Efficacy and Safety of an Extravascular Implantable Cardioverter-Defibrillator.

BACKGROUND: The extravascular implantable cardioverter-defibrillator (ICD) has a single lead implanted substernally to enable pause-prevention pacing, antitachycardia pacing, and defibrillation energy similar to that of transvenous ICDs. The safety and efficacy of extravascular ICDs are not yet known. METHODS: We conducted a prospective, single-group, nonrandomized, premarket global clinical study involving patients with a class I or IIa indication for an ICD, all of whom received an extravascular ICD system. The primary efficacy end point was successful defibrillation at implantation. The efficacy objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients with successful defibrillation was greater than 88%. The primary safety end point was freedom from major system- or procedure-related complications at 6 months. The safety objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients free from such complications was greater than 79%. RESULTS: A total of 356 patients were enrolled, 316 of whom had an implantation attempt. Among the 302 patients in whom ventricular arrhythmia could be induced and who completed the defibrillation testing protocol, the percentage of patients with successful defibrillation was 98.7% (lower boundary of the one-sided 97.5% confidence interval [CI], 96.6%; P<0.001 for the comparison with the performance goal of 88%); 299 of 316 patients (94.6%) were discharged with a working ICD system. The Kaplan-Meier estimate of the percentage of patients free from major system- or procedure-related complications at 6 months was 92.6% (lower boundary of the one-sided 97.5% CI, 89.0%; P<0.001 for the comparison with the performance goal of 79%). No major intraprocedural complications were reported. At 6 months, 25 major complications were observed, in 23 of 316 patients (7.3%). The success rate of antitachycardia pacing, as assessed with generalized estimating equations, was 50.8% (95% CI, 23.3 to 77.8). A total of 29 patients received 118 inappropriate shocks for 81 arrhythmic episodes. Eight systems were explanted without extravascular ICD replacement over the 10.6-month mean follow-up period. CONCLUSIONS: In this prospective global study, we found that extravascular ICDs were implanted safely and were able to detect and terminate induced ventricular arrhythmias at the time of implantation. (Funded by Medtronic; ClinicalTrials.gov number, NCT04060680.).

Prognostic Impact of High-Molecular-Weight von Willebrand Factor Multimer Ratio in Classical Low-Flow Low-Gradient Aortic Stenosis.

INTRODUCTION: High-molecular-weight (HMW) von Willebrand factor (VWF) multimer deficiency occurs in classical low-flow, low-gradient (LF/LG) aortic stenosis (AS) due to shear force-induced proteolysis. The prognostic value of HMW VWF multimer deficiency is unknown. Therefore, we sought to evaluate the impact of HMW VWF multimer deficiency on clinical outcome. METHODS: In this prospective research study, a total of 83 patients with classical LF/LG AS were included. All patients underwent dobutamine stress echocardiography to distinguish true-severe (TS) from pseudo-severe (PS) classical LF/LG AS. HMW VWF multimer ratio was calculated using densitometric Western blot band quantification. The primary endpoint was all-cause mortality. RESULTS: Mean age was 79 ± 9 years, and TS classical LF/LG AS was diagnosed in 73% (n = 61) and PS classical LF/LG AS in 27% (n = 22) of all patients. Forty-six patients underwent aortic valve replacement (AVR) and 37 were treated conservatively. During a mean follow-up of 27 ± 17 months, 47 deaths occurred. Major bleeding complications after AVR (10/46; 22%) were more common in patients with HMW VWF multimer ratio <1 (8/17; 47%) in comparison to patients with a normal multimer pattern (2/29; 7%) at baseline (p = 0.003). In a multivariable Cox regression analysis, HMW VWF multimer deficiency was a predictor of all-cause mortality (HR: 3.02 [95% CI: 1.31-6.96], p = 0.009) in the entire cohort. This association was driven by higher mortality rates in the AVR group (multivariable-adjusted HR: 9.4; 95% CI 2.0-43.4, p = 0.004). CONCLUSIONS: This is the first study to demonstrate the predictive value of HMW VWF multimer ratio for risk stratification in patients with classical LF/LG AS. HMW VWF multimer deficiency was associated with an increased risk of all-cause mortality and major bleeding complications after AVR.

