8/29/2018 1 Chest Pain and Risk Stratification Joseph L. Kummer, MD, FACC Bryan Heart Fall Conference September 1 st , 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
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Chest Pain and Risk Stratification - bryanhealth.com file8/29/2018 3 Patient Style/Behavior • A study had physicians watch videos of an actress complaining to a doctor of chest pain
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8/29/2018
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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
• 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
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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
• Evaluates the six week risk of MACE following ER evaluation
• MACE includes:
– Myocardial Infarction
– PTCA
– CABG
– Death
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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):795-8022. Mahler, et al. The HEART...early discharge. Circ Cardiovasc Qual Outcomes. 2015 Mar;8(2):195-203
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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):795-8022. 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
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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
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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.
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
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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
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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-cTropTjust 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
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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
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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
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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
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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 was <1%
• Compared well vs 2 hour or longer time for second Troponin
• Likely more effective than single absolute cut-off value if CP onset within the prior three hours
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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
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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
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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-cTntest with a validated 0h/1h algorithm is available
ER Protocols
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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