Kurt Stromberg

A Leadless Intracardiac Transcatheter Pacing System

BACKGROUND A leadless intracardiac transcatheter pacing system has been designed to avoid the need for a pacemaker pocket and transvenous lead. METHODS In a prospective multicenter study without controls, a transcatheter pacemaker was implanted in patients who had guideline-based indications for ventricular pacing. The analysis of the primary end points began when 300 patients reached 6 months of follow-up. The primary safety end point was freedom from system-related or procedure-related major complications. The primary efficacy end point was the percentage of patients with low and stable pacing capture thresholds at 6 months (≤2.0 V at a pulse width of 0.24 msec and an increase of ≤1.5 V from the time of implantation). The safety and efficacy end points were evaluated against performance goals (based on historical data) of 83% and 80%, respectively. We also performed a post hoc analysis in which the rates of major complications were compared with those in a control cohort of 2667 patients with transvenous pacemakers from six previously published studies. RESULTS The device was successfully implanted in 719 of 725 patients (99.2%). The Kaplan-Meier estimate of the rate of the primary safety end point was 96.0% (95% confidence interval [CI], 93.9 to 97.3; P<0.001 for the comparison with the safety performance goal of 83%); there were 28 major complications in 25 of 725 patients, and no dislodgements. The rate of the primary efficacy end point was 98.3% (95% CI, 96.1 to 99.5; P<0.001 for the comparison with the efficacy performance goal of 80%) among 292 of 297 patients with paired 6-month data. Although there were 28 major complications in 25 patients, patients with transcatheter pacemakers had significantly fewer major complications than did the control patients (hazard ratio, 0.49; 95% CI, 0.33 to 0.75; P=0.001). CONCLUSIONS In this historical comparison study, the transcatheter pacemaker met the prespecified safety and efficacy goals; it had a safety profile similar to that of a transvenous system while providing low and stable pacing thresholds. (Funded by Medtronic; Micra Transcatheter Pacing Study ClinicalTrials.gov number, NCT02004873.).

Performance of ICD Lead Integrity Alert to Assist in the Clinical Diagnosis of ICD Lead Failures: Analysis of Different ICD Leads

Background —The Lead Integrity Alert (LIA) was developed for Medtronic ICDs to reduce inappropriate shocks for rapid, oversensing caused by conductor fractures and reported for Medtronic FidelisTM conductor fractures. The goal of this study was to compare the performance of LIA with conventional impedance monitoring for identifying lead system events (LSE) and lead failures (LF) in lead families that differ from FidelisTM. Methods and Results —We analyzed data from 12,793 LIA enabled ICD and lead combinations including 6,123 St. Jude RiataTM or DurataTM, 5,114 Boston Scientific EndotakTM, and 1,556 FidelisTM combinations followed in the CareLinkTM remote monitoring network for LSEs and LFs. Each alert was adjudicated based on ICD stored EGMs/diagnostics and clinical data as a LSE or non-lead system event (NLE) by two physicians after reviewing the EGMs and clinical data. During 13,562 patient-years of LIA follow-up, there were 179 adjudicated alerts, of which 84 were LSE (including 65 LFs) and 95 were NLE. LIA identified greater than 66% more LSE and 67% more LF compared to conventional impedance monitoring and did not differ by lead family for LSE (P=0.573) or LF (P=0.332). Isolated spikes on EGM were associated more often with LF in St. Jude leads (71%) compared to EndotakTM (9%; P<0.001) and FidelisTM leads (11%; P<0.001). The NLE detection rate was different among lead families (P<0.001) ranging from one in every 78.5 years (EndotakTM), 228.9 years (St. JudeTM leads), and 627.6 years (FidelisTM). Conclusions —LIA markedly increased the detection rate of LSE over conventional impedance monitoring.Background—The Lead Integrity Alert (LIA) was developed for Medtronic implantable cardioverter defibrillators to reduce inappropriate shocks for rapid oversensing caused by conductor fractures and reported for Medtronic Fidelis conductor fractures. The goal of this study was to compare the performance of LIA with conventional impedance monitoring for identifying lead system events (LSEs) and lead failures (LFs) in lead families that differ from Fidelis. Methods and Results—We analyzed data from 12 793 LIA enabled implantable cardioverter-defibrillator and lead combinations including 6123 St. Jude Riata or Durata, 5114 Boston Scientific Endotak, and 1556 Fidelis combinations followed in the CareLink remote monitoring network for LSEs and LFs. Each alert was adjudicated based on implantable cardioverter-defibrillator stored electrograms/diagnostics and clinical data as an LSE or non–lead system event by 2 physicians after reviewing the electrograms and clinical data. During 13 562 patient-years of LIA follow-up, there were 179 adjudicated alerts, of which 84 were LSEs (including 65 LFs) and 95 were non–lead system events. LIA identified >66% more LSE and >67% more LF compared with conventional impedance monitoring and did not differ by lead family for LSE (P=0.573) or LF (P=0.332). Isolated spikes on electrogram were associated more often with LF in St. Jude leads (71%) compared with Endotak (9%; P<0.001) and Fidelis leads (11%; P<0.001). The non–lead system event detection rate was different among lead families (P<0.001) ranging from 1 in every 78.5 years (Endotak), 228.9 years (St. Jude leads), and 627.6 years (Fidelis). Conclusions—LIA markedly increased the detection rate of LSE compared with conventional impedance monitoring.

