Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
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        AMI Redefined (update), Newspath April 2002

Myocardial Infarction Redefined:

A Follow-up Study

[NewsPath, April 2002, Dr. John Carter]

In May 2001 we presented "Redefined Laboratory Diagnostic Criteria for Acute Myocardial Infarction" as published by a joint consensus of the European and  American Colleges of Cardiology.  (JACC 2000; 36:959-69) A copy of this publication and our original newsletter are available on request (936-8226) and are highly recommended for all physicians responsible for the diagnosis and care of patients with possible coronary heart disease. 

As a quality assurance follow-up, for several months we reviewed discharge summaries via the EMR on patients who had Troponin-I peak levels in the "redefined" diagnosis range (0.8-2.5 ng/ml).  These patients would have been considered as negative for AMI by previous diagnostic criteria.  The objective was to be certain that these patients in the "redefined" diagnostic range for early or minimal myocardial injury/infarction would be recognized and thoroughly evaluated. 

Clinical recognition of the significance of these "redefined" cardiac marker profiles progressed significantly early in the program.  During the first month, 2/3 of the patients so identified were thoroughly evaluated; 1/3 were not acknowledged as having an abnormality or evidence of myocardial injury.  One month later the ratio of recognition had improved to 88% vs. only 12% unacknowledged.  Four months later we discontinued the review as it was a rare situation in which patients with early or minimal elevation of cardiac Troponin-I levels were not identified as having evidence of myocardial injury/infarction.

Responding to occasional concerns that we were identifying false-positive cases: The new AMI profile criteria and diagnostic ranges were defined by an international consensus of cardiologists.  The redefined diagnostic protocol is capable of identifying microscopic areas of myocardial necrosis - - micro-infarcts that would not previously have been classified as acute infarction.  Several publications have noted that these patients, if they do not have obvious acute infarction, do have a significantly more hazardous prognosis at 6 and 12 month reviews.  Our objective is to identify patients that warrant further cardiology review and it is to be expected that occasionally these patients with biochemical evidence of minimal myocardial injury will not have a readily apparent cardiac abnormality. 

The type of patient with under-interpreted, "redefined" abnormal AMI profiles was varied but, if a specific clustering exists, it appears to be that of middle-aged, often overweight ladies in whom the pain or discomfort symptoms were too often mis-attributed to a non-cardiac cause. 

We hope to help continue to decrease the number of "unpredictable/unpreventable" or "silent AMI" complications which too often progress to serious or tragic consequences. 

Redefined Cardiac Troponin-I Determinations: Validation Studies

The very important redefinition of acute myocardial infarction as outlined in the May 2001 News Path was taken from the international consensus publication in the Journal of American College of Cardiology, September 2000.  This publication is filled with cutting edge diagnostic and clinical guidelines which will warrant discussion and learning with experience over the coming months/years.  It is important that we are fully aware of these new guidelines and of the very significant shift in AMI diagnosis and risk stratification.  As the consensus publication recommended that each laboratory establish and validate its own analytic standards, the following studies were performed at LMC:

Normal range validation:
We were admonished to determine our own "normal" or reference ranges for cardiac Troponin-I determinations.  We did precisely that, using a population of 500 well patients, without clinical complaints, presenting to an LMC Occupational Health program.  These patients were all 40+ years of age, approximately equal of male and female gender.  None had cardiac Troponin-I levels >0.3 ng/ml

Precision validation:

The published suggested abnormal cutoff for Troponin-I levels was 0.5 ng/ml.  We therefore did precision studies of Troponin-I at that range.  Using an average of 25 repeat determinations each on single serum samples in which the Troponin-I level was 0.5 ng/ml, the variation (mean ±2 S.D.) was ±0.1 ng/ml.  Thus a cardiac Troponin-I determination in LMC's laboratory in the 0.5 ng/ml range could be expected with 95% confidence to fall within the 0.4-0.6 ng/ml range. 

Abnormal cutoff point validation:

LMC's laboratory uses the Abbott Axsym analytic system for Troponin-I determinations.  Nationally published statistics and our own validation studies of this method show that the coefficient of variation is ±10% at a level of 0.8 ng/ml, the precision point recommended for setting the abnormal cutoff/reference range.

Validation summary:

These statistics indicate that a Troponin-I result from LMC's laboratory of > or = 0.8 ng/ml is strongly suggestive of acute myocardial injury/infarction and that a Troponin-I level of 0.5-0.8 ng/ml may reflect analytical "static", but certainly warrants at least one follow-up determination.

