Cardiac Contractility Modulation (CCM) for Heart Failure

February 7, 2025

Tamara Syrek-Jensen
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
7500 Security Boulevard
Baltimore, MD 21244

Re: National Coverage Analysis (NCA) for Cardiac Contractility Modulation (CCM) for Heart Failure (CAG-00469N)

Dear Ms. Syrek-Jensen,

On behalf of the MedTech Association (AdvaMed), we appreciate the opportunity to submit comments on the National Coverage Analysis (NCA) for Cardiac Contractility Modulation (CCM) for Heart Failure (CAG-00469N). AdvaMed and CMS share a common goal – the establishment of a clear and expeditious coverage process, based on scientifically sound clinical evidence with appropriate safeguards, for emerging technologies that will benefit Medicare-eligible patients, including the 54 percent of Medicare-eligible patients enrolled in Medicare Advantage organizations in 2023(1).

AdvaMed member companies produce the medical devices, diagnostic products, and health information systems that are transforming health care through earlier disease detection, less invasive procedures, and more effective treatments. AdvaMed members range from the largest to the smallest medical technology innovators and companies. We are committed to ensuring patient access to lifesaving and life-enhancing devices and other advanced medical technologies in the most appropriate settings.

AdvaMed supports efforts to expand options, such as CCM, for heart failure patients. According to the Centers for Disease Control and Prevention, approximately 6.2 million adults in the United States have heart failure (2). Heart failure is the leading cause of hospitalization among adults, and Medicare beneficiaries with heart failure have the highest readmission rate of any condition (3).

Additionally, AdvaMed supports CMS’ efforts to expand access to CCM as part of the Transitional Coverage for Emerging Technologies (TCET) pilot. Pathways such as TCET are intended to facilitate faster beneficiary access to new and novel technologies and procedures, and we appreciate the agency’s ready collaboration with the submitter to review the evidence supporting CCM. Moreover, we are encouraged to see a technology from a small innovator in the TCET pilot, as such technologies may have distinct considerations from those of a larger company more versed in CMS processes. Inclusion of small innovators into the TCET pathway will help to better inform the TCET program moving forward.

We encourage CMS to work quickly in issuing a Proposed Decision Memo, following the close of this comment period, and subsequently a final decision memo. We look forward to continuing our work with the Agency. If you have questions regarding these comments or if you require additional information, please contact me at tburke@advamed.org.

Sincerely,

Tara Burke, PhD
VP, Payment & Healthcare Delivery Policy
AdvaMed

References
(1) “July 2024: A Data Book: Healthcare Spending and the Medicare Program.” Medicare Payment Advisory Committee (MedPAC), Chapter 9, 16 July 2024, www.medpac.gov/document-type/data-book/. Accessed 03 Feb 2025.
(2) Centers for Disease Control and Prevention. https://www.cdc.gov/heartdisease/heart_failure.htm
(3) Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare feefor-service program. N Engl J Med. 2009; 360:1418–1428. doi: 10.1056/NEJMsa0803563

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February 7, 2025

Tamara Syrek-Jensen
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
7500 Security Boulevard
Baltimore, MD 21244

Re: National Coverage Analysis (NCA) for Cardiac Contractility Modulation (CCM) for Heart Failure (CAG-00469N)

Dear Ms. Syrek-Jensen:

Thank you for the opportunity to comment on the National Coverage Analysis for Cardiac Contractility Modulation Therapy (CAG-00469N). Impulse Dynamics is a medical device manufacturer dedicated to transforming the treatment of chronic heart failure. We have developed the Optimizer® System, which provides CCM therapy for appropriately indicated heart failure patients, many of whom are not indicated for any other drug- or device-based therapy to address their heart failure symptoms. The scope of heart failure’s impact on the Medicare-eligible community has been well-documented as a leading cause of heart failure hospitalization, rehospitalization, decreased quality of life and impaired functional capacity. Our comments regarding this NCA are listed below.

Please see the attached evidence table, which contains a list of key global publications on CCM. CCM has been successfully implanted in more than 10,000 patients worldwide and has been studied extensively in more than 2,000 patients. In concert with these existing publications, Impulse Dynamics holds utmost confidence in our ability to develop additional evidence during the TCET transitional coverage period that bolsters the already robust battery of clinical evidence that underpins CCM. We also remain confident that this additional real-world evidence will meet all of the stipulations explained in the TCET rule and relevant MedCAC for heart failure outcomes. Additionally, we have demonstrated the ability as an organization to develop, manage and enroll well-designed clinical trials.

Impulse Dynamics appreciates CAG’s endeavors to expand access to CCM as a Transitional Coverage for Emerging Technologies (TCET) pilot. TCET aims to facilitate faster access to new therapies that benefit an at-risk portion of the Medicare-eligible population. Further, Impulse Dynamics appreciates CAG’s collaboration with a small medical device company given the differences in resources between smaller innovators and larger, more well-established medical device companies. Participation by smaller companies in the TCET pathway is likely to inform operational processes and also encourage continued innovation in therapy areas of particular concern to the Medicare-eligible population.

Impulse Dynamics encourages CMS to work expeditiously in issuing a Proposed Decision Memo on behalf of Medicare-eligible patients who need access to CCM therapy, and we look forward to continuing our work with the Agency on this NCA and the TCET pathway more broadly. Most importantly, we look forward to collaborating with qualified providers to help as many indicated patients as possible realize the benefits CCM has been proven to provide. If you have questions regarding these comments or if you require additional information regarding CCM therapy, please contact me at cbrooks@impulsedynamics.com.

