Comparative data on left atrial appendage occlusion efficacy and clinical outcomes by age group in the Amplatzer™ Amulet™ Occluder Observational Study.

AIMS: Left atrial appendage occlusion (LAAO) may be considered for patients with non-valvular atrial fibrillation (NVAF) and a relative/formal contraindication to anticoagulation. This study aimed to summarize the impact of aging on LAAO outcomes at short and long-term follow-up. METHODS AND RESULTS: We compared subjects aged <70, ≥70 and <80, and ≥80 years old in the prospective, multicentre Amplatzer™ Amulet™ Occluder Observational Study (Abbott, Plymouth, MN, USA). Serious adverse events (SAEs) were reported from implant through a 2-year post-LAAO visit and adjudicated by an independent clinical events committee. Overall, 1088 subjects were prospectively enrolled. There were 265 subjects (24.4%) <70 years old, 491 subjects (45.1%) ≥70 and <80 years old, and 332 subjects (30.5%) ≥80 years old, with the majority (≥80%) being contraindicated to anticoagulation. As expected, CHA2DS2-VASc and HAS-BLED Scores increased with age. Implant success was high (≥98.5%) across all groups, and the proportion of subjects with a procedure- or device-related SAE was similar between groups. At follow-up, the observed ischaemic stroke rate was not significantly different between groups, and corresponding risk reductions were 62, 56, and 85% when compared with predicted rates for subjects <70, ≥70 and <80, and ≥80 years old, respectively. Major bleeding and mortality rates increased with age, while the incidence of device-related thrombus tended to increase with age. CONCLUSIONS: Despite the increased risk for ischaemic stroke with increasing age in AF patients, LAAO reduced the risk for ischaemic stroke compared with the predicted rate across all age groups without differences in procedural SAEs.

Ablation strategies for different types of atrial fibrillation in Europe: results of the ESC-EORP EHRA Atrial Fibrillation Ablation Long-Term registry.

AIMS: The ESC EORP EHRA Atrial Fibrillation (AF) Ablation Long-Term registry was designed to assess management and outcomes of AF catheter ablation procedures in Europe. To investigate the current ablation approaches and their outcomes for patients with paroxymal AF (PAF) and non-PAF in Europe. METHODS AND RESULTS: Data from index ablations were collected in 27 European countries at 104 centres in a prospective fashion. Pre-procedural, procedural, and 1-year follow-up data were captured on a web-based electronic case record form. Data on the ablation procedure were available for 3446 patients. Of these, 2513 patients and 933 patients underwent pulmonary vein isolation (PVI) or PVI plus (PVIplus) additional ablation, respectively. The ablation strategy was limited to PVI in 81% and 56% of patients in the PAF and non-PAF group, respectively (P < 0.001). In the non-PAF group, left atrial linear ablation and ablation of complex fragmented atrial electrograms were more commonly performed. Arrhythmias recurrence after PVI was 29% and 39% in the PAF and non-PAF group, respectively (P < 0.001) and 42% after PVIplus in both groups. Atrial fibrillation related hospital admissions were more common in the PVIplus group (20% vs. 14%). A very low procedural complication rate was observed. No relevant differences were observed with regard to repeat ablation (PVI 9% and PVIplus 11%). CONCLUSION: In patients with PAF and non-PAF, the ablation strategies of PVI and PVIplus led to similar arrhythmia-free survival rates after 1 year. A considerable hospital readmission rate was noted.

Autoantibody prevalence with an improved immunoassay for detecting cardiac troponin-specific autoantibodies.

