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2007 ACC/AHA UA/NSTEMI Guideline Revision
NSTEMI
2014
Οξύ Έµφραγµα του Μυοκαρδίου χωρίς ανάσπαση του ST
ΘΩΜΑΣ ΜΠΕΛΕΒΕΣΛΗΣ Αρχίατρος – Επεµβατικός Καρδιολόγος
2007 ACC/AHA UA/NSTEMI Guideline Revision
Acute Coronary Syndrome (ACS)
! Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion.
[----UA---------NSTEMI----------STEMI----]
2014
2007 ACC/AHA UA/NSTEMI Guideline Revision
Decreased O2 Supply • Flow- limiting stenosis
• Anemia
• Plaque rupture/clot
Increased O2 Demand
O2 supply/demand mismatch→Ischemia
Myocardial ischemia→necrosis
Pathophysiology ACS
Asy
mpt
omat
ic
Ang
ina
Myo
card
ial I
nfar
ctio
n
Pathophysiology of Stable Angina and ACS
2014
2007 ACC/AHA UA/NSTEMI Guideline Revision 2014
Sudden Thrombus or Thromboembolism Ruptured
Fibrous CapSuperficial
Erosion
Modified from Libby P Circ 104:365,2001
2007 ACC/AHA UA/NSTEMI Guideline Revision
No ST Elevation ST Elevation
Acute Coronary Syndrome
NQMI Qw MI
NSTEMI
Myocardial Infarction
Davies MJ Heart 83:361, 2000
Ischemic Discomfort Presentation
Working Dx
ECG
Biochem. Marker
Hamm Lancet 358:1533,2001
Unstable Angina Final Dx
2007 ACC/AHA UA/NSTEMI Guideline Revision
Hospitalizations in the U.S. Due to Acute Coronary Syndromes (ACS)
Acute Coronary Syndromes*
1.57 Million Hospital Admissions - ACS
UA/NSTEMI† STEMI
1.24 million Admissions per year
.33 million Admissions per year
Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69-171. *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA.
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Placebo Event Rates in Recent Trials of UA and NSTEMI
! PRISM1 7.1% ! PRISM-PLUS2 11.9% ! PURSUIT3 15.7% ! GUSTO-IV ACS4 8.0%
! PARAGON A5 11.7%
Death/MI at 30 days
1. PRISM Study Investigators. N Engl J Med 1998;338:1498-1505. 2. PRISM-PLUS Study Investigators. N Engl J Med 1998;338:1488-1497. 3. Harrington RA. Am J Cardiol 1997;80:34B-38B. 4. The GUSTO IV-ACS Investigators. Lancet 2001;357:1915-1924. 5. The PARGON Investigators. Circulation 1998;97:2386-2395.
UA and NSTEMI
2014
2007 ACC/AHA UA/NSTEMI Guideline Revision
Initial Evaluation and management of Non ST-elevation ACS
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Initial Evaluation and Management • History and Physical • ECG • Cardiac Biomarkers
Establish the Likelihood that Clinical Presentation Represents an ACS Secondary to CAD
Risk Stratify for Short-term Adverse Outcomes
2007 ACC/AHA UA/NSTEMI Guideline Revision
Class I Patients with suspected ACS and high-risk
features such as 1. continuing chest pain, 2. severe dyspnea, 3. syncope/presyncope, 4. or palpitations should be referred immediately to the ED
2014
Initial Evaluation
2007 ACC/AHA UA/NSTEMI Guideline Revision
Likelihood of ACS by Hx/PE
! History/Examination " Pain in Chest or Left Arm " CP Radiation ○ Right Shoulder ○ Left Arm ○ Both Left & Right Arm
" Diaphoresis " 3rd Heart Sound " SBP < 80 mm Hg " Pulmonary Crackles Panju AA. JAMA. 1998;280:1256.
Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1)
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2007 ACC/AHA UA/NSTEMI Guideline Revision
·∙ Nonischemic (e.g., aortic dissection, expanding aortic aneurysm, pericarditis, pulmonary embolism) ·∙ Noncardiovascular discomfort include: o Pulmonary causes (e.g., pneumonia, pleuritis, pneumothorax) o Gastrointestinal causes (e.g., gastroesophageal reflux, esophageal spasm, peptic ulcer, pancreatitis, biliary disease) o Musculoskeletal causes (e.g., costochondritis, cervical radiculopathy) o Psychiatric disorders o Other etiologies (e.g., sickle cell crisis, herpes zoster)
Differential diagnosis of NSTE-ACS
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Electrocardiogram
2014
Changes on ECG in patients with NSTE-ACS 1. ST depression, 2. transient ST elevation, or 3. new T-wave inversion
A normal ECG does not exclude ACS and occurs in 1% to 6% A normal ECG may also be associated with left circumflex or right coronary artery occlusions, which can be electrically silent (in which case posterior electrocardiographic leads [V7 to V9] may be helpful).
2007 ACC/AHA UA/NSTEMI Guideline Revision
How Sensitive is the ECG Alone?
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Wellens’ syndrome
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2007 ACC/AHA UA/NSTEMI Guideline Revision 2014
Kaplan-Meier Estimates of Probability of Death Based on Admission Electrocardiogram
Anderson, J. L. et al. J Am Coll Cardiol 2007;50:e1-e157
2007 ACC/AHA UA/NSTEMI Guideline Revision 2014
Biomarkers of Myocardial Necrosis
2007 ACC/AHA UA/NSTEMI Guideline Revision
1,01,7
3,4 3,7
6,0
7,5
012345678
0 to <0.4 0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0 9,0
Cardiac troponin I (ng/ml)
Mor
talit
y at
42
Day
s
831 174 148 134 50 67
≥
% %
% %
%
%
Risk Stratification by Troponin
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Non ACS causes of Troponin Elevation 1. Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac
surgery, after-interventional closure of ASDs) 2. Congestive heart failure (acute and chronic) 3. Aortic valve disease and HOCM with significant LVH 4. Hypertension 5. Hypotension, often with arrhythmias 6. Noncardiac surgery 7. Renal failure 8. Critically ill patients, especially with diabetes, respiratory failure 9. Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) 10. Hypothyroidism 11. Coronary vasospasm, including apical ballooning syndrome 12. Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, 13. Post-PCI 14. Pulmonary embolism, severe pulmonary hypertension 15. Sepsis 16. Burns, especially if TBSA greater than 30% 17. Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma 18. Acute neurologic disease, including CVA, subarchnoid bleeds 19. Rhabdomyolysis with cardiac injury 20. Transplant vasculopathy 21. Vital exhaustion
Modified from Apple FS, et al Heart J. 2002;144:981-986.
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Combined Sensitivities for ACS
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Image
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Chest roentgenogram Transthoracic echocardiography Transesophageal echocardiography Computed tomography (CT) Coronary CT angiography Myocardial perfusion imaging
2007 ACC/AHA UA/NSTEMI Guideline Revision
Risk Stratification
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Risk Assessment Dependent on Contingent Probabilities
! Likelihood of obstructive CAD as cause of symptoms " Dominated by acute
findings ○ Exam ○ Symptoms ○ Markers
" Traditional risk factors are of limited utility
! Does this patient have symptoms due to acute ischemia from obstructive CAD?
! Risk of bad outcome " Dominated by acute
findings ○ Older age very
important ○ Hemodynamic
abnormalities critical
○ ECG, markers ! What is the
likelihood of death, MI, heart failure?