Respectfully,

Christopher J. Brooks

Christopher J. Brooks
Sr. Director of Healthcare Economics and Reimbursement

Cardiac Contractility Modulation Evidence Table

STUDY TITLE
LOCATION DEVICE N DESIGN ENDPOINTS RESULTS INCLUSION CRITERIA MATCH FDA LABELLING
Pilot study
(FIX-HF-1)
2001 EU External, line-powered 24 Treatment only, acute
Single Center
Cardiac Function Cardiac function is enhanced when 2 electrodes delivering CCM signal to the RV septum applied.

Pappone, Am J Cardiol (2002) No
Chronic feasibility study (FIX-HF-2)
2001 EU Implantable Optimizer® I, Primary Battery (non-rechargeable) 6 Treatment only, 8 weeks feasibility study
Single Center Echo, CPX, 6 MW, Holter Improvement with CCM vs sham therapy in all measures. No clinically significant adverse events. No
Chronic safety and performance study (FIX-HF-3)
2002
EU Optimizer® II, Primary Battery (non-rechargeable) 22 Treatment only, 8 weeks, safety and functionality
Multicenter NYHA Class, Quality of Life (QoL), LVEF All endpoints showed improvement with CCM therapy. CCM therapy did not increase the incidence of arrhythmias. Adverse event profile was acceptable for the patient population. No
Randomized double-blind study of CCM (FIX-CHF-4)
2002 EU Optimizer® II (non-rechargeable) and Optimizer® III (rechargeable), Optimizer® III Charger
164 Prospective, randomized to CCM ON or OFF, double-blind study.
Effectiveness evaluation, double-crossover, 6 months
Multicenter LVEF, pVO2, MLWHFQ, Holter Monitoring for changes in nature of arrhythmias The device improved quality of life, and exercise tolerance and appeared safe when used over a period of 3 months.

Borggrefe, Eur HJ (2008)
No
Feasibility IDE Trial (FIX-HF-5 Phase I)
2004 US Optimizer® II 49 Prospective, randomized to Optimizer with CCM ON or CCM OFF, double-blind, 6 months
Multicenter Primary: 6MWD, NYHA, pVO2, and MLWHFQ.
Secondary: LVEF, LVEDD, VO2 at AT Even though the CCM ON group was sicker at baseline, event-free survival, adverse event profiles, and measures of effectiveness trended to be better in the treatment group.

Neelagaru, Heart Rhythm (2006) No
Pivotal IDE Trial (FIX-HF-5 Phase II)
2005 US Optimizer® III, Optimizer® III Charger 428 Randomized, unblinded, 12 months
Multicenter Efficacy: VO2 at Anaerobic threshold (primary endpoint), pVO2, and MLWHFQ score at 6 months.
Primary safety: 12-month composite all-cause mortality and hospitalizations The primary endpoint was not met as there was no improvement in VAT. However, there was improvement in pVO2 and quality of life questionnaire.

Abraham Am Heart J (2008),
Kadish, Am Heart J (2011) No
Impact of Optimization of lead position on CCM clinical effects (FIX-HF-9)
2005 Hong Kong Optimizer® III,
Optimizer® III Charger 40 Randomized to dP/dt testing or not, double-blind, 6 months
Single Center
Changes in dP/dtmax, MLWHFQ, exercise tolerance, safety, and LV reverse remodeling. No added benefit to using invasive pressure measurements for CCM lead placement. Reduce implant time and safety risks. CCM induced reverse remodeling and increased ejection fraction.
No
Report of Long Term (1 year) Safety Evaluation of the Optimizer® III System in Subjects with Heart Failure Resulting from Systolic Dysfunction (FIX-HF-10)
2004 EU Optimizer® III,
Optimizer® III Charger 110 Un-blinded, non-randomized, treatment only, safety evaluation, 1 year. Subjects served as their own control group.
Multicenter NYHA and MLWHFQ score. Improvement in quality of life was noted. The severity and rate of adverse events were consistent with prior studies and no new safety concerns were identified. Improvement in long-term, all-cause mortality when compared to matched cohort up to 7 years.

Liu, Int J of Cardiology (2016) No
CCM in CRT non-responders (FIX-CHF-12)
2008 EU Optimizer® III,
Optimizer® III Charger 17 Open-label trial of CRT non-responders, treatment only, feasibility study, 6 months
Multicenter
MLWHFQ, pVO2, exercise tolerance, and ejection fraction CCM therapy improved the quality of life, heart failure symptoms, and exercise tolerance in CRT non-responders. The rate and type of adverse events were low.

Nägele, Europace (2008) No
Comparison of 5 versus 12 CCM hours per day (FIX-CHF-13)
2008 EU Optimizer® III Optimizer® III Charger 19 Double-blind, active control study, 6 months
Single center MLWHFQ and exercise tolerance Both 5 CCM hours and 12 CCM hours benefited subjects suffering from heart failure with no undue risk. Adverse events were reported to be not related to the device or procedure.

Kloppe, Cardiol J (2016) No
CCM-HF (FIX-HF-16)
2010 EU Optimizer® III,
Optimizer® III Charger 143 24 months follow up period
Multicenter NYHA, MLWHFQ, LVEF, pVO2 and rate of SAEs The NYHA classification, MLWHFQ and LVEF showed significant improvement. The SAE rate was comparable to the rates observed in prior studies of CCM in patients with heart failure.

