Leadless CRT a Safe, Effective Way to Deliver Pacing: SOLVE-CRT

Leadless pacing within the LV endocardium via the WiSE CRT System (EBR Systems) is a safe and effective option for cardiac resynchronization therapy (CRT), according to results from the SOLVE-CRT study.

“This novel system may represent an alternative to conventional CRT implants in some HF patient populations,” Jagmeet P. Singh, MD, DPhil (Massachusetts General Hospital, Boston), and colleagues conclude in a recently published JAMA Cardiology paper. Around 40% of patients with heart failure who are eligible for conventional CRT, they point out, “either fail to respond or are untreatable due to anatomical constraints.”

The WiSE CRT System uses a transmitter to send ultrasonic energy to a wireless receiver implanted within the endocardium, which the receiver then converts into electrical energy to pace the LV. The transmitter, powered by a battery implanted subcutaneously at the left midaxillary line, is synchronized with RV pacing—the latter is provided by an existing pacemaker, implantable cardioverter defibrillator, or CRT. Notably, WiSE CRT received CE Mark approval in Europe nearly a decade ago and received a Breakthrough Device Designation from the US Food and Drug Administration in 2019.

Singh predicted that WiSE CRT could see broader use beyond biventricular pacing—the subject of the SOLVE-CRT study—amid growing enthusiasm for conduction-system pacing, which directly activates the heart’s conduction system at the level of the His bundle or left bundle branch (LBB).

“This leadless approach allows you to individualize now where you pace the heart,” Singh told TCTMD. “So you can actually potentially in the future pace the electrical axis inside the heart and optimize the way you’re delivering electrical energy. . . . Certainly, in the future I think none of us are going to be putting leads in the heart.”

Fred M. Kusumoto, MD (Mayo Clinic, Jacksonville, FL), in an invited commentary, agrees that WiSE CRT is innovative and says it offers several potential advantages “since the receiver can be placed anywhere in the left ventricle to deliver more physiologic endocardial stimulation without anatomic constraint.”

While the current study had relatively short follow-up and did not address patients who fail to respond to conventional CRT, Kusumoto cautions, it still speaks to the future. “More fundamentally, this technology is the harbinger for a world of connected and innovative devices that use different strategies and modalities to communicate, with the ultimate and hoped-for promise that these links will lead to better health for all,” he comments.

Safety Improved With Experience

SOLVE-CRT, which enrolled patients between January 2018 and September 2022 at 36 centers across Australia, Europe, and the US, experienced some hiccups along the way. Initially it was designed as a randomized trial of treatment versus control in three groups:

• Previously untreatable (PU) patients who had a full or partial CRT system but because of a failed LV lead were not receiving CRT
• Patients with high-risk upgrades (HRU), a group that included those whose initial CRT had implantation or lead issues but were not suitable for a standard CRT upgrade, as well as those with a leadless intracardiac pacemaker requiring an upgrade to CRT
• Nonresponders who, due to various pathophysiological reasons, had suboptimal responses to conventional CRT

When the COVID-19 pandemic upended research, however, the study paused recruitment in March 2020. With input from the FDA, SOLVE-CRT investigators then added a single-arm nonrandomized component that enrolled an additional 75 patients, either PU or HRU, as a way of completing the study. The trial was terminated in 2023 after meeting prespecified criteria.

Ultimately, SOLVE-CRT included 183 PU/HRU patients (68.1 years; 77% male) who were implanted with the WiSE CRT system—the nonresponders who enrolled in the trial’s first few years were excluded from analysis. Around two-thirds were NYHA class III and the rest were class II.

Freedom from type 1 complications through 6 months, the study’s primary safety endpoint, was 80.9% (exceeding the performance goal of 70%; P < 0.001). Complications included 12 study device system events (6.6%), five vascular events (2.7%), and three strokes (1.6%). Seven cardiac perforations (3.8%) occurred in the first 2 years of the study—four treated with surgery and three with pericardiocentesis—after which operators were required to do refresher training on an implant simulator before every case and to use real-time echocardiography. Subsequently, two perforations occurred and neither required surgical treatment.

Reduction in mean LV end-systolic volume (LVESV), the study’s primary efficacy endpoint, was assessed in 100 PU/HRU patients: 75 from the single arm and 25 from the randomized treatment arm. This endpoint was also met, with a 16.4% reduction in mean LVESV (exceeding the performance goal of a 9.3% reduction; P = 0.003).

Certainly, in the future I think none of us are going to be putting leads in the heart. Jagmeet P. Singh

In his editorial, Kusumoto says the learning curve early in the study isn’t surprising and praises the addition of training and other measures to counter complications. “This lesson of continued surveillance should be extended to the introduction of any new technology into clinical practice and emphasizes the necessity for meticulous planning, continuous evaluation, and review,” he writes.

And while the efficacy of WiSE CRT is less than what was seen for the conventional approach in the 2014 MADIT-CRT trial, Kusumoto says this likely relates to differences in patient characteristics and the effects of modern guideline-directed medical therapy.

The possible applications of leadless pacing are many, according to Kusumoto.

“In addition to cardiac stimulation, the ability to transform acoustic energy into electrical energy could be beneficial for stimulating the nervous system, eg, spinal nerve stimulation to treat back pain, phrenic nerve stimulation for central sleep apnea, or vagal nerve stimulation for the treatment of arrhythmias,” he writes. “Even more, the WiSE-CRT system provides proof of concept that separate implanted devices from different manufacturers can communicate and coordinate therapy, in this case using combined sensed electrical signals and ultrasound.”

Singh highlighted two studies that are currently underway: TLC, in which WiSE is being paired with a leadless pacemaker, as well as ACCESS-CRT, in which WiSE is specifically targeting the LBB. Going forward, it will be important to continue developing the technology with an eye toward operator’s ease of use, lengthening battery life, and other improvements, he said.

According to manufacturer EBR Systems, once launched, the market size in the United States alone could exceed 90,000 WiSE CRT devices sold per year at a cost of $35,000-45,000 each.