Acute Coronary Syndromes and "Myocardial Micro-Infarction"

For several years we were of the impression that cardiac troponin testing was sufficiently sensitive to detect microscopic-size infarcts and that low-level Troponin elevations may reflect situations later noted as "interstitial myocardial fibrosis" at autopsy studies.  Published confirmation of this concept was lacking until recently when a cardiologist group from the University of Lubeck (Clin Chem  2002; 48:673-675) notes that "...micro-infarction, defined as cardiac troponin elevations with normal electrocardiograms and (normal) creatine kinase MB activity."  In other words acute myocardial micro-infarction was defined as patients with mild troponin elevations, normal EKG and normal range CK-MB.

The kinetics of Troponin elevation in patients with micro-infarction show lower peak levels and absence of the significant early peak elevation noted in patients with large infarcts.  The low level Troponin elevations with micro-infarction tend to persist an average of 5-6 days in contrast with the low level troponin elevations noted in patients with pulmonary embolism which last an average of 36-40 hours.

Echocardiography and AMI Diagnosis

In our systematic review of EMR charts on patients with low-level Troponin-I elevations, we noted that many patients with evidence of minimal myocardial injury/infarction (Troponin-I levels of 0.8-2.5 ng/ml) were further evaluated by echocardiography for evidence of left ventricular wall abnormalities.  With the impression that the newly defined AMI profile is capable of identifying micro-infarcts, we posed the question to Dr. Allan Jaffe of the Mayo Clinic, one of the participants in the September 2000 JACC  special report.  Dr. Jaffe replied that "In regard to using regional wall motion as a way of excluding myocardial infarction, that is obviously inappropriate.  The echocardiogram is not nearly as sensitive as the (biochemical) markers so those who use this strategy are simply trying to reassure themselves that there is not a large area that is involved."  Dr. Jaffe offered some recent and supportive published references which we have on file. 

Clinical Symptoms of Minimal Myocardial Injury/Infarction

Since upgrading the diagnostic criteria for acute myocardial infarction (May 2001) we have daily monitored the cases in which cardiac Troponin-I results were above the diagnostic threshold by new criteria (> or = 0.8 ng/ml) but less than the diagnostic threshold for infarction by previous diagnostic criteria (<2.5 ng/ml).  Patients within this "new diagnostic range" often did not present with the traditional and classic symptoms of acute myocardial infarction.  Specifically the presentation of acute constricting substernal chest pain radiating to the left shoulder and arm was unusual in these patients.  Far more commonly these patients presented with the "anginal-equivalent" symptoms as noted in the previous newsletter.  (And in Dr. Braunwald's text).  

These anginal equivalent syndromes reflecting minimal myocardial injury/infarction included dizziness, weakness and/or faintness - - often associated with falling, chest discomfort or a "burning sensation" (but not pain), nausea, vomiting and diarrhea, but far more commonly dyspnea or shortness of breath.

Very importantly, unexplained dyspnea or shortness of breath is noted to be a common presenting complaint and symptom of patients with acute minimal myocardial injury or infarction as noted on biochemical AMI profiling.  Thus patients with unexplained dyspnea should be suspect of myocardial injury and warrant a period of observation and sequential AMI profiling.  

Cardiac Troponin Elevations with Pulmonary Embolism

Since the "redefinition" of diagnostic criteria for acute myocardial infarction (Newspath, May 2001) we have noted a number of patients with new abnormal range Troponin-I elevations who had characteristic clinical, laboratory and imaging features of acute pulmonary embolism.

We suspected that these Troponin elevations were not false-positive results, but rather reflected true myocardial injury.  Recent publications (Clin Chem  2002; 48:673-675; JACC  2000; 36:1632-6) confirm this impression.  Troponin elevations associated with acute pulmonary embolism are believed to be the result of myocardial damage resulting from acute right ventricular stress and myocardial ischemia caused by pulmonary embolism-induced hypoxia. 

The kinetics of Troponin elevations associated with pulmonary embolism differ from those associated with acute myocardial infarction.  The peak elevations are lower than noted in AMI and remain elevated for a shorter period of time.  (Av: 40 hours)

Thus cardiac troponin elevations associated with pulmonary embolism are not false-positive results, but do reflect pulmonary embolism-induced myocardial injury. 

(posted May 2002)

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