Muller, Clin Res Cardiol. 2017 No
A Randomized Comparison: CCM Delivered from 1 versus 2 Leads (FIX-CHF-18)
2009 EU Optimizer® III and Optimizer® IVs, Mini-Charger 50 All subjects received a 2-lead system and randomized to either 1 or 2 leads active, Blinded study, effectiveness evaluation, 6 months
Single center MLWHFQ and pVO2 There were no significant differences between groups for any of the study endpoints. This suggests that CCM delivered through 1 lead is not inferior to CCM delivered through 2 leads after 6 months of therapy.

Röger J Cardiol (2017) No
CCM Registry (CCM-REG) EU Optimizer® IVs, Optimizer® Smart 140 36 months follow up period
Multicenter Mortality vs. SHFM, NYHA, MLWHFQ, LVEF Mortality numerically lower vs. SHFM in the overall cohort and statistically significant in the 35-45% EF cohort.
Sustainable benefits for MLWHF, LVEF, NYHA.

Anker, Eu J of HF (2019) Yes
Confirmatory IDE clinical trial
(FIX-HF-5C) US, EU Optimizer® IVs 160 Randomized (CCM+OMT vs OMT alone), 6-months.
Multicenter pVO2, MLWHFQ, NYHA, safety, hospitalizations CCM significantly improved pVO2, MLWHFQ, and NYHA.

Abraham JACC:HF (2018) Yes
Confirmatory Extension Study
(FIX-HF-5C2) US, EU Optimizer® Smart (2-lead) 60 Prospective, single-arm, 6 months follow up period Multicenter pVO2, NYHA, CCM delivery, complications The 2-lead device is equally safe and effective as the 3-lead device and enables CCM in patients with atrial fibrillation.

Wiegn Circulation-HF (2019) Yes
A comprehensive individual patient data meta-analysis of the effects of cardiac contractility modulation on functional capacity and heart failure-related quality of life US, EU Optimizer® Smart (2-lead and 3-lead) 801 Single-patient Meta-analysis (please note this trial summarized data for existing CCM patients and did not include additional patients) QOL, exercise tolerance, functional capacity CCM provides statistically significant and clinically meaningful benefits in measures of functional capacity and HF-related quality of life.

Giallauria et al ESC Heart Failure (2020) Yes
Long-term clinical experience with cardiac contractility modulation therapy delivered by the Optimizer system (CCM-REG) EU Optimizer® Smart (3-lead) 503 Prospective registry, Multicenter NYHA, LVEF, hospitalizations for 2 years, survival for 3 years CCM improved functional status, QOL, LVEF, and, compared to patients’ prior history, reduced HF hospitalization rates. Survival at 1 and 3 years was significantly better than predicted by the MAGGIC score.

Kuschyk Eur J Heart Failure (2021) No (Anker et al publication is a sub-study from this cohort that includes patients matching FDA-labelled indication for CCM therapy)
Cardiac Contractility Modulation in Patients with Ischemic versus Non-ischemic Cardiomyopathy: Results from the MAINTAINED Observational Study
EU Optimizer® Smart (2-lead) 174 Retrospective, single center, observational study LVEF, TAPSE, NT-proBNP levels, NYHA functional class, and KDIGO CKD stage up to 5 years of follow-up CCM therapy improved LVEF by 5% (p = 0.0211) in NICM patients after 3 years and TAPSE by 3 units (p = 0.0437) after 5 years. No significant differences were seen in other parameters. 35% mortality observed in the cohort, with ICM patients showing lower than predicted mortality (35% vs. 43%, p = 0.0395) at 3 years.

Fastner Int J Cardiol 2021 No
Cardiac contractility modulation therapy improves health status in patients with heart failure with preserved ejection fraction: a pilot study (CCM-HFpEF)
EU Optimizer® Smart (2-lead) 47 Prospective, multicenter, single-arm, pilot study KCCQ OSS, Event-free rate for device- and procedure-related complications CCM therapy improved the KCCQ OSS score by 18.0 points (p < 0.001) in patients with HFpEF after 24 weeks. Significant improvements were also seen in the KCCQ CSS and total symptom score (p < 0.001). The event-free rate for device- and procedure-related complications was 93.6%, with no significant safety concerns.

Linde C Eur J Heart Fail (2022) No
Effects of Cardiac Contractility Modulation Electrodes on Tricuspid Regurgitation in Patients with Heart Failure with Reduced Ejection Fraction: A Pilot Study EU Optimizer® Smart (2-lead) 30 Single-center, prospective, observational study Severity of tricuspid regurgitation (TR) 6-month follow-up CCM therapy implantation did not worsen tricuspid regurgitation (TR) in HFrEF patients with ICD. The vena contracta (VC) value remained unchanged (0.40 ± 0.19 cm vs. 0.45 ± 0.21 cm, p = 0.33) and PISA radius also showed no significant difference (0.54 ± 0.22 cm vs. 0.62 ± 0.20 cm, p = 0.18).