Performance of Lead Integrity Alert to Assist in the Clinical Diagnosis of Implantable Cardioverter Defibrillator Lead Failures Analysis of Different Implantable Cardioverter Defibrillator Leads

Background —The Lead Integrity Alert (LIA) was developed for Medtronic ICDs to reduce inappropriate shocks for rapid, oversensing caused by conductor fractures and reported for Medtronic FidelisTM conductor fractures. The goal of this study was to compare the performance of LIA with conventional impedance monitoring for identifying lead system events (LSE) and lead failures (LF) in lead families that differ from FidelisTM. Methods and Results —We analyzed data from 12,793 LIA enabled ICD and lead combinations including 6,123 St. Jude RiataTM or DurataTM, 5,114 Boston Scientific EndotakTM, and 1,556 FidelisTM combinations followed in the CareLinkTM remote monitoring network for LSEs and LFs. Each alert was adjudicated based on ICD stored EGMs/diagnostics and clinical data as a LSE or non-lead system event (NLE) by two physicians after reviewing the EGMs and clinical data. During 13,562 patient-years of LIA follow-up, there were 179 adjudicated alerts, of which 84 were LSE (including 65 LFs) and 95 were NLE. LIA identified greater than 66% more LSE and 67% more LF compared to conventional impedance monitoring and did not differ by lead family for LSE (P=0.573) or LF (P=0.332). Isolated spikes on EGM were associated more often with LF in St. Jude leads (71%) compared to EndotakTM (9%; P<0.001) and FidelisTM leads (11%; P<0.001). The NLE detection rate was different among lead families (P<0.001) ranging from one in every 78.5 years (EndotakTM), 228.9 years (St. JudeTM leads), and 627.6 years (FidelisTM). Conclusions —LIA markedly increased the detection rate of LSE over conventional impedance monitoring.Background—The Lead Integrity Alert (LIA) was developed for Medtronic implantable cardioverter defibrillators to reduce inappropriate shocks for rapid oversensing caused by conductor fractures and reported for Medtronic Fidelis conductor fractures. The goal of this study was to compare the performance of LIA with conventional impedance monitoring for identifying lead system events (LSEs) and lead failures (LFs) in lead families that differ from Fidelis. Methods and Results—We analyzed data from 12 793 LIA enabled implantable cardioverter-defibrillator and lead combinations including 6123 St. Jude Riata or Durata, 5114 Boston Scientific Endotak, and 1556 Fidelis combinations followed in the CareLink remote monitoring network for LSEs and LFs. Each alert was adjudicated based on implantable cardioverter-defibrillator stored electrograms/diagnostics and clinical data as an LSE or non–lead system event by 2 physicians after reviewing the electrograms and clinical data. During 13 562 patient-years of LIA follow-up, there were 179 adjudicated alerts, of which 84 were LSEs (including 65 LFs) and 95 were non–lead system events. LIA identified >66% more LSE and >67% more LF compared with conventional impedance monitoring and did not differ by lead family for LSE (P=0.573) or LF (P=0.332). Isolated spikes on electrogram were associated more often with LF in St. Jude leads (71%) compared with Endotak (9%; P<0.001) and Fidelis leads (11%; P<0.001). The non–lead system event detection rate was different among lead families (P<0.001) ranging from 1 in every 78.5 years (Endotak), 228.9 years (St. Jude leads), and 627.6 years (Fidelis). Conclusions—LIA markedly increased the detection rate of LSE compared with conventional impedance monitoring.

