Impact of Access Site on Periprocedural Bleeding and Cerebral and Coronary Events in High-Bleeding-Risk Percutaneous Coronary Intervention: Findings from the RIVA-PCI Trial.

INTRODUCTION: The preference for using transradial access (TRA) over transfemoral access (TFA) in patients requiring percutaneous coronary intervention (PCI) is based on evidence suggesting that TRA is associated with less bleeding and fewer vascular complications, shorter hospital stays, improved quality of life, and a potential beneficial effect on mortality. We have limited study data comparing the two access routes in a patient population with atrial fibrillation (AF) undergoing PCI, who have a particular increased risk of bleeding, while AF itself is associated with an increased risk of thromboembolism. METHODS: Using data from the RIVA-PCI registry, which includes patients with AF undergoing PCI, we analyzed a high-bleeding-risk (HBR) cohort. These patients were predominantly on oral anticoagulants (OAC) for AF, and the PCI was performed via radial or femoral access. Endpoints examined were in-hospital bleeding (BARC 2-5), cerebral events (TIA, hemorrhagic or ischemic stroke) and coronary events (stent thrombosis and myocardial infarction). RESULTS: Out of 1636 patients, 854 (52.2%) underwent TFA, while 782 (47.8%) underwent the procedure via TRA, including nine patients with brachial artery puncture. The mean age was 75.5 years. Groups were similar in terms of age, sex distribution, AF type, cardiovascular history, risk factors, and comorbidities, except for a higher incidence of previous bypass surgeries, heart failure, hyperlipidemia, and chronic kidney disease (CKD) with a glomerular filtration rate (GFR) < 60 ml/min in the TFA group. No clinically relevant differences in antithrombotic therapy and combinations were present at the time of PCI. However, upon discharge, transradial PCI patients had a higher rate of triple therapy, while dual therapy was preferred after transfemoral procedures. Radial access was more frequently chosen for non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UAP) cases (NSTEMI 26.6% vs. 17.0%, p < 0.0001; UAP 21.5% vs. 14.5%, p < 0.001), while femoral access was more common for elective PCI (60.3% vs. 44.1%, p < 0.0001). No differences were observed for ST-segment elevation myocardial infarction (STEMI). Both groups had similar rates of cerebral events (TFA 0.2% vs. TRA 0.3%, p = 0.93), but the TFA group had a higher incidence of bleeding (BARC 2-5) (4.2% vs. 1.5%, p < 0.01), mainly driven by BARC 3 bleeding (1.5% vs. 0.4%, p < 0.05). No significant differences were found for stent thrombosis and myocardial infarction (TFA 0.2% vs. TRA 0.3%, p = 0.93; TFA 0.4% vs. TRA 0.1%, p = 0.36). CONCLUSIONS: In HBR patients with AF undergoing PCI for acute or chronic coronary syndrome, the use of TRA might be associated with a decrease in in-hospital bleeding, while not increasing the risk of embolic or ischemic events compared to femoral access. Further studies are required to confirm these preliminary findings.

Current status of antithrombotic therapy and in-hospital outcomes in patients with atrial fibrillation undergoing percutaneous coronary intervention in Germany.

BACKGROUND: Little is known about current patterns of antithrombotic therapy in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) in clinical practice in Germany. METHODS: The RIVA-PCI is a prospective, non-interventional, multicenter study with follow-up until hospital discharge including consecutive patients with AF undergoing PCI. RESULTS: Between January 2018 and March 2020, 1636 patients (elective in 52.6%, non-ST elevation acute coronary syndrome [NSTE-ACS] in 39.3%, ST-elevation myocardial infarction in 8.2%) from 51 German hospitals were enrolled in the study. After PCI a dual antithrombotic therapy (DAT) consisting of OAC and a P2Y12 inhibitor was given to 66.0%, triple antithrombotic therapy (TAT) to 26.0%, dual antiplatelet therapy to 5.5%, and a mono-therapy to 2.5% of the patients. Non-vitamin K antagonist oral anticoagulants (NOACs) were given to 82.4% and vitamin K antagonists to 11.5% of the patients. In-hospital events included death in 12 cases (0.7%), myocardial infarction, stent thrombosis, and ischemic stroke in four (0.2%) patients each, while 2.8% of patients had bleeding complications. The recommended durations for DAT or TAT at discharge were 1 month (1.5%), 3 months (2.1%), 6 months (43.1%), and 12 months (45.6%), with a 6-month course of DAT (47.7%) most often recommended after elective PCI and a 12-month course of DAT (40.1%) after ACS. CONCLUSION: The preferred therapy after PCI in patients with AF is DAT with a NOAC and clopidogrel. In-hospital ischemic and bleeding events were rare. The recommended durations for combination therapy vary considerably.

