Chest Pain and Risk Stratification - Bryan Health
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8/29/2018
Chest Pain and
Risk Stratification
Joseph L. Kummer, MD, FACC
Bryan Heart
Fall Conference
September 1st, 2018
Chest Pain Demographics
• Chest Pain is the second most common
complaint in the ER and among the most
common complaints in the general medical
practice clinical setting
• 6 million ER visits annually in the US
Etiologies
• Usually benign, but need to exclude
potentially emergent causes
• Life-threatening causes:
– Acute Myocardial Infarction
– Pulmonary Embolus
– Aortic Dissection
– Tension Pneumothorax
– Esophageal, Gastric Perforation
– Cardiac Tamponade
18/29/2018
ER Chest Pain Etiology
CAUSE PREVALENCE
Musculoskeletal 36
Gastrointestinal 19
Cardiac 16
+ Stable Angina 10.5
+ USA/MI 1.5
+ Other Cardiac 4
Psychiatric 8
Pulmonary 5
Unknown 16
ER Chest Pain Etiology
Non-Ischemic Cardiac Pulmonary Gastrointestinal
Aortic Dissection Pleurisy Biliary
Myocarditis Pneumonia + Cholangitis
Pericarditis Pulmonary Embolus + Choledocholithiasis
Tension Pneumothorax + Cholecystitis
Chest Wall + Colic
Cervical Disc Disease Psychiatric Esophageal
Costochondritis Depression + GERD
Herpes Zoster Anxiety Disorders + Esophagitis
Neuropathic + Primary Anxiety + Spasm
Rib Fracture + Hyperventilation + Rupture
Arthritis + Panic Disorder Pancreatitis
Somatiform Disorders Peptic Ulcer Disease
Trauma Secondary Gain + Non-perforating
+ Perforating
Missed Diagnosis
• An estimated 2.2% of patients with an Acute
Coronary Syndrome are mistakenly
discharged from the ED
• Typical characteristics:
– Women less than 55 years of age
– Nonwhite
– Shortness of breath as the major symptom
– Normal or non-diagnostic ECG
28/29/2018
Patient Style/Behavior
• A study had physicians watch videos of an
actress complaining to a doctor of chest
pain using a scripted interview
• One setting, the actress was
“businesslike,” in the other, she was
“histrionic”
Patient Style/Behavior
• Coronary disease was suspected in 50%
of the “businesslike” patient but only 13%
of the “histrionic” patient
• Evaluation recommend in 93% of the
“businesslike” group but only 53% in the
“histrionic” group
Diagnostic Testing
• Laboratory
– CBC, BMP, LFT’s, U/A
– Cardiac Enzymes
– Rheumatoid Factor, ESR
• Radiography
– Chest X-Ray
– Rib, Shoulder Films
– CT Chest, Abdomen
• EKG
38/29/2018
Physical Examination
• General Appearance
• Vitals (pulse discrepancy)
• Palpation (reproducibility)
• Auscultation
– Murmur (AS, MR, AI), Rub
– Breath Sounds (Present, Crackles, Wheezes)
– Abdominal Exam (Bowel Sounds, RUQ
Tenderness, Abdominal Aorta)
CXR
• Aortic Dissection
• Pneumothorax
• Pulmonary Edema
• Pneumonia
• Neoplasm, PE, Pericardial Effusion
EKG
• A normal EKG at the time of chest pain
markedly reduces the likelihood of cardiac
ischemia
• A truly “normal” EKG is seen in less than
4% of patients in the ER with an acute MI
48/29/2018
Validity of Chest Pain
Characteristics
Characteristic Likelihood Ratio
Radiation to Right Arm or Shoulder 4.7
Radiation to Bilateral Arms/Shoulders 4.1
Exertional 2.4
Radiation to Left Arm 2.3
Diaphoresis 2.0
Nausea/Vomiting 1.9
Worse than or similar to previous MI 1.8
Pressure 1.3
Validity of Chest Pain