The rationale and design of the Micra Transcatheter Pacing Study: Safety and efficacy of a novel miniaturized pacemaker

AIMS Recent advances in miniaturization technologies and battery chemistries have made it possible to develop a pacemaker small enough to implant within the heart while still aiming to provide similar battery longevity to conventional pacemakers. The Micra Transcatheter Pacing System is a miniaturized single-chamber pacemaker system that is delivered via catheter through the femoral vein. The pacemaker is implanted directly inside the right ventricle of the heart, eliminating the need for a device pocket and insertion of a pacing lead, thereby potentially avoiding some of the complications associated with traditional pacing systems. METHODS AND RESULTS The Micra Transcatheter Pacing Study is currently undergoing evaluation in a prospective, multi-site, single-arm study. Approximately 720 patients will be implanted at up to 70 centres around the world. The study is designed to have a continuously growing body of evidence and data analyses are planned at various time points. The primary safety and efficacy objectives at 6-month post-implant are to demonstrate that (i) the percentage of Micra patients free from major complications related to the Micra system or implant procedure is significantly higher than 83% and (ii) the percentage of Micra patients with both low and stable thresholds is significantly higher than 80%. The safety performance benchmark is based on a reference dataset of 977 subjects from 6 recent pacemaker studies. CONCLUSIONS The Micra Transcatheter Pacing Study will assess the safety and efficacy of a miniaturized, totally endocardial pacemaker in patients with an indication for implantation of a single-chamber ventricular pacemaker. CLINICALTRIALSGOV REGISTRATION ID NCT02004873.

Long-term outcomes in leadless Micra transcatheter pacemakers with elevated thresholds at implantation: Results from the Micra Transcatheter Pacing System Global Clinical Trial

BACKGROUND Device repositioning during Micra leadless pacemaker implantation may be required to achieve optimal pacing thresholds. OBJECTIVE The purpose of this study was to describe the natural history of acute elevated Micra vs traditional transvenous lead thresholds. METHODS Micra study VVI patients with threshold data (at 0.24 ms) at implant (n = 711) were compared with Capture study patients with de novo transvenous leads at 0.4 ms (n = 538). In both cohorts, high thresholds were defined as >1.0 V and very high as >1.5 V. Change in pacing threshold (0-6 months) with high (1.0 to ≤1.5 V) or very high (>1.5 V) thresholds were compared using the Wilcoxon signed-rank test. RESULTS Of the 711 Micra patients, 83 (11.7%) had an implant threshold of >1.0 V at 0.24 ms. Of the 538 Capture patients, 50 (9.3%) had an implant threshold of >1.0 V at 0.40 ms. There were no significant differences in patient characteristics between those with and without an implant threshold of >1.0 V, with the exception of left ventricular ejection fraction in the Capture cohort (high vs low thresholds, 53% vs 58%; P = .011). Patients with an implant threshold of >1.0 V decreased significantly (P < .001) in both cohorts. Micra patients with high and very high thresholds decreased significantly (P < .01) by 1 month, with 87% and 85% having 6-month thresholds lower than the implant value. However, when the capture threshold at implant was >2 V, only 18.2% had a threshold of ≤1 V at 6 months and 45.5% had a capture threshold of >2 V. CONCLUSIONS Pacing thresholds in most Micra patients with elevated thresholds decrease after implant. Micra device repositioning may not be necessary if the pacing threshold is ≤2 V.

A Multicenter Study of Shock Pathways for Subcutaneous Implantable Defibrillators

A purely subcutaneous implantable cardioverter defibrillator (ICD) requires higher energy but may be an effective alternative to transvenous ICDs to deliver lifesaving therapies.