Masarone, D J Clin Med (2022) No
One-Year Outcome of Cardiac Contractility Modulation in Patients With Reduced Ejection Fraction, Atrial Fibrillation, and Previous Resynchronization: A Pilot Study EU Optimizer® Smart (3-lead) 20 Prospective, single center, clinical trial NYHA, LVEF, 6MWT changes from baseline to 1 year follow-up CCM therapy improved LVEF by 9.92% (p < 0.0001), NYHA class by 1.8 classes (p < 0.0001), and exercise tolerance by 259.1 meters (p < 0.00001) in patients with atrial fibrillation and cardiac resynchronization therapy

Tint D, Am J Ther (2023) No
Mid term clinical outcomes and cardiac function in patients receiving cardiac contractility modulation
US Optimizer® Smart (2-lead) 31 Observational, single center, retrospective registry NYHA, Hospitalization rate, LVEF, diastolic dysfunction, weight change changes from baseline to 1.4 years CCM therapy improved NYHA by 0.97 classes (p < 0.001), hospitalizations (0.8 to 0.4/year, p = 0.048), EF by 8% (p = 0.002), weight loss by 8.5 lbs (p = 0.002).

Deak, A J Interv Card Electrophysiol (2024) Yes
Long-Term Renal Function with Cardiac Contractility Modulation Therapy EU Optimizer ® II, III, IV or Optimizer® Smart (2-lead) 187 Observational, retrospective, registry Changes in kidney function (Cr, eGFR) from baseline to 60 months
NYHA, LVEF, Hospitalization and CV events

eGFR and serum creatinine remained relatively stable overall. Improvements in functional status (NYHA) and LVEF were observed (P <0.01)

Yuecel, G Cardiorenal Med (2024) No

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February 7, 2025

Tamara Syrek Jensen, JD
Director, Coverage & Analysis Group
Centers for Medicare & Medicaid Services
7500 Security Blvd.
Baltimore, MD 21244

RE: CAG-00469N Cardiac Contractility Modulation for Heart Failure

The American College of Cardiology, Heart Rhythm Society, and Heart Failure Society of America represent the physicians and healthcare professionals dedicated to the care of heart failure (HF) patients undergoing cardiac contractility modulation (CCM). These societies strongly support a National Coverage Determination (NCD) for CCM in HF under coverage with evidence development (CED). We appreciate the opportunity to comment on the national coverage analysis (NCA).

CCM is a device-based therapy that delivers relatively high-voltage, long-duration electrical signals to the right ventricular (RV) septal wall during the absolute myocardial refractory period. CCM therapy has shown significant benefits in the management of HF. One of the key mechanisms by which CCM operates is by increasing intracellular systolic calcium, which acutely improves myocyte inotropy (Burkhoff et al., Am J Physiol, 2005). This enhancement in contractility occurs without a corresponding increase in myocyte oxygen consumption, making it an efficient therapeutic option (Lawo et al., JACC, 2005). Importantly, CCM therapy has been demonstrated to be safe and not proarrhythmic, addressing a critical concern in HF treatments (Neelagaru et al., Heart Rhythm, 2006).

Beyond its immediate effects, CCM also induces modifications in gene expression and surface proteins implicated in HF. These changes occur both locally and, after several weeks, in areas remote from the site of CCM therapy (Imai et al., JACC, 2007; Butter, JACC, 2008). In patients with an ejection fraction (EF) between 25% and 45%, CCM has been shown to improve the Minnesota Living with Heart Failure (MLWHF) score, NYHA Class, EF, ventilatory anaerobic threshold (VAT), and 6-minute walk test (6MWT) distance (Abraham et al., Am Heart J, 2008). Further studies have demonstrated that CCM improves VO2 and significantly reduces cardiovascular death and HF hospitalizations by 50% in this patient group (Kadish et al., Am Heart J, 2011; Abraham, JACC HF, 2018). These clinical trial findings have been repeated in a registry study, which showed similar outcomes: improvements in NYHA Class, MLWHF score, and EF (Kuschyk et al., Eur J Heart Fail. 2021; Yucel G, Pacing Clin Electrophysiol, 2022).CCM therapy has similar effects in patients with both ischemic and non-ischemic cardiomyopathy (Fastner, Int J Cardiol, 2021). It also improves cardiac diastolic function and promotes weight loss in HF patients (Deak et al., Interv Card Electrophysiol, 2024). Long-term studies indicate that, unlike the typical decline seen in HF patients, renal function remains stable in those receiving CCM (Yuecel et al., Cardiorenal Med, 2024).Additionally, in HF patients with prolonged QRS duration (120-149 msec), CCM improves NYHA Class, reduces HF hospitalizations, and enhances EF and MLWHF score to a similar degree as in those with a QRS duration of less than 120 msec (Fastner et al., Heart Rhythm, 2024). These findings collectively underscore the efficacy and safety of CCM therapy in improving clinical outcomes for HF patients, making it a valuable addition to the therapeutic arsenal for this condition.

Patient Criteria

The Optimizer Smart Mini system is currently the sole CCM device approved by the U.S Food & Drug Administration (FDA). The Optimizer is indicated to improve 6-minute hall walk distance, quality of life, and functional status of NYHA Class III heart failure patients who remain symptomatic despite guideline directed medical therapy, are not receiving Cardiac Resynchronization Therapy (CRT), and have a left ventricular ejection fraction ranging from 25% to 45%. The Societies broadly supports applying the FDA-approved indications to the patient coverage criteria.

NYHA Class III:
Typically, NYHA Class is determined through clinical history, which has been widely accepted for decisions regarding defibrillator implants and CRT candidacy. While advanced testing such as 6MWT or Cardiopulmonary Exercise Testing (CPET) could provide more precise differentiation of symptoms, these tests may not be widely available and could pose an obstacle to accessing beneficial therapy due to their cost and availability.

