Monocenter Investigation Micra® MRI study (MIMICRY): feasibility study of the magnetic resonance imaging compatibility of a leadless pacemaker system.

AIMS: As in vivo real-life data are still scarce, we conducted a study to assess the safety and feasibility of cardiac magnetic resonance imaging (MRI) in patients with a leadless pacemaker system. METHODS AND RESULTS: In this prospective non-randomized interventional trial, we enrolled 15 patients with an MRI conditional Micra® leadless pacemaker system to undergo either a 1.5 T or 3.0 T cardiac MRI scan. Clinical adverse events as well as device parameters such as pacing threshold, sensing, impedance, and battery life were assessed at baseline as well as 1 and 3 months after the scan. Device parameter changes between different time points were tested for statistical significance and compared with pre-set cut-off values. Fourteen patients underwent the cardiac MRI scan according to the protocol as well as the scheduled follow-up visits. One participant was excluded from analysis, as the MRI scan was not possible because of severe claustrophobia. Other clinical events did not occur during the scan and the follow-up period. Device parameters stayed stable and changes during the observational period were statistically not significant (changes vs. baseline: pacing threshold: 0.01 ± 0.05 V, P = 0.308, 0.01 ± 0.07 V, P = 0.419, sensing: -0.15 ± 1.11 mV, P = 0.658, -0.19 ± 1.17 mV, P = 0.800, impedance: -7.86 ± 30.7 Ohm, P = 0.447, -7.86 ± 25.77 Ohm, P = 0.183, at 1 and 3 months follow-up, respectively). Parameter changes were not statistically different between patients who underwent imaging at 1.5 T (n = 7) or 3.0 T (n = 7). CONCLUSION: In our set of patients with a Micra® leadless pacemaker, cardiac magnetic resonance imaging at either 1.5 T or 3.0 T proved feasible and safe with no relevant changes in device parameters within 3 months of follow-up.

Potential mechanisms of endothelialisation in individuals implanted with a leadless pacemaker systems: An experimental in vitro study.

BACKGROUND: Leadless pacemaker technology is a promising upcoming field in clinical rhythmology. Today, the most commonly used system in the clinical setting is the Micra™ leadless pacemaker system (Medtronic). In autopsies of patients who witnessed non-pacemaker associated death, unexpected ingrowth/encapsulation within the wall of the right ventricle was reported. The occurrence of a complete encapsulation was not expected and the process of endothelialisation remains unclear. We hypothesized, that a local inflammatory response might be the cause of these findings. The aim of our experimental in-vitro study was to investigate the effect of the Micra™ system and its single components on inflammatory processes. METHODS: For this purpose, whole Micra™ pacemakers were incubated in heparin plasma from 25 healthy volunteers for 48 h at 37 °C. Furthermore, 1 g gold, steel, titanium, tungsten and nitinol wires were incubated in heparin plasma for 48 h at 37 °C as well (n = 10). To detect eventual inflammatory processes, interleukin- (IL) 1ß, IL-6, and tumor necrosis factor alpha (TNF-α), the chemokine IL-8 were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, the level of transforming growth factor beta 1 (TGF-ß1) and vascular endothelial growth factor (VEGF) were analysed. RESULTS: ELISA analyses showed that the whole Micra system leads to a significant increase in the inflammatory cytokine IL-6 which correlates with the data gained by the incubation of whole blood with the different wires. In particular, 0.5 g of tungsten showed a significant rise of IL-6 which could also be found for IL-1ß and IL-8. CONCLUSIONS: The in vitro study of the Micra system showed that the material composition led to an onset of inflammatory processes in whole blood. Consequently, one may speculate that the composition of Micra pacemaker may have a local inflammatory, though subclinical, effects in patients implanted with a Micra™ pacemakers.

