May 2001, Dr. John Carter]
2002 update of this topic]
provided the Midland’s first STAT, 24-hr-available (24/7/365),
acute-MI profiling in March ’96. Experience
with that profile, particularly with cardiac troponin results,
soon suggested the ability to detect minimal myocardial injury
or micro-infarcts to a much more sensitive degree than with the
previous diagnostic profiles (cardiac isoenzymes). While
practice guidelines initially defined cases of acute infarction
as those with a peak troponin level >2.5 ng/ml AND defined patients
with the AMI profile series of troponin levels (0, 3, 6 hours)
remaining <0.5 ng/ml as having “No evidence of infarction”,
it became evident that many patients with borderline troponin elevations
(0.5-2.5 ng/ml) had some type of myocardial injury or micro-infarcts. Some
of these patients had clinical evidence of unstable angina, congestive
heart failure, myocarditis or cardiomyopathy. The
term “Minimal Myocardial Injury” entered the literature
and it became evident that patients with borderline troponin
elevations had an overall worse prognosis than patients with no
elevation of cardiac troponin levels.
joint consensus document published by the European
Society of Cardiology and the American College of Cardiology
(JACC 2000; 36:959-69) verifies
this concept of “Minimal Myocardial Injury” and
the sensitivity and clinical importance of laboratory diagnosis
and its prognostic implications. Highlights
of this document are outlined below, as are extracts from three
other recent and relevant publications. Copies of this
important consensus publication and the other reviewed papers
are available on request (791-2413).
CONSENSUS DOCUMENT SUMMARY
Cardiac troponin is the preferred biomarker
for myocardial damage, reflecting even microscopic areas of myocardial
necrosis. Any amount
of myocardial necrosis caused by ischemia should be labeled as
an infarct. [Troponin-I
and Troponin-T are essentially equivalent tests with current technology,
the choice determined by the analytical system.]
Cases formerly diagnosed as having
severe stable or unstable angina might be diagnosed today as
having a small AMI.
The resulting increase
in the sensitivity of the defining criteria for MI will mean more
cases identified…and the fatality rate to fall…thereby
allowing appropriate intervention and secondary prevention.
cardiac troponin results are associated with a worsened prognosis.
Elevated troponin values should be recorded
from two successive blood samples…and related to very recent
clinical symptoms…to diagnose AMI (clinical correlation
Myocardial infarction as a diagnostic
term should be qualified and described as to:
1) infarct size (based
on degree of troponin elevation);
2) clinical setting
(spontaneous, post-op, post-angioplasty, etc.)
3) timing (acute,
or evolving, recent or healing, or healed MI).
Coronary angioplasty: "…the
risks of subsequent ischemic complications (death or MI) is related
to the extent of cardiac troponin increase, if any" (during
or after the procedure).
Each individual laboratory should confirm the reference
or “normal” range (99th percentile) of
serum troponin values…and the degree of precision (variation)
at the abnormal cutoff point. (Study currently in progress at
LMC.); Results to be reported in follow-up newsletter.)
JOINT CONSENSUS DOCUMENT INCLUDES THE FOLLOWING SUMMARIES:
Clinical Presentations --
a description of varied atypical symptoms “in the absence of
Pathophysiology of Acute Infarction -- a brief summary.
EKG and Imaging Studies -- a summary discussion.
Social and Public Policy Implications of Redefining MI -- a
brief summary discussion.
The Redefined Definitions of Acute Myocardial Infarction :
Documentation of a typical rise (any elevation above normal) and gradual fall
of cardiac troponin levels (or
a more rapid rise and fall of CK-MB) with
at least one of the following:
1) Ischemic symptoms (typical or atypical);
2) Pathologic Q-waves on EKG;
3) Ischemic ST segment elevation or depression; or
4) Coronary artery interventional procedures.
Atypical Clinical Presentations of
1) Atypical pain patterns (without chest symptoms).
2) Unexplained nausea and vomiting.
3) Persistent dyspnea.
4) Unexplained weakness, dizziness, lightheadedness or syncope.
Missed Diagnosis of
Acute Coronary Syndromes
H. P. Selker, NE Med
NEJM, April 20 ’00
summary: The majority of patients with missed AMI diagnosis… were considered
to have either unstable angina or a myocardial infarction without
Myocardial infarction patients who are discharged prematurely without having
been diagnosed as AMI have a high mortality rate (25-33%).
Many of these missed diagnoses might be avoided by more careful history taking
and EKG evaluation. [And CDU monitoring with laboratory AMI profiling].
Physicians are under considerable pressure to cut costs, a strategy that could
serve to increase the rate of missed diagnoses…
The accuracy of diagnosis of acute coronary syndromes can be maximized
by a careful history and physical examination, risk factor assessment
[and AMI profile testing for myocardial injury].