Characteristics
Characteristic Likelihood Ratio
Pleuritic 0.2
Positional 0.3
Sharp 0.3
Reproducible 0.3
Inframammary Location 0.8
Nonexertional 0.8
Other Pain Characteristics
• Chest pain lasting only seconds and
present for months is almost never angina
• Relief with eating is likely GI in origin
• Relief (or lack thereof) with NTG or GI
Cocktail does not change likelihood of a
cardiac etiology
58/29/2018
Age
• In a study of those with an AMI younger
than 40 years of age, 98% had at least
one conventional CAD risk factor
– 80% smoked
– 40% had a family history of early CAD
– 26% were hypertensive
– 20% were hyperlipidemic
– Sympathomimetic drugs were seen in 7%
Risk Stratification/Prevalence
(Diamond-Forrester)
Non-Cardiac Chest Atypical Chest Typical Chest Pain
Pain Pain
Age Male Female Male Female Male Female
30-39 4 2 34 12 76 26
40-49 13 3 51 22 87 55
50-59 20 7 65 31 93 73
60-69 27 14 72 51 94 86
Very Low Probability
• If initial ER evaluation (H&P, CXR, EKG)
places patient in ACS risk of8/29/2018
Risk Models
• Multiple models have been used for risk
stratification
– TIMI
– GRACE
– PURSUIT
– FRISC
– HEART SCORE
HEART SCORE
• www.heartscore.nl
• http://annals.org/aim/article/2622872/effect-using-
heart-score-patients-chest-pain-emergency-
department-stepped
• Effect of Using the HEART Score in Patients With
Chest Pain in the Emergency Department: A Stepped-
Wedge, Cluster Randomized Trial. Poldervaart JM, et
al. Ann Intern Med. 2017;166(10):689-697.
HEART SCORE
• Heart Score is now widely used for risk
stratification and hence, disposition
planning for ER patients
• Superior to TIMI and GRACE for risk
stratification
78/29/2018
HEART SCORE
• Primary objective is disposition
A) URGENT REVASCULARIZATION
B) ADMIT TO OBSERVATION
C) DISCHARGE WITH OUTPATIENT FOLLOW-UP
HEART SCORE
• Primary objective is disposition
– Not the final word on whether or not the
patient has CAD/Ischemia
– Some patients with symptomatic CAD will be
discharged from ER and eventually undergo
revascularization as outpatients
HEART SCORE
• Points are assigned based upon 5
categories
– 0, 1, or 2 points are assigned per category
– Sum of all components guides disposition
88/29/2018
HEART SCORE
• Categories:
–History
–EKG
–Age
–Risk Factors
–Troponin
H - HISTORY
• 0: Not Suspicious for Angina
• 1: Moderately Suspicious for Angina
• 2: Highly Suspicious for Angina
E - EKG
• 0: Normal EKG
• 1: Non-Specific Repolarization
Abnormalities; LBBB; Paced Rhythm
• 2: Significant ST Deviation
98/29/2018
A - AGE
• 0: ≤ 45 Years Old
• 1: 45 – 65 Years Old
• 2: ≥ 65 Years Old
R – Risk Factors
• 0: No Risk Factors
• 1: One or Two Risk Factors
• 2: ≥ Three Risk Factors OR Known CAD
R – Risk Factors
Dyslipidemia Cigarette Smoking
Hypertension Family History of Early CAD
Diabetes Mellitus Obesity (BMI ≥ 30 kg/m2)
108/29/2018
T - Troponin
• 0: < Normal Limit
• 1: One to Three Times Normal Limit
• 2: ≥ Three Times Normal Limit
HEART SCORE
• Evaluates the six week risk of MACE
following ER evaluation
• MACE includes:
– Myocardial Infarction
– PTCA
– CABG
– Death
118/29/2018
HEART SCORE - Prognosis
HEART SCORE - Disposition
SCORE Prevalence MACE/n MACE % Death Policy
0-3 32% 38/1993 1.9% 0.05% Discharge
4-6 51% 413/3136 13% 1.3% Observation.