Left Ventricular Ejection Fraction 25-45%:
Current FDA approval for CCM does not specify the method of EF assessment. Transthoracic echocardiogram is generally accepted for EF assessment. Although the FDA has approved CCM for patients with an EF of 25-45%, data from Europe suggests that patients with EF <25% benefit similarly to those with EF >25% (Kuschyk et al., Eur J Heart Fail. 2021; Yucel et al., Pacing Clin Electrophysiol, 2022). Coverage could be extended to patients with EF <25% if FDA approval is obtained.

On Guideline-Directed Medical Therapy:
This requirement is prevalent across nearly all criteria for advanced HF therapies, and all data on CCM is in patients who are on guideline-directed medical therapy (GDMT).

Not Candidates for CRT:
It is crucial that the patient coverage criteria use more specific language than "not receiving CRT." The prior FDA criteria, “not candidates for CRT” was clearer. The current language, “not receiving CRT”, may allow for simply turning off CRT before a CCM implant and then reactivating it afterward. We ask for clarification, although not necessarily limitation. For example, there is some evidence which suggests that CRT non-responders may benefit from CCM, though more investigation is necessary (Kuschyk et al., Int J Cardiol. 2019). As CRT non-responders may have no other options for symptom palliation, CCM may be appropriate to use. Additionally, the data suggests that CCM benefits patients who are not suitable for CRT and may provide similar advantages to CRT (Yuecel et al., ESC Heart Fail. 2024). This supports the idea that we should strive to make CCM accessible to all patients who could benefit from it. However, more investigation is needed to understand the effect of CCM in CRT non-responders. As more robust research becomes available, CMS should consider updating the patient criteria.

Institution & Operator Criteria

CCM implant procedures closely resemble those for pacemakers, so the institutional requirements for CCM can be aligned with those for pacemaker implants. Physicians who are qualified to implant cardiac pacemakers and implantable cardiac defibrillators should also be deemed capable of implanting CCM devices, as they possess the necessary technical skills and experience to manage the more complex cases typically seen in sicker HF patients. However, specific considerations must be taken into account. For patients with concomitant defibrillators, it is appropriate to require training or licensure in Cardiac Electrophysiology, as assessing any interaction between the CCM device and the Implantable Cardioverter Defibrillator (ICD) during the procedure is necessary.

It is necessary to awaken the patient mid-procedure to assess for pain with active CCM therapy, which may not be feasible with "conscious sedation" alone. Therefore, CCM placement may need to be performed with local anesthesia only or at hospitals where short-acting drip medications can be used for sedation.

Health Disparities and Equity

Health disparities and equity are critical considerations in the implementation of CCM therapy. As with all therapeutic opportunities, obstacles to qualification—such as the need for more testing and additional visits—disproportionately affect patients with lower socioeconomic status and those in underserved areas. These barriers can limit access to CCM for the very patients who might benefit the most. HF symptoms are extremely severe, similar to those experienced by patients on dialysis and with major depressive disorder (Juenger et al., Heart, 2002). With an average survival rate of only 50% at five years (Taylor et al., Brit Med J, 2019), it is crucial to ensure that CCM therapy is accessible to our sickest patients, whose time remaining is the most valuable because of limited longevity. Moreover, the timing of CCM implantation is essential for achieving optimal outcomes. Evidence from cardiac resynchronization therapy (CRT) shows that earlier implantation after meeting criteria is associated with better mortality rates and reduced HF hospitalizations (Leyva et al., EP Europace, 2023). Therefore, any obstacles to qualification and coverage that delay CCM implantation could significantly mitigate its benefits. Addressing these disparities and ensuring equitable access to CCM is vital for improving outcomes and quality of life for HF patients.

Essential Conditions for CCM Success and Urgent Research Priorities
To achieve the outcomes demonstrated in clinical studies for CCM, specific treatment conditions must be met. Patient selection is paramount, as excluding patients with comorbidities that would negate improvements from CCM is critical. While improving systolic function theoretically enhances mortality, this benefit should not be assumed in the absence of symptom improvement. For instance, a patient with morbid obesity might experience an improvement in EF but still remain short of breath. Until more definitive data demonstrates a mortality benefit from CCM, it would be premature to recommend it solely for mortality improvement without symptom relief. The CCM-REG study suggested that patients with an EF between 25% and 45% had better-than-expected mortality rates compared to the MAGGIC score, but this finding has not been conclusively determined (Kuschyk et al., Eur J of Heart Fail, 2019).

Future research should urgently address several key questions. One area of investigation is whether single-lead CCM can achieve similar outcomes to two-lead CCM. A small study indicated this might be true, which could alleviate concerns about tricuspid regurgitation caused by multiple leads across the tricuspid valve. If single-lead CCM proves equally effective, it could reduce morbidity related to infections and device extraction in the future (Röger et al., J Cardiol, 2017). Another critical area is the timing of CCM implantation. It has been shown that the timing of cardiac resynchronization therapy (CRT) affects outcomes, and similar investigations are needed for CCM to determine if earlier or later implantation influences patient results (Leyva et al., EP Europace, 2023). Additionally, in a population already vulnerable to both atrial and ventricular arrhythmias, it is essential to explore whether CCM reduces the burden of arrhythmias, including the risk of defibrillator therapies such as anti-tachycardia pacing and shocks. Addressing these questions with urgency will help optimize CCM therapy and improve outcomes for heart failure patients.

