Primary results from the LEADLESS II study have shown positive efficacy and safety outcomes with the Nanostim leadless pacemaker (St Jude Medical) for patients who require a single-chamber ventricular pacemaker.
Data were presented by principal investigator Vivek Reddy (Mount Sinai Hospital, New York, USA) at a Hot Line session of the European Society of Cardiology Congress (ESC; 28 August – 2 September, London, UK) and published online in The New England Journal of Medicine (NEJM).
Results from the first-in-man LEADLESS trial, also presented by Reddy at the Heart Rhythm Society Scientific Sessions in 2013 and published in Circulation, demonstrated the feasibility and safety of the device in 33 patients with 97% successful implantation rate and 94% complication free rate.
Reddy noted that Nanostim eliminates the surgical pocket and leads, which represent the most vulnerable component of traditional pacing systems. The device is entirely self-contained and at approximately 1.5 inches long and under 6mm in diameter is less than 10% the size of a conventional pacemaker. Unlike conventional pacemakers, which require more invasive surgery, the device is designed to be implanted minimally invasively via the femoral vein in the right ventricle.
The prospective, multicentre, non-randomised, investigational device exemption LEADLESS II study is the largest published study to date to evaluate leadless pacing technology with 526 patients at 56 centres across the United States, Canada and Australia. Patients were enrolled between February 2014 and June 2015.
The majority of the patients (55.9%) included in the study had chronic atrial fibrillation with second or third grade atrioventricular or bifascicular bundle-branch block (BBB), including slow ventricular rates associated with atrial fibrillation. Nearly 9% of patients were in sinus rhythm and had high grade atrioventricular or BBB and a slow level of physical activity or short expected lifespan and 35.4% of patients had sinus bradycardia with infrequent pauses or unexplained syncope with electrophysiology findings.
Reddy noted that the endpoint data presented included the primary analysis of efficacy and safety in the initial 300 patients who were followed for six months, which constitutes the primary cohort. Outcomes for all 526 patients who were enrolled as June 2015 constitute the total cohort.
Pacemaker implantation was successful in 95% of the total cohort of patients. Procedural and fluoroscopy times were 28.6±17.8 minutes and 13.9±9.1 minutes, respectively.
After six months, Reddy reported, the study met both endpoints for primary effectiveness (appropriate pacing and sensing in 90% of patients) and safety (freedom from serious adverse device effects in 93.3% of patients). “The mean pacing threshold and sensing values at six months were similar to those observed with conventional transvenous leads,” Reddy et al write in NEJM.
In addition, results demonstrated the device to be retrievable. Reddy explained that the device was retrieved successfully in seven patients who needed a replacement at a mean of 160 days after implantation without any associated complications. Reasons for retrieval were elevated pacing thresholds in four patients, worsening heart failure in two patients, and elective explantation in one patient.
In terms of battery longevity, Reddy said, the device has the potential to last from 8.8 to 18.9 years depending on pacing needs. He highlighted that according with what they “observed” based on electrical parametres in the primary cohort, “battery longevity is estimated at 15.0±6.7 years, which is very encouraging.”
In the study, a total of 6.7% serious adverse device effects were observed over six months, including cardiac perforation, device dislodgement, and elevated pacing capture thresholds at rates of 1.3%, 1.7%, and 1.3%, respectively. Reddy pointed out that “the complication rate is likely to improve with operator experience.” The study included 100 operators and only one operator had previous experience with leadless pacing before entering the study, he mentioned.
Regarding limitations of the study, Reddy noted that because the mean follow-up was six months, it is not possible to discuss what happens after battery depletion at five, ten or fifteen years. More importantly, he said, this is a single-chamber device only and this addresses 15% to 20% of all patients who require pacemakers.
In conclusion, Reddy noted, “the observed safety and efficacy of the leadless pacemaker supports its use as an alternative to standard pacemakers in patients requiring single-chamber ventricular pacing.”
Carina Blomstrom-Lundqvist (Uppsala University, Uppsala, Sweden), discussant of the study, argued that LEADLESS II did not compare leadless pacing with established therapy in a randomised fashion; therefore, “there is a need for a randomised study to assess efficacy, safety and superiority,” she said. “We also need large registries and include consecutive patients. European patients have been implanted with the device and we do not have those figures, which makes difficult to draw conclusions on safety of retrieval because of the small numbers.”
“Nevertheless, this is a very new technique, which probably has potential for the future,” she noted.
The Nanostim leadless pacemaker originally received the CE mark in October 2013. The device does not have FDA approval. LEADLESS II is currently ongoing and enrolling patients.