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2007 ACC/AHA UA/NSTEMI Guideline Revision
24h 3-4 days 6 months
Ris
k
Physiological monitoring Periodic physical exams Cardiac markers ECG
Time
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Unstable angina/NSTEMI cardiac care
! Evaluate for conservative vs. invasive strategy based upon: ○ Likelihood of actual ACS ○ Risk stratification by risk scores ○ ACS risk categories per AHA guidelines
Low Intermediate
High
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Risk Scores TIMI GRACE Future
History
Age Hypertension Diabetes Smoking ↑cholesterol Family history History of CAD
Age Continuous assessment
Presentation
Severe angina Aspirin within 7 days Elevated markers ST segment deviation
Heart rate Systolic BP Elevated markers Heart failure Cardiac arrest Elevated markers ST segment deviation
New markers Electronic health records
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2007 ACC/AHA UA/NSTEMI Guideline Revision
TIMI Risk Score
Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Predicted 6-month mortality Risk of future adverse cardiovascular events
1.5% or below Lowest
> 1.5 to 3.0% Low
> 3.0 to 6.0% Intermediate
> 6.0 to 9.0% High
over 9.0% Highest
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TIMI Risk Score
2007 ACC/AHA UA/NSTEMI Guideline Revision
Perform rapid determination of likelihood of ACS, including a 12-lead ECG within 10 min of arrival at an emergency facility, in patients whose symptoms suggest ACS
I C
Perform serial ECGs at 15- to 30-min intervals during the first hour in symptomatic patients with initial non diagnostic ECG
I C
Measure cardiac troponin (cTnI or cTnT) in all patients with symptoms consistent with ACS*
I A
Measure serial cardiac troponin I or T at presentation and 3–6 h after symptom onset* in all patients with symptoms consistent with ACS
I A
Use risk scores to assess prognosis in patients with NSTE-ACS I A Risk-stratification models can be useful in management IIa B Obtain supplemental electrocardiographic leads V7 to V9 in patients with initial nondiagnostic ECG at intermediate/high risk for ACS
IIa B
Continuous monitoring with 12-lead ECG may be a reasonable alternative with initial nondiagnostic ECG in patients at intermediate/high risk for ACS
IIb B
BNP or NT–pro-BNP may be considered to assess risk in patients with suspected ACS
IIb B
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Early Hospital Care
2014
! Anti-Ischemic Therapy ! Anti-Platelet Therapy ! Anticoagulant Therapy
2007 ACC/AHA UA/NSTEMI Guideline Revision
Early Hospital Care Anti-Ischemic Therapy
! Class I " Bed/Chair rest and Telemetry " Oxygen (maintain saturation >90%) " Nitrates (SLx3 Oral/topical. IV for ongoing
iscemia, heart failure, hypertension) " Oral B-blockers in First 24-hours if no
contraindications. (IV B-blockers class IIa indication)
" Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers
" ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant)
" Statins
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Early Hospital Care Anti-Platelet Therapy
! Class I " Aspirin (162-325 mg), non enteric coated " P2Y12 inhibitors Clopidogrel or Ticagrelor " GI prophylaxis if a Hx of GI bleed " GP IIb/IIIa inhibitors should be evaluated based on
whether an invasive or conservative strategy is used
" GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Early Hospital Care Anticoagulant Therapy
! Class I " Unfractionated Heparin " Enoxaparin " Bivalarudin " Fondaparinux " Argatroban
" Relative choice depends on invasive vs conservative strategy and bleeding risk
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Early Hospital Care Statin Therapy
! In patients recently hospitalized within 10 days for an acute coronary syndrome:
• “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005)
• Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up
• Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Invasive or Conservative Strategy
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Invasive vs Conservative Strategy Clinical Trials
TIMI IIIB (94)
Conservative Strategy Favored
N=920
Invasive Strategy Favored
N=7,018
VANQWISH (98)
MATE
FRISC II (99)
TACTICS- TIMI 18 (01)
VINO
RITA-3 (02)
TRUCS
ISAR- COOL
ICTUS (05)
No difference N=2,874
Weight of the evidence
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Invasive Strategies
FRISC-II trial ICTUS RITA-3 trial
Absolute reductions of 2.0% to 3.8% in cardiovascular death or MI in the low- and intermediate-risk and an 11.1% absolute risk reduction in the highest-risk patients. The invasive strategy demons t ra ted i t s g rea tes t advantage in the highest-risk stratum of patients with no significant benefit on mortality over the noninvasive approach in moderate- and low-risk patients
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Diagnosis of UA/NSTEMI is Likely or Definite
Ischaimia – Guided strategy
Early inasive strategy
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2007 ACC/AHA UA/NSTEMI Guideline Revision
Immediate invasive (within 2 h)
Refractory angina Signs or symptoms of HF or new or worsening mitral regurgitation Hemodynamic instability Recurrent angina or ischemia at rest or with low-level activities despite intensive medical therapy
Sustained VT or VF Ischemia-guided strategy
Low-risk score (e.g., TIMI [0 or 1], GRACE [<109]) Low-risk Tn-negative female patients Patient or clinician preference in the absence of high-risk features
Early invasive (within 24 h)
None of the above, but GRACE risk score >140 Temporal change in Tn (Section 3.4) New or presumably new ST depression
Delayed invasive (within 25-72 h)
None of the above but diabetes mellitus Renal insufficiency (GFR <60 mL/min/1.73 m²) Reduced LV systolic function (EF <0.40) Early postinfarction angina PCI within 6 mo Prior CABG GRACE risk score 109–140; TIMI score ≥2
2014
Early Invasive Strategy or Ischemia-Guided Strategy in Patients With NSTE-ACS
2007 ACC/AHA UA/NSTEMI Guideline Revision 2014
NSTE-ACS : Definite or Likely
Ishemia-Guided Strategy Early Invasive Strategy
Initiate DAPT and Anticoagulant Therapy 1. ASA 2. P2Y12 inhibitor (in addition to
ASA) Clopidogrel or Ticagrelor 3. Anticoagulant : UFH Enoxaparin Fondaparinux
Initiate DAPT and Anticoagulant Therary 1. ASA 2. P2Y12 inhibitor (in addition to ASA) Clopidogrel or Ticagrelor 3. Anticoagulant : UFH Enoxaparin Fondaparinux Bivalirudin
Can consider GPI in addition to ASA and P2Y12 inhibitor in high-risk (e.g., troponine positive) pts Eptifibatide Tirofiban
Medical therapy chosen based on cath findings
Therapy ineffective Therapy effective
PCI CABG
(Continued) Stress tests
2007 ACC/AHA UA/NSTEMI Guideline Revision 2014
Therapy effective Therapy ineffective
PCI With Stenting Initiate/ continue antiplatelet and anticoagulant
therapy 1. ASA 2. P2Y12 inhibitor (in addition to ASA0 Cloprdogrel Prasugrel Ticagrelor 3. GPI (if not treated with bivalirudin at time of PCI High-risk features, not adequately pretreated with clopidogrel (Class I) High-risk features adequately pretreated with clopidogrel (class Iia) 4. Anticoagulant : UFH Enoxaparin Bivalirudin Fondaparinux class III as the sole anticoagulant
CABG Initiate / continue ASA therapy and
discontinue P2Y12 and / or GPI therapy
1. ASA 2. Discontinue clopidogrel/ticagrelor 5
d before, and prasugrel at least 7 d before elective CABG
3. Discontinue clopidogrel/ticagrelor up to 24h before urgent CABG. May perfotm urgent CABG< 5 d after clopidogrel/ticagrelor and < 7 d after prasugrel discontinued
4. Discontinue eptifibatide/ tirofiban at least 2-4h before, and abciximab ≥ 12h before CABG
Late Hospital / Possthospital Care 1. ASA 2. P2Y12 inhibitor (clopidogrel or ticagrelor), in
addition to ASA, up to 12 mo if medically treated
3. P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor), in addition to ASA, at least 12 mo if treated with coronary stenting