BACKGROUND: Cardiac troponin-specific autoantibodies (cTnAAb) can interfere with the measurement of cardiac troponin I (cTnI) by immunoassays used for the diagnosis of myocardial infarction (MI). Here, an improved version of a previous autoantibody assay was validated and used to evaluate the cTnAAb prevalence in a cohort of consecutive chest pain patients presenting to an emergency department. METHODS: Admission samples from 510 patients with suspected MI were analyzed in parallel with two sandwich-type cTnAAb assays based on different cTnI epitopes used to capture cardiac troponin-bound cTnAAbs. RESULTS: Sample-specific backgrounds were lower for the new assay than for the old assay (median 1225 vs. 2693 counts, p<0.001). Net signals of cTnAAb-positive samples were higher for the new assay than for the old assay (median 5076 vs. 3921 counts, p<0.001). Of all patients, 9.2% were cTnAAb-positive for the new assay and 7.3% for the old assay (p=0.013). Previous cardiac problems were not associated with cTnAAb status and cTnAAb status did not correlate with the 12-month outcome. CONCLUSIONS: With our new and more sensitive autoantibody assay, approximately one out of ten patients who presented to the initial cardiac triage had detectable amounts of cTnAAbs in the circulation. Because these cTnAAbs can interfere with state-of-the-art cTnI assays, their high prevalence should be acknowledged by clinical chemists, physicians, and kit manufacturers.

Embolization of percutaneous left atrial appendage closure devices: Timing, management and clinical outcomes.

BACKGROUND: Left atrial appendage (LAA) occluder embolization is an infrequent but serious complication. OBJECTIVES: We aim to describe timing, management and clinical outcomes of device embolization in a multi-center registry. METHODS: Patient characteristics, imaging findings and procedure and follow-up data were collected retrospectively. Device embolizations were categorized according to 1) timing 2) management and 3) clinical outcomes. RESULTS: Sixty-seven centers contributed data. Device embolization occurred in 108 patients. In 70.4 % of cases, it happened within the first 24 h of the procedure. The device was purposefully left in the LA and the aorta in two (1.9 %) patients, an initial percutaneous retrieval was attempted in 81 (75.0 %) and surgery without prior percutaneous retrieval attempt was performed in 23 (21.3 %) patients. Two patients died before a retrieval attempt could be made. In 28/81 (34.6 %) patients with an initial percutaneous retrieval attempt a second, additional attempt was performed, which was associated with a high mortality (death in patients with one attempt: 2.9 % vs. second attempt: 21.4 %, p < 0.001). The primary outcome (bailout surgery, cardiogenic shock, stroke, TIA, and/or death) occurred in 47 (43.5 %) patients. Other major complications related to device embolization occurred in 21 (19.4 %) patients. CONCLUSIONS: The majority of device embolizations after LAA closure occurs early. A percutaneous approach is often the preferred method for a first rescue attempt. Major adverse event rates, including death, are high particularly if the first retrieval attempt was unsuccessful. CONDENSED ABSTRACT: This dedicated multicenter registry examined timing, management, and clinical outcome of device embolization. Early embolization (70.4 %) was most frequent. As a first rescue attempt, percutaneous retrieval was preferred in 75.0 %, followed by surgical removal (21.3 %). In patients with a second retrieval attempt a higher mortality (death first attempt: 2.9 % vs. death second attempt: 24.1 %, p < 0.001) was observed. Mortality (10.2 %) and the major complication rate after device embolization were high.

[Can strokes be prevented by cardiac catheterization procedures?]. / Voidaanko aivoverenkierron häiriöitä estää sydämen katetritoimenpiteillä?

Most strokes associated with atrial fibrillation are caused by thrombi generated at the left auricle of the heart. Anticoagulation effectively prevents strokes associated with atrial fibrillation, but may in some patients cause severe bleeding complications that lead to cessation of therapy. Catheter closure of the left auricle of the heart is an effective but technically demanding treatment alternative in cases where severe bleedings prevent anticoagulation therapy and the patient carries a high risk of developing stroke. Some strokes of unknown origin may also be caused by a patent foramen ovale.

Three two-site apoA-I immunoassays using phage expressed detector antibodies - Preliminary clinical evaluation with cardiac patients.

