By Sree Roy, SLEEP REVIEW Magazine

Respicardia remedē System

Respicardia remedē System

Information source: Robin Germany, MD, chief medical officer

Size: 39 cc (similar size to implantable cardiac defibrillators)

Implant location: The pulse generator is placed under the skin in either the right or left side of the upper chest. In most cases, physicians select the right side as cardiac devices are typically placed in the left side of the upper chest.

Lead location: The stimulation lead is placed transvenously in either the left pericardiophrenic vein or right brachiocephalic vein (in close proximity to the phrenic nerve for unilateral stimulation of the diaphragm). In some cases, physicians also place a sensing lead to monitor respiration.

How it works: During sleep, the remedē System delivers low amplitude electrical stimulation pulses to the phrenic nerve, contracting the diaphragm and restoring a normal breathing pattern and volume. The device turns on automatically each night.

Treats: Moderate to severe central sleep apnea in adult patients. This is usually defined as an AHI ≥ 15 events/hr with predominantly central events. In the pivotal trial, the mean AHI was 46 events/hr and the mean central apnea index was 28 events/hr.

Titration: The system is typically activated one month after implant. During this month, the device gathers data about the patient’s sleep habits (sleeping patterns, positional data, and nighttime respiration). Then the patient returns for activation, during which the device is individually programmed using the data. The device then auto-titrates over the next 4–6 weeks. This gives the patient time to acclimate to the therapy. A sleep study may be administered after titration to assess efficacy and/or direct the physician toward additional device programming to optimize results.

Future titrations: Physicians typically perform device checks 2 to 4 times per year. Diagnostic information (such as nighttime respiration, sleeping patterns, and the number of hours of delivered therapy) along with patient feedback can be used during an office visit to adjust device settings or program the device’s auto-titration, which allows for therapy adjustments for changing patient needs over time.

Overall efficacy: The remedē System pivotal trial met its primary endpoint, percentage of subjects demonstrating a ≥50% reduction in AHI, and all 7 secondary endpoints, comprehensively demonstrating improvements in sleep metrics, sleep quality, and quality of life. The remedē System is the only CSA treatment to demonstrate significant improvements in arousals, percent of REM sleep, or quality of life in a randomized trial (Costanzo MR, et al. Lancet. 2016;388:974-82. Costanzo MR, et al. Am J Cardiol. 2018;121:1400-18). 88% of patients demonstrated decreased apnea and hypopnea events, with a mean reduction of 81% in the central apnea index from baseline; 79% of patients reported a quality of life improvement; 95% of patients reported they would “elect to have the medical procedure again”; 91% freedom from serious adverse events; and 97% implant success rate.

Efficacy by demographic: Various subgroups were analyzed following the pivotal trial demonstrating treatment effects were consistent across subgroups. There are less women than men with CSA, but efficacy was the same in both men and women. Similar efficacy was seen when separated by age, including those over age 65. There was no difference in efficacy in patients with an AHI in either the moderate or severe range or in patients with atrial fibrillation. In light of the limited treatment options for patients with heart failure and CSA, Costanzo et al. showed in a post hoc analysis that the heart failure subgroup responded similarly to the non-heart failure cohort with regard to safety and efficacy (Constanzo MR, et al, European Journal of Heart Failure. 2018; doi:10.1002/ejhf.131).

Compliance monitoring: The system activates automatically each night, alleviating most compliance concerns. It retains approximately 30 days of data on nighttime respiration, sleeping patterns (positional, activity, etc), and hours of delivered therapy.

Long-term outcomes: Outcomes data has been published showing 6-, 12-, and 18-month results, and we expect our 24- and 36-month data to be published in mid-2019. Observed safety and efficacy have been consistent over time. We are following patients from the remedē System pivotal trial out to 5 years.

Third-party payer status: Aetna was the first private payer to cover the remedē System in early 2018. Also in 2018, CMS granted the remedē System a Transitional Pass-through Payment. The remedē System is also included on the Federal Supply Schedule for the VA. Until broad coverage is established, the remedē System is being reviewed by payers on a case-by-case basis.

To find physicians qualified to do the implant (list of current implant sites)

Surgeon appointment(s): This can vary, but the minimum visits include a follow-up visit approximately one month after the procedure to activate and begin auto-titration of the therapy. In most cases, at least one additional appointment would be needed in the next 3 months to assess the device diagnostics and optimize programming. These follow-up visits can be done in either the sleep clinic or with the implanting cardiologist.

Extraction information: Like a cardiac pacemaker, when the battery of the device nears expiration an electrophysiologist would replace the implanted pulse generator, requiring the previously implanted device to be extracted—a common, routine procedure. Occasionally, one or more of the leads also need to be replaced. While the experience and implant duration here is limited, we have thus far seen almost all extracted leads come out safely with simple traction. A small number required extraction techniques and instrumentation similar to cardiac pacemaker leads. Patients typically go home the morning after the extraction procedure.

Expected developments in the next 12 months: The focus will be working with 30-40 new centers to build out their sleep and cardiology suite of services to include the remedē System. There will also be some exciting advances in clinical and product development. New clinical data is expected to be published including 3-year follow-up from the pivotal trial and a meta-analysis combining the pilot and pivotal patient populations. Additionally, a multi-center, prospective, post-market trial is beginning enrollment now, seeking approximately 500 subjects in both the United States and Europe to collect additional safety and effectiveness data. Finally, the next generation of the system is underway, but we have not released a projected availability date.

Additional information: The remedē system activates the diaphragm to generate negative pressure, similar to how people breathe naturally. This is in contrast to the positive pressure generated from mask-based therapies. Users are highly compliant, as the device activates automatically each night when three conditions are met: 1) it is within the patient’s designated sleeping hours, 2) the patient is in a reclined position, and 3) the patient is not moving. The patient’s body is the controller—the patient can roll over or sit up to suspend therapy; the device will reactivate once the patient is still again.

A doctor will need to evaluate the patient’s condition to determine if the remedē System is appropriate. Patients will not be able to have an MRI or diathermy (special heat therapies) if the remedē System is implanted. The remedē System may be used with another stimulation device such as a heart pacemaker or defibrillator; special testing will be needed to ensure the devices are not interacting. As with any surgically implanted device, there are risks related to the surgical procedure itself which may include, but are not limited to, pain, swelling, and infection. Once the therapy is turned on, some patients may experience discomfort from stimulation and/or from the presence of the device. The majority of these events are resolved either on their own or by adjusting the therapy settings. The remedē System may not work for everyone. There are additional risks associated with removing the system. If it is decided to remove the system, another surgery will be required. Be sure to understand all of the risks and benefits associated with the implantation of the remedē System.

The remedē System is contraindicated for use in patients with an active infection or patients known to require magnetic resonance imaging (MRI). See the Instructions for Use for complete information regarding the procedure, indications for use, contraindications, warnings, precautions, and potential adverse events.

More information: Costanzo MR, et al. Transvenous neurostimulation for central sleep apnoea: a randomised controlled trialLancet. 2016;388:974–82.