Soluble ST2 predicts 1-year outcome in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Soluble ST2 (sST2) has been introduced as a novel biomarker in patients suffering from heart failure for risk stratification. In this study, we sought to investigate whether sST2 is useful for risk stratification and prediction of mortality in patients undergoing transcatheter aortic valve implantation (TAVI). MATERIALS AND METHODS: A total of 274 patients undergoing TAVI were included in this study (149 female; age 81 ± 1 years; EUROSCORE 25 ± 1; STS score 3·8 ± 0·2). Plasma samples were obtained preinterventional and analysed for sST2. Patients were followed up 1 month and 1 year after TAVI. RESULTS: In a Cox regression analysis, sST2 plasma concentration was associated with increased mortality (changes per pg/mL sST2 concentration; HR 1·00006 95% (1·00004-1·00009); P < 0·001). A cut-off by means of the Youden Index was calculated (10 070·27 pg/mL), and patients were retrospectively divided into two cohorts, in those above (31·3%) and those below (68·7%) this value. These two groups were then compared regarding mortality both after 30 days and 1 year: whereas 1-month mortality did not differ (7·0% vs. 10·3%, OR 1·50 95% CI (0·60-3·79; P = 0·46)), patients with a sST2 concentration above the cut-off of 10 070·27 pg/mL showed a significantly worse outcome after 1 year (49·2% vs. 23·2%; OR 3·21 95% CI (1·70-6·04); P < 0·001). After correction for confounders in a multivariate Cox regression analysis, sST2 (1·0002 95% CI (1·0001-1·0003); P = 0·001) concentration remained associated with mortality. CONCLUSIONS: sST2 levels were associated with 1-year mortality after TAVI. Based on these results, we assume that sST2 might help to identify patients at high risk for death in whom conservative treatment should be considered.

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.

Leadless Cardiac Pacemaker Implantation After Lead Extraction in Patients With Severe Device Infection.

BACKGROUND: Conventional pacemaker therapy is limited by short- and long-term complications, most notably device infection. Transcatheter pacing systems (TPS) may be beneficial in this kind of patients as they eliminate the need for a device pocket and leads and thus may reduce the risk of re-infection. METHODS: We assessed a novel procedure in 6 patients with severe device infection who were pacemaker dependent. After lead extraction a single chamber TPS was implanted into the right ventricle. RESULTS: Of the 6 patients who underwent lead extraction due to severe device infection at our institution, 3 were diagnosed with a pocket infection only, whereas the other 3 showed symptoms of both pocket and lead infection. Successful lead extraction and TPS implantation was accomplished in all patients. Four patients were bridged with a temporary pacemaker between 2 hours and 2 days after lead extraction, whereas 2 patients had the TPS implanted during the same procedure just before traditional pacemaker system removal. All patients stayed free of infection during the follow-up period of 12 weeks. An additional positron emission tomography scan was performed in each patient and indicated no signs of an infection around the TPS. CONCLUSION: Transcather pacemaker implantation was safe and feasible in 6 patients and did not result in re-infection even if implanted before removal of the infected pacemaker system within the same procedure. Therefore, implantation of a TPS may be an option for patients with severe device infection, especially in those with blocked venous access or who are pacemaker dependent.

Clinical safety of an MRI conditional implantable cardioverter defibrillator system: A prospective Monocenter ICD-Magnetic resonance Imaging feasibility study (MIMI).

BACKGROUND: The aim of this study was to evaluate the safety and efficacy of the Lumax 740(®) Implantable Cardioverter Defibrillator (ICD) system in patients undergoing a defined 1.5 Tesla (T) MRI. MATERIALS AND METHODS: Between November 2013 and April 2014, eighteen patients (age range, 41-78 years; mean age, 64 years) implanted with a Lumax 740(®) ICD system for at least 6 weeks before an MRI were enrolled into this single-center feasibility study. The local ethics committee approved the study before patients gave written informed consent. Patients underwent defined MRI 1.5T of the brain and lower lumbar spine with three safety follow-up evaluations obtained during the 3-month study period. Data were analyzed descriptively. Study endpoints were the absence of either MRI and pacing system related serious adverse device effects (SADE), or of a ventricular pacing threshold increase >0.5V, or of an R-wave amplitude attenuation < 50%, or of an R-wave amplitude < 5.0 mV at 1-month follow-up. The assessment of safety and efficacy was supported by recording of all adverse events, changes in pacing threshold, R-wave sensing, pacing impedances and in battery status. RESULTS: Sixteen patients completed the MRI and the follow-up period. As no SADE occurred, the SADE free rate was 100%. Freedom from ventricular pacing threshold increase was 100% (16/16; 95%CI: 82.9%; 100.0%). There were no significant differences between baseline and follow-up measurements of sensing amplitudes (-0.58 ± 2.07 mV, P = 0.239, -0.41 ± 1.04 mV, P = 0.133, and -0.25 ± 1.36 mV, P = 0.724, for immediately after, 1 month and 3 months after MRI scan, respectively) and pacing thresholds (-0.047 ± 0.18 V, P = 0.317, -0.019 ± 0.11 V, P = 0.490, and 0.075 ± 0.19 V, P = 0.070, for immediately after, 1 month and 3 months after MRI scan, respectively). Lead impedances after the MRI scan were significantly lower as compared with baseline values (-22.8 ± 21.69 Ω, P = 0.001, -21.62 ± 39.71 Ω, P = 0.040, and -33.68 ± 57.73 Ω, P = 0.018, for immediately after, 1 month and 3 months after MRI scan, respectively). CONCLUSION: MRI scans in patients with MRI conditional ICD system (Lumax 740(®) ) are feasible and can be performed safely under defined conditions in a hospital setting.

