Development and validation of a risk score for predicting pericardial effusion in patients undergoing leadless pacemaker implantation: experience with the Micra transcatheter pacemaker.

AIMS: There is limited information on what clinical factors are associated with the development of pericardial effusion after leadless pacemaker implantation. We sought to determine predictors of and to develop a risk score for pericardial effusion in patients undergoing Micra leadless pacemaker implantation attempt. METHODS AND RESULTS: Patients (n = 2817) undergoing implant attempt from the Micra global trials were analysed. Characteristics were compared between patients with and without pericardial effusion (including cardiac perforation and tamponade). A risk score for pericardial effusion was developed from 18 pre-procedural clinical variables using lasso logistic regression. Internal validation and future prediction performance were estimated using bootstrap resampling. The scoring system was also externally validated using data from the Micra Acute Performance European and Middle East (MAP EMEA) registry. There were 32 patients with a pericardial effusion [1.1%, 95% confidence interval (CI): 0.8-1.6%]. Following lasso logistic regression, 11 of 18 variables remained in the model from which point values were assigned. The C-index was 0.79 (95% CI: 0.71-0.88). Patient risk score profile ranged from -4 (lowest risk) to 5 (highest risk) with 71.8% patients considered low risk (risk score ≤0), 16.6% considered medium risk (risk score = 1), and 11.7% considered high risk (risk score ≥2) for effusion. The median C-index following bootstrap validation was 0.73 (interquartile range: 0.70-0.75). The C-index based on 9 pericardial effusions from the 928 patients in the MAP EMEA registry was 0.68 (95% CI: 0.52-0.83). The pericardial effusion rate increased significantly with additional Micra deployments in medium-risk (P = 0.034) and high-risk (P < 0.001) patients. CONCLUSION: The overall rate of pericardial effusion following Micra implantation attempt is 1.1% and has decreased over time. The risk of pericardial effusion after Micra implant attempt can be predicted using pre-procedural clinical characteristics with reasonable discrimination. CLINICAL TRIAL REGISTRATION: The Micra Post-Approval Registry (ClinicalTrials.gov identifier: NCT02536118), Micra Continued Access Study (ClinicalTrials.gov identifier: NCT02488681), and Micra Transcatheter Pacing Study (ClinicalTrials.gov identifier: NCT02004873).

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.).

Leadless pacemaker implant in patients with pre-existing infections: Results from the Micra postapproval registry.

INTRODUCTION: Leadless pacemakers may provide a safe and attractive pacing option to patients with cardiac implantable electronic device (CIED) infection. We describe the characteristics and outcomes of patients with a recent CIED infection undergoing Micra implant attempt. METHODS AND RESULTS: Patients with prior CIED infection and device explant with Micra implant within 30 days, were identified from the Micra post approval registry. Procedure characteristics and outcomes were summarized. A total of 105 patients with prior CIED infection underwent Micra implant attempt ≤30 days from prior system explant (84 [80%] pacemakers and 13 [12%] ICD/CRT-D). All system components were explanted in 93% of patients and explant occurred a median of 6 days before Micra implant, with 37% occurring on the day of Micra implant. Micra was successfully implanted in 99% patients, mean follow-up duration was 8.5 ± 7.1 months (range 0-28.5). The majority of patients (91%) received IV antibiotics preimplant, while 42% of patients received IV antibiotics postprocedure. The median length of hospitalization following Micra implant was 2 days (IQR, 1-7). During follow-up, two patients died from sepsis and four patients required system upgrade, of which two patients received Micra to provide temporary pacing support. There were no Micra devices explanted due to infection. CONCLUSION: Implantation of the Micra transcatheter pacemaker is safe and feasible in patients with a recent CIED infection. No recurrent infections that required Micra device removal were seen. Leadless pacemakers appear to be a safe pacing alternative for patients with CIED infection who undergo extraction.

Patient selection, pacing indications, and subsequent outcomes with de novo leadless single-chamber VVI pacing.

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 < 0.001). The overall occurrence of the composite outcome at 24 months was 1.8% with no difference between the AF and non-AF groups (hazard ratio 1.36, 95% confidence interval 0.45-4.2; P = 0.59). CONCLUSION: Nearly one-third of patients selected to receive Micra VVI therapy were for indications not associated with AF. Non-AF VVI patients required less frequent pacing compared to patients with AF. Risks associated with VVI therapy were low and did not differ in those with and without AF.

Incidence and outcomes of systemic infections in patients with leadless pacemakers: Data from the Micra IDE study.

