Two-year outcomes of leadless vs. transvenous single-chamber ventricular pacemaker in high-risk subgroups.

AIMS: This study compares clinical outcomes between leadless pacemakers (leadless-VVI) and transvenous ventricular pacemakers (transvenous ventricular permanent-VVI) in subgroups of patients at higher risk of pacemaker complications. METHODS AND RESULTS: This study is based on the Micra Coverage with Evidence Development (CED) study. Patients from the Micra CED study were considered in a high-risk subgroup if they had a diagnosis of chronic kidney disease Stages 4-5 (CKD45), end-stage renal disease, malignancy, diabetes, tricuspid valve disease (TVD), or chronic obstructive pulmonary disease (COPD) 12 months prior to pacemaker implant. A pre-specified set of complications and reinterventions were identified using diagnosis and procedure codes. Competing risks models were used to compare reinterventions and complications between leadless-VVI and transvenous-VVI patients within each subgroup; results were adjusted for multiple comparisons. A post hoc comparison of a composite outcome of reinterventions and device complications was conducted. Out of 27 991 patients, 9858 leadless-VVI and 12 157 transvenous-VVI patients have at least one high-risk comorbidity. Compared to transvenous-VVI patients, leadless-VVI patients in four subgroups [malignancy, HR 0.68 (0.48-0.95); diabetes, HR 0.69 (0.53-0.89); TVD, HR 0.60 (0.44-0.82); COPD, HR 0.73 (0.55-0.98)] had fewer complications, in three subgroups [diabetes, HR 0.58 (0.37-0.89); TVD, HR 0.46 (0.28-0.76); COPD, HR 0.51 (0.29-0.90)) had fewer reinterventions, and in four subgroups (malignancy, HR 0.52 (0.32-0.83); diabetes, HR 0.52 (0.35-0.77); TVD, HR 0.44 (0.28-0.70); COPD, HR 0.55 (0.34-0.89)] had lower rates of the combined outcome. CONCLUSION: In a real-world study, leadless pacemaker patients had lower 2-year complications and reinterventions rates compared with transvenous-VVI pacing in several high-risk subgroups. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT03039712.

Resource utilization associated with hospital and office-based insertion of a miniaturized insertable cardiac monitor: results from the RIO 2 randomized US study.

Background: Previous studies support operational benefits when moving insertable cardiac monitor (ICM) insertions outside the cardiac catheterization/electrophysiology laboratories, but this has not been directly assessed in a randomized trial or when the procedure is specifically moved to the office setting. To gain insight, the RIO 2 US study collected resource utilization and procedure time intervals for ICM insertion in-office and in-hospital and these data were used to calculate costs associated with staff time and supply use in each setting.Methods and results: The Reveal LINQ In-Office 2 US study (randomized [1:1], multicenter, unblinded) included 482 patients to undergo insertion of the ICM in-hospital (in an operating room or CATH/EP laboratory) (n = 251) or in-office (n = 231). Detailed information on resource utilization was collected prospectively by the study and used to compare resource utilization and procedure time intervals during ICM insertion procedures performed in-office vs. in-hospital. In addition, costs associated with staff time and supply use in each setting were calculated retrospectively. Total visit duration (check-in to discharge) was 107 min shorter in-office vs. in-hospital (95% CI = 97-116 min; p < 0.001). Patient preparation and education in-office were more likely to occur in the same room as the procedure, compared with in-hospital (91.6% vs. 34.2%, p < 0.001 and 87.3% vs. 22.1%, p < 0.001, respectively). There was a reduction in registered nurse and cardiovascular/operating room technologist involvement in-office, accompanied by higher physician and medical assistant participation. Overall staff time spent per case was 75% higher in-hospital, leading to 50% higher staffing costs compared to in-office.Conclusions: ICM insertion in a physician's office vs. a hospital setting resulted in reduced patient visit time and reduced overall staff time, with a consequent reduction in staffing costs. Clinical trial registration: ClinicalTrials.gov NCT02395536.

