By Cara Pellegrini, MD
Assistant Professor of Medicine, UCSF; Cardiology Division, Electrophysiology Section, San Francisco VA Medical Center
Dr. Pellegrini reports no financial relationships relevant to this field of study.
SOURCES: Reddy VY, et al. Percutaneous implantation of an entirely intracardiac leadless pacemaker. N Engl J Med 2015. [Epub ahead of print].
Ritter P, et al. Early performance of a miniaturized leadless cardiac pacemaker: The Micra Transcatheter Pacing Study. Eur Heart J 2015. [Epub ahead of print].
Nearly 1 million pacemakers are implanted annually for bradycardia or heart block. Adverse events are relatively common and build cumulatively with each generator replacement. The transvenous lead(s) have often been viewed as a “weak link” susceptible to dislodgement, fracture, and insulation failure, and potentially contributing to infection, cardiac perforation, hemo- and pneumothorax, venous occlusion, and tricuspid regurgitation. Extraction of chronically placed leads can be a morbid procedure with a mortality risk of 1-2%. Despite their shrinking size, pulse generators also are associated with risk of infection, pocket hematoma, and skin erosion. For these reasons, a cardiac pacing system devoid of leads and not requiring a subcutaneous pocket is quite attractive.
Two recent multicenter, nonrandomized studies have reported early outcomes with the Nanostim (St. Jude Medical) and Micra transcatheter pacing system (TPS, Medtronic). Both devices are entirely self-contained pacing systems that are delivered to the right ventricle via a percutaneous approach and affixed with a helical screw (Nanostim) or tines (TPS); the Nanostim is longer (42 mm vs 26 mm) but slightly thinner (6 mm vs 6.7 mm diameter). Each device can be repositioned at implantation before it is fully released from the delivery system. The LEADLESS II trial by St. Jude Medical involved 100 operators at 56 sites. In this planned interim analysis, efficacy was assessed in the first 300 patients to have 6-month follow-up, and safety outcomes were reported for the entire 526 patient cohort. Medtronic’s study reported on efficacy in 60 patients over 3 months and safety outcomes for a larger 140-patient cohort with a shorter overall follow-up period; 37 operators implanted the Micra TPS device at 23 sites. In both studies, mean patient age was approximately 75 years, approximately 60% of patients were male, and the majority had an indication of heart block with atrial fibrillation, though a sizable portion also had sinus node dysfunction with minimal pacing expected, allowing for the placement of a ventricular-only device.
Success rates for implantation were high: 95.8% for Nanostim and 100% for Micra TPS, with 30% and 41% repositioning rates, respectively. Efficacy exceeded the prespecified performance goal for both. Ninety percent of Nanostim patients (93.4% of those with a successful implant) had a therapeutically accepted pacing threshold (≤ 2 volts, at 0.4 milliseconds pulse width) and sensing amplitude through 6 months, exceeding the performance goal of 85%. Among the 60 patients receiving the Micra TPS device, no patient had a pacing threshold > 2 volts (at 0.24 milliseconds). In LEADLESS, there was a 6.7% incidence of device-related serious adverse events with the Nanostim in the primary cohort (6.5% in the total cohort), split among cardiac perforation (1.3%), device dislodgement (1.7%), and elevated pacing threshold necessitating device retrieval and replacement (1.3%). Two deaths were classified as procedure-related, but not device-related. In the smaller Medtronic TPS study, there was one pericardial effusion that required intervention (0.7%) and a higher rate of groin complications: bleeding (2.1%), hematoma (1.4%), and pseudoaneurysm (1.4%); notably, the patient with the effusion had had 18 device repositionings and also suffered a myocardial infarction. There were no procedure-related fatalities. The authors concluded that the leadless pacemakers appeared to be effective and relatively safe in short-term follow-up and noted that more data will be forthcoming.
COMMENTARY
While it is obviously the early days for this technology (both devices have CE mark for sale in Europe, but are not FDA approved), the mounting evidence of feasibility, efficacy, and relative safety is encouraging and exciting. However, it is disappointing that a device whose touted advantage is the potential to decrease complications associated with pacemaker implantation has thus far had adverse event rates in excess of what would be expected with implantation of a standard transvenous device. That said, many of the disadvantages of transvenous leads and subcutaneous pockets are not immediately evident but develop over a time course well beyond the 6 month horizon of these studies. Further, complication rates with new technology generally decrease with time and more operator experience; indeed, the complication rate decreased by almost half among the experienced operators who had already performed 10 Nanostim implants in LEADLESS.
Comparison between the two devices is premature, yet a few points can be made. There were more patients with a large number of repositionings in the Medtronic TPS study (4.3% with greater than or equal to five redeployments vs 4.4% with greater than two in LEADLESS). Whether this reflects greater or perceived ease of moving the TPS device or different philosophy of the operators is unclear, but it may explain the slightly better implant rate and capture thresholds with the TPS device. Battery longevity with both is estimated to be comparable to conventional pacing systems — 15.0 ± 6.7 years with the Nanostim and 12.6 (8.6-14.4) years with TPS — though confidence in precise predictive ability is low given limited follow-up thus far. Removal of the Nanostim device has successfully been performed, with little data on the feasibility of extraction beyond 1 year.
The biggest current limitation of this technology is that it has only been applied to right ventricular pacing, which constitutes a small minority of implanted pacemakers, particularly in the United States. Clearly, these studies are just a first step. Exactly what the niche for these products will be remains an open question. Will they be used in very few selected cases, say for patients with significant venous obstruction, much as what seems to be occurring for the subcutaneous defibrillator, or will they truly become the preferred option for pacing, and in which cardiac chambers? Time will tell.
