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SEMPA 2019
Cruising the LiteratureCardiology 2019
Corey M. Slovis, M.D.Vanderbilt University Medical Center
Metro Nashville Fire DepartmentNashville International Airport
Nashville, TN
CPREpinephrine
Arrest S/P Sex
Epinephrine
New Engl J Med 2018;379:711-21
• Large double blind placebo controlled trial
• 8,014 pts, UK EMS, adults ≥ 16 yo
• 4,015 pts, 1 mg epi Q 3-5 min
• 3,999 placebo receiving patients
What is the role of epinephrine in cardiac arrest?
The study evaluated 30 day outcomes and functional neurologic outcomes at
discharge and at 3 months
New Engl J Med 2018;379:711-21
0%
10%
20%
30%
40%
50%
60%
Hundreds
30.7
ROSC and EMS Transport
ROSC EMS Transport
11.7
Placebo Epi Placebo Epi
New Engl J Med 2018;379:711-21
36.3
50.8
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0%
1%
2%
3%
4%
5%
2.4%
30 Day Survival
Placebo
3.2%
Epinephrine
New Engl J Med 2018;379:711-21
OR = 1.39p = 0.02
NNT = 112
New Engl J Med 2018;379:711-21
30 Day Neurologic Outcomes
0.0
0.5
1.0
1.5
2.0
2.51.9%
Rankin 0 - 3
Placebo
2.2%
Epinephrine
New Engl J Med 2018;379:711-21
OR = 1.18CI = 0.86-1.61
0.00.10.20.30.40.50.60.70.80.91.01.11.21.31.41.51.6
1.35%
Favorable Neurologic OutcomeRankin 0 - 2
Placebo
1.29%
Epinephrine
New Engl J Med 2018;379:711-21
0%
10%
20%
30%
40%
50%
60%
17.8%
Severe Neurologic Disability (30 d)Rankin 4, 5
Placebo
31.0%
Epinephrine
New Engl J Med 2018;379:711-21
Adjusted AnalysisParamedic Witnessed
Favors Placebo Favors Epinephrine
New Engl J Med 2018;379:711-21
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Adjusted AnalysisVF/pVT vs Non Shockable
Favors Placebo Favors Epinephrine
New Engl J Med 2018;379:711-21
Adjusted AnalysisMedical vs Traumatic
Favors EpinephrineFavors Placebo
New Engl J Med 2018;379:711-21
Positive Result Conclusion
Epinephrine in OOHCA arrest improves ROSC and likelihood
for hospital discharge
Neutral Result Conclusion
Epinephrine does not improve neurologically intact survival
in OOHCA
Negative Result Conclusion
Epinephrine in OOHCA just increases the likelihood of being neurologically
devastated without significantly increasing the number of neurologically
intact survivors
Circulation 2018;137:1638-40
Only 47% received CPR in these witnessed arrests
Maybe put on defib pads and hook up AED during the warm up
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NTG in AMI
Acute Hypotension with NTG5 Causes
• Right Ventricular AMI
• Relative or Absolute Volume depletion
• Viagra, Levitra, Cialis
• Bezold-Jarisch Reflex
• Drug Sensitivity (valvular dsx, idiopathic)
• 1,466 STEMIs, 56% received NTG
• Montreal Quebec EMS 2010-2012
• Evaluated BP changes in Inf vs Non-Inf AMIs
• BP < 90 or BP > 30mm Hg s/p NTG
Prehosp Emerg Care 2016;20:76-81
How dangerous is NTG in Inferior AMI?
0%
5%
10%
15%
20%
25%
STEMI BP Changes Post NTGPrehosp Emerg Care 2016;20:76-81
BP < 90 BP > 30mm Hg
8.2%
InfNot-Inf InfNot-Inf
23.4%
P=NS
P=NS8.9%
23.9%
PreHospital Emerg Care 2019 online
How safe is NTG in r/o AMI and does it effectively relieve pain?