Risk Mgmt
7-10 17% 518/1045 50% 2.8% Early aggressive
Mgmt
HEART SCORE
• US studies with over 2000 patients1,2
– > 99% sensitivity for 30-day events
– 30-40% of patients can be discharged safely
without stress testing
.
1. Mahler, et al. Identifying patients…chest pain. Int J Cardiol. 2013 Sep;168(2):795-802
2. Mahler, et al. The HEART...early discharge. Circ Cardiovasc Qual Outcomes. 2015 Mar;8(2):195-203
128/29/2018
HEART SCORE
• US studies with over 2000 patients1,2
– Decreased cardiac testing by 12%
– Time to discharge was decreased by 12 hours
– 21% increase in early discharge with no
adverse events in this group
.
1. Mahler, et al. Identifying patients…chest pain. Int J Cardiol. 2013 Sep;168(2):795-802
2. Mahler, et al. The HEART...early discharge. Circ Cardiovasc Qual Outcomes. 2015 Mar;8(2):195-203
Cardiac Biomarkers
• Multiple biomarkers used in past, these
continue to evolve
• Sensitivity is most important, balance vs
specificity
• Troponin is gold standard – multiple
assays exist
Cardiac Biomarkers –
Creatine Kinase
• Creatine Kinase (CK)
– Formerly Creatine Phosphokinase (CPK)