Correlation between AV synchrony and device collected AM-VP sequence counter in atrioventricular synchronous leadless pacemakers: A real-world assessment.

INTRODUCTION: Micra atrioventricular (AV) provides leadless atrioventricular synchronous pacing by sensing atrial contraction (A4 signal). Real-world operation and reliability of AV synchrony (AVS) assessment using device data have not been described. The purposes of this study were to (1) assess the correlation between AVS and atrial mechanical sensed-ventricular pacing (AM-VP) percentages in patients with permanent high-degree AV block and (2) report on the real-world effectiveness of Micra AV. METHODS: The correlation between ECG-determined AVS in-clinic and device-collected %AM-VP was assessed using data from 40 patients with high-degree AV block enrolled in the Micra Atrial tRacking using a Ventricular AccELerometer (MARVEL) 2 study. A retrospective analysis to assess continuously-sampled %AM-VP since last session, device programming, and electrical parameters was performed using Micra AV transmissions from the Medtronic CareLink database. Patients with transmissions ≥180 days postimplant were included. RESULTS: Among the 40 MARVEL 2 AV block patients with a median %VP of 99.7%, AVS was highly correlated with AM-VP (median AVS 87.1%, median AM-VP 79.1%; R2 = 0.764, p < .001). The CareLink cohort included 4384 patients programmed to VDD mode. The mean A4 amplitude was 2.3 ± 1.8 m/s2 at implant and 2.3 ± 1.6 m/s2 at 28 weeks. In patients with %VP >90% (n = 1662), the median %AM-VP was 74.7%. For the full cohort, median %VP was 65.6% and median projected battery longevity was 10.5 years. CONCLUSION: In patients with a high pacing burden, %AM-VP provides a reasonable estimation of AVS. The first large real-world analysis of Micra AV patients with >90% VP showed stable atrial sensing over time with a median %AM-VP, a correlate of AVS, of 74.7%.

ECG Electrode Localization: 3D DS Camera System for Use in Diverse Clinical Environments.

Models of the human body representing digital twins of patients have attracted increasing interest in clinical research for the delivery of personalized diagnoses and treatments to patients. For example, noninvasive cardiac imaging models are used to localize the origin of cardiac arrhythmias and myocardial infarctions. The precise knowledge of a few hundred electrocardiogram (ECG) electrode positions is essential for their diagnostic value. Smaller positional errors are obtained when extracting the sensor positions, along with the anatomical information, for example, from X-ray Computed Tomography (CT) slices. Alternatively, the amount of ionizing radiation the patient is exposed to can be reduced by manually pointing a magnetic digitizer probe one by one to each sensor. An experienced user requires at least 15 min. to perform a precise measurement. Therefore, a 3D depth-sensing camera system was developed that can be operated under adverse lighting conditions and limited space, as encountered in clinical settings. The camera was used to record the positions of 67 electrodes attached to a patient's chest. These deviate, on average, by 2.0 mm ±1.5 mm from manually placed markers on the individual 3D views. This demonstrates that the system provides reasonable positional precision even when operated within clinical environments.

Ertugliflozin to reduce arrhythmic burden in ICD/CRT patients (ERASe-trial) - A phase III study.

Sodium glucose cotransporter 2 (SGLT2) have proven profound positive effects in heart failure with reduced ejection fraction (HFrEF). These effects are independent from the presence of diabetes. Metabolic effects, antiinflammatory, and antifibrotic properties are discussed as underlying mechanisms. Despite a strong correlation of ventricular arrhythmias with HFrEF, the impact of ertugliflozin on the ventricular arrhythmic burden has not been investigated, yet. Therefore, the Ertugliflozin to Reduce Arrhythmic burden in ICD ± CRT patientS (ERASe) trial was designed to investigate the efficacy and safety of ertugliflozin in patients with reduced and midrange ejection fraction (EF) with or without diabetes. METHODS: Within a multicentre, national, randomized, double-blind, placebo-controlled, phase 3b trial we aim to enrol a total of 402 patients across Austria. Patients with reduced or midrange EF and ICD ± CRT therapy >3 months and previous ventricular tachycardia (at least 10 documented VT episodes within the last 12 months) are randomized in a 1:1 ratio to ertugliflozin (5 mg once daily orally administered) or matching placebo. The primary endpoint of the ERASe trial is to investigate the impact of ertugliflozin on total burden of ventricular arrhythmias. Further objectives will include number of therapeutic interventions of implanted devices, atrial fibrillation and heart failure biomarkers. CONCLUSION: The ERASe trial will be the first trial to test ertugliflozin in heart failure patients with nonpreserved ejection fraction and ongoing ICD ± CRT therapy regardless of their diabetic status. The ERASe trial may therefore extend the concept of SGLT2 inhibition to improve cardiac remodelling, including reduced arrhythmic burden. Trial registration Identifier EudraCT Nr. 2020-002581-14 / ClinicalTrials.gov Identifier: NCT04600921.