Safety of in-hospital insertable cardiac monitor procedures performed outside the traditional settings: results from the Reveal LINQ in-office 2 international study.

BACKGROUND: Historically, the majority of insertable cardiac monitor (ICM) procedures were performed in the cardiac catheterization (cath) lab, electrophysiology (EP) lab, or operating room (OR). The miniaturization of ICMs allows the procedure to be relocated within the hospital without compromising patient safety. We sought to estimate the rate of untoward events associated with procedures performed within the hospital but outside the traditional settings and to characterize resource utilization, procedure time intervals, and physician experience. METHODS: The Reveal LINQ in-Office 2 (RIO 2) International study was a single arm, multicenter, prospective study. Patients indicated for an ICM and willing to undergo device insertion outside the cath/EP lab or OR were eligible and followed for 90 days after insertion. RESULTS: A total of 191 patients (45.5% female aged 63.8 ± 26.9 years) underwent successful Reveal LINQ ICM insertion at 17 centers in Europe, Canada and Australia. The median total visit duration was 106 min (interquartile range [IQR]: 55-61). Patient preparation and patient education accounted for 10 min (IQR: 5-20) and 10 min (IQR: 8-15) of total visit duration, respectively. Preparation and education occurred in the procedure room for 90.6 and 60.2% of patients, respectively. There were no untoward events (0.0, 95% CI: 0.0-2.1%) though four patients presented with procedure-related adverse events that did not require invasive intervention. Physicians rated procedure location as convenient or very convenient. CONCLUSIONS: The Reveal LINQ™ ICM insertion can be safely and efficiently performed in the hospital outside the cath/EP lab or OR. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02412488 ; registered on April 9, 2015.

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

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

In-office insertion of a miniaturized insertable cardiac monitor: Results from the Reveal LINQ In-Office 2 randomized study.

BACKGROUND: Recent miniaturization of an insertable cardiac monitor (ICM) may make it possible to move device insertion from a hospital to office setting. However, the safety of this strategy is unknown. OBJECTIVES: The primary objective was to compare the safety of inserting the Reveal LINQ ICM in an office vs a hospital environment. Ancillary objectives included summarizing device- and procedure-related adverse events and responses to a physician questionnaire. METHODS: Five hundred twenty-one patients indicated for an ICM were randomized (1:1 ratio) to undergo ICM insertion in a hospital or office environment at 26 centers in the United States in the Reveal LINQ In-Office 2 study (ClinicalTrials.gov identifier NCT02395536). Patients were followed for 90 days. RESULTS: ICM insertion was successful in all 482 attempted patients (office: 251; hospital: 231). The untoward event rate (composite of unsuccessful insertion and ICM- or insertion-related complications) was 0.8% (2 of 244) in the office and 0.9% (2 of 227) in the hospital (95% confidence interval, -3.0% to 2.9%; 5% noninferiority: P < .001). In addition, adverse events occurred during 2.5% (6 of 244) of office and 4.4% (10 of 227) of hospital insertions (95% confidence interval [office minus inhospital rates], -5.8% to 1.9%; 5% noninferiority: P < .001). Physicians indicated that for procedures performed in an office vs a hospital, there were fewer delays >15 minutes (16% vs 35%; P < .001) and patient response was more often "very positive." Physicians considered the office location "very convenient" more frequently than the hospital location (85% vs 27%; P < .001). CONCLUSION: The safety profile for the insertion of the Reveal LINQ ICM is excellent irrespective of insertion environment. These results may expand site of service options for LINQ insertion.

Early performance of a miniaturized leadless cardiac pacemaker: the Micra Transcatheter Pacing Study.