High density lipoproteins (HDL) are a heterogenous group of subpopulations differing in protein/lipid composition and in their anti-atherogenic function. There is a lack of specific and robust assays which can target the functionality of HDL with respect to atherosclerosis. With recently generated CAD HDL targeted, single chain recombinant antibodies (scFvs) we set out to design and optimize apo A-I tests to compare it with conventional HDL-C and apo A-I analyses for diagnosis and risk assessment of coronary artery disease (CAD) and its outcome. Three highly sensitive two-site apo A-I assays: 022-454, 109-121 and 110-525 were optimized. A preliminary clinical evaluation of these assays, after proper sample dilution procedure, was performed using samples derived from 195 chest pain patients (myocardial infarction (MI), n = 86 and non-MI, n = 109), collected at the time of admission and at discharge from hospital (hospital stay ≤ 24 h). The clinical performance of the assays was compared with apo A-I measured with polyclonal anti-apo A-I antibody using conventional ELISA. Apo A-I data was in addition compared with HDL-C concentration of the samples. The concentration of apo A-I was significantly lower in MI patients than in non-MI individuals with assay 022-454 (admission and discharge samples, P < 0.0001 and = 0.004); assay 109-121 (admission and discharge samples, P = 0.04 and 0.0009), and, ELISA based apo A-I test (admission and discharge samples, P = 0.008 and < 0.0001). HDL-C (admission and discharge samples, P = 0.002 and P = 0.01) was also significantly lower in MI patients. In Kaplan- Meier analysis, two-site assay 109-121 assay predicted mortality from admission samples at 1.5 yrs (whole cohort, P = 0.01 and in MI patients, P = 0.05) and at 6 months (whole cohort, P = 0.04). Assay 110-525 predicted mortality at 1.5 yrs from admission samples of non-MI patients (P = 0.01) and at 6 months from whole discharge sample cohort (P = 0.04). Polyclonal anti-apo A-I based conventional assay predicted mortality at 1.5 yrs from admission samples of whole cohort (P = 0.03). Two-site apo A-I assay 022-454 and HDL-C provided no capability of predicting mortality in the whole cohort or any sub-group. In conclusion, two of the tested recombinant apo A-I antibody combinations (sc 109-121 and sc 110-525) display promising outcome to improve diagnosis and prediction of future cardiac events in cardiac patients over polyclonal apo A-I ELISA and HDL-C assays. The noted differences, while interesting, are preliminary and need however to be verified in extensive cohorts of pathological cardiac conditions and healthy controls.

Incidence and clinical impact of major bleeding following left atrial appendage occlusion: insights from the Amplatzer Amulet Observational Post-Market Study.

BACKGROUND: Major bleeding (MB) events are independent predictors of mortality after cardiac interventional procedures. The clinical relevance of MB following left atrial appendage occlusion (LAAO) remains unclear. AIMS: This study aimed to investigate the incidence and clinical impact of MB after LAAO in a real-world population at high risk for bleeding and contraindicated to anticoagulation. METHODS: The two-year results of the Amplatzer Amulet Observational Post-Market Study were analysed. An independent committee adjudicated MBs according to the Bleeding Academic Research Consortium scale. Cox proportional hazards regression identified variables associated with MB events and mortality. RESULTS: The MB rate was 7.2%/year, with a rate of 10.1%/year during year one, decreasing to 4.0%/year over year two. The most common bleeding location was gastrointestinal, accounting for 48% of MBs. Pre-LAAO MB was associated with an increased risk for post-LAAO MB (HR 2.34, 95% CI: 1.37-3.99). The occurrence of post-LAAO MB was associated with increased mortality (37.3% vs 12.7%; p<0.0001), driven mainly by events occurring beyond the periprocedural period. The annualised rate of ischaemic stroke or TIA was similar in patients with and without MB (2.3% vs 3.3%; p=0.446). MB post LAAO was a strong independent predictor of mortality (HR 3.07, 95% CI: 2.15-4.40). CONCLUSIONS: In real-world patients at high bleeding risk, MB following LAAO was not uncommon and associated with a significant increase in mortality, without increasing the risk of stroke. ClinicalTrials.gov Identifier: NCT02447081. https://clinicaltrials.gov/ct2/show/NCT02447081.

Clinical outcomes of patients undergoing percutaneous left atrial appendage occlusion in general anaesthesia or conscious sedation: data from the prospective global Amplatzer Amulet Occluder Observational Study.