Subcutaneous Double "Purse String Suture"-A Safe Method for Femoral Vein Access Site Closure after Leadless Pacemaker Implantation.

BACKGROUND: Leadless cardiac pacemaker (LCP) requires large-caliber venous sheaths for device placement. Sheath sizes for these procedures vary from 18- to 23-French (F). The most common complications are hematomas, pseudoaneurysms, and arteriovenous fistulas. Complete and secure closure of the venous access is an important step at the end of such a procedure. METHODS: We performed a retrospective analysis of all patients who had undergone LCP implantation at our institution. Patients and procedural characteristics as well as groin complications at 30 days and 3 months were evaluated. After sheath removal venous access sites were closed performing a so-called "purse-string" suture (PSS). RESULTS: Seventy-seven patients received an LCP at our institution. In 27 (35%) of these patients a heparin bolus was given at the beginning of the procedure. Anticoagulation therapy with phenprocoumon was present in 32 (40%) of patients. In 76 (98.7%) patients, the LCP was implanted without complications. In one (1.3%) patient a perforation occurred during implantation, which required surgical intervention. Access site complications occurred in three (3.9%) patients, two (2.6%) groin hematomas, and one (1.3%) arteriovenous fistula. The hematomas disappeared completely after 3 weeks, and the fistula was not detectable by ultrasound anymore after 4 weeks. CONCLUSION: Use of subcutaneous absorbable double PSS closure after removal of large-caliber venous sheaths is a safe technique to achieve immediate postprocedural hemostasis. Especially for sheath sizes with an inner diameter of 23F, this technique creates a very secure and also cosmetically appealing closure.

Analysis of Ambient Influences Affecting Interleukin-6 Secretion in the Context of Clinical Trials of Stem Cell Therapy for Myocardial Infarction.

BACKGROUND: Contradictory results of large clinical trials of stem cell therapy in acute myocardial infarction (AMI) have impeded a wider clinical use. As signalling via paracrine factors in AMI has received more and more attention recently, we sought to compare processing protocols with special emphasis on interleukin-6 (IL-6), a factor of major relevance for triggering cardioprotective signals via STAT3 and PI3K. METHODS: Bone marrow and peripheral blood mononuclear cells were processed according to protocols used in the REPAIR-AMI and ASTAMI study. RESULTS: Keeping cells at higher temperatures significantly boosted secretion of IL-6. Moreover, the use of autologous serum and X-Vivo medium was superior over reagents used in the protocol of the ASTAMI study. CONCLUSIONS: External influencing factors (higher temperature, use of a modern cell culture medium supplemented with serum) led to higher concentrations of IL-6. These results could provide an explanation for the superior results found in the REPAIR-AMI study.

Removal of active-fixation coronary sinus leads using a mechanical rotation extraction device.

BACKGROUND: Active fixation coronary sinus (CS) leads are widely used in cardiac resynchronization therapy (CRT). Due to their low dislodgement rates they are an attractive option for implanters. However, extraction of active fixation leads is a complex procedure that bears potential fatal risks for patients. METHODS: We analyzed all patients undergoing StarFix® (Medtronic Inc., Minneapolis, MN, USA) extraction because of severe infection at our institution. Indication for extraction was severe device infection. Procedural outcomes as well as patient characteristics are reported. For removal of the leads a 9-Fr Evolution® (Cook Intravascular Inc., Leechburg, PA, USA) mechanical rotation extraction sheath was used. RESULTS: Between 2011 and 2014, six patients underwent extraction of StarFix® leads. One patient was female, whereas the others were males (mean age 64 ± 12 years). Implant duration was 46.5 ± 8.2 months before removal. All leads could be successfully extracted totally with the Evolution®. In one patient (16.6%) pericardial tamponade occurred immediately requiring surgical intervention. After establishment of cardiopulmonary bypass a 5-mm sharp cut in the lateral vein of the CS could be identified. It was fixed and the patient survived. On all leads, significant tissue growth between the fixation lobes could be observed. CONCLUSION: As illustrated by our cases, Attain StarFix® leads implanted years ago can be extracted with the help of a mechanical extraction sheath. However, this procedure bears potential risks and should only be performed with a cardiac surgery standby. If clinicians evaluate the implantation of Attain StarFix® leads in patients who are young or at high risk for device infection, they should be aware of these findings.