Rivaroxaban in Patients With Atrial Fibrillation Who Underwent Percutaneous Coronary Intervention in Clinical Practice.

Little is known about the efficacy and safety of rivaroxaban in patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI) in clinical practice. We therefore conducted a prospective observational study to determine the rate of ischemic, embolic, and bleeding events in patients with AF and PCI treated with rivaroxaban in a real-world experience. The RIVA-PCI ("rivaroxaban in patients with AF who underwent PCI") (clinicaltrials.gov NCT03315650) is a prospective, noninterventional, multicenter study with a follow-up until 14 months, including patients with AF who underwent PCI discharged with rivaroxaban. Between January 2018 and March 2020, 700 patients with PCI treated with rivaroxaban (elective in 50.1%, non-ST-elevation acute coronary syndrome 43.0%, ST-elevation myocardial infarction in 6.9%) were enrolled at 51 German hospitals. After PCI, a dual antithrombotic therapy consisting of rivaroxaban and a P2Y12 inhibitor was administered in 70.7% and triple antithrombotic therapy in 27.9%, respectively. Follow-up information could be obtained in 695 patients (99.3%). Rivaroxaban has been stopped prematurely in 21.6% of patients. Clinical events under rivaroxaban during the 14-month follow-up compared with those observed in the PIONEER-AF PCI trial included cardiovascular death (2.0% % vs 2.0%), myocardial infarction (0.9% vs 3.0%), stent thrombosis (0.2% vs 0.8%), stroke (1.3% vs 1.3%), International Society on Thrombosis and Haemostasis major (4.2% vs 3.9%), and International Society on Thrombosis and Haemostasis nonmajor clinically relevant bleeding (15.3% vs 12.9%). Therefore, in this real-world experience, rivaroxaban in patients with AF who underwent PCI is associated with ischemic and bleeding event rates comparable with those observed in the randomized PIONEER-AF PCI trial.

Carotid endarterectomy or stenting or best medical treatment alone for moderate-to-severe asymptomatic carotid artery stenosis: 5-year results of a multicentre, randomised controlled trial.

BACKGROUND: The optimal treatment for patients with asymptomatic carotid artery stenosis is under debate. Since best medical treatment (BMT) has improved over time, the benefit of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. Randomised data comparing the effect of CEA and CAS versus BMT alone are absent. We aimed to directly compare CEA plus BMT with CAS plus BMT and both with BMT only. METHODS: SPACE-2 was a multicentre, randomised, controlled trial at 36 study centres in Austria, Germany, and Switzerland. We enrolled participants aged 50-85 years with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70%, according to European Carotid Surgery Trial criteria. Initially designed as a three-arm trial including one group for BMT alone (with a randomised allocation ratio of 2·9:2·9:1), the SPACE-2 study design was amended (due to slow recruitment) to become two substudies with two arms each comparing CEA plus BMT with BMT alone (SPACE-2a) and CAS plus BMT with BMT alone (SPACE-2b); in each case in a 1:1 randomisation. Participants and clinicians were not masked to allocation. The primary efficacy endpoint was the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years. The primary safety endpoint was any stroke or death from any cause within 30 days after CEA or CAS. The primary analysis was by intention-to treat, which included all randomly assigned patients in SPACE-2, SPACE-2a, and SPACE-2b, analysed using meta-analysis of individual patient data. We did two-step hierarchical testing to first show superiority of CEA and CAS to BMT alone then to assess non-inferiority of CAS to CEA. Originally, we planned to recruit 3640 patients; however, the study had to be stopped prematurely due to insufficient recruitment. This report presents the primary analysis at 5-year follow-up. This trial is registered with ISRCTN, number ISRCTN78592017. FINDINGS: 513 patients across SPACE-2, SPACE-2a, and SPACE-2b were recruited and surveyed between July 9, 2009, and Dec 12, 2019, of whom 203 (40%) were allocated to CEA plus BMT, 197 (38%) to CAS plus BMT, and 113 (22%) to BMT alone. Median follow-up was 59·9 months (IQR 46·6-60·0). The cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2·5% (95% CI 1·0-5·8) with CEA plus BMT, 4·4% (2·2-8·6) with CAS plus BMT, and 3·1% (1·0-9·4) with BMT alone. Cox proportional-hazard testing showed no difference in risk for the primary efficacy endpoint for CEA plus BMT versus BMT alone (hazard ratio [HR] 0·93, 95% CI 0·22-3·91; p=0·93) or for CAS plus BMT versus BMT alone (1·55, 0·41-5·85; p=0·52). Superiority of CEA or CAS to BMT was not shown, therefore non-inferiority testing was not done. In both the CEA group and the CAS group, five strokes and no deaths occurred in the 30-day period after the procedure. During the 5-year follow-up period, three ipsilateral strokes occurred in both the CAS plus BMT and BMT alone group, with none in the CEA plus BMT group. INTERPRETATION: CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution. FUNDING: German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG).

