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  1. Duray GZ, Ritter P, El-Chami M, Narasimhan C, Omar R, Tolosana JM, et al.
    Heart Rhythm, 2017 05;14(5):702-709.
    PMID: 28192207 DOI: 10.1016/j.hrthm.2017.01.035
    BACKGROUND: Early performance of the Micra transcatheter pacemaker from the global clinical trial reported a 99.2% implant success rate, low and stable pacing capture thresholds, and a low (4.0%) rate of major complications up to 6 months.

    OBJECTIVE: The purpose of this report was to describe the prespecified long-term safety objective of Micra at 12 months and electrical performance through 24 months.

    METHODS: The Micra Transcatheter Pacing Study was a prospective single-arm study designed to assess the safety and efficacy of the Micra VVIR leadless/intracardiac pacemaker. Enrolled patients met class I or II guideline recommendations for de novo ventricular pacing. The long-term safety objective was freedom from a system- or procedure-related major complication at 12 months. A predefined historical control group of 2667 patients with transvenous pacemakers was used to compare major complication rates.

    RESULTS: The long-term safety objective was achieved with a freedom from major complication rate of 96.0% at 12 months (95% confidence interval 94.2%-97.2%; P < .0001 vs performance goal). The risk of major complications for patients with Micra (N = 726) was 48% lower than that for patients with transvenous systems through 12 months postimplant (hazard ratio 0.52; 95% confidence interval 0.35-0.77; P = .001). Across subgroups of age, sex, and comorbidities, Micra reduced the risk of major complications compared to transvenous systems. Electrical performance was excellent through 24 months, with a projected battery longevity of 12.1 years.

    CONCLUSION: Long-term performance of the Micra transcatheter pacemaker remains consistent with previously reported data. Few patients experienced major complications through 12 months of follow-up, and all patient subgroups benefited as compared to transvenous pacemaker historical control group.

  2. Lloyd M, Reynolds D, Sheldon T, Stromberg K, Hudnall JH, Demmer WM, et al.
    Heart Rhythm, 2017 02;14(2):200-205.
    PMID: 27871854 DOI: 10.1016/j.hrthm.2016.11.016
    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 system's 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.

  3. Ritter P, Duray GZ, Steinwender C, Soejima K, Omar R, Mont L, et al.
    Eur Heart J, 2015 Oct 1;36(37):2510-9.
    PMID: 26045305 DOI: 10.1093/eurheartj/ehv214
    Permanent cardiac pacing is the only effective treatment for symptomatic bradycardia, but complications associated with conventional transvenous pacing systems are commonly related to the pacing lead and pocket. We describe the early performance of a novel self-contained miniaturized pacemaker.
  4. Steinwender C, Khelae SK, Garweg C, Chan JYS, Ritter P, Johansen JB, et al.
    JACC Clin Electrophysiol, 2020 01;6(1):94-106.
    PMID: 31709982 DOI: 10.1016/j.jacep.2019.10.017
    OBJECTIVES: This study reports on the performance of a leadless ventricular pacemaker with automated, enhanced accelerometer-based algorithms that provide atrioventricular (AV) synchronous pacing.

    BACKGROUND: Despite many advantages, leadless pacemakers are currently only capable of single-chamber ventricular pacing.

    METHODS: The prospective MARVEL 2 (Micra Atrial tRacking using a Ventricular accELerometer 2) study assessed the performance of an automated, enhanced accelerometer-based algorithm downloaded to the Micra leadless pacemaker for up to 5 h in patients with AV block. The primary efficacy objective was to demonstrate the superiority of the algorithm to provide AV synchronous (VDD) pacing versus VVI-50 pacing in patients with sinus rhythm and complete AV block. The primary safety objective was to demonstrate that the algorithm did not result in pauses or heart rates of >100 beats/min.

    RESULTS: Overall, 75 patients from 12 centers were enrolled; an accelerometer-based algorithm was downloaded to their leadless pacemakers. Among the 40 patients with sinus rhythm and complete AV block included in the primary efficacy objective analysis, the proportion of patients with ≥70% AV synchrony at rest was significantly greater with VDD pacing than with VVI pacing (95% vs. 0%; p 

  5. Garweg C, Khelae SK, Chan JYS, Chinitz L, Ritter P, Johansen JB, et al.
    J Cardiovasc Electrophysiol, 2021 07;32(7):1947-1957.
    PMID: 33928713 DOI: 10.1111/jce.15061
    INTRODUCTION: MARVEL 2 assessed the efficacy of mechanical atrial sensing by a ventricular leadless pacemaker, enabling a VDD pacing mode. The behavior of the enhanced MARVEL 2 algorithm during variable atrio-ventricular conduction (AVC) and/or arrhythmias has not been characterized and is the focus of this study.

    METHODS: Of the 75 patients enrolled in the MARVEL 2 study, 73 had a rhythm assessment and were included in the analysis. The enhanced MARVEL 2 algorithm included a mode-switching algorithm that automatically switches between VDD and ventricular only antibradycardia pacing (VVI)-40 depending upon AVC status.

    RESULTS: Forty-two patients (58%) had persistent third degree AV block (AVB), 18 (25%) had 1:1 AVC, 5 (7%) had variable AVC status, and 8 (11%) had atrial arrhythmias. Among the 42 patients with persistent third degree AVB, the median ventricular pacing (VP) percentage was 99.9% compared to 0.2% among those with 1:1 AVC. As AVC status changed, the algorithm switched to VDD when the ventricular rate dropped less than 40 bpm. During atrial fibrillation (AF) with ventricular response greater than 40 bpm, VVI-40 mode was maintained. No pauses longer than 1500 ms were observed. Frequent ventricular premature beats reduced the percentage of AV synchrony. During AF, the atrial signal was of low amplitude and there was infrequent sensing.