OBJECTIVE: To evaluate the safety and efficacy of percutaneous left atrial appendage occlusion (LAAO) using conscious sedation (CS). BACKGROUND: Several percutaneous structural heart disease interventions are safely and efficiently performed using CS instead of general anaesthesia (GA). This concept has not been evaluated in a large multicenter cohort of patients undergoing LAAO. METHODS: Patients from the prospective, global Amplatzer Amulet Occluder Observational Study were divided into two groups (GA vs CS). Baseline information, periprocedural and postprocedural efficacy and complications, as well as outcomes through 7 days post implant were compared. RESULTS: Patients undergoing transesophageal-guided implants were categorised by GA (n=607, 64%) or CS (n=342, 36%) usage. Mean age was 75 years in both groups. LAAO technical success was achieved in 99% of both groups. The procedure duration (GA: 35±22 min vs CS: 27±19 min, p<0.001), total amount of contrast medium (GA: 105±81 mL vs CS: 86±66 mL, p<0.001) and fluoroscopic time (GA: 13±9 min vs CS: 12±13 min, p<0.001) were less in CS cases. Procedure-related or device-related serious adverse events during the first 7 days were numerically higher in the CS group (GA: 4.9% vs CS: 7.6%, p=0.114). Peridevice residual flow was absent or ≤5 mm 1-3 months after the procedure in 99.7% of the GA and in 100% of the CS group (p=1.000). CONCLUSIONS: In a large global study, LAAO with the Amplatzer Amulet occluder is safe and feasible using CS. Procedure duration and total amount of contrast were less with CS than GA cases. TRIAL REGISTRATION NUMBER: NCT02447081; Results.

Gender difference in left atrial appendage occlusion outcomes: Results from the Amplatzer™ Amulet™ Observational Study.

BACKGROUND: Percutaneous LAAO represents an alternative for stroke prevention in patients not tolerating anticoagulation. While women are at higher risk of complications during percutaneous coronary or valvular interventions, the impact of gender on LAAO outcomes is not well characterized. The current study assessed potential gender-related differences in procedural and long-term outcomes following left atrial appendage occlusion (LAAO). METHODS: 1088 AF patients were enrolled in the prospective, multicenter, Amplatzer™ Amulet™ Observational Study and followed for 2 years with scheduled adverse event assessments. The prespecified primary outcome was ischemic stroke, systemic embolism or cardiovascular (CV) death at 2 years. We also compared the rate of procedural success, device-related thrombus (DRT) and major bleeding between genders. RESULTS: 702 men and 386 women underwent LAAO. Implant successwas high, and similar between men and women (98.9 vs 99.5%, p = 0.58). Similarly, no difference was observed in the primary outcome (12.0 vs 12.5%, p = 0.82). Compared to the CHA2DS2-VASc predicted rate, we observed a numerically greater absolute risk reduction of ischemic stroke in women (from 7.6 to 2.1%/year) than men (from 6.2 to 2.2%/year). DRT through 2 years was similar between groups (1.6%, p = 0.96). We found no significant gender difference in terms of periprocedural or long-term (7.1 vs 7.6%/year) major bleeding. CONCLUSIONS: In this large group of patients undergoing LAAO using the Amplatzer™ Amulet™ device we found no significant gender difference in terms of procedural or long-term clinical outcomes. Similarly to oral anticoagulation, device-based LAA occlusion renders AF-related stroke risk similar in women and men. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02447081.https://clinicaltrials.gov/ct2/show/NCT02447081.

Length of stay following percutaneous left atrial appendage occlusion: Data from the prospective, multicenter Amplatzer Amulet Occluder Observational Study.