Ultrasonography Grading of Internal Carotid Artery Disease: Multiparametric German Society of Ultrasound in Medicine (DEGUM) versus Society of Radiologists in Ultrasound (SRU) Consensus Criteria.

PURPOSE: We sought to determine the diagnostic agreement between the revised ultrasonography approach by the German Society of Ultrasound in Medicine (DEGUM) and the established Society of Radiologists in Ultrasound (SRU) consensus criteria for the grading of carotid artery disease. MATERIALS AND METHODS: Post-hoc analysis of a prospective multicenter study, in which patients underwent ultrasonography and digital subtraction angiography (DSA) of carotid arteries for validation of the DEGUM approach. According to DEGUM and SRU ultrasonography criteria, carotid arteries were independently categorized into clinically relevant NASCET strata (normal, mild [1-49 %], moderate [50-69 %], severe [70-99 %], occlusion). On DSA, carotid artery findings according to NASCET were considered the reference standard. RESULTS: We analyzed 158 ultrasonography and DSA carotid artery pairs. There was substantial agreement between both ultrasonography approaches for severe (κw 0.76, CI95 %: 0.66-0.86), but only fair agreement for moderate (κw 0.38, CI95 %: 0.19-0.58) disease categories. Compared with DSA, both ultrasonography approaches were of equal sensitivity (79.7 % versus 79.7 %; p = 1.0) regarding the identification of severe stenosis, yet the DEGUM approach was more specific than the SRU approach (70.2 % versus 56.4 %, p = 0.0002). There was equality of accuracy parameters (p > 0.05) among both ultrasonography approaches for the other ranges of carotid artery disease. CONCLUSION: While the sensitivity was equivalent, false-positive identification of severe carotid artery stenosis appears to be more frequent when using the SRU ultrasonography approach than the revised multiparametric DEGUM approach.

Anticoagulation versus antiplatelet therapy after percutaneous left atrial appendage closure-subanalysis from the multicenter LAARGE registry.

PURPOSE: Data regarding post-procedural antithrombotic therapy following percutaneous left atrial appendage (LAA) in real-world populations using various occluder systems is limited. In the present analysis, anticoagulation (AC) was compared against antiplatelet therapy (APT) using data from the real-world multi-center LAARGE study. METHODS: Patients following LAA closure enrolled in the LAARGE study were assigned to two groups depending on initial post-implantation antithrombotic regime consisting of either AC or APT. Selection of antithrombotic medication was at the discretion of the treating center and/or physician. RESULTS: From July 2014 until January 2016, a total of 627 patients at 38 centers were included. A total of 75 patients (12%) received AC and 552 patients (88%) received APT, respectively. No significant differences were found between the groups regarding the composite of death, stroke and systemic embolism 1 year after LAA closure (Kaplan-Meier estimated rate 9.4% for AC vs. 12.8% for APT; p log rank = 0.45). With respect to bleeding events also, no differences were observed 1 year after the procedure (major bleeding 4.0% vs. 2.0%, p = 0.23; moderate bleeding 4.0% vs. 4.9%, p = 1.00; any bleeding 8.0% vs. 6.9%, p = 0.73). CONCLUSIONS: Postprocedural antithrombotic treatment with AC and APT showed comparable results regarding the composite of death, stroke, and systemic embolism as well as regarding bleeding complications after LAA closure in a real-world all-comers population.

Survey of clinical practice pattern in Germany's certified chest pain units : Adherence to the European Society of Cardiology guidelines on non-ST-segment elevation acute coronary syndrome.