BACKGROUND: The Micra clinical trials have enrolled more than 2500 patients without any reported device-related infections that required removal during follow-up. Leadless pacemakers might be more resistant to bacterial seeding due to smaller surface area and a greater tendency for encapsulation. OBJECTIVE: To analyze the incidence and outcomes of serious infectious events (SIEs: bacteremia or endocarditis) that developed during follow-up in patients with history of Micra leadless pacemaker implantation. METHODS: SIE and outcomes were characterized based upon adverse event reports. Among 720 patients implanted with Micra in the investigational device exemption trial, we identified 16 patients who had documented 21 SIEs during follow-up. RESULTS: Among patients with SIEs, mean age was 71.9 ± 11.7 years. SIEs occurred at a mean 4.8 ± 4.5 months after implant and patients were followed for 13.1 ± 9.1 months after documentation of SIE. All events were adjudicated as unrelated to the Micra device or procedure. Bacteremia was documented to be related to a gram-positive organism in 13 events (seven Staphylococcus, three Streptococcus, two Enterococcus, and one uncharacterized gram-positive bacteria), and gram-negative organisms in three events. In five events, the type of organism was not characterized (two patients with endocarditis). No persistent cases of bacteremia after antibiotic cessation were seen over the duration of follow-up CONCLUSION: In this small series of Micra patients who developed SIEs postimplant, the occurrence of bacteremia and/or endocarditis did not appear to lead to persistent bacteremia off antibiotics; most events resolved with antibiotic treatment.

Physical activity detection in patients with intracardiac leadless pacemaker.

INTRODUCTION: The Micra Transcatheter Pacing System provides a rate adaptive pacing using an individually programmable three-axis accelerometer. We evaluated the short- and mid-term performance of the Micra activity sensor by testing all three available activity vectors during the exercise tests. METHODS AND RESULTS: Implantation and follow-up data were prospectively collected from the patients undergoing Micra implantation at our institution. Patients underwent a 5-minute exercise test for each vector at predischarge (initial testing) and at scheduled in-office visits (repeat testing). On the basis of measurements of activity counts during the test, vectors were categorized to be adequate (excellent or acceptable) or poor. A total of 278 tests with 818 vector measurements were analyzed in 51 patients during follow-up (median duration was 18 months). Initial testing revealed the adequate quality of the nominal Vector 1 in 74.5% of the patients. Upon repeated testing at subsequent in-office visits, Vectors 1 and 3 were comparable (adequate quality in 64.7% vs 68.6% of the patients; P = 0.65) but better compared with Vector 2 (51.0%; P = 0.10 vs Vector 1, P = 0.01 vs Vector 3). In a subgroup of 45 patients programmed to VVIR mode, Vector 1 was selected in 46.7% of the patients after the initial test (Vector 2, 8.9%; Vector 3, 44.4%). Vector change was performed in 10 patients (22.2%) following repeated tests within 3 months of postimplantation. CONCLUSION: The three-axis accelerometer-based rate adaptive pacing feature proved to be feasible after manual selection of an adequate activity vector. Vector testing in Micra patients with chronotropic incompetence appears to be beneficial compared with the use of nominal Vector 1.

Health-related quality of life impact of a transcatheter pacing system.

BACKGROUND: Transcatheter pacing systems (TPS) provide a novel, minimally invasive approach in which a miniaturized, leadless pacemaker (PM) is transfemorally implanted in the right ventricle. We evaluated the health-related quality of life (HRQoL) impact, patient satisfaction, and activity restrictions following TPS in a large prospective multicenter clinical trial. METHODS AND RESULTS: Patients who underwent a Micra TPS implantation between December 2013 and May 2015 were included. HRQoL impact was evaluated using the Short-Form-36 (SF-36) questionnaire at baseline, 3, and 12 months. Patient satisfaction was assessed using a three-item questionnaire determining recovery, activity level, and esthetic appearance at 3 months. Implanting physicians compared the patient activity restrictions for TPS to traditional PM therapy. A total of 720 patients were implanted with a TPS (76 ± 11 years; 59% male). Of these patients, 702 (98%), 681 (95%), and 635 (88%) completed the SF-36 at baseline, 3 and 12 months, respectively. Improvements were observed at 3 and 12 months in all SF-36 domains and all attained statistical significance. Of 693 patients who completed the patient satisfaction questionnaire, 96%, 91%, 74% were (very) satisfied with their esthetic appearance, recovery, and level of activity, respectively. TPS discharge instructions were rated less restrictive in 49%, equally restrictive in 47%, and more restrictive in 4% of cases compared with traditional PM systems. CONCLUSIONS: TPS resulted in postimplant HRQoL improvements at 3 and 12 months, and high levels of patient satisfaction at 3 months. Further, TPS was associated with less activity restrictions compared with traditional PM systems.