AIMS: To evaluate factors influencing the length of stay in patients undergoing percutaneous left atrial appendage occlusion (LAAO). METHODS AND RESULTS: Patient characteristics, procedural data and the occurrence of serious adverse events were analyzed from the AmplatzerTM AmuletTM Occluder Observational Study. Patients were divided into three groups: same day (S, 0day, n = 60, 5.6%) early (E, 1day, n = 526, 48.9%), regular (R, 2-3days, n = 338, 31.4%) and late (L, ≥4days, n = 152, 14.1%) discharge and followed up for 60 days. Procedure and device related SAE during the in-hospital stay (S: 0.0% vs. E: 1.0% vs. R: 2.1% vs. L: 23%, p<0.0001) were a major trigger for a prolonged in-hospital stay. Of the 37 subjects in the late discharge group with an SAE prior to discharge, cardiac or bleeding complications were the most common underlying conditions, occurring in 26 subjects. Multinomial logistic analysis only identified HAS-BLED score as an independent influencing factor (p = 0.04) for a late discharge. After 60 days, mortality tended to be greatest in the late discharge group (S: 0.0% vs. E: 1.0% vs. R: 1.2% vs. L: 3.3%, p = 0.1066). CONCLUSION: Over half of the subjects receiving an Amplatzer Amulet occluder were discharged within 1 day of the implant procedure. Serious adverse events were a major trigger for a late discharge after LAAO. Increased HAS-BLED score was associated with a prolonged in-hospital stay.

Free vs total pregnancy-associated plasma protein A (PAPP-A) as a predictor of 1-year outcome in patients presenting with non-ST-elevation acute coronary syndrome.

BACKGROUND: The free fraction of pregnancy-associated plasma protein A (FPAPP-A) was found to be the PAPP-A form released to the circulation in acute coronary syndrome (ACS). We estimated the prognostic value of FPAPP-A vs total PAPP-A (TPAPP-A) concentrations in forecasting death and nonfatal myocardial infarction (combined endpoint) in patients with non-ST-elevation ACS. METHODS: We recruited 267 patients hospitalized for symptoms consistent with non-ST-elevation ACS and followed them for 12 months. FPAPP-A, TPAPP-A, C-reactive protein (CRP), and cardiac troponin I (cTnI) were measured at admission; cTnI was also measured at 6-12 h and 24 h. Because of the recently shown interaction between PAPP-A and heparin, we excluded patients treated with any heparin preparations before the admission blood sampling. RESULTS: During the follow-up, 57 (21.3%) patients met the endpoint (22 deaths and 35 nonfatal myocardial infarctions). According to FPAPP-A (<1.27, 1.27-1.74, >1.74 mIU/L) and TPAPP-A (<1.98, 1.98-2.99, >2.99 mIU/L) tertiles, this endpoint was met by 12 (13.5%), 18 (20.2%), 27 (30.3%) (P = 0.02), and 17 (19.1%), 17 (19.1%), 23 (25.8%) (P = 0.54) patients, respectively. After adjusting for age, sex, diabetes, previous myocardial infarction, and ischemic electrocardiogram (ECG) findings, FPAPP-A >1.74 mIU/L [risk ratio (RR) 2.0; 95% CI 1.0-4.1, P = 0.053), increased cTnI, and CRP >/=2.0 mg/L were independent predictors of an endpoint. The prognostic performance of TPAPP-A was inferior to that of FPAPP-A. CONCLUSIONS: FPAPP-A seems to be superior as a prognostic marker compared to TPAPP-A, giving independent and additive prognostic information when measured at the time of admission in patients hospitalized for non-ST-elevation ACS.

Clinical and laboratory risk factors of thrombotic complications after pacemaker implantation: a prospective study.