AIMS: 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. METHODS AND RESULTS: Patients having Class I or II indication for VVI pacing underwent implantation of a Micra transcatheter pacing system, from the femoral vein and fixated in the right ventricle using four protractible nitinol tines. Prespecified objectives were >85% freedom from unanticipated serious adverse device events (safety) and <2 V 3-month mean pacing capture threshold at 0.24 ms pulse width (efficacy). Patients were implanted (n = 140) from 23 centres in 11 countries (61% male, age 77.0 ± 10.2 years) for atrioventricular block (66%) or sinus node dysfunction (29%) indications. During mean follow-up of 1.9 ± 1.8 months, the safety endpoint was met with no unanticipated serious adverse device events. Thirty adverse events related to the system or procedure occurred, mostly due to transient dysrhythmias or femoral access complications. One pericardial effusion without tamponade occurred after 18 device deployments. In 60 patients followed to 3 months, mean pacing threshold was 0.51 ± 0.22 V, and no threshold was ≥2 V, meeting the efficacy endpoint (P < 0.001). Average R-wave was 16.1 ± 5.2 mV and impedance was 650.7 ± 130 ohms. CONCLUSION: Early assessment shows the transcatheter pacemaker can safely and effectively be applied. Long-term safety and benefit of the pacemaker will further be evaluated in the trial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02004873.

Novel anti-filamin-A antibody detects a secreted variant of filamin-A in plasma from patients with breast carcinoma and high-grade astrocytoma.

Identification of tumor-derived proteins in the circulation may allow for early detection of cancer and evaluation of therapeutic responses. To identify circulating tumor-derived proteins, mice were immunized with concentrated culture medium conditioned by human breast cancer cells. Antibodies generated by hybridomas were screened against conditioned media from both normal epithelial cells and tumor cells. Antibody selectively reacting with tumor cell-conditioned media was further characterized. This led to the development of a monoclonal antibody (Alper-p280) that reacts with a newly identified 280-kDa secreted variant of human filamin-A. Circulating filamin-A was detected in patient plasma samples using Alper-p280 in an ELISA assay. Human plasma samples from 134 patients with brain, breast, or ovarian cancer, 15 patients with active arthritis, and 76 healthy controls were analyzed. Filamin-A protein levels in human cell lines and tissues were analyzed by western blotting, immunohistochemistry, and electron and confocal microscopy. Circulating filamin-A was detected in the plasma of 109 of 143 patients with breast cancer and primary brain tumors. Plasma levels of filamin-A showed 89.5% sensitivity (95% confidence interval [CI] = 0.67% to 0.99%) and 97.8% specificity (95% CI = 0.88% to 0.99%) for glioblastoma at a cut-off of 21.0 ng/mL. Plasma levels of filamin-A (>36.0 ng/mL) had 96.7% sensitivity (95% CI = 0.80% to 0.99%) and 67.8% specificity (95% CI = 0.54% to 0.79%) for metastatic breast cancer. Filamin-A levels were increased in malignant breast or brain tissues, but not in normal control tissues. Filamin-A localized to lysosomes in MDA.MB.231 breast cancer cells, but not in normal human mammary epithelial cells, suggesting that filamin-A may undergo cancer-specific processing. Plasma filamin-A appears to be a specific and sensitive marker for patients with high-grade astrocytoma or metastatic breast cancer. Additional novel cancer biomarkers have been identified and are being developed alongside Alper-p280 for use in diagnosis of breast carcinoma and high-grade astrocytoma, and for use in the evaluation of therapeutic responses.

Simultaneous suppression of epidermal growth factor receptor and c-erbB-2 reverses aneuploidy and malignant phenotype of a human ovarian carcinoma cell line.

Coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 in 47-68% of ovarian cancer cells indicate their strong association with tumor formation. We examined the effects of simultaneous antisense- or immunosuppression of EGFR and c-erbB-2 expression on the invasive phenotype, aneuploidy, and genotype of cultured human ovarian carcinoma cells (NIH:OVCAR-8). We report here that suppression of both EGFR and c-erbB-2 results in regression of aneuploidy and genomic imbalances in NIH:OVCAR-8 cells, restores a more normal phenotype, and results in a more normal gene expression profile. Combined with cytogenetic analysis, our data demonstrate that the regression of aneuploidy is due to the selective apoptosis of double antisense transfected cells with highly abnormal karyotype.