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).

Leadless pacemakers in critically ill patients requiring prolonged cardiac pacing: A multicenter international study.

BACKGROUND: Temporary transvenous pacing in critically ill patients requiring prolonged cardiac pacing is associated with a high risk of complications. We sought to evaluate the safety and efficacy of self-contained intracardiac leadless pacemaker (LPM) implantation in this population. METHODS AND RESULTS: Consecutive patients implanted with a Micra LPM during the hospitalization in an intensive care unit were retrospectively included. Inclusion criteria were: more than or equal to 1 supracaval central venous line, or a ventilation tube, or intravenous antibiotic therapy for ongoing sepsis or bacteremia. Patients with a history of the previous implantation of a pacemaker were excluded. Out of 1016 patients implanted with an LPM, 99 met the inclusion criteria. Mean age was 75 years and Charlson comorbidity index 7. LPM implantation was successfully performed in 98% of cases, with a perioperative complication rate of 5%, mainly cardiac injuries. In-hospital mortality rate was 6%. No late (>30 days) device-related complication occurred, especially no infection. CONCLUSIONS: LPM appears as an acceptable alternative to conventional temporary transvenous pacing in selected critically ill patients requiring prolonged cardiac pacing, especially regarding the risk of infection.

Behavior of AV synchrony pacing mode in a leadless pacemaker during variable AV conduction and arrhythmias.

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.

Usefulness of updated logistic clinical SYNTAX score based on MI-SYNTAX score in patients with ST-elevation myocardial infarction.

OBJECTIVES: To compare the predictive performances of the prewiring, postwiring MI-SYNTAX scores, prewiring, and postwiring Updated Logistic Clinical SYNTAX score (LCSS) for 2-year all-cause mortality post percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients. BACKGROUND: In patients with STEMI and undergoing primary PCI, coronary stenosis(es) distal to the culprit lesion is often observed after the restoration of coronary flow. To address comprehensively the complex coronary anatomy in these patients, prewiring and postwiring MI-SYNTAX scores have been reported in the literature. Furthermore, to enable individualized risk estimation for long-term all-cause mortality, the Updated LCSS has been developed by combining the anatomical SYNTAX score and clinical factors. METHODS: In the randomized GLOBAL LEADERS trial, anatomical SYNTAX score analysis was performed by an independent angiographic corelab for the first 4,000 consecutive patients as a prespecified analysis; of these, 545 presented with STEMI. The efficacy of the mortality predictions of the four scores at 2 years were evaluated based on their discrimination and calibration abilities. RESULTS: Complete data was available in 512 patients (93.9%). When the patients were stratified into two groups based on the median of the scores, the prewiring and postwiring Updated LCSSs demonstrated that the high-score groups were associated with higher rates of 2-year all-cause mortality compared to the low-score groups (6.6 vs. 1.2%; log-rank p = .001 and 6.6 vs. 1.2%; log-rank p = .001, respectively). There were no statistically significant differences for predicting the mortality between the prewiring (area under the curve [AUC] 0.625), postwiring MI-SYNTAX score (AUC 0.614), prewiring (AUC 0.755), and postwiring Updated LCSS (AUC 0.757). In the integrated discrimination improvement (IDI), the prewiring MI-SYNTAX score had a better discrimination for the mortality than the postwiring MI-SYNTAX score (IDI -0.0082; p = .029). The four scores had acceptable calibration abilities for 2-year all-cause mortality. CONCLUSIONS: The prewiring Updated LCSS predicts long-term all-cause mortality with clearly useful discrimination and acceptable calibration. Since the postwiring MI-SYNTAX score does not improve mortality prediction, the prewiring MI-SYNTAX score may be preferred for the 2-year mortality prediction using the Updated LCSS.

