It was encouraging to see the focus on device-based therapy for heart failure patients in your recent editorial entitled “Neuromodulation for Heart Failure: An EP Perspective.”1 Advances in treating heart failure have been slow to arrive, and for nearly two decades cardiac resynchronization therapy (CRT) has stood as the singular device-based therapeutic option. Now, in the last year alone, we have seen two new entrants in this space (cardiac contractility modulation [CCM] therapy and baroreflex activation therapy [BAT]); either greatly enhances our capability to improve patients’ lives.
CCM therapy delivers high-amplitude (7.5 V), long pulse width (20 ms) electrical therapy during the cardiac absolute refractory period. Importantly, it is non-excitatory, non-pro-arrhythmic, and does not risk R-on-T phenomena. Instead, it phosphorylates key proteins and improves calcium handling (notably, by improving SERCA2a reuptake of calcium into the sarcoplasmic reticulum), thus increasing cardiac contractility.2 CCM also induces reversal of abnormal, pathologic gene expression characteristics in the failing heart, returning them to a normal “adult” gene expression.3 Together, these changes produce reverse remodeling.
Though CCM is new to the commercial U.S. market, it has been studied in over 1,500 patients in clinical trials and implanted in almost 5,000 patients worldwide.
Recent subgroup analyses of the FIX-HF-5 pivotal trial showed that NYHA III patients with an ejection fraction of 25-45%, who were ineligible for CRT and were in sinus rhythm at the time of implant, fared significantly better with CCM. This prompted the confirmatory FIX-HF-5C trial using these parameters as the inclusion criteria. Again, statistically significant improvement in peak VO2, 6MW, and QoL were seen. Importantly, a remarkable 81% of patients realized an improvement of ≥ one NYHA heart failure class, and 43% had improved by two classes!
The FDA states that the OPTIMIZER Smart System (Impulse Dynamics) “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, who are in normal sinus rhythm, are not indicated for Cardiac Resynchronization Therapy, and have a left ventricular ejection fraction ranging from 25% to 45%.”4
CCM is delivered via a pacemaker-like system (consisting of a pulse generator and two RV septal leads) and carries the same low level of procedural risk, short implant duration, and minimal post-op care. As such, it is uniquely able to deliver this remarkable therapy in a same-day outpatient procedure.
Recent Medicare policy changes in most states have opened access to CCM in outpatient facilities — the care setting most physicians find appropriate for this type of procedure. Transitional pass-through payment is now in place for CCM implants, and new technology add-on payments are recommended in the 2021 inpatient prospective payment system (IPPS) rule. As such, CCM is poised to be readily adopted by EP service lines.
Recent advances in device-based therapy for the treatment of refractory heart failure herald an encouraging new era for patients with heart failure. Patients with an EF ≤35% now have the possibility of improvement via CCM, CRT, or BAT, and CCM brings hope to those with an EF up to 45%.
Ishu V. Rao, MD
Medical Director, Impulse Dynamics
1 Knight BP. Neuromodulation for heart failure: an EP perspective. EP Lab Digest. 2020;20(7):6.
2 Lyon A, Samara M, Feldman D. Correction: Cardiac contractility modulation therapy in advanced systolic heart failure. Nat Rev Cardiol. 2014;11:188. doi:10.1038/nrcardio.2014.14
3 Butter C, Rastogi S, Minden HH, Meyhöfer J, Burkhoff D, Sabbah HN. Cardiac contractility modulation electrical signals improve myocardial gene expression in patients with heart failure. J Am Coll Cardiol. 2008;51(18):1784-1789. doi:10.1016/j.jacc.2008.01.036
4 Premarket Approval (PMA). U.S. Food & Drug Administration. Published March 22, 2019. Available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P180036. Accessed July 14, 2020.