There is also an ongoing study evaluating a combined CCM and ICD device. This device aims to provide both therapies in a single implant, potentially reducing the number of procedures patients with heart failure may require. Given the potential benefits of this combined device, it may be necessary to establish specific qualifications for future Medicare coverage. These qualifications could ensure that patients who would benefit most from this "higher use" device—those at high risk for both heart failure symptoms and sudden cardiac death—have access to it. By doing so, we can limit the total number of procedures these patients may need, improving their overall quality of care and reducing healthcare costs.

CED Requirements
Coverage with Evidence Development (CED) is an extremely powerful mechanism offering significant value to payers, clinicians, and patients. CED has been demonstrated to be an ingenious technique allowing the diffusion of diverse innovative cardiovascular technologies and services into the marketplace while simultaneously promoting timely clinical safety and effectiveness evaluations. The societies support the use of CED to provide Medicare beneficiaries with prompt access to newer technologies and services when early evidence suggests, but does not yet convincingly demonstrate, a net benefit for beneficiaries.

Registry Participation
The societies recommend that the heart team and hospital participate in a prospective, national, audited registry. The success of the National Cardiovascular Data Registry (NCDR) is well-established. It is recommended that reporting to the NCDR EP Device Implant RegistryTM under CED will facilitate understanding of patient selection, post-market surveillance, outcome measurement, and comparative effectiveness research for this emerging technology. The existing EP Device Implant Registry is accepting data on CCM procedures as of January 2025.

Participation in society-run registries is essential for several reasons:

1. Real-World Insights: These registries capture data from routine clinical practice, providing insights into how treatments and interventions perform outside the controlled environment of clinical trials. This real-world relevance is vital for understanding the practical effectiveness of medical procedures and treatments.


2. Longitudinal Data: Society-run registries often track patients over time, allowing for the collection of longitudinal data. This data reveals trends, which are valuable for assessing the effectiveness and safety of treatments over time, as well as determining if a treatment is reasonable and necessary.


3. Breadth of Data: By including data from a wide range of institutions and patient populations, the NCDR provides a comprehensive picture of how treatments work across different demographics and clinical settings. This variety ensures that the findings are applicable to a broad spectrum of patients and hospitals.

The societies support Medicare coverage of CCM therapy for HF and appreciate the opportunity to provide feedback on the NCA. Please direct any questions or concerns to Amanda Stirling, Regulatory Affairs Associate, at 202-375-6553 or astirling@acc.org.

Sincerely,

Cathleen Biga, MSN, FACC
President, American College of Cardiology

Kenneth A. Ellenbogen, MD, FHRS
President, Heart Rhythm Society

Michael Felker, MD, FHFSA
President, Heart Failure Society of America

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Yuecel G, Yazdani B, Schreiner K, et al. Long-Term Renal Function with Cardiac Contractility Modulation Therapy. Cardiorenal Med. 2024;14(1):385-396.
Fastner C, Varma N, Rao I, et al. Cardiac contractility modulation in heart failure with reduced ejection fraction patients with QRS duration 120-149 ms: Reduction in heart failure hospitalizations and improvement in functional outcome. Heart Rhythm. 2024 Sep 19:S1547-5271(24)03366-6.
Kuschyk J, Nägele 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 Feb 15;277:173-177.
Juenger J, Schellberg D, Kraemer S, et al. Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables. Heart. 2002 Mar;87(3):235-41.
Taylor CJ, Ordóñez-Mena JM, Roalfe AK, et al. Trends in survival after a diagnosis of heart failure in the United Kingdom 2000-2017: population based cohort study. BMJ. 2019 Feb 13;364:l223.
Leyva F, Zegard A, Patel P, et al. Timing of cardiac resynchronization therapy implantation. Europace. 2023 May 19;25(5):euad059.
Röger S, Said S, Kloppe A, et al. Cardiac contractility modulation in heart failure patients: Randomized comparison of signal delivery through one vs. two ventricular leads. J Cardiol. 2017 Jan;69(1):326-332.

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Heart failure is a complex clinical syndrome that currently affects an estimated 6 million adults in the United States and will only increase in prevalence in the coming years. Moreover, heart failure is projected to cost at least $70 billion annually in the United States by 2030 (Pipilas et al., 2023). The projected economic burden of heart failure underscores the need for effective treatments that not only improve patient outcomes but also reduce the financial strain on healthcare systems. Given these sobering statistics and the knowledge that heart failure is a leading cause of mortality, treatment modalities that can improve heart failure symptoms, reduce cardiovascular deaths, and decrease heart failure admissions are supported by the American Association of Heart Failure Nurses (AAHFN). Cardiac Contractility Modulation (CCM) is one such FDA-approved therapy that research has shown to improve six-minute walk test scores, improve New York Heart Association functional class (fewer symptoms for patients), increase peak VO2, and reduce heart failure hospitalizations (Pipilas et al., 2023). Several randomized and nonrandomized clinical trials have demonstrated the clinical benefits of CCM in patients with heart failure on mortality and quality of life (Pipilas et al., 2023). Given the plethora of evidence supporting the use of CCM, the AAFHN endorses the use of CCM when clinically appropriate in the care of heart failure patients to promote optimal patient outcomes. We ask CMS to consider the positive impact of this device when making a final decision on a national coverage determination for CCM.

