chest pain: new methods applied to an old problem

Chest Pain: New Methods Chest Pain: New Methods Applied to an Old ProblemApplied to an Old Problem

Jon W. Wahrenberger, MDJon W. Wahrenberger, MD

January 23, 2003January 23, 2003

Chest PainChest Pain

• 5 Million emergency department visits5 Million emergency department visits• 2 million hospitalizations annually with 2 million hospitalizations annually with

cost of more than $8 billioncost of more than $8 billion• Cardiac etiology found in less than one Cardiac etiology found in less than one

thirdthird• 2% of patients with acute MI are 2% of patients with acute MI are

unrecognized and discharged from the unrecognized and discharged from the EDED

Chest PainChest Pain

• Rapid Dx &Tx = saved muscle = Rapid Dx &Tx = saved muscle = improved outcomeimproved outcome

• Largest category of loss from Largest category of loss from malpractice litigation in the malpractice litigation in the emergency departmentemergency department

GoalsGoals

1.1. Rapid recognition of management of true Rapid recognition of management of true ACSACS

2.2. Recognition of other life-threatening Recognition of other life-threatening causes of chest paincauses of chest pain• Aortic dissectionAortic dissection• Pulmonary embolismPulmonary embolism• Tension pneumothoraxTension pneumothorax

3.3. Minimize cost and hospitalization in Minimize cost and hospitalization in patients with chest pain of benign etiology.patients with chest pain of benign etiology.

Chest Pain DiagnosisChest Pain Diagnosis

• Clinical diagnosisClinical diagnosis• Diagnosis using computer algorithmsDiagnosis using computer algorithms• Chest pain centersChest pain centers

Chest Pain: Chest Pain: Clinical Clinical

DiagnosisDiagnosis

““Classic” AnginaClassic” Angina

• Location: central chestLocation: central chest• Quality: squeezing, heavinessQuality: squeezing, heaviness• Radiation: arm(s), neck, jawRadiation: arm(s), neck, jaw• Associated symptoms: dyspnea, Associated symptoms: dyspnea,

diaphoresis, nauseadiaphoresis, nausea• Eliciting factors: exertionEliciting factors: exertion• Relieving factors: rest, nitroglycerinRelieving factors: rest, nitroglycerin

Differential DiagnosisDifferential Diagnosis

• MusculoskeletalMusculoskeletal• GastrointestinalGastrointestinal• CardiacCardiac

• PsychiatricPsychiatric• PulmonaryPulmonary• Other/unknownOther/unknown

Cardiovascular Chest PainCardiovascular Chest Pain

• Coronary Heart Coronary Heart DiseaseDisease• Stable angina pectorisStable angina pectoris• Unstable anginaUnstable angina• Myocardial infarctionMyocardial infarction

• Coronary Vasomotor Coronary Vasomotor DiseaseDisease• Variant anginaVariant angina• Microvascular anginaMicrovascular angina

• PericarditisPericarditis

• MyocarditisMyocarditis• Valvular Heart Valvular Heart

DiseaseDisease• Aortic stenosisAortic stenosis• Mitral stenosisMitral stenosis• Hypertrophic Hypertrophic

cardiomyopathycardiomyopathy

• Aortic DissectionAortic Dissection• Post-pericardiotomyPost-pericardiotomy

• Cardiac or not?Cardiac or not?• If cardiac, how to manage?If cardiac, how to manage?

Chest Pain Diagnosis: What are Chest Pain Diagnosis: What are we Seeking?we Seeking?

• Pathologic: MI or No MIPathologic: MI or No MI• Management Based: ST Elevation MI or Management Based: ST Elevation MI or

not?not?• PrognosticPrognostic• Anatomic: Correlating with cath findingsAnatomic: Correlating with cath findings• Functional: Correlating with ischemia Functional: Correlating with ischemia • Detailed DiagnosisDetailed Diagnosis

Traditional Classification of Pts Traditional Classification of Pts with CPwith CP