Safety of cryoballoon ablation for the treatment of atrial fibrillation: First European results from the cryo AF Global Registry.

BACKGROUND: Cryoballoon ablation for the treatment of patients with atrial fibrillation (AF) has been utilized in Europe for >15 years. OBJECTIVES: Report patient and procedural characteristics that influence the safety of cryoablation for the treatment of AF. METHODS: Patients enrolled in the prospective, multicenter Cryo AF Global Registry were treated at 38 European centers. Freedom from a ≥30s episode of AF/atrial flutter (AFL)/atrial tachycardia (AT) at 12-months and serious complications were analyzed. Univariate and multivariable models identified baseline patient and procedural characteristics that predicted a procedure-related complication. RESULTS: Of the 1418 subjects who completed an index procedure, the cohort was 62 ± 11 years of age, 37.7% female, and 72.2% paroxysmal AF (PAF). The mean procedure, left atrial dwell, and fluoroscopy times were 81 ± 34, 54 ± 25, and 14 ± 13 min, respectively. Among the 766 patients with 12-month follow-up, freedom from a ≥30 s AF/AFL/AT recurrence was 83.3% (95% CI: 79.8%-86.3%) and 71.6% (95% CI: 64.6%-77.4%) in patients with PAF and persistent AF. The serious procedure- and device-related adverse event rates were 4.7% and 2.0%. No baseline patient characteristic independently predicted a procedure-related adverse event; however, prolonged procedure duration (OR = 1.01 [95% CI: 1.00-1.01]), use of general anesthesia (OR = 1.71 [95% CI: 1.01-2.92]), and delivery of a cavotricuspid isthmus line (OR = 3.04 [95% CI: 1.01-9.20]) were each independently associated with the occurrence of a serious procedural safety event (all p < .05). CONCLUSIONS: Cryoballoon ablation is safe and effective in real-world use across a broad cohort of patients with AF.

Association of adipocytokines serum levels with left atrial thrombus formation in atrial fibrillation patients on oral anticoagulation (Alert) - A cross-sectional study.

BACKGROUND AND AIMS: Oral anticoagulation is effective for stroke prevention in atrial fibrillation (AF). However, strokes may still occur in high-risk individuals. We conducted a prospective trial to assess the association between adipocytokine serum levels and surrogate parameters for thromboembolic events. METHODS AND RESULTS: In this cross-sectional multicenter trial, we enrolled 189 patients with AF who were on oral anticoagulation. The primary endpoint was defined as either the presence of spontaneous echo contrast (SEC), a left atrial appendage (LAA), or a left atrial (LA) thrombus on transesophageal echocardiography. We investigated the association of adipocytokine serum levels with the combined endpoint using logistic regression analysis. Forty-eight individuals (25%) were assigned to group 1 (G1) due to the occurrence of at least one of the components of the combined endpoint (41 [21.7%] SEC, 3 [1.6%] LA thrombus, 13 [6.9%] LAA thrombus), whereas the remaining patients formed group 2 (G2). The BMI, logarithmized (loge) leptin (G1: 2.0 ± 1.3 µg/ml, G2: 2.0 ± 1.1 µg/ml, p = 0.746) and visfatin serum levels (G1: 3.4 ± 0.3 ng/ml, G2: 3.4 ± 0.5 ng/ml, p = 0.900) did not significantly differ between the groups. Conversely, logarithmized adiponectin (G1: 3.3 ± 0.6 ng/ml, G2: 3.1 ± 0.7 ng/ml, p = 0.036) and resistin levels (G1: 1.8 ± 0.5 ng/ml, G2: 1.6 ± 0.5 ng/ml, p = 0.009) were higher in patients with the primary endpoint. Multivariate logistic regression analysis using a score that combined the individual adiponectin and resistin values in each patient corroborated this association. CONCLUSIONS: Our results suggest that adiponectin and resistin may act as potential biomarkers to identify individuals with AF who are at high thromboembolic risk.