Thank you

Reference:
Pipilas, D. C., Hanley, A., Singh, J. P., & Mela, T. (2023). Cardiac Contractility modulation for heart failure: current and future directions. Journal of the Society for Cardiovascular Angiography & Interventions, 2(6), 101176. https://doi.org/10.1016/j.jscai.2023.101176

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I appreciate the opportunity to comment in support of a National Coverage Decision for CCM. My particular involvement with the treatment has occurred for > 10 years and primarily manifest in significant research as Director of Electrophysiologic Services at the University of Kentucky. Over time my work has included efforts to fill the deficit in technical knowledge for managing the therapy (Hesselson AB. Cardiac contractility modulation: a technical review. J Innov Cardiac Rhythm Manage. 2022;13(9):1-14), as well determining if genetic link(s) exist within non-ischemic cardiomyopathy that may predict super-response to the treatment (Hesselson AB et al. Normalization of ventricular function after cardiac contractility modulation in noncompaction cardiomyopathy heterozygous positive for a pathologic TTN gene variant. Heart Rhythm Case Reports 2022;8:449-452; Hesselson AB et al. Genetic cardiomyopathy and significant systolic heart failure treated with cardiac contractility modulation. Heart Rhythm O2 2024;5:592-596.)
Genetic data are non-existent within all other studies to date. Thus, it is unknown how well represented genetic cardiomyopathy is within the randomized trials to date. Our data may explain the greater response to the therapy on average in non-ischemic cardiomyopathy versus ischemic as represented in the European registry data. This is not to say, however, that ischemic cardiomyopathy patients may not benefit as well to the treatment. They certainly have in my experience. Thank you for the opportunity to support the NCD.

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I strongly support the Centers for Medicare & Medicaid Services (CMS) in undertaking a National Coverage Analysis (NCA) for Cardiac Contractility Modulation (CCM). CCM represents a significant advancement in the management of heart failure, offering therapeutic benefits to patients who have limited options under current standard treatments. A comprehensive review and potential nationwide coverage of CCM would allow Medicare beneficiaries to access this evidence-based, innovative therapy, reduce health disparities, and promote equity in cardiovascular care.

CCM therapy has demonstrated significant clinical benefits in managing symptomatic heart failure patients, particularly those with reduced ejection fraction (HFrEF) who remain symptomatic despite guideline-directed medical therapy (GDMT). Numerous peer-reviewed studies provide robust evidence for CCM's efficacy and safety:

FIX-HF-5 and FIX-HF-5C Trials: These pivotal trials evaluated CCM therapy in patients with HFrEF and demonstrated improved quality of life, functional capacity, and exercise tolerance, as measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and peak oxygen consumption (VO2). FIX-HF-5C specifically identified CCM benefits in patients with EF between 25–45%, filling a gap where treatment options are often inadequate.

Meta-Analyses and Long-Term Outcomes: A meta-analysis of multiple CCM trials showed significant improvements in patient-reported outcomes, exercise tolerance, and a reduction in hospitalizations for heart failure exacerbations. These findings underscore the role of CCM in improving morbidity and quality of life.

Safety and Device Performance: Prior studies have highlighted the safety of CCM devices, with low rates of device-related complications and a high success rate in achieving sustained therapeutic benefit.

Heart failure disproportionately affects underserved populations, including racial and ethnic minorities and those with socioeconomic disadvantages. Barriers to advanced therapies, such as the cost of implantation and device coverage, exacerbate health inequities. National coverage for CCM would address these disparities by: (1) Expanding access: CMS coverage would make CCM therapy available to Medicare beneficiaries, particularly those in low-income and rural areas who cannot afford out-of-pocket expenses for emerging technologies; (2) Reducing hospitalizations and economic burden: By improving functional capacity and quality of life, CCM could reduce heart failure-related hospitalizations, a significant driver of healthcare costs for patients and CMS alike. Reducing preventable hospitalizations would benefit socioeconomically disadvantaged populations who are more likely to face financial hardship from medical care; and (3) Encouraging provider and patient awareness: A NCA could facilitate greater awareness of CCM among providers and patients, ensuring equitable consideration of this therapy for all eligible individuals, regardless of socioeconomic or geographic factors.

A National Coverage Analysis for CCM would represent a critical step in addressing the unmet needs of heart failure patients, ensuring equitable access to evidence-based care, and fostering innovation in cardiac care delivery. I urge CMS to move forward with this analysis, recognizing the significant potential of CCM to improve patient outcomes, reduce disparities, and support the broader goals of equitable healthcare delivery.

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Cardiac contractility modulation (CCM) is an important therapy for patients with symptomatic heart failure who are not candidates for cardiac resynchronization therapy (CRT). With careful patient selection, CCM can deliver meaningful benefits, including significant reductions in heart failure symptoms and, in many cases, improvement in left ventricular ejection fraction. Currently, CCM stands as the only proven therapy within the electrophysiology space for this specific patient population. Expanding access to CCM has the potential to benefit a broader group of similar patients, solidifying its role as a critical therapy now and in the future.

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As a cardiac electrophysiologist working directly with heart failure patients, I have seen first hand the magnitude of benefit provided by the cardiac contractiltiy modulation (CCM) device. There is sound clinical research and science demonstrating its effectiveness. Our practice has been utilizing this device in our patients for the last several years and have seen improvement in both clinical heart failure symptoms as well as objective measurements in LVEF in a patient population who had little to no other therapeutic options. The fact that it is implanted similar to a CIED allows for a quick learning curve for new implanters as well. I ask that you strongly consider a National Coverage Determination for the CCM device.