BACKGROUND: We aimed to analyze the 2020 standard of care in certified German chest pain units (CPU) with a special focus on non-ST-segment elevation acute coronary syndrome (NSTE-ACS) through a voluntary survey obtained from all certified units, using a prespecified questionnaire. METHODS: The assessment included the collection of information on diagnostic protocols, risk assessment, management and treatment strategies in suspected NSTE-ACS, the timing of invasive therapy in non-ST-segment elevation myocardial infarction (NSTEMI), and the choice of antiplatelet therapy. RESULTS: The response rate was 75%. Among all CPUs, 77% are currently using the European Society of Cardiology (ESC) 0/3­h high-sensitive troponin protocol, and only 20% use the ESC 0/1­h high-sensitive troponin protocol as a default strategy. Conventional ergometry is still the commonly performed stress test with a utilization rate of 47%. Among NSTEMI patients, coronary angiography is planned within 24 h in 96% of all CPUs, irrespective of the day of the week. Prasugrel is the P2Y12 inhibitor of choice in ST-segment elevation myocardial infarction (STEMI), but despite the impact of the ISAR-REACT 5 trial on selection of antiplatelet therapy, ticagrelor is still favored over prasugrel in NSTE-ACS. If triple therapy is used in NSTE-ACS with atrial fibrillation, it is maintained up to 4 weeks in 51% of these patients. CONCLUSION: This survey provides evidence that Germany's certified CPUs ensure a high level of guideline adherence and quality of care. The survey also identified areas in need of improvement such as the high utilization rate of stress electrocardiogram (ECG).

Successful implementation of best medical treatment for patients with asymptomatic carotid artery stenosis within a randomized controlled trial (SPACE-2).

BACKGROUND: Asymptomatic carotid artery stenosis (ACS) can be treated with carotid endarterectomy (CEA), carotid artery stenting (CAS), or best medical treatment (BMT) only. For all treatment options, optimization of vascular risk factors such as arterial hypertension, hyperlipidemia, smoking, obesity, and insufficient physical activity is essential. Data on adherence to BMT and lifestyle modification in patients with ACS are sparse. The subject of this investigation is the implementation and quality of risk factor adjustment in the context of a randomized controlled trial. METHODS: A total of 513 patients in the prematurely terminated, randomized, controlled, multicenter SPACE-2 trial (ISRCTN 78592017) were analyzed within one year after randomization into 3 groups (CEA, CAS, and BMT only) for implementation of prespecified BMT recommendations and lifestyle modifications. Measurement time points were the screening visit and visits after one month (D30), 6 months (M6), and one year (A1). Differences between groups and follow-up visits (FUVs) relative to the screening visit were investigated. FINDINGS: For all FUVs, a significant increase in statin medication (91% at A1; p < 0.0001) was demonstrated to be associated with a significant decrease (p < 0.01) in cholesterol levels (median 167 mg/dl at A1) and LDL cholesterol levels (median 93 mg/dl at A1). The lowest cholesterol levels were achieved by patients in the BMT group. Seventy-eight percent of all patients reached predefined target cholesterol levels (< 200 mg/dl), with significantly better rates in the BMT group (p = 0.036 at D30). Furthermore, a significant decrease in arterial blood pressure at all FUVs (p < 0.05) was associated with a significant increase in antihypertensive medication (96% at A1, p < 0.0001). However, only 28% of patients achieved the predefined treatment goal of a systolic blood pressure of ≤ 130 mmHg. Forty-two of a total of 100 smokers at the screening visit quit smoking within one year, resulting in a significant increase in nonsmokers at all FUVs (p < 0.0001). Recommended HbA1c levels (< 7%) were achieved in 82% without significant changes after one year. Only 7% of obese (BMI > 25) patients achieved sufficient weight reduction after one year without significant changes at all FUVs (median BMI 27 at A1; p = 0.1201). The BMT group showed significantly (p = 0.024) higher rates of adequate physical activity than the intervention groups. Furthermore, after one year, the BMT group showed a comparatively significantly better implementation of risk factor modification (77%; p = 0.027) according to the treating physician. INTERPRETATION: SPACE-2 demonstrated sustained improvement in the noninterventional management of vascular risk factors in patients treated in a clinical trial by general practitioners, internists and neurologists. The best implemented treatment targets were a reduction in cholesterol and HbA1c levels. In this context, a significant increase in statin use was demonstrated. Blood pressure control missed its target but was significantly reduced by intensification of antihypertensive medication. Patients on BMT only had better adjusted lipid parameters and were more physically active. However, all groups failed to achieve sufficient weight reduction. Due to insufficient patient recruitment, the results must be interpreted cautiously. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN78592017, Registered 16 June 2007, https://www.isrctn.com/search?q=78592017 .