• Prospective study, 780 pts, suspected STEMI
• LA County EMS and UCLA
• “Suspected STEMI” by ECG plus paramedic
• 0.4 mg SL NTG, up to 2 more doses
• BP < 100 mm SBP pts excluded0%
1%
2%
3%
4%
5%
6%
7%
8%
9%
10%
NTG in suspected STEMISystolic BP fall > 30 mm Hg
NTG
5.3%
No NTG
6.7%
PreHospital Emerg Care 2019 online
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0.0%
0.5%
1.0%
1.5%
2.0%
2.5%
3.0%
3.5%
4.0%
NTG in suspected STEMIPain Relief
NTG
2.6%
No NTG
1.4%
PreHospital Emerg Care 2019 online
P < 0.0001
NTG for r/o AMI
• NTG is safe in AMI
• NTG is safe in Inferior AMI
• NTG relieves Anginal pain in ACS
• Respect NTG but use it
Chest Pain andScoring Systems
Acad Emerg Med 2018;26:41-50
How does the HEART pathway perform in a randomized trial-over a 1 year study?
• 282 patients, single center trial
• ACC/AHA std care vs HEART pathway
• 1 year MACE and downstream testing
• Used 0 and 3 hour troponins
• HEART 0-3 pts: DC’d, follow up with PCP
• Pathway for early ED D/C
• Troponins at 0 and 3 hours
• Used HEART Score
Circulation: Cardiovasc Qual Outcomes 2015;8:195-203
The HEART Score
H History
E ECG
A Age
R Risk Factors
T Troponin
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MD Calc for HEART Score HEAR Performance1 Year Results
• 66/141 patients had negative 0-3 hour troponin and a HEAR score of 0-3
• None of these discharged patients had a major adverse cardiac event (MACE) by 1 year
• NPV % 100%; Sensitivity for MACE: 100%
• But only 8% reduction in 1 year for cardiac testing
Acad Emerg Med 2018;26:41-50
HEART Score and PathwayTake Homes
• First 1 year study of HEAR
• No longer HEART
• A subjective “objective” test
• Beware positive Trop
Am J Emerg Med 2017;35:704-9
Is “Low Risk” by HEART and other scoring systems really low risk?
• 434 pts from 7 EDs
• Average age 57 (49-64)
• Used HEART, TIMI, GRACE, EDACS
• Compared HEART ≤ 3 vs ≤ 2
HEART ≤ 3 has a miss rate of 3.6%
HEART ≤ 2 had a miss rate of 0
Am J Emerg Med 2017;35:704-9
The 0 and 1 hour rule out protocols yield at NPV for ACS of 99.8 for HS
Troponin T and 99.7 for HS Troponin I and allows early discharge for
1/2 - 2/3 of patients
JAMA Cardio 2018;3:112-113
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Circ 2018;138:2061-2063
• 536 pts, Parkland Hospital, HS and Trop T
• Uses delta changes
• Above 52 ng/L = AMI, < 6 ng/L ≥ 3 hrs = R/O
• < 3 ng at 1 hr = R/O
• < 7 ng from baseline at 3 hrs = R/O
Can a multi-step 0, 1 and 3 hour protocol deal with the “indeterminate” patients when using
high-sensitivity Troponin (hsTrop)
Protocol providing 100%Sensitivity for AMI and 100%
Negative predictive values for R/O
Circ 2018;138:2061-2063
Annals Emerg Med 2018 Sept;in press
• Used a fifth generation HS Trop T (cTnT)
• 569 pts from Henry Ford Hospital
• < 6 ng/L on ED entry
• < 8 ng/L on entry + < 3 ng rise at 30 min
• 100% rule-out in 28% and 41% of pts
Is a 0 and 30 minute R/O possible?
Take Homes onHigh Sensitivity Troponins
• Undetectable at 0-1 or 0-3 rules out AMI
• Delta testing excludes evolving AMI
• Early AMI presenters need values over time
• Using the 99th percentile may not be optimal
• Beware detectable Troponin
At the current time there is no universally accepted high sensitivity
Troponin protocol and objective scoring system that is “proven” to be optimal
All important decisions are made onincomplete information….