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Dear CMS,

As a healthcare provider who has witnessed the positive impact of Cardiac Contractility Modulation (CCM) devices in my patient population, I strongly support national coverage of CCM by CMS. CCM has proven to be an outstanding therapeutic option for select heart failure (HF) patients who remain symptomatic despite guideline-directed medical therapy (GDMT) and are ineligible for cardiac resynchronization therapy (CRT).

In my practice, patients who have received CCM therapy have reported significant improvements in quality of life, functional capacity, and exercise tolerance. One patient in particular, a Medicare beneficiary with advanced HF and persistent symptoms, experienced not only symptomatic relief but also an enhanced ability to engage in daily activities that were previously challenging. Some patients also experienced improvement in the heart function as measured by ejection fraction. This aligns with the device’s mechanism of action, which strengthens heart contractions and addresses the unmet needs of a challenging patient population.

From a health equity perspective, expanding coverage for CCM ensures that more patients, regardless of socioeconomic status, have access to this innovative therapy. This is critical, as HF disproportionately affects underserved populations, and therapies like CCM can help reduce disparities by improving outcomes in these vulnerable groups. The current barriers put up by insurance companies to obtain access to this FDA approved technology are unbearable, unjust and simply put harm our patients.

I endorse CMS's efforts to evaluate and potentially expand coverage for CCM through the TCET pilot. This technology has the potential to significantly impact HF management, enhance overall quality of life and hopefully also result in a downstream reduction of hospitalizations. I encourage CMS to consider the growing body of evidence supporting the efficacy and safety of CCM and to prioritize equitable access for all Medicare beneficiaries.

Thank you for considering this important step toward advancing care for heart failure patients.

Marat Fudim, MD, MHS
Associate Professor
Duke University Medical Center

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I am writing to provide input regarding the National Coverage Analysis (NCA) for Cardiac Contractility Modulation (CCM) therapy for heart failure. This comment includes an overview of some of the scientific evidence supporting CCM therapy and considerations related to health disparities and equity that are pertinent to the review process.

Scientific Evidence Supporting CCM
CCM therapy has emerged as a promising treatment option for patients with heart failure who remain symptomatic despite guideline-directed medical therapy (GDMT). Multiple peer-reviewed studies, including randomized controlled trials and real-world registry data, have demonstrated the safety and efficacy of CCM in improving functional capacity, quality of life (health status), and exercise tolerance in this patient population. For example:

FIX-HF-5 Study: This pivotal trial showed significant improvements in exercise tolerance (measured by peak VO2) and quality-of-life metrics (Minnesota Living with Heart Failure Questionnaire scores) in patients with NYHA class III or IV heart failure with reduced ejection fraction (HFrEF) receiving CCM therapy compared to control groups.

FIX-HF-5C Confirmatory Study: This study further validated the effectiveness of CCM in a broader range of patients, including those with an ejection fraction between 25% and 45%, highlighting its utility beyond traditional primary prevention ICD populations. We also observed reduced mortality and hospitalizations for heart failure for patients treated with CCM, although this study was not powered for detecting these differences as prespecified endpoints.

Registry Data: Real-world evidence, such as the European CCM Registry, underscores the long-term safety and efficacy of CCM therapy in improving patient-reported outcomes and reducing hospitalizations for heart failure.

Addressing Health Disparities and Equity
While CCM offers significant promise for all candidate patients with heart failure, presently only patients with regular Medicare have clear access to the therapy. Patients with Medicare Advantage, Medicaid, Commercial or Self-Pay have significant barriers to access, which contributes to furthering of disparities and marginalization of underrepresented groups.

Geographic and Socioeconomic Barriers: Patients in rural or underserved areas often face limited access to advanced heart failure therapies. Expanding CMS coverage of CCM could reduce these barriers and enhance equity in heart failure care.

Underrepresentation in Clinical Trials: Historically, clinical trials for heart failure therapies, have underrepresented women, racial and ethnic minorities, and low-income populations. CMS should encourage post-approval studies and data collection that focus on these populations to ensure equitable benefits across diverse groups.

Cost Implications: The cost of advanced therapies often disproportionately affects underserved populations. Coverage by CMS could alleviate financial burdens, enabling more equitable access to this life-improving technology.

Conclusion
In summary, the available scientific evidence supports the safety and efficacy of CCM therapy as an adjunctive treatment for patients with heart failure. Including CCM in the CMS coverage policy would provide significant benefits, particularly for populations that are often underserved or experience disparities in access to care. I strongly urge CMS to consider the evidence, along with equity implications, to ensure that all eligible patients can access this potentially life-changing therapy.

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Several of my patients in whom this therapy has been utilized have experienced a profound improvement in their quality of life. I have seen a 30-year-old mother whose dream was to simply walk around the block with her toddler without having to stop several times be able to swim daily and exercise daily like a normal 30-year-old woman since her CCM was implanted. I have seen men who struggled to bring the trash can out to the curb and walk back home feeling exhausted that can now shop around Walmart without any problems. These are people who are on maximal medical therapy with primary purpose of reducing the patient's threat of death and hospitalization but not necessarily addressing to any substantial degree their quality of life. As such, I would urge that this therapy be kept available and offered as a hope for a better quality of life for our patients who suffer from life - limiting heart failure symptoms.

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