Transcript What does an indeterminate troponin really mean?

What does an
indeterminate troponin
really mean?...other than
another 3am rule out ACS admit
Jamie Navel, MD
September 30th, 2009
Noon Conference
Contra Costa Regional
Medical Center
Goals
• Discuss the definition of a troponin leak
• Discuss diagnosis of AMI
• Discuss new classifications of AMI
• Discuss in detail mechanisms of Type 2
AMI and indeterminate troponins
• Clinical significance of elevated troponins
Introduction
• Troponins are a commonly ordered test in
the Emergency room
• The appropriate interpretation of a positive
or negative troponin is important in
determining correct course of intervention
(namely Percutaneous Coronary
Intervention/anti-thrombotics)
• Clinical correlation is still very important in
determining cause of an elevated troponin
What are troponins?
• Regulatory proteins that control the
calcium-mediated interaction of actin and
myosin
• 3 sub-units Troponin T, Troponin I and
Troponin C
• Found in all muscle but our assays test for
the cardiac specific troponins of I and T
• Troponin C not clinically significant
Troponin I Range
• Troponin T was the first troponin used but
now Troponin I is considered superior and
the newer assays are very sensitive (can
detect <1g myocardial necrosis)
• <0.05 is normal (At CCRMC our cutoff is
<0.07)* >99% of controls
• >0.05 - <0.5 is indeterminate
• 0.5 or greater considered suggestive of
acute myocardial ischemia
Troponin costs
• Single test $78
• CARP (not just cool fish) ~$200
• Number of rule out ACS admits because of
indeterminate troponins-priceless
Significance of a
“positive troponin”
• There are clear standards for the
interpretation of positive (>0.5) in setting of
high suspicion of coronary artery disease.
This leads to a protocalized approach with
the common goal being early
revascularization
On the other hand there’s the gray area…
• Troponin leak-a common term often
synonymous with indeterminate troponin,
or positive troponin secondary to a non
coronary artery pathology cause.
Troponin leak
• Not a standardized term
• Typically denotes a non coronary artery
disease pathology that does not require
cardiac cath or anti-thrombotic agents
• Sounds gentler and is often explained
away but does have prognostic importance
• Treatment strategies are varied based on
the underlying pathology and goals of care
Indeterminate Troponin
• 0.05 (0.07)-0.49
• Has outpatient clinical significance in
providing marker of increased mortality
• Does not rule out concurrent CAD but
clinical suspicion and risk factors are very
important in guiding initial management
• Cause should be indentified and treatment
based on treating underlying pathology
The diagnosis of Acute
Myocardial Infarction
• The reason we initially order a troponin
• Myocardial Infarction is cell death
secondary to ischemia- evidenced by
coagulation necrosis or contraction band
necrosis under a microscope
(Interestingly normal apoptosis does not
cause measurable troponin levels)
Three Pathologic Phases of AMI
• Acute MI-First 6 hours coagulation
necrosis. After 6 hours there is PMN
invasion
• Healing MI-can take up to 5-6 weeks with
mononuclear and fibroblast invasion
• Healed MI-scar tissue with no cellular
infiltration
Clinical Classification of AMI
• Type 1-spontaneous AMI secondary to
primary coronary event
• Type 2-MI secondary to ischemia from
increased oxygen demand or decreased
supply
Clinical Classification of AMI cont.
• Type 3- sudden cardiac death with
evidence of ischemia but no biomarkers
• Type 4a- PCI
• Type 4b- Stent thrombosis
• Type 5- CABG
Diagnosis of AMI
• High clinical suspicion
• EKG changes
• Elevated biomarkers (troponin >0.5)
Symptoms of Acute MI
• 25% have no symptoms
• Classic crescendo crushing chest pain
• Discomfort in upper back, neck, jaw, teeth
• Diaphoresis, SOB, nausea, vomiting or
syncope
Signs of AMI
• Pale and diaphoretic
• Cool extremities
• Soft heart sounds
• S3 or S4
• Tachy or bradycardia
• Hyper and hypotension
EKG findings
• STEMI-new ST elevation at the J point in
two contiguous leads
>0.1mV in two contiguous anatomic leads
New LBBB
*inferior leads >0.05 acceptable if high suspicion
• NSTEMI-new horizontal or down-sloping
ST depression
0.05mV in two contiguous leads and/or T
wave inversion >0.1mV in two contiguous
leads with prominent R wave
EKG limitations/pitfalls
• Meaning of Q waves (acute or prior MI)
• Posterior MI
look for ST↓ V1-V2 and ST↑ lateral leads
• Right Ventricular Infarction
V4R ST ↑, ST↑ in lateral leads
• J point elevation
Echocardiography
• Outcome data still being studied
• Very helpful in early MI when troponins
aren’t elevated yet
• Large wall motion abnormality helps guide
decision for immediate cardiac cath
• Not always immediately available and
requires further training of personnel
Use of troponins in initial
evaluation of AMI
• When the pretest probability of Acute
Myocardial infarction secondary to
coronary artery occlusion (Type 1) is high
a positive troponin is very helpful and part
of the diagnostic criteria
• When pretest probability is low this can
lead to unnecessary cardiac evaluation
including cardiac cath (i.e. Type 2 AMI)
Nonthrombus Ischemia/Type 2 AMI
Increased Myocardial Oxygen Demand
Tachycardia
Changes in cardiac loading conditions
Increased cardiac output
Myocardial depression
Decreased Oxygen Supply
Reduced coronary perfusion
Decreased systemic oxygenation
CAD in setting of Type 2 AMI
• Type 2 AMI can be caused by increased
demand in the setting of stable coronary
artery disease (won’t necessarily be
immediately improved by
PCI/anticoagulation)
• Often cause of Type 2 AMI might be
contraindication to PCI or anti-coagulation
but worth discussing risks/benefits
Does negative cardiac cath rule
out coronary artery disease?