Tumor necrosis factor alpha-an underestimated risk predictor in patients undergoing transcatheter aortic valve replacement (TAVR)?

BACKGROUND: Systemic inflammation has been identified as a major cardiovascular risk factor in patients undergoing transcatheter aortic valve replacement (TAVR), yet currently, it is not adequately portrayed in scores for pre-interventional risk assessment. The aim of this study was to investigate the predictive ability of TNF-α in TAVR. METHODS: A total of 431 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were drawn prior to intervention, 24 h post-intervention, 4, 5, and 7 days post-intervention, and 1, 3, and 6 months post-TAVR. RESULTS: In a univariate Cox proportional hazard analysis, plasma concentrations of TNF-α after 24 h and after 5 days were associated with mortality after 12 months (after 24 h: HR 1.002 (1.000-1.004), p = 0.028; after 5d: HR 1.003 (1.001-1.005), p = 0.013). This association remained significant even after correction for confounders in a multivariate Cox regression analysis. Additionally, cut-offs were calculated. Patients above the cut-off for TNF-α after 5d had a significantly worse 12-month mortality than patients below the cut-off (18.8% vs. 2.8%, p = 0.046). CONCLUSION: Plasma levels of TNF-α after 24 h and 5 days were independently associated with 12-month mortality in patients undergoing TAVR. Thus, TNF-α could represent a novel biomarker for enhanced risk stratification in these patients.

Usefulness of the updated logistic clinical SYNTAX score after percutaneous coronary intervention in patients with prior coronary artery bypass graft surgery: Insights from the GLOBAL LEADERS trial.

OBJECTIVES: We aimed to investigate the prognostic utility of the anatomical CABG SYNTAX and logistic clinical SYNTAX scores for mortality after percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass grafts (CABG). BACKGROUND: The anatomical SYNTAX score evaluated the anatomical complexity of coronary artery disease and helped predict the prognosis of patients undergoing PCI. The anatomical CABG SYNTAX score was derived from the anatomical SYNTAX score in patients with prior CABG, whilst the logistic clinical SYNTAX score was developed by incorporating clinical factors into the anatomical SYNTAX score. METHODS: We calculated the anatomical CABG SYNTAX score and logistic clinical SYNTAX score in 205 patients in the GLOBAL LEADERS trial. The predictive abilities of these scores for 2-year all-cause mortality were evaluated. RESULTS: Using the median scores as categorical thresholds between low and high score groups, the logistic clinical SYNTAX score was able to discriminate the risk of 2-year mortality, unlike the anatomical CABG SYNTAX score. The logistic clinical SYNTAX was significantly better at predicting 2-year mortality, compared to the anatomical CABG SYNTAX score, as evidenced by AUC values in receiver-operating characteristic curve analysis (0.806 vs. 0.582, p < .001) and integrated discrimination improvement (0.121, p < .001). CONCLUSIONS: The logistic clinical SYNTAX score was superior to the anatomical CABG SYNTAX score in predicting 2-year mortality.

Soluble platelet endothelial cell adhesion molecule 1 (sPECAM-1) improves diagnostic accuracy of D-Dimer in patients with suspected deep vein thrombosis (DVT).

D-Dimer has a high sensitivity but a low specificity for the diagnosis of deep vein thrombosis (DVT) which limits its implementation as a general screening parameter. There is a demand for additional biomarkers to improve its diagnostic accuracy. Soluble platelet endothelial cell adhesion molecule 1 (sPECAM-1) is generated at the site of venous thrombosis, thus, represents a promising biomarker. Patients with clinically suspected DVT (N = 159) were prospectively recruited and underwent manual compression ultrasonography (CCUS) to confirm or exclude DVT. The diagnostic value of D-Dimer, sPECAM-1 and the combination of both was assessed. sPECAM-1 levels were significantly higher in patients with DVT (N = 44) compared to patients without DVT (N = 115) (85.9 [76.1/98.0] ng/mL versus 68.0 [50.1/86.0] ng/mL; p < 0.001) with a diagnostic sensitivity of 100% and a specificity of 28.7% at the cut point > 50.2 ng/mL. sPECAM-1 improved the diagnostic accuracy of D-Dimer: the combination of both biomarkers yielded a ROC-AUC of 0.925 compared to 0.905 for D-Dimer alone and 0.721 for sPECAM-1 alone with a reduction of false-positive D-Dimer cases 72- > 43 (Δ = - 31.9%). The discrimination mainly occurred in a subgroup of patients characterized by an inflammatory background (defined by c-reactive protein level > 1 mg/mL). sPECAM-1 represents a novel diagnostic biomarker for venous thrombosis. It does not qualify as a diagnostic biomarker alone but improves the diagnostic accuracy of D-Dimer in patients with suspected DVT.