    CONCLUSION: The mode switching algorithm reduced VP in patients with 1:1 AVC and appropriately switched to VDD during AV block. No pacing safety issues were observed during arrhythmias.

  6. Garweg C, Khelae SK, Steinwender C, Chan JYS, Ritter P, Johansen JB, et al.
    Heart Rhythm, 2020 12;17(12):2037-2045.
    PMID: 32717315 DOI: 10.1016/j.hrthm.2020.07.024
    BACKGROUND: The MARVEL (Micra Atrial TRacking Using a Ventricular AccELerometer) 2 study assessed the efficacy of atrioventricular (AV) synchronous pacing with a Micra leadless pacemaker. Average atrioventricular synchrony (AVS) was 89.2%. Previously, low amplitude of the Micra-sensed atrial signal (A4) was observed to be a factor of low AVS.

    OBJECTIVE: The purpose of this study was to identify predictors of A4 amplitude and high AVS.

    METHODS: We analyzed 64 patients enrolled in MARVEL 2 who had visible P waves on electrocardiogram for assessing A4 amplitude and 40 patients with third-degree AV block for assessing AVS at rest. High AVS was defined as >90% correct atrial-triggered ventricular pacing. The association between clinical factors and echocardiographic parameters with A4 amplitude was investigated using a multivariable model with lasso variable selection. Variables associated with A4 amplitude together with premature ventricular contraction burden, sinus rate, and sinus rate variability (standard deviation of successive differences of P-P intervals [SDSD]) were assessed for association with AVS.

    RESULTS: In univariate analysis, low A4 amplitude was inversely related to atrial function assessed by E/A ratio and e'/a' ratio, and was directly related to atrial contraction excursion (ACE) and atrial strain (Ɛa) on echocardiography (all P ≤.05). The multivariable lasso regression model found coronary artery bypass graft history, E/A ratio, ACE, and Ɛa were associated with low A4 amplitude. E/A ratio and SDSD were multivariable predictors of high AVS, with >90% probability if E/A <0.94 and SDSD <5 bpm.

    CONCLUSION: Clinical parameters and echocardiographic markers of atrial function are associated with A4 signal amplitude. High AVS can be predicted by E/A ratio <0.94 and low sinus rate variability at rest.

  7. Chinitz L, Ritter P, Khelae SK, Iacopino S, Garweg C, Grazia-Bongiorni M, et al.
    Heart Rhythm, 2018 09;15(9):1363-1371.
    PMID: 29758405 DOI: 10.1016/j.hrthm.2018.05.004
    BACKGROUND: Micra is a leadless pacemaker that is implanted in the right ventricle and provides rate response via a 3-axis accelerometer (ACC). Custom software was developed to detect atrial contraction using the ACC enabling atrioventricular (AV) synchronous pacing.

    OBJECTIVE: The purpose of this study was to sense atrial contractions from the Micra ACC signal and provide AV synchronous pacing.

    METHODS: The Micra Accelerometer Sensor Sub-Study (MASS) and MASS2 early feasibility studies showed intracardiac accelerations related to atrial contraction can be measured via ACC in the Micra leadless pacemaker. The Micra Atrial TRacking Using A Ventricular AccELerometer (MARVEL) study was a prospective multicenter study designed to characterize the closed-loop performance of an AV synchronous algorithm downloaded into previously implanted Micra devices. Atrioventricular synchrony (AVS) was measured during 30 minutes of rest and during VVI pacing. AVS was defined as a P wave visible on surface ECG followed by a ventricular event <300 ms.

    RESULTS: A total of 64 patients completed the MARVEL study procedure at 12 centers in 9 countries. Patients were implanted with a Micra for a median of 6.0 months (range 0-41.4). High-degree AV block was present in 33 patients, whereas 31 had predominantly intrinsic conduction during the study. Average AVS during AV algorithm pacing was 87.0% (95% confidence interval 81.8%-90.9%), 80.0% in high-degree block patients and 94.4% in patients with intrinsic conduction. AVS was significantly greater (P

  8. Piccini JP, Stromberg K, Jackson KP, Kowal RC, Duray GZ, El-Chami MF, et al.
    Europace, 2019 Nov 01;21(11):1686-1693.
    PMID: 31681964 DOI: 10.1093/europace/euz230
    AIMS: Patient selection is a key component of securing optimal patient outcomes with leadless pacing. We sought to describe and compare patient characteristics and outcomes of Micra patients with and without a primary pacing indication associated with atrial fibrillation (AF) in the Micra IDE trial.

    METHODS AND RESULTS: The primary outcome (risk of cardiac failure, pacemaker syndrome, or syncope related to the Micra system or procedure) was compared between successfully implanted patients from the Micra IDE trial with a primary pacing indication associated with AF or history of AF (AF group) and those without (non-AF group). Among 720 patients successfully implanted with Micra, 228 (31.7%) were in the non-AF group. Reasons for selecting VVI pacing in non-AF patients included an expectation for infrequent pacing (66.2%) and advanced age (27.2%). More patients in the non-AF group had a condition that precluded the use of a transvenous pacemaker (9.6% vs. 4.7%, P = 0.013). Atrial fibrillation patients programmed to VVI received significantly more ventricular pacing compared to non-AF patients (median 67.8% vs. 12.6%; P 

  9. Reynolds D, Duray GZ, Omar R, Soejima K, Neuzil P, Zhang S, et al.
    N Engl J Med, 2016 Feb 11;374(6):533-41.
    PMID: 26551877 DOI: 10.1056/NEJMoa1511643
    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.).
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