• New studies showing evidence of AMI on
cardiac MRI despite negative cardiac cath
• Cardiac Syndrome X-patients with
symptoms of angina but normal coronary
arteries
• Microvascular occlusion can cause
angina, EKG changes and cell death with
normal coronary arteries
Cardiac Syndrome X
• Endothelial Cell Dysfunction-reduced
vasodilator or enhanced vasoconstrictor
response to medications or exercise
• Autonomic Dysfunction-increased
sympathetic tone
• Occult coronary artery disease-diagnosed
by intravascular ultrasound
• Enhanced pain sensitivity
What causes troponin release?
• Cell death- When myocytes are
irreversibly damaged the cell membrane
degrades releases the contents. Some
believe this is always the cause regardless
of evidence of coronary artery disease
• Increased membrane permeability coupled
with myocardial depressive factorsDegradation to smaller fragments that
“leak” out-not completely understood
Non-thrombotic causes of
elevated troponins
Demand Ischemia
• Tachy or bradyarrhythmias
• Critically ill patients
• Hypotension
• Hypovolemia
• LVH
• HCM
• Burns (>25%)
Nonthrombotic Myocardial
Ischemia
• Coronary vasospasm
• Acute Stroke
• Ingestion of
Sympathomimetics
• Aortic dissection
• Aortic valve disease
•
Apical ballooning syndrome
Myocardial Strain
• CHF
• Pulmonary embolism
• Extreme exertion
• Aortic valve disease
Direct Myocardial Damage
• Infiltrative diseases
• Inflammatory diseases including
myocarditis
• Drug toxicity
• Rhabdomyolysis
• Cardiac Trauma including surgery
• Defibrillation
Multi-factorial
• Renal disease
Troponins in CKD
• Troponin I is still the most helpful in
distinguishing AMI
• Troponin T is more often elevated in
asymptomatic patients
• Elevated troponin associated with poorer
prognosis at same GFR
Diagnosis of AMI in CKD
• Difficult because many ESRD/CKD
patients have co-morbid CAD
• Troponin I more specific as both
myoglobin and CK-MB can be falsely
elevated with elevated GFR
• Many dialysis patients have elevated CK
but generally less than 3x normal
• Trend is very important in CKD patients for
determining presence of new ischemia
Mechanism of Elevated Troponin
in CKD
• LVH
• Endothelial dysfunction
• Loss of membrane integrity
• Impaired renal excretion
• Stretch mediated troponin release
Pounce demonstrating stretching
Left Ventricular Hypertrophy
•
Degree of troponin elevation increases as
degree of LVH increases.
• Occult subendocardial ischemia from
increased oxygen demand from increased
muscle mass
• Decreased flow reserve due remodeled
coronary microcirculation
Heart Failure
• Troponin release via strain and cell death
• Close correlation between BNP and troponin
• Wall stress leads to subendocardial ischemia
• Cell death secondary to RAS, sympathetic
stimulation, inflammatory mediators
• Elevations associated with advanced heart
failure
Pulmonary Embolism
• Secondary to acute right heart strain
• Usually resolves in 40 hours (more quickly
then with ischemic heart disease)
Pulmonary Hypertension
• Tachycardia
• Lower mixed venous oxygen saturation
• Higher BNP elevation
• Independently COPD exacerbations with
elevated troponins have higher in hospital
mortality
Sepsis
• Myocardial depression secondary to
circulating factors (TNF-a, IL-6, CRP)
• Hypoperfusion
• LV dysfunction generally reversible and
can be exacerbated by norepinephrine
Burns
• Related to extent of burns rather than age
or co-existing conditions
• Generally seen when greater than 25-30%
surface area is affected
Stroke
• Imbalance of autonomic nervous system
• Increased sympathetic activity and
cathecholamine release
• Difficult to interpret secondary to high
degree of co-existing CAD
Stress induced cardiomyopathy
• Otherwise known as Takotsobu’s or
Broken Heart Syndrome
• Classic apical ballooning seen on Echo
• Increased levels of circulating
catecholamines
Direct myocardial Damage
• Cardiac contusion
• ICD shock
• Infiltrative disorders (amyloidosis via
compression of myocytes)
• High dose chemo
• Myocarditis or Myopericarditis
• Immune response after cardiac
transplantation
Conclusion
• The cause of a positive troponin must be immediately
classified for appropriate intervention
• An indeterminate troponin is not normal
• There are many causes of an indeterminate troponin.
• Still give an ASA if any suspicion
• Regardless of the cause of elevation there is
increased mortality/poor prognosis
Resources
Chaudhary, Imran. ”Cardiac Syndrome X”. UTDOL updated
10/16/08
Gibson MD MS, C Michael. “Serum Cardiac Enzymes in patients
with Renal Failure” UTDOL updated 6/13/08
Henrich MD MACP, William L. “Serum cardiac enzymes in patients
with renal failure” UTDOL updated 6/19/09
Jaffe MD, Allan S. “Troponins and creatinine kinase as biomarkers
of cardiac injury” UTDOL updated 6/19/09
Jeremias MD, Allen. “Narrative review:Alternative cause for
elevated cardiac troponin levels when Acute Coronary
Syndrome are excluded. Annals of Internal Medicine. Vol 142.
No 9. Pg786-791
Senter MD MS, Shaun. “A new, precise definition of acute
myocardial infarction” Cleveland Clinic Journal of Medicine.
Volume 76. Number 3. March 2009. pg 159-166
Questions?