tolerated, and had at least 1 hospitalization for worsening HF during the previous year.  After a mean follow-up of 15 months, 9 patients were alive, while 1 patient died for worsening HF precipitated by pneumonia.  Among the remaining 9 patients, LVEF improved non-significantly from 29.4 ± 8 % to 32.2 ± 10 % (p = 0.092), 6MWD improved from 179 ± 73 m to 304 ± 99 m (p < 0.001), NYHA class reduced from 3.0 ± 0.4 to 1.6 ± 0.5 (p = 0.003) and MLWHFQ score improved from 59.6 ± 49 to 34.2 ± 32 (p = 0.037).  Only 2 patients have been hospitalized during the 12 months.  Overall, a net clinical benefit was detected in 6 out of 9 patients.  The authors concluded that CCM could be effective in improving QOL, symptoms and exercise tolerance, and reduced hospitalizations in patients with symptomatic CHF on top of optimal medical and electrical therapy.  Moreover, these researchers stated that a prospective registry has been designed to identify the subsets of patients gaining more benefit, and to evaluate the long-term effect of CCM on those clinical end-points.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes
Code Code Description

Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :

CPT codes not covered for indications listed in the CPB :

Impulse Dynamics' Optimizer system - no specific code:

0408T Insertion or replacement of permanent cardiac contractility modulation system, including contractility evaluation when performed, and programming of sensing and therapeutic parameters; pulse generator with transvenous electrodes
0409T Insertion or replacement of permanent cardiac contractility modulation system, including contractility evaluation when performed, and programming of sensing and therapeutic parameters; pulse generator only
0410T Insertion or replacement of permanent cardiac contractility modulation system, including contractility evaluation when performed, and programming of sensing and therapeutic parameters; atrial electrode only
0411T Insertion or replacement of permanent cardiac contractility modulation system, including contractility evaluation when performed, and programming of sensing and therapeutic parameters; ventricular electrode only

HCPCS codes not covered for indications listed in the CPB :

C1824 Generator, cardiac contractility modulation (implantable)

The above policy is based on the following references:

  1. Abraham WT, Lindenfeld J, Reddy VY, et al. A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation in patients with moderately reduced left ventricular ejection fraction and a narrow QRS duration: Study rationale and design. Journal of cardiac failure. 2015;21(1):16-23.
  2. Abraham WT, Kuck K-H, Goldsmith RL, et al. A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation. Foot Ankle Surg. 2019;25(4):441-448.
  3. Campbell CM, Kahwash R, Abraham WT, et al. Optimizer Smart in the treatment of moderate-to-severe chronic heart failure. Future Cardiol. 2020;16(1):13-25. 
  4. Giallauria F, Cuomo G, Parlato A, et al. A comprehensive individual patient data meta-analysis of the effects of cardiac contractility modulation on functional capacity and heart failure-related quality of life. ESC Heart Fail. 2020;7(5):2922-2932.
  5. Impulse Dynamics. Cardiac contractility modulation: Innovative therapy for the treatment of chronic heart failure. Impulse Dynamics N.V. Available at: http://www.impulse-dynamics.com/us/wp-content/uploads/sites/3/2017/01/Therapy_Brochure_Optimizer_IVs_English_PDF.pdf.  Accessed March 5, 2018.
  6. Impulse Dynamics. Evaluate safety and efficacy of the Optimizer system in subjects with moderate-to-severe heart failure: FIX-HF-5C (FIX-HF-5C). ClinciaTrials.gov Identifier: NCT01381172. Bethseda, MD: National Library of Medicine; February 28, 2018.
  7. Kadish A, Nademanee K, Volosin K, et al. A randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. Am Heart J. 2011;161(2):329-337.e1-2.
  8. Kuschyk J, Nagele H, Heinz-Kuck K, et al. Cardiac contractility modulation treatment in patients with symptomatic heart failure despite optimal medical therapy and cardiac resynchronization therapy (CRT). Int J Cardiol. 2019;277:173-177.
  9. Mando R, Goel A, Habash F, et al. Outcomes of cardiac contractility modulation: A systematic review and meta-analysis of randomized clinical trials. Cardiovasc Ther. 2019;2019:9769724.
  10. Mann JA, Abraham WT. Cardiac contractility modulation and baroreflex activation therapy in heart failure patients. Curr Heart Fail Rep. 2019;16(1):38-46.
  11. Matta M, Devecchi C, De Vecchi F, et al. Cardiac contractility modulation in left ventricular systolic dysfunction: one-year experience in a pilot study and design of a prospective registry. Minerva Cardioangiol. 2020 Jul 10 [Online ahead of print].
  12. Muller D, Remppis A, Schauerte P, et al. Clinical effects of long-term cardiac contractility modulation (CCM) in subjects with heart failure caused by left ventricular systolic dysfunction. Clinical Research in Cardiology. 2017;106(11):893-904.
  13. Tint D, Florea R, Micu S. New generation cardiac contractility modulation device-filling the gap in heart failure treatment. J Clin Med. 2019;8(5).
  14. Wiegn P, Chan R, Jost C, et al. Safety, performance, and efficacy of cardiac contractility modulation delivered by the 2-lead Optimizer Smart system: The FIX-HF-5C2 study. Circ Heart Fail. 2020;13(4):e006512.