Cardiac contractility modulation for the treatment of moderate to severe HF

ABSTRACT

Introduction: Heart failure (HF) affects over 6 million Americans and approximately 650,000 new cases are diagnosed annually, with patients evenly split between HFrEF and HFpEF. Recent advances in therapy for these patients have been limited to pharmaceutical agents, with CRT remaining the most reliable device therapy option since its advent almost twenty years ago. In 2019, after almost two decades without the introduction of a new device therapy for the treatment of moderate HF, the FDA approved CCM® therapy, delivered by the Optimizer Smart device, for patients with NYHA Class III HF who are on guideline-directed medical therapy (GDMT), in normal sinus rhythm (NSR), and with EF ranging from 25% to 45%, and who are ineligible for CRT.

Areas covered: Multiple clinical trials support the use of CCM to improve quality of life, functional class, and 6-min hall walk distance. This article will discuss the science behind CCM therapy, the presumed mechanisms of action, the pre-clinical studies that shaped subsequent endeavors, and the clinical trials that support its use.

Expert opinion: The introduction of CCM therapy bridges a therapeutic gap for patients with few or no other therapeutic options for NYHA III heart failure.

KEYWORDS:

• Cardiac contractility modulation
• CCM
• heart failure
• HFrEF
• HFpEF
• optimizer
• SERCA2a

Article highlights

• CCM is a novel therapy that uses high voltage currents delivered during the absolute refractory period (ARP) of the cardiac cycle.

• The Optimizer Smart device and two commercially available pacing leads with low polarization coating are implanted in a procedure similar to dual-chamber pacemaker implantation, with complication rates and recovery times that parallel that procedure.

• The mechanisms of action are felt to be twofold:

  • Improvement of calcium handling within the myocyte.

  • Normalization of abnormal gene expression seen in HF.

• The improvement in contractility does not come at the expense of increased myocardial oxygen consumption (MVO₂).

• Clinical trials have demonstrated improvement in peak VO_2, six-minute walk distance (6 MW), and New York Heart Association (NYHA) functional class.

• Patients indicated for CCM include those with:

  • NYHA Class III status.

  • EF 25–45%.

  • Normal sinus rhythm at the time of implantation.

  • No current indication for CRT.

Information resources

www.impulse-dynamics.com

Declaration of interest

I Rao is employed as the Medical Director of Impulse Dynamics; and is the owner of stock options in Impulse Dynamics. D Burkhoff is a consultant to Impulse Dynamics; and is the owner of stock options in Impulse Dynamics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.