AIMS: Venous lesions, including obstruction and thromboembolism (VTE), are not uncommon after pacemaker implantation. The purpose of this prospective study was to assess the role of various patient and procedure-related risk factors in the development of these complications. METHODS AND RESULTS: A prospective venography-based study of 150 consecutive pacemaker implantations with a 6-month follow-up was conducted. Current case-control study included all cases (n = 47) with a new venous lesion, and their matched controls. Several surgical and technical factors, i.e. lead burden, choice of venous access, operator experience and procedure duration, as well as patient-related classic risk factors of VTE were assessed. Plasma markers of coagulation and endothelial activation [prothrombin fragment 1 + 2 (F1 + 2), D-dimer (DD), von Willebrand factor (vWF), thrombomodulin (Tm)] were used to evaluate the extent of acute surgical trauma. All cases with venous lesions were also screened for thrombophilia. None of the procedure-related variables were predictive of VTE. Mean levels of vWF, F1 + 2 and DD increased significantly (P < 0.001) and equally in both cases and controls. No single clinical factor predicted venous lesions, but significant (P < 0.05) clustering of classic clinical VTE risk factors was seen among the cases. Thrombophilia was overrepresented in patients with symptomatic pulmonary embolism (2/5, 40%). CONCLUSION: Pacemaker implantation induces a transient hypercoagulable state, but its degree does not predict subsequent venous thromboembolism, and neither did the grade of endothelial damage as reflected by plasma markers. The aetiology of these lesions seems to be multifactorial, and clustering of classic thrombotic risk factors plays a role in the pathogenesis.

The etiology and prognostic significance of cardiac troponin I elevation in unselected emergency department patients.

BACKGROUND: Cardiac troponin elevations are associated not only with acute coronary syndromes (ACS) but also with multiple other cardiac and non-cardiac conditions. STUDY OBJECTIVES: To investigate the etiology and clinical significance of cardiac troponin I elevations in an unselected Emergency Department (ED) patient cohort. METHODS: The study population consisted of 991 consecutive troponin-positive patients admitted to the ED of a university hospital with ACS as the presumptive diagnosis. Cardiac troponin I was measured on admission and a follow-up sample was obtained at 6-12 h. Clinical diagnosis was ascertained retrospectively using all the available information including electrocardiogram, clinical data, laboratory tests, and available coronary angiograms. RESULTS: At admission, 805 (81.2%) patients were already troponin positive; of these, the troponin elevation was related to myocardial infarction (MI) in 654 (81.2%) patients. Finally, 83.0% of the troponin elevations were due to MI, 7.9% were related to other cardiac causes, and 9.1% to non-cardiac diseases. The leading non-cardiac causes were pulmonary embolism, renal failure, pneumonia, and sepsis. Non-cardiac patients with elevated troponin I at admission showed significantly higher in-hospital mortality (26.7% vs. 13.4%, p = 0.002) compared to cardiac patients. CONCLUSION: Elevated troponin levels for reasons other than MI are common in the ED and are a marker of poor in-hospital prognosis.

Percutaneous left atrial appendage closure in patients with prior intracranial bleeding and thromboembolism.

BACKGROUND: Percutaneous left atrial appendage closure (LAAC) is an alternative treatment in atrial fibrillation patients with contraindication to oral anticoagulation. However, patient selection criteria for LAAC are debated. OBJECTIVE: The purpose of this study was to evaluate the outcome after LAAC in patients with prior intracranial bleeding and thromboembolism. METHODS: Consecutive patients with atrial fibrillation and prior intracranial bleeding who underwent LAAC from February 2009 to August 2018 at the Turku University Hospital, Finland, were included in a prospective registry. Patients were followed through clinical visits and annual phone calls up to 5 years. RESULTS: Overall 104 patients (mean age 73 ± 7 years; 30% women; CHA2DS2-VASc score 4.7 ± 1.4; HAS-BLED score 3.3 ± 0.9) with atrial fibrillation and prior intracranial bleeding underwent successful LAAC using mainly (n = 102) Amplatzer devices. Median time from intracranial bleeding to LAAC was 7 months, and median follow-up 3.6 years. Antithrombotic treatment was ≤6 months in 71 patients (68%), and 48 patients (46%) received aspirin or clopidogrel alone. The rates of thromboembolism and intracranial bleeding (per 100 patient-years) were 3.4 and 1.9, respectively. In 39 patients with previous thromboembolism, the rate of thromboembolism was 3.6 per 100 patient-years (95% confidence interval 1.5-7.0), yielding a 69% relative risk reduction with respect to predicted risk based on median CHA2DS2-VASc score. Overall, rates of thromboembolism and intracranial bleeding were broadly similar in patients with and those without prior thromboembolism. CONCLUSION: Percutaneous LAAC with minimized antithrombotic treatment was demonstrated to be a valid treatment option in high-risk patients with prior intracranial bleeding and thromboembolism.