To retrieve, or not to retrieve: System revisions with the Micra transcatheter pacemaker

BACKGROUND Early experience with leadless pacemakers has shown a low rate of complications. However, little is known about system revision in patients with these devices. OBJECTIVE The purpose of this study was to describe the system revision experience with the Micra Transcatheter Pacing System (TPS). METHODS Patients with implants from the Pre-market Micra Transcatheter Pacing Study and the Micra Transcatheter Pacing System Continued Access Study (N = 989) were analyzed and compared with 2667 patients with transvenous pacemakers (TVPs). Revisions included TPS retrieval/explant, repositioning, replacement, or electrical deactivation (with or without prior attempt at retrieval, generally followed by TVP implant) for any reason. Kaplan-Meier revision rates were calculated to account for varying follow-up duration and were compared using a Fine-Gray competing risk model. RESULTS The actuarial rate for revision at 24 months postimplant was 1.4% for the TPS group (11 revisions in 10 patients), 75% (95% confidence interval 53%-87%; P < .001) lower than the 5.3% for the TVP group (123 revisions in 117 patients). TPS revisions occurred 5-430 days postimplant for elevated pacing thresholds, need for alternate therapy, pacemaker syndrome, and prosthetic valve endocarditis; none were due to device dislodgment or device-related infection. TPS was disabled and left in situ in 7 cases, 3 were retrieved percutaneously (range 9-406 days postimplant), and 1 was surgically removed during aortic valve surgery. CONCLUSION The overall system revision rate for patients with TPS at 24 months was 1.4%, 75% lower than that for patients with TVPs. TPS was disabled and left in situ in 64% of revisions, and percutaneous retrieval was successful as late as 14 months postimplant.

Impact of operator experience and training strategy on procedural outcomes with leadless pacing: Insights from the Micra Transcatheter Pacing Study

Leadless pacemaker systems have been designed to avoid the need for a pocket and transvenous lead. However, delivery of this therapy requires a new catheter‐based procedure. This study evaluates the role of operator experience and different training strategies on procedural outcomes.

Rate adaptive pacing in an intracardiac pacemaker

BACKGROUND The Micra transcatheter pacemaker was designed to have similar functionality to conventional transvenous VVIR pacing systems. It provides rate adaptive pacing using a programmable 3-axis accelerometer designed to detect patient activity in the presence of cardiac motion. OBJECTIVE The purpose of this study was to evaluate the systems performance during treadmill tests to maximum exertion in a subset of patients within the Micra Transcatheter Pacing Study. METHODS Patients underwent treadmill testing at 3 or 6 months postimplant with algorithm programming at physician discretion. Normalized sensor rate (SenR) relative to the programmed upper sensor rate was modeled as a function of normalized workload in metabolic equivalents (METS) relative to maximum METS achieved during the test. A normalized METS and SenR were determined at the end of each 1-minute treadmill stage. The proportionality of SenR to workload was evaluated by comparing the slope from this relationship to the prospectively defined tolerance margin (0.65-1.35). RESULTS A total of 69 treadmill tests were attempted by 42 patients at 3 and 6 months postimplant. Thirty tests from 20 patients who completed ≥4 stages with an average slope of 0.86 (90% confidence interval 0.77-0.96) confirmed proportionality to workload. On an individual test basis, 25 of 30 point estimates (83.3%) had a normalized slope within the defined tolerance range (range 0.46-1.08). CONCLUSION Accelerometer-based rate adaptive pacing was proportional to workload, thus confirming rate adaptive pacing commensurate to workload is achievable with an entirely intracardiac pacing system.

Performance of Leadless Pacemaker in Japanese Patients vs. Rest of the World ― Results From a Global Clinical Trial ―

BACKGROUND A global study designed to demonstrate the safety and efficacy of a transcatheter pacing system included 38 Japanese patients enrolled at 4 sites. Subgroup analysis to evaluate the performance of the leadless intracardiac transcatheter pacing system in Japanese patients was performed.Methods and Results:Safety and efficacy outcomes, patient and implant procedure characteristics, and patient and physician acceptability from the Japanese population were compared with those from outside Japan. Differences in patient characteristics, implant procedure characteristics and patient acceptability were observed. There were no major complications in Japanese patients and pacing thresholds remained low and stable throughout follow-up. There were no observable differences between Japanese patients and patients from outside Japan in the freedom from major complication rate at 12-months post-implant (100.0% vs. 95.7%, P=0.211) or physician acceptability. CONCLUSIONS Although some differences in specific baseline characteristics, such as body size and pacing indication, and in implant procedure characteristics, including anticoagulation strategy and hospitalization period, were observed in the Japanese patients, transcatheter pacemaker performance was similar to that in the global trial. (Clinical Trial Registration: ClinicalTrials.gov ID NCT02004873.).