Group 1Group 1

• MI with ST MI with ST elevation or new elevation or new LBBBLBBB

• MI without ST MI without ST elevationelevation

Group 2Group 2

• Unstable angina-Unstable angina-high riskhigh risk

• Unstable angina – Unstable angina – low risklow risk

• Non-ischemic chest Non-ischemic chest painpain

Ideal Categorization of Patients Ideal Categorization of Patients with CPwith CP

Group 1Group 1

MI with ST MI with ST elevationelevation

New LBBBNew LBBB

Primary PCIPrimary PCI ororThrombolyticThrombolytic

ss

Group 2Group 2

MI without MI without ST elevation ST elevation and no and no LBBBLBBB

Unstable Unstable angina – angina – high riskhigh risk

Heparin, Heparin, GP IIbIIIa GP IIbIIIa

inhibitorinhibitor

Group 3Group 3

Unstable Unstable angina – angina – low risklow risk

Heparin,Heparin,

admissioadmissionn

Group 4Group 4

Non-cardiac Non-cardiac chest painchest pain

DischargeDischarge

oror

Treat as Treat as condition condition warrantswarrants

Clinical Evaluation of Chest Clinical Evaluation of Chest Pain:Pain:

Meta AnalysisMeta Analysis• Medline search from 1980-1998Medline search from 1980-1998• Inclusion Criteria:Inclusion Criteria:

• Evaluation of pts thought to have cardiac Evaluation of pts thought to have cardiac ischemiaischemia

• Tool: history, PE, ECGTool: history, PE, ECG• Outcome assessed: MI or no MIOutcome assessed: MI or no MI• Sample size > 200 patientsSample size > 200 patients

• Statistical methods: pool studies and Statistical methods: pool studies and determine likelihood ratiosdetermine likelihood ratios

Panju, et al. JAMA 1998;280:14:1256-1263Panju, et al. JAMA 1998;280:14:1256-1263

Features Increasing Likelihood Features Increasing Likelihood of AMIof AMI

Clinical FeatureClinical Feature Likelihood Ratio (95% CI)Likelihood Ratio (95% CI)Pain in chest or left armPain in chest or left arm 2.72.7

Chest pain radiationChest pain radiation

Right ShoulderRight Shoulder 2.9 (1.4-6.0)2.9 (1.4-6.0)

Left armLeft arm 2.3 (1.7-3.1)2.3 (1.7-3.1)

Both left and right armBoth left and right arm 7.1 (3.6-14.2)7.1 (3.6-14.2)

Chest pain most important symptomChest pain most important symptom 2.02.0

History of MIHistory of MI 1.5-3.01.5-3.0

Nausea or vomitingNausea or vomiting 1.9 (1.7-2.3)1.9 (1.7-2.3)

DiaphoresisDiaphoresis 2.0 (1.9-2.2)2.0 (1.9-2.2)

Third heart soundThird heart sound 3.2 (1.6-6.5)3.2 (1.6-6.5)

Hypotension (SBP<80)Hypotension (SBP<80) 3.1 (1.8-5.2)3.1 (1.8-5.2)

Pulmonary rales on examPulmonary rales on exam 2.1 (1.4-3.1)2.1 (1.4-3.1)

Features Decreasing Likelihood Features Decreasing Likelihood of AMIof AMI

Clinical FeatureClinical Feature Likelihood Ratio (95% CI)Likelihood Ratio (95% CI)Pleuritic chest painPleuritic chest pain 0.2 (0.2-0.3)0.2 (0.2-0.3)

Chest pain sharp or stabbingChest pain sharp or stabbing 0.3 (0.2-0.5)0.3 (0.2-0.5)

Positional chest painPositional chest pain 0.3 (0.2-0.4)0.3 (0.2-0.4)

Chest pain reproduced with palpationChest pain reproduced with palpation 0.2-0.40.2-0.4


ECG Features Increasing ECG Features Increasing Likelihood of MILikelihood of MI


Clinical Symptoms and Clinical Symptoms and Angiographic DiseaseAngiographic Disease

• Goal: determine correlation between clinical Goal: determine correlation between clinical characteristics and angiographic diseasecharacteristics and angiographic disease

• Population: Population: • 65 of 1022 patients undergoing angiography and 65 of 1022 patients undergoing angiography and

with normal coronarieswith normal coronaries• 65 consecutive age-matched controls and with 65 consecutive age-matched controls and with

angiographic CAD (> 70 diameter narrowing)angiographic CAD (> 70 diameter narrowing)