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.).

Three-year clinical outcomes of patients treated with everolimus-eluting bioresorbable vascular scaffolds: Final results of the ABSORB EXTEND trial.

BACKGROUND: There is still limited data on the very long term clinical outcomes after ABSORB BRS in daily practice. We sought to evaluate the 3 year-performance of the Absorb bioresorbable vascular scaffolds for the treatment of low/moderate complexity patients enrolled in the ABSORB EXTEND trial. METHODS: ABSORB EXTEND is a prospective, single-arm, open-label clinical study in which 812 patients were enrolled at 56 sites. This study allowed the treatment of lesions ≤28 mm in length and reference vessel diameter of 2.0-3.8 mm (as assessed by on-line QCA). To determine the independent predictors of MACE, a multivariable logistic regression model was built using a stepwise (forward/backward) procedure. RESULTS: Average population age was 61 years and 26.5% had diabetes. Most patients had single target lesion (92.4%). Adequate scaffold deployment (PSP) was achieved in 14.2% of the cases. At three years, the composite endpoints of MACE and ischemia-driven target vessel failure were 9.2% and 10.6%, respectively. The cumulative rate of ARC definite/probable thrombosis was 2.2%, with 1.2% of the cases occurring after the 1st year. Independent predictors of MACE were hypertension and the need for "bail out" stent. CONCLUSION: At three-year follow-up, the use of ABSORB in low/moderate complex PCI was associated with low and acceptable rates of major adverse clinical events, despite the infrequent use of the recommended contemporary scaffold deployment technique. However, scaffold thrombosis rate was higher than reported with current generation of metallic DES. The study is registered on clinicaltrials.gov (unique identifier NCT01023789).

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.

Clinical safety of the ProMRI implantable cardioverter-defibrillator systems during head and lower lumbar magnetic resonance imaging at 3 T: results of the ProMRI 3T ENHANCED Master study.

AIMS: There have been no published studies on the safety of magnetic resonance imaging (MRI) at 3 Tesla (3 T) in patients with MRI-conditional implantable cardioverter-defibrillators (ICDs). The aim of this study was to assess clinical safety of the Biotronik ProMRI ICD system during non-diagnostic head and lower lumbar scans under 3 T MRI conditions. METHODS AND RESULTS: The study enrolled 129 patients at 12 sites in Australia, Singapore, and Europe. Predefined head and lower lumbar MR scans (total duration ≈30 min) were performed in 112 patients. Three primary endpoints were evaluated from the pre-MRI to the 1-month post-MRI visit: (i) freedom from serious adverse device effects (SADEs) related to MRI (hypothesized to be >90%); (ii) pacing threshold invariance for all leads (geometric mean of the patient-wise ratios for 1 month vs. pre-MRI was hypothesized to be <1.07); and (iii) sensing amplitude invariance (geometric mean of the ratios was hypothesized to be >0.993). No MRI-related SADE occurred (SADE-free rate 100%, 95% confidence interval 95.98-100%). Pacing threshold and sensing amplitudes fulfilled the invariance hypotheses with high statistical significance (P < 0.0013). No threshold increase >0.5 V or sensing amplitude decrease by >50% was observed (secondary endpoints). Lead impedances, battery capacity, and detection and treatment of arrhythmias by ICDs were not affected by MRI scans. CONCLUSION: The head and lower lumbar scans under specific 3 T MRI conditions were safe in the investigated MR-conditional ICD systems. There was no evidence of harm to the patients or any negative influence of the MRI scan on the implanted systems.

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.