Interventional occlusion of left atrial appendage in patients with atrial fibrillation. Gender-related outcomes in the German LAARGE Registry.

INTRODUCTION: Gender-based differences in atrial fibrillation have been identified, but limited data exist for patients undergoing left atrial appendage occluder (LAAO) implantation. This study reports gender-related periprocedural and 1-year outcomes of the prospective, multicenter German left atrial appendage occlusion registry (LAARGE). METHODS: LAARGE enrolled 641 patients who were scheduled for LAAO implantation from July 2014 to January 2016 in 38 hospitals in Germany. The data collected included demographics, clinical characteristics, details of implantation, and outcome. Efficacy and safety at 1-year follow-up were assessed by the occurrence of thrombembolic and bleeding events, as well as mortality. RESULTS: Of 638 patients undergoing LAAO implantation 38.9% were female and 61.1% male. Females were older (76.4 ± 8.2 [females] vs. 75.6 ± 7.7 [males], p = .042) and had a higher stroke risk (CHA2 DS2 -VASc score: 4.9 ± 1.5 vs. 4.3 ± 1.5, p < .001). In contrast, males suffered more often from coronary artery (33.1% vs. 53.8%, p < .001) and vascular disease (18.5% vs. 31.0%, p < .001). Technical success was high and similar for both genders (98.4% vs. 97.2%, p = .33). Severe periprocedural complications (6.9% vs. 3.1%, p = .032) occurred more often in females. At 1-year follow-up the rates of all-cause stroke (0.5% vs. 1.3%, p = .65) and severe bleeding (0.0% and 1.0%, p = .29) were low and comparable between the genders. Also, one-year all-cause mortality (9.2% vs. 13.1%, p = .14) did not differ significantly. CONCLUSION: LAARGE documented in this elderly patient population undergoing LAAO implantation a higher rate of severe periprocedural complications in females. At 1-year follow-up similar efficacy and safety outcomes were observed for both genders.

Contralateral Stenosis and Echolucent Plaque Morphology are Associated with Elevated Stroke Risk in Patients Treated with Asymptomatic Carotid Artery Stenosis within a Controlled Clinical Trial (SPACE-2).

BACKGROUND: Asymptomatic carotid artery stenosis (ACS) has a low risk of stroke. To achieve an advantage over noninterventional best medical treatment (BMT), carotid endarterectomy (CEA) or carotid artery stenting (CAS) must be performed with the lowest possible risk of stroke. Therefore, an analysis of risk-elevating factors is essential. Grade of ipsilateral and contralateral stenosis as well as plaque morphology are known risk factors in ACS. METHODS: The randomized, controlled, multicenter SPACE-2 trial had to be stopped prematurely after recruiting 513 patients. 203 patients were randomized to CEA, 197 to CAS, and 113 to BMT. Within one year, risk factors such as grade of stenosis and plaque morphology were analyzed. RESULTS: Grade of contralateral stenosis (GCS) was higher in patients with any stroke (50%ECST vs. 20%ECST; p=0.012). Echolucent plaque morphology was associated with any stroke on the day of intervention (OR 5.23; p=0.041). In the periprocedural period, any stroke was correlated with GCS in the CEA group (70%ECST vs. 20%ECST; p=0.026) and with echolucent plaque morphology in the CAS group (6% vs. 1%; p=0.048). In multivariate analysis, occlusion of the contralateral carotid artery (CCO) was associated with risk of any stroke (OR 7.00; p=0.006), without heterogeneity between CEA and CAS. CONCLUSION: In patients with asymptomatic carotid artery stenosis, GCS, CCO, as well as echolucent plaque morphology were associated with a higher risk of cerebrovascular events. The risk of stroke in the periprocedural period was increased by GCS in CEA and by echolucent plaque in CAS. Due to small sample size, results must be interpreted carefully.

Management of Pulmonary Embolism: Results from the German Chest Pain Unit Registry.