• Method: all patients interviewed within 24 Method: all patients interviewed within 24 hours of angiogram by interviewers blinded hours of angiogram by interviewers blinded to angio resultsto angio results

Reference: Cook, et al. Heart 1997;78:142-6Reference: Cook, et al. Heart 1997;78:142-6


Results:Results:

1.1. No correlation between site of pain, radiation, No correlation between site of pain, radiation, quality of pain, or relief with NTG and presence of quality of pain, or relief with NTG and presence of diseasedisease

2.2. Only four clinical variables separated groups:Only four clinical variables separated groups:

a. Reproducibility with exercise (10/10 v. 1-9/10)a. Reproducibility with exercise (10/10 v. 1-9/10)

b. Lack of rest symptoms (0-1/10 v. 2-10/10)b. Lack of rest symptoms (0-1/10 v. 2-10/10)

c.c. Duration of 5 minutes or less (5 min. v > 5 min) Duration of 5 minutes or less (5 min. v > 5 min)

d.d. Age (<55 v. ≥55)Age (<55 v. ≥55)




No Typical SymptomsNo Typical Symptoms Probability (%) Of CADProbability (%) Of CAD

<55 years:<55 years:

0/30/3 2%2%

1/31/3 6-12%6-12%

2/32/3 25-44%25-44%

3/33/3 69%69%

≥ ≥55 years:55 years:

0/30/3 12%12%

1/31/3 29-48%29-48%

2/32/3 69-84%69-84%

3/33/3 93%93%

Clinical Symptoms and MI in Clinical Symptoms and MI in Patient with Non-diagnostic ECGPatient with Non-diagnostic ECG

Goal: measure ability of clinical features to predict Goal: measure ability of clinical features to predict AMI or ACS in those with non-diagnostic ECGAMI or ACS in those with non-diagnostic ECG

Study Population: 893 pts presenting to large Study Population: 893 pts presenting to large teaching hospital in the UK with suspected AMI teaching hospital in the UK with suspected AMI or ACS.or ACS.

Study Protocol:Study Protocol:

History, PE, ECG & CXRHistory, PE, ECG & CXR

Baseline CK-MB, Trop T at six hoursBaseline CK-MB, Trop T at six hours

If enzymes negative, stress test and dischargeIf enzymes negative, stress test and discharge

Reference: Goodacre, et al. Acad. Emerg Med 2002;9:20308Reference: Goodacre, et al. Acad. Emerg Med 2002;9:20308

Clinical Symptoms and ACS/MIClinical Symptoms and ACS/MI in Patient with Non-diagnostic in Patient with Non-diagnostic

ECGECG

• Pain sitePain site• RadiationRadiation• NatureNature• DurationDuration

• Associated Associated symptomssymptoms

• Pleuritic NaturePleuritic Nature• Response to Response to

exerciseexercise• Chest wall Chest wall

tendernesstenderness• Response to NTGResponse to NTG


• Endpoints:Endpoints:• AMI by WHO criteriaAMI by WHO criteria• ACS defined by AMI on presentation or w/i 6 ACS defined by AMI on presentation or w/i 6

mo.mo.

Clinical Symptoms and ACS/MIClinical Symptoms and ACS/MI in Patient with Non-diagnostic in Patient with Non-diagnostic

ECGECG


Chest Pain: Evaluation Based on Chest Pain: Evaluation Based on PrognosisPrognosis

Prediction of Risk for Patients Prediction of Risk for Patients with Unstable Anginawith Unstable Angina

Evidence Report/Technology Evidence Report/Technology Assessment No. 31Assessment No. 31

Agency for Healthcare Research and Agency for Healthcare Research and QualityQuality

AHRQ Meta AnalysisAHRQ Meta Analysis

• MEDLINE search 1966-1998 of MEDLINE search 1966-1998 of studies performing studies performing multivariate multivariate analysisanalysis of of clinicalclinical and/or and/or ECGECG predictors of adverse clinical events predictors of adverse clinical events in patients with suspected or in patients with suspected or diagnosed diagnosed unstable anginaunstable angina..