An electrical plasma surgery tool for device replacement--retrospective evaluation of complications and economic evaluation of costs and resource use.

BACKGROUND: Device replacements bear many potential risks for patients. Electrocautery should be used cautiously because of heating of the cautery tip which may lead to insulation melting. The PEAK PlasmaBlade™ (Medtronic Inc., Minneapolis, MN, USA) uses a novel technology to cut tissue. The objective of this study was to evaluate if this instrument is less destructive and can decrease complications and shorten procedure times. METHODS AND RESULTS: Two groups were compared: in group 1, surgery was done with scissors and conventional electrocautery, whereas the PEAK PlasmaBlade™ was used in group 2. Procedure time and complication rates were retrospectively investigated. Group 1 comprised 509 patients, while group 2 consisted of 102 patients. Procedure time in group 2 was significantly shorter with 28.4 ± 8.9 minutes than in group 1 with 47.5 ± 24.5 minutes (P < 0.001). The hospital stay was also reduced (2.1 ± 2.2 days versus 3.1 ± 2.4 days, P < 0.001). One major complication occurred in only 2.4% (two patients) of group 2 and in 6.9% (35 patients) of group 1. There were no damaged leads in group 2 compared to 5.7% in group 1 (P = 0.008). Cost analyses showed that the use of The PEAK PlasmaBlade™ instead of conventional electrocautery resulted in cost savings of €120/patient. CONCLUSION: Device replacement is associated with a notable complication risk. Our investigation showed that a new device for generator replacement resulted in significantly reduced procedure time and length of hospital stay while completely avoiding lead damage, which translated into considerable cost savings in a real world setting.

Coronary Pan-Ischemia as a First Sign of a Fulminant Host-Versus-Graft Reaction Eight Years After Orthotopic Heart Transplantation.

Acute graft rejection in patients after heart transplantation can cause arrhythmias and acute angina pectoris with electrocardiographic ST-segment elevation. We report a case of a 53-year old female patient who had undergone cardiac transplantation 8 years previously. She developed bradycardia with co-existent ST-segment elevation caused by a histologically proven acute graft rejection. After administration of methylprednisolone and immune absorption leading to initial clinical improvement, the patient died unexpectedly. The reasons remain unclear, but a degeneration of the conduction system as well as impaired blood flow in the right coronary caused by cellular and humoral rejection most likely have both contributed.

Gold-coated pacemaker implantation for a patient with type IV allergy to titanium.

A 65-year-old man was scheduled for pacemaker implantation for symptomatic sick-sinus-syndrome (SSS). He suffered from multiple drug-allergies and allergies to several metals like quicksilver and titanium. Gold-coated pacemaker generators and polyurethane leads are effective in avoiding allergic reactions to pacing system components. Therefore, we decided to implant a custom-made gold-coated DDDR-pacemaker generator and polyurethane leads.

Long-term outcomes in patients with atrioventricular block undergoing septal ventricular lead implantation compared with standard apical pacing.

AIMS: Left ventricular function may be altered by right ventricular apical pacing. The aims of the study were to compare the long-term course of different parameters of left ventricular dysfunction in patients undergoing implantation of a dual-chamber pacemaker with the ventricular lead in a septal position vs. in a standard apical position. METHODS: We randomized 98 patients with atrioventricular block (AV-block) undergoing pacemaker implantation to positioning the ventricular lead in the high or mid septum (n = 53) or in the apex (n = 45) of the right ventricle. N-terminal pro-brain natriuetic peptide (BNP) levels, left ventricular ejection fraction (LVEF), and exercise capacity were analysed 3 days, 3 months, and 18 months after the implantation. The primary endpoints were the changes of these parameters from baseline to 18 months. RESULTS: Changes of BNP levels, LVEF, and exercise capacity from baseline to 18 months were statistically not different between septal and apical stimulation. The clinical occurrence or deterioration of overt heart failure was similar in both treatment arms. CONCLUSION: With regard to different parameters of congestive heart failure, a septal stimulation site is not superior to conventional apical pacing in unselected patients undergoing pacemaker implantation for AV-block.

In-stent restenosis in bare metal stents versus sirolimus-eluting stents after primary coronary intervention for acute myocardial infarction and subsequent transcoronary transplantation of autologous stem cells.