The Impact of CHA2DS2-VASc and HAS-BLED Scores on Clinical Outcomes in the Amplatzer Amulet Study.

OBJECTIVES: The aim of this study was to evaluate the impact of CHA2DS2-VASc and HAS-BLED scores on ischemic and bleeding events of patients enrolled in the Amplatzer Amulet Observational Study. BACKGROUND: Baseline CHA2DS2-VASc and HAS-BLED scores have been validated in atrial fibrillation patients to guide about anticoagulation but not in patients treated by left atrial appendage occlusion (LAAO). METHODS: Subjects were stratified according to CHA2DS2-VASc and HAS-BLED scores. Clinical outcomes were collected through 2 years and adjudicated by an independent committee. RESULTS: Subjects were considered at low (n = 156), moderate (n = 715), and high (n = 215) risk for ischemic stroke, corresponding to CHA2DS2-VASc scores of <3, 3 to 5, and ≥6, respectively. The annual rates of ischemic stroke were 1.1%, 2.0%, and 3.5%, respectively. When compared with the predicted rate, LAAO reduced the risk of ischemic stroke by 56%, 69%, and 68%. Device-related thrombus occurred in 0.7%, 1.5%, and 3.0% of subjects at low, moderate, and high risk for ischemic stroke, respectively. The HAS-BLED score was ≤3 in 629 subjects and >3 in 456 subjects, respectively. Non-peri-procedural major bleeding was reduced by 11% and 9% compared with predicted rates in the low and high bleeding risk groups, respectively. CONCLUSIONS: LAAO with the Amplatzer Amulet reduced the risk of ischemic stroke compared with the predicted rate, with a greater magnitude among patients at high thromboembolic risk without increasing the bleeding risk. (Amplatzer™Amulet™ Post-Market Study [Amulet™PMS]; NCT02447081).

Effectiveness of Only Aspirin or Clopidogrel Following Percutaneous Left Atrial Appendage Closure.

Percutaneous left atrial appendage closure (LAAC) offers a feasible option for stroke prevention in patients with atrial fibrillation (AF), but the optimal antithrombotic treatment strategy for patients with strict contraindications to oral anticoagulation (OAC) remains uncertain. We sought to evaluate short- and long-term outcome after percutaneous LAAC in these very patients discharged on single antiplatelet therapy (SAPT) alone. All consenting AF patients who underwent LAAC from February 2009 to August 2018 in Turku University Hospital, Finland, were enrolled into a prospectively maintained registry. Only patients discharged on SAPT alone were considered for the present analysis. Patients were prospectively followed up to 5 years. The primary end points were thromboembolic event (stroke, transient ischemic attack, or systemic embolism) and intracranial bleeding. Of the 165 LAAC patients, 81 patients (mean age 75 ± 7 years; 44% women; CHA2DS2-VASc 4.8 ± 1.4; HAS-BLED 3.2 ± 0.8) were discharged on SAPT only (77 with aspirin 100 mg) after successful LAAC using Amplatzer devices. The duration of SAPT was ≤6 months in 61 (75%) patients. The most common contraindication to OAC was previous intracranial bleeding in 48 (59%) patients. During a mean follow-up of 2.9 years, there were 6 thromboembolic events (2.7 of 100 patient-years; 73% lower-than-predicted rate of thromboembolism). Eight patients (3.6 of 100 patient-years) had a major bleeding event after discharge, and 4 patients had intracerebral bleeding (1.7 of 100 patient-years). At 6-month landmark analysis, freedom from thromboembolism and intracranial bleeding at 3-year follow-up was similar in those with discontinued and life-long SAPT (95.1% vs 88.9% and 97.6% vs 91.7%, respectively). In conclusion, long-term outcome is satisfactory after LAAC in selected AF patients with strict contraindications to OAC receiving short-term SAPT. However, adverse events are not infrequent during early postoperative months.