• Separate analysis of predictive value Separate analysis of predictive value of troponin and Chest Pain Unitsof troponin and Chest Pain Units


Clinical Predictors:Clinical Predictors:

• Demographics (age, sex, ethnicity)Demographics (age, sex, ethnicity)• Medical history (prior MI, CHF, diabetes, etc)Medical history (prior MI, CHF, diabetes, etc)• Symptom Characteristics Symptom Characteristics • Initial Exam findingsInitial Exam findings• Initial ECG featuresInitial ECG features

Outcomes: Cardiac death, MI, other major cardiac Outcomes: Cardiac death, MI, other major cardiac complicationscomplications


• Demographic features correlating Demographic features correlating with poor prognosis:with poor prognosis:• Increasing ageIncreasing age• Male genderMale gender

• Prior Medical Conditions:Prior Medical Conditions:• Prior MIPrior MI• DiabetesDiabetes• (Prior CHF, HTN, smoking)(Prior CHF, HTN, smoking)

1


• Symptom characteristics: not Symptom characteristics: not predictorspredictors

• Initial exam features:Initial exam features:• Low BPLow BP• CHFCHF• Cardiogenic shockCardiogenic shock

1

Clinical Diagnosis of Chest Clinical Diagnosis of Chest PainPain

• Location, quality of pain generally not Location, quality of pain generally not predictive of cardiac causepredictive of cardiac cause

• Response to nitroglycerine not a reliable Response to nitroglycerine not a reliable predictorpredictor

• While radiation and associated symptoms While radiation and associated symptoms may be predictive, their sensitivity and may be predictive, their sensitivity and specificity are quite lowspecificity are quite low

• More than a history and physical are More than a history and physical are needed!needed!


• Clinical diagnosisClinical diagnosis• Diagnosis using computer algorithmsDiagnosis using computer algorithms• Chest pain centerChest pain center

Computer Guided Chest Pain Computer Guided Chest Pain DiagnosisDiagnosis

• Goldman Chest Pain ProtocolGoldman Chest Pain Protocol• Acute Coronary Ischemia Time-Acute Coronary Ischemia Time-

insensitive Predictive instrument insensitive Predictive instrument (ACI-TIPI)(ACI-TIPI)

Goldman Chest Pain ProtocolGoldman Chest Pain Protocol

• Computer derived decision aidComputer derived decision aid• Designed to improve triage to CCUDesigned to improve triage to CCU• Initially developed in prospective study Initially developed in prospective study

of 1379 patients presenting with acute of 1379 patients presenting with acute chest painchest pain

• ““Recursive partitioning” used to divide Recursive partitioning” used to divide subjects into subgroups correlating with subjects into subgroups correlating with high or low risk of MIhigh or low risk of MI

Goldman, et al. N Engl J Med Goldman, et al. N Engl J Med 1982;307:588-961982;307:588-96

Goldman Chest Pain Protocol Goldman Chest Pain Protocol

Goldman, et al. N Engl J Med 1982;307:588-96Goldman, et al. N Engl J Med 1982;307:588-96


• Validated prospectively in Validated prospectively in second trial of 4770 patientssecond trial of 4770 patients

ParametersParameters Physician Physician EvaluationEvaluation

Goldman Goldman ProtocolProtocol

P-valueP-value

SensitivitySensitivity 8888 8888 NSNS

SpecificitySpecificity 7171 7474 <.00001<.00001

Positive PVPositive PV 2929 3232 .10.10

Overall Overall AccuracyAccuracy

7373 7676 <.00001<.00001

Goldman et al. N Engl J Med. 1988;318:797-803Goldman et al. N Engl J Med. 1988;318:797-803


• Advantages: Advantages: • Higher specificity than MDHigher specificity than MD

• Disadvantages:Disadvantages:• Predicts only AMI (not USA)Predicts only AMI (not USA)• Never shown to alter:Never shown to alter:

• Hospitalization rateHospitalization rate• Length of stayLength of stay• CostCost

ACI-TIPIACI-TIPI(Acute coronary ischemia time-(Acute coronary ischemia time-

insensitive predictive insensitive predictive instrument)instrument)