INTRODUCTION: Since 2008, specialized chest pain units (CPUs) were implemented across Germany ensuring structured diagnostics in acute chest pain. This study aims to analyze the management of pulmonary embolism (PE) patients in such certified CPUs. METHODS: Data were retrieved from 13,902 patients enrolled in the German CPU registry and analyzed for the diagnosis of PE including patient characteristics, critical time intervals, diagnostic workup, treatment, and prognosis. PE patients were compared to the overall CPU patient cohort. Only patients with a complete 3-month follow-up were included. RESULTS: Overall, 1.1% of all CPU patients were diagnosed with PE. Chest pain and dyspnea were the leading symptoms. Patients with PE were older, presented with higher heart rates, and more frequently exhibited signs of heart failure, despite a normal left ventricular function. PE patients showed significantly longer time delays between symptom onset and the first medical contact, while PE patients with chest pain presented earlier than PE patients with dyspnea only. Whereas more PE patients had to be transferred to the intensive care unit, in-CPU mortality and event rates over 3 months were low. DISCUSSION/CONCLUSION: This study suggests a certain risk for underdiagnosis and consecutive potential undertreatment of PE patients in German Cardiac Society (GCS)-certified CPUs, which is thought to result from an anticipated focus on patients with acute coronary syndrome (ACS). Public awareness for PE beyond chest pain should be improved. Certified CPUs should be urged to implement strategic pathways for a better simultaneous diagnostic workup of differential diagnosis beyond ACS.

WATCHMAN versus ACP or Amulet devices for left atrial appendage occlusion: a sub-analysis of the multicentre LAARGE registry.

AIMS: Several left atrial appendage (LAA) closure systems are available. Due to differences in device design, the results of specific occluders derived from trials cannot simply be generalised to all devices. The present analysis sought to assess two contemporary LAA closure devices in clinical practice. METHODS AND RESULTS: The work represents a non-randomised sub-analysis of the prospective, multicentre, Left-Atrium-Appendage Occluder Register - GErmany (LAARGE) registry. The WATCHMAN (group 1) and the AMPLATZER Cardiac Plug (ACP) or Amulet occluder (group 2) were assessed. A total of 641 patients at 38 centres were enrolled. Of these, 278 (43%) and 340 (53%) patients received the WATCHMAN and ACP/Amulet occluder, respectively. High technical success was achieved with a slight difference between the groups (96% in group 1 vs 99% in group 2; p=0.007). Procedural safety did not differ (98% in group 1 vs 97% in group 2; p=0.55). The Kaplan-Meier estimated one-year composite of death or stroke was 12.0% and 12.9%, respectively (p=0.79). CONCLUSIONS: Both the WATCHMAN and the ACP/Amulet occluder provide excellent procedural results with comparable implantation success and no differences with respect to procedural safety and long-term effectiveness.

Left atrial appendage closure in patients with a reduced left ventricular ejection fraction: results from the multicenter German LAARGE registry.

BACKGROUND: Interventional left atrial appendage closure (LAAC) effectively prevents thromboembolic events in atrial fibrillation patients. Impaired left ventricular ejection fraction (LVEF) increases not only the thromboembolic risk but also the complication rates of cardiac interventions. The LAAC procedure's benefit in patients with an impaired LVEF, therefore, has yet to be investigated. METHODS: LAARGE is a prospective, non-randomized registry depicting the clinical reality of LAAC in Germany. Procedure was conducted with different standard commercial devices, and follow-up period was one year. In the sense of an as-treated analysis, patients with started procedure and documented LVEF were selected from the whole database. RESULTS: 619 patients from 37 centers were categorized into one of three groups: LVEF > 55% (56%), 36-55% (36%), and ≤ 35% (8%). Prevalence of cardiovascular comorbidity increased with LVEF reduction (p < 0.001 for trend). CHA2DS2-VASc score was 4.3, 4.8, and 5.1 (p < 0.001), and HAS-BLED score was 3.7, 4.1, and 4.2 (p < 0.001). Implantation success was consistently high (97.9%), rates of intra-hospital MACCE (0.5%), and other major complications (4.2%) were low (each p = NS). Kaplan-Meier estimation showed a decrease in survival free of stroke with LVEF reduction during one-year follow-up (89.3 vs. 87.0 vs. 79.8%; p = 0.067), a trend which was no longer evident after adjustment for relevant confounding factors. Rates of non-fatal strokes (0.4 vs. 1.1 vs. 0%) and severe bleedings (0.7 vs. 0.0 vs. 3.1%) were consistently low across all groups (each p = NS). CONCLUSIONS: LVEF reduction neither influenced the procedural success nor the effectiveness and safety of stroke prevention by LAAC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02230748.