PCI CABG
Stress tests
2007 ACC/AHA UA/NSTEMI Guideline Revision
Risk Stratification Before Discharge for Patients With an Ischemia-Guided Strategy of NSTE-ACS: recommendations Class I 1. Noninvasive stress testing is recommended in low- and intermediate-risk
patients who have been free of ischemia at rest or with low-level activity for a minimum of 12 to 24 hours. (Level of Evidence: B)
2. Treadmill exercise testing is useful in patients able to exercise in whom the ECG is free of resting ST changes that may interfere with interpretation (Level of Evidence: C) 3. Stress testing with an imaging modality should be used in patients who are able to exercise but have ST changes on resting ECG that may interfere with interpretation. In patients undergoing a low-level exercise test, an imaging modality can add prognostic information (Level of Evidence: B) 4. Pharmacological stress testing with imaging is recommended when physical limitations preclude adequate exercise stress. (Level of Evidence:C)
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2007 ACC/AHA UA/NSTEMI Guideline Revision 2014
Therapy effective Therapy ineffective
PCI With Stenting Initiate/ continue antiplatelet and anticoagulant
therapy 1. ASA 2. P2Y12 inhibitor (in addition to ASA0 Cloprdogrel Prasugrel Ticagrelor 3. GPI (if not treated with bivalirudin at time of PCI High-risk features, not adequately pretreated with clopidogrel (Class I) High-risk features adequately pretreated with clopidogrel (class Iia) 4. Anticoagulant : UFH Enoxaparin Bivalirudin Fondaparinux class III as the sole anticoagulant
CABG Initiate / continue ASA therapy and
discontinue P2Y12 and / or GPI therapy
1. ASA 2. Discontinue clopidogrel/ticagrelor 5
d before, and prasugrel at least 7 d before elective CABG
3. Discontinue clopidogrel/ticagrelor up to 24h before urgent CABG. May perfotm urgent CABG< 5 d after clopidogrel/ticagrelor and < 7 d after prasugrel discontinued
4. Discontinue eptifibatide/ tirofiban at least 2-4h before, and abciximab ≥ 12h before CABG
Late Hospital / Possthospital Care 1. ASA 2. P2Y12 inhibitor (clopidogrel or ticagrelor), in
addition to ASA, up to 12 mo if medically treated
3. P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor), in addition to ASA, at least 12 mo if treated with coronary stenting
PCI CABG
Stress tests
2007 ACC/AHA UA/NSTEMI Guideline Revision
PCI—General Considerations:
Recommendation Class IIb
A strategy of multivessel PCI, in contrast to culprit lesion-only PCI, may be reasonable in patients undergoing coronary revascularization as part of treatment for NSTE-ACS (Level of Evidence: B)
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2007 ACC/AHA UA/NSTEMI Guideline Revision
ACS With Normal Coronary Arteries
2014
Class IIb 1. If coronary angiography reveals normal coronary arteries and endothelial dysfunction is suspected, invasive physiological assessment such as coronary flow reserve measurement may be considered). (Level of Evidence: B)
Stress (Takotsubo) Cardiomyopathy Class I 1. Stress (Takotsubo) cardiomyopathy should be considered in patients who present with apparent ACS and nonobstructive CAD at angiography. (Level of Evidence: C) 2. Imaging with ventriculography, echocardiography, or magnetic resonance imaging should be performed to confirm or exclude the diagnosis of stress (Takotsubo) cardiomyopathy. (Level of Evidence: B)
2007 ACC/AHA UA/NSTEMI Guideline Revision
Preparation for Discharge After UA/NSTEMI ! Beta Blocker ! ACEI / ARB
– Especially if DM, HF, EF <40%, HTN ! Statin
– LDL <100 mg/dL (ideally <70 mg/dL) ! Secondary Prevention Measures
– Smoking Cessation – BP <140/90 mm HG or <130/80 mm HG for DM or chronic kidney
disease – HbA1C <7% – BMI 18.5-24.9 – Physical Exercise 30-60 min at least 5 days/wk
2014
2007 ACC/AHA UA/NSTEMI Guideline Revision 2014
THANK YOU
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