Yet we are responsible for everydecision we make.
Sheldon Kopp 1972
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Acad Emerg Med 2018;25:293-300
Does shared decision making lead to decreased testing without increased risk to
patients and/or physicians?
• 834 CP patients evaluated 45 days s/p ED
• Multicenter trial, 5 EDs across USA
• All eligible for Stress or MD CT
• All kept health care diaries
• Compared usual care to shared decision making
Key FindingsAcad Emerg Med 2018;25:293-300
Shared decision making patients had 25.8% less advanced testing than
routine care over 45 days –without any worsening of outcomes
or increased number of adverse conditions
So what should you do:
- Do a very careful history
- Use HEART but diaphoresis &/or radiationto R arm or shoulder, Abn ECG = high risk
- Beware a single Troponin; use Delta too
- Be more careful in HS = 3
- Always involve the patient and family
Male vs Femalein AMI Dx and Rx
Circulation 2018;137:781-90
How different is AMI in males vs females less than age 55?
• 2,009 women, 976 men with AMI
• Young defined as 18-55
• About 90% of M and F pts has chest sx:- pain, pressure, tightness, discomfort
• Women had more additional symptoms
• 50% more F than M had no CP
Physicians much more likely to attribute AMI symptoms to another
disease in women than men
53.4% F vs 36.7% M, p < 0.001
Circulation 2018;137:781-90
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Women and AMI
We need to be careful
“Atypical symptoms” may be typical in women
Be aware of our unconscious biases
Are women really treated differently for ACS if they are troponin positive?
• 7,272 pts from Vancouver, 2008-2013
• All pts troponin positive with ischemic CP
• 2,933 females: 4,339 males
• Evaluated % PCI, meds, mortality
• All had cTnI > 99th percentile
Acad Emerg Med 2018;25:413-24
Symptoms & Diagnosis in EDTroponin Positive Females
Acad Emerg Med 2018;25:413-24
• More respiratory symptoms(22.4% vs 14.8% F:M)
• Less classic chest pain symptoms(77.6% vs 85.2%)
• AMI less frequently diagnosed in ED(35.4% vs 52.5%)
• Less likely to be using evidence based meds:(ACE-I / ARB 0.32; BB 0.52, Statin 0.31)
05
101520253035404550556065
64.3
Troponin PositivePCI and MACE
PCI MACE
48.4
Female Male Female Male
OR = 0.52(0.39 – 0.70)
HR = 1.24*(0.94 – 1.65)*p – NS onceadjusted for difference
18.822.7
Acad Emerg Med 2018;25:413-24
How We Treat Women vs Men with ACS
Take Homes
• We are less aggressive with women and they do worse
• Even if Troponin positive, we are less aggressive with emergent PCI and/or cardiac meds
PNAS 2018;115:8569-74
• Higher mortality seen when women with STEMI treated by male ED physician
• Female=Male when treated by female ED physicians
• Male physicians do better if more females in ED practice or they have treated more females in past
• Be careful of unconscious gender bias
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MortalityPatient vs Doctor Gender
M Doc
F Pt
M Doc
M Pt
F Doc
F Pt
Atrial Fibrillation
Acad Emerg Med 2018;25:641-9
Can a simple to follow protocol allow more discharges in AFib/AFlut patients?
• 1,108 patients
• Retrospective before-after trial
• Academic community hospital
• Evaluated percent of pts admitted in 1 year
• Also 3 and 30 day returnsAcad Emerg Med 2018;25:641-9
• Arranged follow up within 3d
• Seen then in cardiology clinic
• Anticoagulation held until then
• Discharged on BB or Calcium Blocker
• Metoprolol 50 BID
• Diltiazem 120-180 ext release
Acad Emerg Med 2018;25:641-9
St. Joseph Murphy AlgorithmExclusions and Admit
• Underlying Acute Illness(sepsis, PE, etc.)