– Found in skeletal muscle
– Very non-specific for cardiac muscle injury
– Affected by total body muscle mass
138/29/2018
Cardiac Biomarkers –
CK-MB
• CK-MB
– Significantly more specific for cardiac muscle
injury, but also present in skeletal muscle
– Increase mildly delayed compared to Troponin
and resolution within 48 hours
• Troponin detectable for up to 2 weeks
– Troponin has better prognostic significance
Cardiac Biomarkers –
Myoglobin
• Myoglobin
– Also found in skeletal muscle
– Rises slightly before earlier Troponin assays
– With more sensitive contemporary Troponin
testing, this is no longer the case
Cardiac Biomarkers –
Copeptin
• Copeptin
– AVP precursor secreted by pituitary with AMI
– Very sensitive early in ACS
– Combined with Troponin in patients within 6
hours of CP onset, Negative Predictive Value
of 99.2% for ACS1
– However, 1h hs-cTnT is superior to Copeptin
with NPV up to 99.6%2
1. Maisel A., et al. Copeptin helps…CHOPIN Trial. J Am Coll Cardiol. 2013;62(2):150.
2. Hillinger P, et al. Optimizing early…Copeptin. Clin Chem. 2015;61(12):1466
148/29/2018
Cardiac Biomarkers –
Heart-Type Fatty Acid Binding Protein
• Heart-Type Fatty Acid Binding Protein
– Released very early in ACS
– Similar to myoglobin but more cardiospecific
– Strong association with prognosis1
– May be more sensitive at 2 hours than older
but likely not newer Troponin assays
– Not well studied, not available in US
1. O’Donoghue M, et al. Prognostic utility…syndromes. Circulation. 2006;114(6):550.
Cardiac Biomarkers –
Glycogen Phosphorylase BB
• Glycogen Phosphorylase BB
– Very sensitive early on in ACS
– Combined with hs-cTn, can achieve extremely
high sensitivity but only 30-40% specific
– Likely not superior to current Troponin
1. Shortt C, et al. Comparison of cTnI…onset. Clinica Chimica Acta 419 (2013) 39-41.
Cardiac Biomarkers
• Lactate Dehydrogenase
– Sensitive but much less specific that Troponin
– Rises later (10 hours) after ACS
– No current clinical utility
158/29/2018
Compared to Troponin
SENSITIVITY SPECIFICITY
Creatine Kinase Worse Worse
CK-MB Worse Worse
Myoglobin Worse Worse
Copeptin Worse/?Similar Worse
HT-FABP Worse/?Similar Worse
Glycogen Phosphorylase BB Worse/?Similar Worse
LDH Worse Worse
Clinical Decision Making
Twin Patient A Twin Patient B
EKG Normal Normal
CP History Atypical Atypical
CK 1000 U/L (0-165 U/L) 50 U/L (0-165 U/L)
CK-MB 100 ng/mL (0.5-3.6 ng/mL) 1 ng/mL (0.5-3.6 ng/mL)
CK-MB Index 10 (0-4) 2 (0-4)
Myoglobin 250 (12-76 ng/mL) 25 (12-76 ng/mL)
Troponin I 0.02 (0.00-0.04 ng/mL) 0.02 (0.00-0.04 ng/mL)
Clinical Decision Making
• What to do with Twin A vs Twin B?
• With both having a normal Troponin, the
elevated CK, CK-MB, and Myoglobin are
basically irrelevant from an ischemic
standpoint
168/29/2018
Why check biomarkers other
than Troponin?
• “It is difficult to find any situation in which
CK-MB adds anything other than cost to the
clinical utility of cardiac troponin”
• “When cTn is available, CK-MB should not be
used for the initial diagnosis of acute MI. If it
is the only assay available, it can be used but
is far less sensitive and specific”
Alan Jaffe, et al. Up To Date
Cardiac Biomarkers
• Jim McCord, MD
Challenge
• $100 to diagnose
an MI with
normal Troponin
Non-ACS Causes of Elevated
Troponin (Type 2 NSTEMI)
Tachycardia Hypertensive Conditions
Critical Illness (Shock, Sepsis) Heart Failure
Myocarditis/Pericarditis Takotsubo Cardiomyopathy
Structural Heart Disease (AS) Aortic Dissection
Pulmonary Embolus/Pulm HTN Renal Dysfunction
Coronary Spasm CVA/SAH
Cardiac Contusion or Surgery/PCI Hyper- or Hypo-Thyroidism
Infiltrative Cardiomyopathy Myocardial Drug Toxicity
Extreme Endurance Activity Rhabdomyolysis
178/29/2018
High Sensitivity Troponin
• Advances in lab technology has increased
sensitivity of cTrop I and cTrop T detection
by a factor of 10-100 times prior assays
• Although used and guideline recommended
internationally for several years, hs-cTropT
just received FDA approval for use in USA
within the last year
High Sensitivity Troponin
• Potential Benefits
– Improved and earlier AMI recognition and
outcomes
– Decreased cost with increased ED discharge for
outpatient evaluation
– Less cardiac testing if clinicians more confident
with rule-out via hs-cTn?
• All above are potentially offset by opposite
clinical behavior due to lower specificity
High Sensitivity Troponin
188/29/2018
High Sensitivity Troponin
High Sensitivity Troponin
• Compared with Standard Troponin Assays
– Higher NPV for Acute MI
– Reduce “Troponin-Blind” Period