• Predictive protocol incorporated into Predictive protocol incorporated into electrocardiogram with automatic electrocardiogram with automatic resultsresults

• ““Time insensitive” so can be used Time insensitive” so can be used either retro- or prospectivelyeither retro- or prospectively

Selker, et al. Ann Intern Med 1998;129: 845-55Selker, et al. Ann Intern Med 1998;129: 845-55

ACI-TIPI: Clinical VariablesACI-TIPI: Clinical Variables

• AgeAge• SexSex• Presence of Presence of

absence of chest absence of chest pain or pressure of pain or pressure of left arm painleft arm pain

• Chest pain as most Chest pain as most important symptomimportant symptom

• ECG Q waves or notECG Q waves or not• Presence and Presence and

degree of ST degree of ST elevation or elevation or depressiondepression

• Presence or Presence or absence of T-wave absence of T-wave elevation or elevation or inversioninversion

Selker, et al. Ann Intern Med 1998;129: 845-55Selker, et al. Ann Intern Med 1998;129: 845-55

ACI-TIPIACI-TIPI

• Validated in 3 trials:Validated in 3 trials:• UCLA Harbor Medical Center N= 189UCLA Harbor Medical Center N= 189• University of Geneva N=605University of Geneva N=605• ACI-TIPI Trial N= 10,689ACI-TIPI Trial N= 10,689

ACI-TIPI TrialACI-TIPI Trial

• Clinical trial at 10 U.S. hospitalsClinical trial at 10 U.S. hospitals• ACI-TIPI protocol installed in all ED ACI-TIPI protocol installed in all ED

electrocardiograph machineselectrocardiograph machines• Clinical intervention: 7 alternating Clinical intervention: 7 alternating

months of:months of:• ACI-TIPI probability of ischemia providedACI-TIPI probability of ischemia provided• ACI-TIPI probability of ischemia ACI-TIPI probability of ischemia notnot provided provided

• 10,689 patients enrolled10,689 patients enrolledSelker, et al. Ann Intern Med. 1998;129:845-55Selker, et al. Ann Intern Med. 1998;129:845-55

ACI-TIPI Trial ResultsACI-TIPI Trial Results

No No IschemiaIschemia

Stable Stable AnginaAngina

Acute MI Acute MI or or Unstable Unstable AnginaAngina

CCU CCU AdmissionAdmission

-32%-32% -50%-50% 00

TelemetryTelemetry

AdmissionAdmission-20%-20% +25%+25% 00

Discharge Discharge to Hometo Home

+25%+25% +10%+10% 00

ACI-TIPI Trial ResultsACI-TIPI Trial Results

• No difference in 30 day mortalityNo difference in 30 day mortality• No difference in in-hospital No difference in in-hospital

complicationscomplications• No difference in re-hospitalization No difference in re-hospitalization

ratesrates


• Clinical diagnosisClinical diagnosis• Diagnosis using Diagnosis using

computer algorithmscomputer algorithms• Chest pain centersChest pain centers

Chest Pain in the Emergency Chest Pain in the Emergency DepartmentDepartment

• 4.5 million annual ED visits for chest pain4.5 million annual ED visits for chest pain• About one fourth have true ACSAbout one fourth have true ACS• Treatments for ACS are time sensitiveTreatments for ACS are time sensitive• About 2-4% of acute MIs are missed in the About 2-4% of acute MIs are missed in the

EDED• Number one cause of ED related malpracticeNumber one cause of ED related malpractice• Strong bias for admissionStrong bias for admission

Chest Pain UnitsChest Pain Units

• Goal: accurately determine presence or Goal: accurately determine presence or absence of acute myocardial ischemiaabsence of acute myocardial ischemia• Rapid efficient treatment of AMIRapid efficient treatment of AMI• Avoid unnecessary hospitalization (and cost)Avoid unnecessary hospitalization (and cost)• Avoid inappropriate dischargeAvoid inappropriate discharge

• Logistics: Often associated with and Logistics: Often associated with and staffed by Emergency room and include staffed by Emergency room and include telemetry and resuscitation equipmenttelemetry and resuscitation equipment