• Acute Coronary Syndrome
• Acute Heart Failure
• Syncope
• Hemodynamic instability
Acad Emerg Med 2018;25:641-9
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0
10
20
30
40
50
60
70
80 63.6%
Hospital Admit Rates
All Patients Low Acuity
80%
Pre Post Pre Post
Acad Emerg Med 2018;25:641-9
16.1%P < 0.001
31.3%P < 0.001
67.4%
43.7%
NOTE
• Pharmacological conversions not attempted
• IV rate control discouraged
• 50 mg PO Metoprolol
• 120-180 mg PO Diltiazem ER
• D/C cardioversion not increased
Acad Emerg Med 2018;25:641-9
Simplified AFib Discharge PathwaysTake Homes
• Single center trial
• Very simple, very impressive
• < 48 hr not specifically cited
• stroke risk ?
• This protocol will have users
NEJM 2019 epub
Can Cardioversion be safely delayed in ED patients with new onset Atrial Fibrillation?
• 427 pts assigned to early vs delayed cardioversion
• Randomized 1:1, multicenter trial
• Atrial Fibrillation of < 36 hours studied
• Evaluated rhythm at 4 weeks
• Also evaluated complications including CVA
Methods
• 15 Hospitals in the Netherlands
• October 2014 - September 2018
• Only hemodynamically patients
• Rate Control via BB, CAB or Digoxin
• Wait and See pts discharged when HR < 110
NEJM 2019 epub
Wait and See patients were seen 24 - 48 hours later and if still in
Atrial Fibrillation were sent to theED for Cardioversion
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Delayed Cardioversion
• 69% (150/218) spontaneously converted by 48 hours
• 28% (61) required ED Cardioversion
• 9 by flecainide and 52 electrically
NEJM 2019 epub NEJM 2019 epub
Sinus Rhythm at 4 Weeks
Complications at 4 weeks
• 1 Stroke / TIA each in Immediate vs Delayed
• 3 ACS episodes in each group
• Same incidence of AF recurrence in both groups (29% vs 30%)
NEJM 2019 epub
Rate Controlling AF and Discharging Take Homes
Appears safe and effective as long as stable patients are discharge rate
controlled AND seen for follow up in 24-48 hours
Acad Emerg Med 2018;in press August
• 450 pts, double-blind, placebo controlled
• 3 groups of pts from 3 Tunisian hospitals
• High dose vs Low dose vs Placebo
• MgSO4 9 grams vs 4.5 grams vs Placebo
• Given over 30 minutes
Is Magnesium effective for rate control in “Rapid” Atrial Fibrillation? Measured effectiveness as HR < 90
or rate lowering by > 20%
Acad Emerg Med 2018;in press August
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0%
10%
20%
30%
40%
50%
60%
70% 59.5%64.2%
EffectivenessHR < 90 or HR > 20%
9 Grams 4.5 Grams
43.6%
--
Acad Emerg Med 2018;in press August
High Dose Mg Low Dose Mg Placebo
This paper is not what it seems
Acad Emerg Med 2018;in press August
• Essentially all patients got other rate control agents
• 45-50% received Digoxin
• 30% received Diltiazem
• 20% received Beta Blockade
Magnesium for Rate Control in AFTake Homes
• Adjunct? – maybe; Primary – NO
• 2.5 grams or 4.5 grams?
• 9 grams = lots of flushing (10-15%)
• Was very safe, < 1% hypotension
• Read this paper carefully
Summary
Epi survival but bad Neuro too
Summary
PCI all VF/VT survivors
Not witnessed, no shock, no ROSC
Respect NTG but use it
HEART works – beware scores > 2
Beware detectable HS Troponin
Summary
Stress tests: do less
Use shared decision making
AFib can be safely discharged
Develop an AFib pathway
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VanderbiltEM.com