Incidence, Characterization, and Clinical Impact of Device-Related Thrombus Following Left Atrial Appendage Occlusion in the Prospective Global AMPLATZER Amulet Observational Study.

OBJECTIVES: This study sought to report the incidence, characteristics, and clinical impact of device-related thrombus (DRT) following left atrial appendage occlusion (LAAO) with the AMPLATZER Amulet device (Abbott, Plymouth, Minnesota). BACKGROUND: DRT is a potential serious complication of LAAO, but the incidence and clinical impact of DRTs in a real-world setting are not well characterized. METHODS: A total of 1,088 patients were enrolled in a multicenter prospective study and followed for 1 year. All events were adjudicated by an independent committee, including the presence of DRT. Patients with DRT were reviewed for suboptimal device implantation and characterization of DRT formation. Multiple Cox regression was performed to identify predictors of DRT formation. RESULTS: Device implantation was successful in 1,078 (99%) patients, with 1-year follow-up completed in 96.3% of patients. A total of 18 DRTs occurred in 17 patients (1.7%/year), as a second DRT developed following complete resolution of an initial DRT in 1 patient. The left upper pulmonary vein ridge was not covered by the Amulet disc in 82% of DRT patients, indicating suboptimal implantation, with most thrombus developing in the untrabeculated area of the LAA ostium between the pulmonary vein ridge and the upper edge of the disc. Three (18%) DRT patients had an ischemic stroke, all within 3 months of DRT diagnosis. Patients with a DRT were at a greater risk for ischemic stroke or transient ischemic attack compared with non-DRT patients (hazard ratio: 5.27; 95% confidence interval: 1.58 to 17.55; p = 0.007). Larger LAA orifice width was a predictor of DRT formation (hazard ratio: 1.09; 95% confidence interval: 1.00 to 1.19; p = 0.04). CONCLUSIONS: Following LAAO with the AMPLATZER Amulet device, DRT was observed infrequently. Although the presence of DRT was associated with an increased rate of ischemic stroke or transient ischemic attack as compared with patients without DRT, the large majority of DRT patients (82%) did not experience any ischemic neurologic events.

Direct Immunoassay for Free Pregnancy-Associated Plasma Protein A (PAPP-A).

BACKGROUND: Pregnancy-associated plasma protein A (PAPP-A), especially in its noncomplexed form (fPAPP-A), is linked to vulnerable atherosclerotic plaques and risk of cardiac events. An assay for sensitive detection of fPAPP-A has been lacking. Our aim was to develop and validate a direct fPAPP-A assay to meet this need. METHODS: Monoclonal antibodies binding exclusively fPAPP-A were produced by immunizing mice with recombinant PAPP-A. In the optimized immunoassay, we used an fPAPP-A-specific capture antibody together with a lanthanide-chelate-labeled monoclonal antibody recognizing all PAPP-A forms. The assay was evaluated with CLSI guidelines and compared to a 2-assay subtractive fPAPP-A approach. Clinical performance was assessed with acute coronary syndrome patients. RESULTS: The limits of detection and quantitation were 0.4 mIU/L and 1.3 mIU/L, respectively, and the assay was linear up to 1000 mIU/L (R2 = 0.999). Both serum and heparin plasma were suitable matrices, and the complexed form of PAPP-A caused no significant interference. Correlation between the developed assay and the 2-assay approach was fair (Pearson's r = 0.819). Median concentration in healthy individuals was 1.0 mIU/L. fPAPP-A concentration was higher in patients who had myocardial infarction or died during the 1-year follow-up period than in those who did not (1.13 mIU/L vs 0.82 mIU/L, P = 0.008, model adjusted with age and sex). fPAPP-A measured with this direct assay predicted this end point as well as (follow-up 1 year) or better (30 days) than the 2-assay fPAPP-A alone or in combination with cTnI. CONCLUSIONS: The new assay enables sensitive and reliable measurement of low cardiac-related fPAPP-A concentrations from blood samples.