Chest Pain UnitsChest Pain Units

1.1. Heart attack programHeart attack program

2.2. Diagnostic (observational) program Diagnostic (observational) program to rule out MIto rule out MI

3.3. Educational outreach programEducational outreach program

Diagnostic Strategies in ACSDiagnostic Strategies in ACS

• Out of hospital ECGOut of hospital ECG• Continuous/serial ECGContinuous/serial ECG• Exercise stress ECGExercise stress ECG• CPK (presentation)CPK (presentation)• CPK (serial)CPK (serial)• CK-MB (presentation)CK-MB (presentation)• CK-MB (serial)CK-MB (serial)• Myoglobin (presentation)Myoglobin (presentation)• Myoglobin (serial)Myoglobin (serial)• Troponin I (presentation)Troponin I (presentation)• Troponin I (serial)Troponin I (serial)

• Troponin T (presentation)Troponin T (presentation)• Troponin T (serial)Troponin T (serial)• Rest echocardiographyRest echocardiography• Stress echocardiographyStress echocardiography• Sestamibi (rest)Sestamibi (rest)• ACI-TIPIACI-TIPI• Goldman Chest Pain Goldman Chest Pain

ProtocolProtocol• Algorithms/protocolsAlgorithms/protocols• Computer based decision Computer based decision

aidsaids

University of CincinnatiUniversity of Cincinnati““Heart ER” StrategyHeart ER” Strategy

Randomized Trials of Chest Pain Randomized Trials of Chest Pain UnitsUnits

AuthorAuthor YearYear NN InterventionIntervention ControlControl Follow-Follow-upup

FarkouhFarkouh 19981998 424424 Chest pain Chest pain unit protocolunit protocol

Routine Routine HospitalHospital

AdmissionAdmission

30 days,30 days,

6 month6 month

GomezGomez 19961996 100100 ED-Based ED-Based rapid rule out rapid rule out protocolprotocol

Routine Routine hospital hospital carecare

30 days30 days

RobertsRoberts 19971997 165165 ED-based ED-based accelerated accelerated diagnostic diagnostic protocolprotocol

Telemetry Telemetry UnitUnit

2 weeks2 weeks

3 weeks3 weeks

From Agency for Healthcare Research and Quality Report, 2000From Agency for Healthcare Research and Quality Report, 2000


AuthorAuthor Early Early EventsEvents

Late Late EventsEvents

Length of Length of StayStay

CostCost

FarkouhFarkouh NSNS NSNS NSNS 61%61%

GomezGomez NSNS NSNS

RobertsRoberts NSNS NSNS


Chest pain evaluation unit versus usual careChest pain evaluation unit versus usual care


AuthorAuthor YearYear NN InterventionIntervention ControlControl Follow-Follow-upup

FarkouhFarkouh 19981998 424424 Chest pain Chest pain unit protocolunit protocol

Routine Routine HospitalHospital

AdmissionAdmission

30 days,30 days,

6 month6 month

GomezGomez 19961996 100100 ED-Based ED-Based rapid rule out rapid rule out protocolprotocol

Routine Routine hospital hospital carecare

30 days30 days

RobertsRoberts 19971997 165165 ED-based ED-based accelerated accelerated diagnostic diagnostic protocolprotocol

Telemetry Telemetry UnitUnit

2 weeks2 weeks

3 weeks3 weeks


ConclusionsConclusions

• Clinical characteristics are the least Clinical characteristics are the least accurate predictor of the etiology of chest accurate predictor of the etiology of chest painpain

• Pattern of pain may be most reliablePattern of pain may be most reliable• Accurate diagnosis and management Accurate diagnosis and management

requires use of clinical history, ECG, and requires use of clinical history, ECG, and other highly specific marker of ischemia or other highly specific marker of ischemia or infarctioninfarction

• Computer aided algorithms may improve Computer aided algorithms may improve diagnostic accuracy and reduce missed dxdiagnostic accuracy and reduce missed dx

Conclusions (continued)Conclusions (continued)

• Chest pain units need further study Chest pain units need further study but may be useful in:but may be useful in:• Reducing unnecessary hospitalizationReducing unnecessary hospitalization• Reducing costReducing cost

chest pain: new methods applied to an old problem

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