Contractility sensor-guided optimization of cardiac resynchronization therapy: results from the RESPOND-CRT trial.

AIMS: Although cardiac resynchronization therapy (CRT) is effective in patients with systolic heart failure (HF) and a wide QRS interval, a substantial proportion of patients remain non-responsive. The SonR contractility sensor embedded in the right atrial lead enables individualized automatic optimization of the atrioventricular (AV) and interventricular (VV) timings. The RESPOND-CRT study investigated the safety and efficacy of the contractility sensor system in HF patients undergoing CRT. METHODS AND RESULTS: RESPOND-CRT was a prospective, randomized, double-blinded, multicentre, non-inferiority trial. Patients were randomized (2:1, respectively) to receive weekly, automatic CRT optimization with SonR vs. an Echo-guided optimization of AV and VV timings. The primary efficacy endpoint was the rate of clinical responders (patients alive, without adjudicated HF-related events, with improvement in New York Heart Association class or quality of life), at 12 months. The study randomized 998 patients. Responder rates were 75.0% in the SonR arm and 70.4% in the Echo arm (mean difference, 4.6%; 95% CI, -1.4% to 10.6%; P < 0.001 for non-inferiority margin -10.0%) (Table 2). At an overall mean follow-up of 548 ± 190 days SonR was associated with a 35% risk reduction in HF hospitalization (hazard ratio, 0.65; 95% CI, 0.46-0.92; log-rank P = 0.01). CONCLUSION: Automatic AV and VV optimization using the contractility sensor was safe and as effective as Echo-guided AV and VV optimization in increasing response to CRT. CLINICALTRIALS.GOV NUMBER: NCT01534234.

Implantable Cardioverter Defibrillators for Primary Prevention of Mortality in Patients With Nonischemic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) improve survival in patients with heart failure due to ischemic cardiomyopathy, but their benefit in nonischemic cardiomyopathy (NICM) has been recently questioned. We performed a meta-analysis of randomized clinical trials to examine the effect of ICDs on total mortality and arrhythmic death in patients with NICM. We also examined the impact of age and cardiac resynchronization therapy (CRT) on the relative effect of ICD compared to control. METHODS AND RESULTS: We searched the MEDLINE and EMBASE databases for randomized trials evaluating the effect of ICD versus control in patients with NICM. Hazard ratios (HR) with 95% confidence interval (CI) were calculated using a random effects model. Six trials involving 2,967 patients were included (ICD, n = 1,553; control, n = 1,414). Based on the pooled estimate across the six studies, the use of ICD was associated with a significant reduction in total mortality (HR = 0.78, 95% CI 0.66-0.92; P = 0.003), as well as arrhythmic death (HR = 0.46, 95% CI 0.29-0.71; P = 0.0005) compared to control. ICD decreased total mortality in younger patients compared to control (HR = 0.63, 95% CI 0.46-0.86; P = 0.004), but not in older patients (HR = 0.97, 95% CI 0.56-1.68; P = 0.92). In patients with CRT, ICD reduced total mortality compared to control (HR = 0.78, 95% CI 0.65-0.95; P = 0.02), but not in patients with CRT (HR = 0.71, 95% CI 0.40-1.26). CONCLUSIONS: ICDs decrease total mortality and arrhythmic deaths in patients with NICM. The benefit of ICD appears to be dependent on age and concomitant use of CRT.

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

BACKGROUND: 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. METHODS: A total of 726 patients underwent implant attempt with the Micra transcatheter pacing system (TPS; Medtronic, Minneapolis, MN, USA) by 94 operators trained in a teaching laboratory using a simulator, cadaver, and large animal models (lab training) or locally at the hospital with simulator/demo model and proctorship (hospital training). Procedure success, procedure duration, fluoroscopy time, and safety outcomes were compared between training methods and experience (implant case number). RESULTS: The Micra TPS procedure was successful in 99.2% of attempts and did not differ between the 55 operators trained in the lab setting and the 39 operators trained locally at the hospital (P = 0.189). Implant case number was also not a determinant of procedural success (P = 0.456). Each operator performed between one and 55 procedures. Procedure time and fluoroscopy duration decreased by 2.0% (P = 0.002) and 3.2% (P < 0.001) compared to the previous case. Major complication rate and pericardial effusion rate were not associated with case number (P = 0.755 and P = 0.620, respectively). There were no differences in the safety outcomes by training method. CONCLUSIONS: Among a large group of operators, implantation success was high regardless of experience. While procedure duration and fluoroscopy times decreased with implant number, complications were low and not associated with case number. Procedure and safety outcomes were similar between distinct training methodologies.