VIDEO: Jagmeet Singh details the SOLVE-CRT study for a leadless CRT system
Jagmeet Singh, MD, professor of medicine with Harvard Medical School and founding director of the Resynchronization and Advanced Cardiac Therapeutics Program and Mass General Hospital, explained results from the SOLVE-CRT pivotal clinical trial he presented as a late-breaker at Heart Rhythm 2023. The trial was designed to see if leadless pacemaker technology can deliver cardiac resynchronization therapy (CRT) to patients who were not able to be treated with conventional CRT and epicardial leads.[1]
For many patients with heart failure, their two ventricles end up beating at different times in a dyssynchronous rhythm. The current standard of care to achieve synchrony is CRT, which uses pacing to synchronize the contraction of the right and left ventricles. However, lead-based pacemakers have known limitations and up to 30% of patients fail to benefit from this therapy. This trial was designed to address that population.
"The SOLVE-CRT trial looks at the roll of a leadless, ultrasound-based cardiac resynchronization therapy, primarily for patients who are unable to get CRT therapy, are at high risk, and also some patients who are non-responders," Singh explained. "I think this system allows more refined targeting of wherever you want to get the electrode. Also, this is endocardial pacing. Resynchronization therapy traditionally is done through the coronary sinus, which is epicardial to endocardial, so it is actually a reversal of the transmural gradient, which is non-physiological."
The endocardial, leadless technology is enabled by a tiny, catheter-delivered transducer, about the size of a grain of rice. This receiver is then stimulated by an ultrasound transmitter implanted subcutaneously just beyond the midaxillary line, which is powered by an implanted battery pack. The electrode coverts the ultrasound energy into electrical energy to enable pacing. The EBR Systems Inc. WiSE CRT system works in concert with existing implanted device that can pace the right ventricle.
Singh said this technology helps better resynchronize the heart than traditional CRT lead placements. It also can do selective induction pacing.
Another advantage of the system is that it is leadless, reducing potential complications and infection issues.
"Our results showed the study was safe, effective and feasible," Singh said.
The SOLVE-CRT study was a prospective, international, multicenter pivotal trial that included a randomized arm and a subsequent single-arm. The randomized part of the study was initially intended to enroll 350 patient participants for three indications. This included patients who were non-responders (NR), those previously untreated, including acute and chronic lead failures (PU), and patients undergoing high-risk upgrades (HRU) from existing implanted cardioverter defibrillators (ICD). All participants underwent device implantation and were then randomized in 1:1 ratio to treatment (system turned on) or control (system turned off) groups. A total of 108 participants were enrolled by March 2020, when enrollment was halted due the COVID-19 pandemic.
The single arm part of the study was approved by the U.S. Food and Drug Administration (FDA) during the pandemic and was designed to enroll up to an additional 192 participants within two indications of PU and HRU. An interim analysis was conducted after 75 participants were enrolled. Data from all 183 participants in both parts were included in the interim safety analysis.
The primary safety endpoint for the SOLVE-CRT study was freedom from Type I (device and procedure-related) complications through six months. Efficacy analysis included all participants in the single arm (75) and those randomized to treatment from the PU and HRU groups only (25), for a total of 100. The primary efficacy endpoint was the improvement in left ventricular systolic volume (LVESV). The study looked at the impact of the EBR system in preventing reverse remodeling, which was set at changing the end systolic volume below a threshold 9.3%.
"We had a success rate of 16.4%, so we really beat that threshold," Singh explained
The WiSE CRT was shown to be safe with an 80.9% freedom from Type I complications from the system and the procedure.
Since both primary endpoints were met at this interim analysis, study enrollment was concluded early.
"Because heart failure is a progressive disease, patients who fail conventional CRT experience worsening symptoms that can result in repeated hospitalizations and reduced life expectancy. The results of SOLVE-CRT offer a new hope for patients with hard-to-treat heart failure," Singh explained.
The data from this trial will be used for an FDA premarket approval submission.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: dfornell@innovatehealthcare.com