Guideline-adherence regarding critical time intervals in the German Chest Pain Unit registry.

BACKGROUND: Since 2008, the German Cardiac Society certified 256 Chest Pain Units (CPUs). Little is known about adherence to recommended performance measures in patients with suspected acute coronary syndrome (ACS) presenting to CPUs. We investigated guideline-adherence regarding critical time intervals and selected performance measures in German Chest Pain Units. METHODS: From 2008 to 2014, 23,804 consecutive patients with suspected ACS were prospectively enrolled in the Chest Pain Unit registry of the German Cardiac Society. RESULTS: Median time from symptom onset to first medical contact was 2 h in patients with ST-elevation myocardial infarction (STEMI) and 4 h in patients with unstable angina and non-STEMI (NSTEMI). In patients with STEMI, median time from hospital admission to percutaneous coronary intervention (PCI) was 40 min and median time from first medical contact to PCI was 1 h 35 min. Primary PCI was performed in 94.7% of patients with STEMI, 70.0% of patients with NSTEMI and 37.4% of patients with unstable angina. PCI was performed during the first 24 h in 79.5% of patients with NSTEMI and the first 72 h in 89.0% of patients with unstable angina. Electrocardiograms were performed in 99.5% after a median of 6 min after admission and obtained within 10 min in 71%. Interestingly, 56.1% of patients were found to have non-ACS diagnoses, underlining the importance of access to additional diagnostic modalities including echocardiography, stress testing or computed tomography. CONCLUSIONS: Guideline-adherence regarding critical time intervals and primary PCI rates is good in German Chest Pain Units. More than half of patients admitted with suspected ACS had non-ACS diagnoses. Improvements in pre-hospital time delays through public awareness programmes are warranted.

Long-term transesophageal echocardiography follow-up after percutaneous left atrial appendage closure.

BACKGROUND: Peri-device leaks and device thrombi are assumed to lead to ischemic events after percutaneous left atrial appendage occlusion (LAAO). While these device-related complications are well assessed until 12 months after LAAO, no data are available beyond this period. OBJECTIVE: The purpose of this study was to assess device-related complications beyond 12 months after LAAO. METHODS: All patients who underwent successful percutaneous LAAO ≥12 months ago in the 2 participating centers were screened for eligibility. After inclusion, structured transesophageal echocardiography (TEE) was performed to assess peri-device leaks, device thrombus, and other device-related complications. RESULTS: A total of 63 patients were enrolled in the present prospective, 2-center, nonrandomized, single-arm trial. The median time from implantation until long-term TEE was 3.1 years (interquartile range 2.0-5.1 years), ranging from 1.0 to 7.5 years. The number of patients without a detectable leak increased significantly at long-term TEE compared with 6-week follow-up (P = .04). Major peri-device leaks (>5 mm) were detected in 2 patients (3%). Device thrombus was found in 8 patients (13%). Patients with device thrombus at long-term follow-up had larger peri-device leaks at 6-week follow-up than did those without thrombus formation (3.0 [interquartile range 2.7-3.5] vs 1.4 [interquartile range 0.0-2.6]; P = .04). Of those who suffered an ischemic stroke during long-term follow-up (n = 5), 1 patient showed a peri-device leak >5 mm. None of the patients with detected device thrombus had a stroke. CONCLUSION: Peri-device leaks and device thrombi continue to occur during long-term follow-up after LAAO. The clinical impact of these late occluder complications requires further evaluation in larger prospective trials.

Interventional occlusion of left atrial appendage in patients with atrial fibrillation. Acute and long-term outcome of occluder implantation in the LAARGE Registry.