Physicians should be familiar with atypical presentations of acute coronary
Laboratory data should be interpreted relative to timing of sample in
relation to time of onset of symptoms. [e.g.
negative markers (CK-MB and/or troponin) and a negative EKG in a patient continuously
symptomatic for 12-18 hours might be truly negative. The
same negative results shortly after symptom onset require immediate follow-up
EKG changes and enzyme elevations may be absent soon after the onset of
symptoms. [Warranting CDU
observation and follow-up AMI profile testing]
Patients thought to be at low risk for acute myocardial infarction warrant careful
assessment of this “low risk” determination, especially
if multiple risk factors are present. [Gender, age, hypertension, lipid abnormalities,
atypical pain patterns, atypical or “angina-equivalent” symptoms]
As physicians attempt to utilize their time
more efficiently by delegating responsibility for history-taking
to a physician’s assistant or even by limiting the history
to a questionnaire…an undesirable trend.
History taking is the most valuable technique available for determining
whether or not the symptoms are caused by heart disease.
Anginal equivalent symptoms include
dyspnea; discomfort or pain in atypical radiation patterns; GI
symptoms of gas, belching, nausea, “indigestion”; dizziness,
diaphoresis [and a general feeling of critical but unexplained
Atypical presentations of AMI include:
1) New-onset or worsening congestive
2) Classic angina symptoms
3) Atypical pain (or discomfort) radiation
4) CNS debility due to sudden decrease
in cardiac output.
5) Apprehension and nervousness.
6) Sudden mania or psychosis.
8) Overwhelming weakness
9) Acute indigestion complaints
10) Peripheral embolization lesions
by: A. S. Jaffe, M. D. (Mayo Clinic)
American Heart Journal, July ’99, p. 9-11.
Many years of traditional CK-MB testing made us familiar with its
imperfections and added to our ability to ignore elevations of
CK-MB when we believed they did not make clinical sense.
Troponin elevations should be completely specific for cardiac damage and
are more sensitive for detection of cardiac injury than CK-MB.
Troponin elevations occur in up to 33% of patients with unstable angina
when CK-MB remains within the normal range.
Troponins are elevated for a longer period after cardiac damage than CK-MB.
Need to attribute each troponin elevation to some type of myocardial injury.
Troponin elevations, whether explained or unexplained, are associated
with an adverse outcome over time.
Acute myocardial infarction is not the only source of elevated serum troponin
levels. A significant number
of patients with unstable angina, cardiomyopathy, myocarditis, congestive
heart failure, ventricular remodeling, adriamycin therapy, etc., can present
with low to intermediate, sub-infarction elevations of serum troponin,
[a finding that reflects Minimal Myocardial Injury in these patients].
The possibility of whether minimal troponin elevations might reflect normal
myocardial cell turnover has not been resolved but more likely reflects
a variety of subtle myocardial disease processes -- even minor elevations
may have physiologic significance.
This re-definition of diagnostic criteria
for acute myocardial infarction is a concept that we've long suspected
and anticipated. The publication of an international consensus
document is very welcome and will go far to improve health care
for cardiac patients.
Medical staff assimilation of these
guidelines is important as, while the NEJM paper states a 25-33%
mortality rate for missed MI diagnosis, recent publications (JAMA,
Dec. 2000, p.3131 & 3138) evaluating coronary interventional
procedures suggest a 95+% survival for AMI patients who are diagnosed
and treated. The survival advantage is very significant,
as is the hazard of "failure to test" and a missed diagnosis.
LMC's Pathologists and Laboratory Team
will assist in the assimilation of these redefined diagnostic guidelines
with follow-up newsletter publications, the first in SC verification
of troponin reference ranges and analytic variability and clinical-laboratory
correlations as necessary and appropriate. Medical staff
comments and suggestions are welcome.
New ("RE-DEFINED") Recommendations
Laboratory Diagnosis of Acute MI:
with acute or recent (within hours) onset of ischemic or atypical
but clinically suspect symptoms:
Acute MI profile*
at 0, 3 and 6 hours; (Repeat @ 12 hrs if clinical suspicion
(repeated) elevation of troponin reflects myocardial injury/infarction.
with persistent (>12-24 hrs) atypical symptoms who present in
CMC's or physician office or routine
level and EKG:
(of these two tests) offers documentation that the atypical symptoms
do not reflect myocardial injury.
reflect myocardial injury and a need for prompt and appropriate
Acute MI profile at LMC still includes cardiac troponin-I and
CK-MB -- only one of these is charged. CK-MB
will be dropped from the profile as medical staff familiarity
with interpretation of troponin-I results progresses. [see Jan. 2008 memo]
Dec. 2001; update 19 January 2008)