• Abnormal earlier after ACS onset
– 4% absolute (and 20% relative) increase in
detection of Type I MI
– 2-Fold increase in diagnosis of Type 2 MI
High Sensitivity Troponin
• A hs-cTnT value < 5 ng/L and a non-
ischemic EKG have a 30-Day negative
predictive value for MI and death of
99.8% and 100%1
1. Bandstein, et al. Undetectable…myocardial infarction. J Am Coll Cardiol. 2014;63(23):2569
198/29/2018
High Sensitivity Troponin
High Sensitivity Troponin
• The higher the level, the more likely an MI
• Expect typical rise & fall pattern with an MI
– Flat/stable elevation less likely due to ischemia
• Abnormal levels frequently present in
healthy individuals (physiologic)
High Sensitivity Troponin
• Levels up to 3 X Upper Limit have only 50-60%
PPV for Type I MI; often due to other causes
• Over 5 X Upper Limit has PPV > 90% for Type I MI
208/29/2018
High Sensitivity Troponin
• Australian study randomized standard
Troponin with/without hs-TropT reporting
• No significant change in discharge, MI
diagnosis, diagnostic testing, outcomes
• Normal standard Troponin subset had lower
MACE at 1 year with hs-TropT reporting1
1. Chew DP, Zeitz C, Worthley M, et al. Randomized comparison of high-sensitivity troponin reporting in undifferentiated chest pain
assessment. Circ Cardiovasc Qual Outcomes . 2016
High Sensitivity Troponin
• Prior study highlights importance of proper
utilization of this test data
– Protocols necessary to guide physician
behavior to affect process and outcomes
– Concern that higher sensitivity could drive
more unnecessary ischemic testing
High Sensitivity Troponin
• Debate remains whether or not to adjust
reference values
– Gender
– Age
– BMI
• Protocols being developed to evaluate “Delta”
= percentage of change with serial tests to
increase specificity
218/29/2018
ER Protocols
• The HEART Score by itself is very good at
triaging patients for early discharge
• Protocols are underway looking at the
additional benefit if high sensitivity
Troponin
ER Protocols
• 0 hour/1hour protocol with hs-cTnT1
– Initial value and amount of change in 1 hour
• 1282 patients in ER with chest pain
– 17% with MI
– 64% Ruled out
– 22% Triaged to Observation
– Negative Predictive Value 99.1%
– Sensitivity 96.7%
– PPV 77.2%, Specificity 96.1%
1. Mueller C, et al. Multicenter Evaluation..Troponin T. Ann Emer Med. 2016 Jul;68(1):76-87.e4. doi:
10.1016/j.annemergmed.2015.11.013. Epub 2016 Jan 12.
ER Protocols
• In above study, 1 year mortality in the “Rule
Out” group was8/29/2018
ER Protocols
• Mueller’s protocol has been further refined
by Twerendbold1 and a 0h/1h algorithm is
now recommended in Europe
• This algorithm has recently been
prospectively validated (for Trop T and I)
1. Twerendbold R, et al. Prospective Validation…Infarction. J Am Coll Cardiol. 2018;72:620-632.
ER Protocols
• 4368 Patients with suspected ACS
– High Sensitivity Troponin T at 0h/1h
• 57% Ruled Out vs 18% Ruled-In
ER Protocols
• For Rule Out with hs-cTnT:
– 0h Troponin < 12 ng/L
– 1h Troponin Change of < 3 mg/L
OR
– If Chest Pain > 3h, then 0h Troponin < 5
ng/L
238/29/2018
ER Protocols
• For Rule In with hs-cTnT:
– 0h Troponin ≥ 52 ng/L
– 1h Troponin Change of ≥ 5 mg/L
ER Protocols
• 5 NSTEMI’s found in the Rule Out group
for Negative PV of 99.8%
• 30 Day Mortality in Rule Out group was
only 0.1%, 1-Year Mortality 0.8%
ER Protocols
• Positive PV in the Rule In group was
74.5%
• 30-Day mortality in the Rule In group was
29X higher than in the Rule Out Group
• 16% were ruled out with a single test at
0h, NPV was 100% in this group
248/29/2018
ER Protocols
• Both Trop T and Trop I were very
effective, with Trop T slightly better
• Protocol very effective in early presenters
and across multiple co-morbidities,
including ESRD
European Society of Cardiology
Guidelines (2015)
• I-A: Measure Troponin with sensitive or
high sensitive assay
• I-B: A rapid rule-out with hs-cTn at 0h and
3h is recommended
• I-B: A rapid rule-in and rule-out protocol
at 0h and 1h is recommended if hs-cTn
test with a validated 0h/1h algorithm is
available
ER Protocols
258/29/2018
Summary
• Chest Pain is the second most common compliant
in the ER, and it has a wide differential diagnosis
• It is usually benign, but exclusion of life-
threatening possibilities needs to be performed in
an effective, cost-efficient, and safe manner
• HEART Score and High Sensitivity Troponin are
promptly becoming the standard of care for risk
assessment and disposition planning
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