BACKGROUND: Left atrial appendage occluder (LAAO) implantation is an alternative method for stroke prevention in atrial fibrillation (AF) patients who are not eligible for long-term oral anticoagulation. The present paper describes the acute and 1-year follow-up outcome data of the prospective, multicenter German left atrial appendage occlusion registry (LAARGE). METHODS: LAARGE enrolled 641 patients who were scheduled for LAAO implantation. The data collected included demographics, clinical characteristics, procedure indication, details of implantation, and outcome; patients were followed at 1-year post-implant. Efficacy and safety during follow-up are assessed by the occurrence of thrombembolic and bleeding events, respectively. RESULTS: A total of 641 consecutive patients (mean age: 75.9 ± 8.0) were enrolled from July 2014 to January 2016 in 38 hospitals in Germany. Patient demographics represent a critically-ill population with a calculated mean CHA2DS2-VASc score and HASBLED score of 4.5 and 3.9, respectively, with bleeding events as the main indication for LAAO implantation (79.4%). One-year all-cause mortality post-procedure was 11.5% with a non-fatal stroke/TIA rate of 1.3% (8 patients) and a rate of major bleeding of 1.6% (10 patients). The anticoagulation regimen after 1 year consisted of oral anticoagulation in 5.5% of patients and an antiplatelet therapy (APT) rate of 84.1% (majority single APT with ASS (74.5%), dual APT in 6.7%). CONCLUSIONS: LAARGE, a prospective multicenter real-world and all-comer registry, is unique in its concept, as it is non-manufacturer sponsored and includes all commercially available devices. LAAO implantation is mainly performed in elderly, critically-ill patients with a history of bleeding. LAARGE demonstrates a favorable outcome at 1-year follow-up in terms of stroke/TIA (1.3%) and major bleeding (1.6%) while using a single APT in the vast majority of patients.

Effect of renal insufficiency and diabetes mellitus on in-hospital mortality after acute coronary syndromes treated with primary PCI. Results from the ALKK PCI Registry.

BACKGROUND: It is known that patients with acute coronary syndromes (ACS) and diabetes mellitus (DM) are at higher risk for in-hospital adverse events. However, we hypothesized that the higher event rate is due to the patients' subgroup with renal failure (RF), a common sequel of DM. METHODS AND RESULTS: We used data of the prospective ALKK-PCI registry including all consecutive percutaneous coronary interventions (PCI) for ACS of 48 hospitals between 2008 and 2013. We divided 69,651 patients in four groups according to their history of DM and RF (GFR < 60 ml/min). All-cause, in-hospital mortality of the following four groups: noDM/noRF, DM/noRF, DM/RF, RF/noDM, was: 3.5%, 6.6%, 21.9%, and 14.1% for STEMI and 1.5%, 2.1%, 7.2%, and 5.4% for NSTE-ACS. In a multivariate analysis we looked for independent mortality-predictors. Odds ratios with confidence intervals for the following variables: DM without RF, DM with RF, RF without DM were: 1.62 (1.37-1.90), 3.02 (2.43-3.76), and 2.13 (1.80-2.52) for STEMI and 1.20 (0.99-1.45), 2.72 (2.18-3.88), and 2.08 (1.69-2.56) for NSTE-ACS. We also calculated mortality in four groups (60-90, 45-60, 45-30, <30 ml/min) according to the estimated glomerular filtration rate (eGFR). Mortality rates were: 5.0%, 12.8%, 17.7%, and 31.5% for STEMI and 2.1%, 3.8%, 7.1%, and 12.0% for NSTE-ACS (p for trend <0.0001 for both). CONCLUSIONS: In-hospital death after PCI in patients with ACS and DM is mainly observed in the subgroup with co-existing RF. In a multivariate analysis, DM without RF was a significant mortality-predictor in STEMI, but not in NSTE-ACS. RF, irrespective of co-existent DM, was a stronger predictor than DM alone for both ACS-types (OR > 3) and mortality increased with decreasing eGFR.

Immediate unselected coronary angiography versus delayed triage in survivors of out-of-hospital cardiac arrest without ST-segment elevation: Design and rationale of the TOMAHAWK trial.

Patients experiencing out-of-hospital cardiac arrest (OHCA) without ST-segment elevation are a heterogenic group with a variety of underlying causes. Up to one-third of patients display a significant coronary lesion compatible with myocardial infarction as OHCA trigger. There are no randomized data on patient selection and timing of invasive coronary angiography after admission. METHODS AND RESULTS: The TOMAHAWK trial randomly assigns 558 patients with return of spontaneous circulation after OHCA with no obvious extracardiac origin of cardiac arrest and no ST-segment elevation/left bundle-branch block on postresuscitation electrocardiogram to either immediate coronary angiography or initial intensive care assessment with delayed/selective angiography in a 1:1 ratio. The primary end point is 30-day all-cause mortality. Secondary analyses will be performed with respect to initial rhythm, electrocardiographic patterns, myocardial infarction as underlying cause, neurological outcome, as well as clinical and laboratory markers. Clinical follow-up will be performed at 6 and 12 months. Safety end points include bleeding and stroke. CONCLUSION: The TOMAHAWK trial will address the unresolved issue of timing and general indication of angiography after OHCA without ST-segment elevation.