BACKGROUND: Following stenting for acute myocardial infarction, transcoronary transplantation of granulocyte-colony stimulating factor (G-CSF) mobilized autologous stem cells (ASC) has been shown to result in an increased in-stent restenosis rate of bare metal stents (BMS). HYPOTHESIS: This study sought to compare the extent of neointimal growth in BMS and sirolimus-eluting stents (SES) after primary implantation, and subsequent transcoronary transplantation of G-CSF mobilized stem cells. METHODS: Patients with stenting of the left anterior descending coronary artery for acute anterior myocardial infarction were randomly assigned to receive a BMS or SES. Intracoronary stem cell injection was performed after G-CSF application for at least 4 d and cell apheresis. The angiograms obtained after cell transplantation and after 6 mo were analyzed by quantitative coronary angiography. RESULTS: We performed primary stenting and stem cell transplantion in 16 patients who received a BMS (n = 8) or an SES (n = 8). In 2 patients with a BMS, late stent thrombosis occurred after 58 d and 177 d, respectively. In the remaining patients, control angiography after 6 mo revealed in-stent restenosis of >50% in no patients with SES but in 4 patients with BMS (67%). Late lumen loss and in-stent plaque volume were significantly higher in patients with BMS compared with patients with SES. CONCLUSIONS: Compared with BMS, SES impair in-stent intima hyperplasia after stenting for acute myocardial infarction and transcoronary transplantation of G-CSF mobilized ASC.

Economic assessment of traditional surgical intervention versus use of a new innovative radiofrequency based surgical system in device replacements.

INTRODUCTION: Intra-operative complications like mechanical damages to the leads, infections and hematomas during generator replacements of implantable pacemakers and defibrillators contribute to additional costs for hospitals. The aim of this study was to evaluate operation room use, costs and budget impact of generator replacements using either a traditional surgical intervention (TSI) with scissors, scalpel and electrocautery vs. a new radiofrequency energy based surgical system, called PEAK PlasmaBladeTM (PPB). MATERIALS AND METHODS: We conducted a retrospective analysis of a population including 508 patients with TSI and 254 patients with PPB who underwent generator replacement at the Kepler University Hospital in Linz or the St. Josef Hospital in Braunau, Austria. The economic analysis included costs of resources used for intra-operative complications (lead damages) and of procedure time for TSI vs. PPB. RESULTS: Proportion of males, mean age and type of generator replaced were similar between the two groups. Lead damages occurred significantly more frequent with TSI than with PPB (5.3% and 0.4%; p< 0.001) and the procedure time was significantly longer with TSI than with PPB (47.9±24.9 and 34.1±18.1 minutes; p<0.001). Shorter procedure time and a lower rate of lead damages with PPB resulted in per patient cost savings of €81. Based on estimated 2,700 patients annually undergoing generator replacement in Austria, the use of PPB may translate into cost savings of €219,600 and 621 saved operating facility hours. CONCLUSION: PPB has the potential to minimize the risk of lead damage with more efficient utilization of the operating room. Along with cost savings and improved quality of care, hospitals may use the saved operating room hours to increase the number of daily surgeries.

Visualization and appearance of artifacts of leadless pacemaker systems in cardiac MRI : An experimental ex vivo study.

BACKGROUND: Leadless pacemaker systems are an important upcoming device in clinical rhythmology. Currently two different products are available with the Micra system (Medtronic) being the most used in the clinical setting to date. The possibility to perform magnetic resonance imaging (MRI) is an important feature of modern pacemaker devices. Even though the Micra system is suitable for MRI, little is yet known about its impact on artifacts within the images. OBJECTIVE: The aim of our ex vivo study was to perform cardiac MRI to quantify the artifacts and to evaluate if artifacts limit or inhibit the assessment of the surrounding myocardium. METHODS: After ex vivo implantation of the leadless pacemaker (LP) in a porcine model, hearts were filled with saline solution and fixed on wooden sticks on a plastic container. The model was examined at 1.5 T and at 3 T using conventional sequences and T2 mapping sequences. In addition, conventional X­rays and computed tomography (CT) scans were performed. RESULTS: Correct implantation of the LP could be performed in all hearts. In almost all MRI sequences the right ventricle and the septal region surrounding the (LP) were altered by an artifact and therefore would sustain limited assessment; however, the rest of the myocardium remained free of artifacts and evaluable for common radiologic diagnoses. A characteristic shamrock-shaped artifact was generated which appeared to be even more intense in magnitude and brightness when using 3 T compared to 1.5 T. CONCLUSION: The use of the Micra system in cardiac MRI appeared to be feasible. In our opinion, it will still be possible to make important clinical cardiac MRI diagnoses (the detection of major ischemic areas or inflammatory processes) in patients using the Micra system. We suggest the use of 1.5 T as the preferred method in clinical practice.