PERM STATE MEDICAL

UNIVERSITY
Academician E. A. Wagner State
Medical University of the Ministry of
Health of the Russian Federation

LABORATORY DIAGNOSTICS OF
MYOCARDIAL INFARCTION,
MYOCARDITIS AND HEART
FAILURE
- ALOOR JOISY JOHNSON
- FINAL YEAR MEDICAL STUDENT, GENERAL FACULTY
 MYOCARDIAL INFARCTION
• Myocardial infarction (MI), commonly known as a heart attack, is defined
pathologically as the irreversible death of myocardial cells caused by
ischemia.
• Clinically, MI is a syndrome that can be recognized by a set of symptoms,
chest pain being the hallmark of these symptoms in most cases, supported by
biochemical laboratory changes, electrocardiographic (ECG) changes, or
findings on imaging modalities able to detect myocardial injury and necrosis.
• According to the WHO criteria as revised in 2000, a cardiac troponin rise
accompanied by either typical symptoms, pathological Q waves, ST elevation
or depression or coronary intervention are diagnostic of MI.
• Previous who criteria formulated in 1979 put less emphasis on cardiac
biomarkers; according to these, a patient is diagnosed with myocardial
infarction if two (probable) or three (definite) of the following criteria are
satisfied:
1. Clinical history of ischemic type chest pain lasting for more than 20
minutes.
2. Changes in serial ECG tracings.
3. Rise and fall of serum cardiac biomarkers such as Creatine Kinase-MB
• APPROACH CONSIDERATIONS:
• The objectives of laboratory testing and imaging include the following:
1. To determine the presence or absence of myocardial infarction (MI) for diagnosis and
differential diagnosis (point–of-care testing and testing in central laboratory of cardiac
troponin levels)
2. To characterize the locus, nature (ST-elevation MI [STEMI] or non–ST-elevation MI
[NSTEMI]), and extent of MI (i.e, to estimate infarct size)
3. To detect recurrent ischemia or MI (extension of MI)
4. To detect early and late complications of MI
5. To estimate the patient's prognosis
• LABORATORY TESTS USED IN THE DIAGNOSIS OF MYOCARDIAL
INFARCTION (MI) INCLUDE THE FOLLOWING:
1. Cardiac biomarkers/enzymes: The American College of Cardiology/American Heart
Association (ACC/AHA) and the European Society of Cardiology (ESC) guidelines
recommend Cardiac Troponin as the only cardiac biomarker that should be measured at
presentation in patients with suspected MI, due to its superior sensitivity and accuracy.
2. Troponin is a contractile protein that is not normally found in serum; it is released only
when myocardial necrosis occurs.
3. Complete blood cell (CBC) count
4. Comprehensive metabolic panel
5. Lipid profile
 SERIAL MEASUREMENT OF CARDIAC TROPONINS
AFTER THE INITIAL LEVEL IS OBTAINED AT
PRESENTATION, 3 TO 6 HOURS AFTER SYMPTOM
ONSET, IS RECOMMENDED. IF INITIAL LEVELS ARE
NEGATIVE, ADDITIONAL MEASUREMENTS BEYOND
THE 6-HOUR MARK SHOULD BE OBTAINED.
CARDIAC TROPONIN
Troponin is a contractile protein that normally is
not found in serum. It is released only when
myocardial necrosis occurs. Of the three troponin
subunits, two (troponin I and troponin T) are
derived from the myocardium.
Serum levels increase within 3-12 hours
from the onset of chest pain, peak at 24-48
hours, and return to baseline over 5-14 days.

TIMING OF RELEASE OF VARIOUS CARDIAC

BIOMARKER PEAKS AFTER THE ONSET OF
MYOCARDIAL INFARCTION
MYOGLOBIN
• Myoglobin is a low molecular weight iron- and oxygen-binding protein
abundantly expressed in the myocardium and skeletal muscle.
• Myoglobin is rapidly released by the injured myocardium. Its blood
levels start to increase within the first 30 min to 2 h after the onset of
ischemia, which makes myoglobin an important marker for the early
detection/exclusion of cardiac injury.
• Its levels increase during the first 6–10 h after AMI, reach a peak12 h
after the acute event, and return to baseline by 24 h after AMI.
• Myoglobin is not found in any other tissue than the muscle, making it
a sensitive marker
• for AMI.
B-TYPE NATRIURETIC PEPTIDE
B-type natriuretic peptide (BNP) is a 32-amino acid LIPID PROFILE
polypeptide secreted by the ventricles of the heart in A lipid profile may be helpful if obtained upon presentation,
response to excessive stretching of cardiomyocytes. because levels can change after 12-24 hours of an acute
Measurement of BNP or N-terminal pro-B-type natriuretic illness.
peptide (NT-pro-BNP) for the diagnosis of acute myocardial
infarction (MI) is not recommended for diagnosis of MI, but
these biomarkers have utility in risk stratification and
prognostication of patients with acute MI who may have OTHER LABORATORY STUDIES
congestive heart failure. COMPLETE BLOOD CELL COUNT

A platelet count is necessary if a IIB/IIIA agent is

considered; furthermore, the patient's white blood cell
(WBC) count may be modestly elevated in the setting of MI,
signifying an acute inflammatory state.
The platelet count may become dangerously low after the
use of heparin because of heparin-induced
thrombocytopenia (HIT).
The leukocyte count may be normal initially, but it generally
increases within 2 hours and peaks in 2-4 days, with
predominance of polymorphonuclear leukocytes and a shift
to the left. Elevations generally persist for 1-2 weeks.
CHEMISTRY PROFILE (COMPREHENSIVE HISTOPATHOLOGY
METABOLIC PANEL) Histopathological examination of the heart may
In the setting of MI, closely monitor potassium and reveal infarction at autopsy. Gross examination
magnesium levels. Blood glucose levels are important to may reveal signs of myocardial infarction.
measure, as many patients are first diagnosed with diabetes
when they present with MI.
Although not routinely measured, the erythrocyte
sedimentation rate (ESR) rises above reference range values
within
The 3 days
serum and may
lactate remain elevated
dehydrogenase (LDH)for weeks.
level rises above
the reference range within 24 hours of MI, reaches a peak
within 3-6 days, and returns to the baseline within 8-12
days.

A ONE-WEEK-OLD MYOCARDIAL INFARCTION OF

THE POSTERIOR LEFT VENTRICLE, WITH FOCAL
RUPTURE, IN FRESH STATE (LEFT) AND AFTER
FORMALIN FIXATION (RIGHT). THE INFARCTED
AREA IS PALE WHEREAS THE RUPTURE IS
 CROSS-SECTION OF THE HEART,
SHOWING AN OLD MYOCARDIAL
INFARCTION OF THE POSTERIOR A COLOR-ENHANCED ANGIOGRAM OF THE HEART
WALL OF THE LEFT VENTRICLE LEFT SHOWS A PLAQUE-INDUCED OBSTRUCTION
(SEEN AS PALE AREAS). (TOP CENTER) IN A MAJOR ARTERY, WHICH CAN
LEAD TO MYOCARDIAL INFARCTION (MI). MIS CAN
UNDER THE MICROSCOPE, MYOCARDIAL
PRECIPITATE HEART FAILURE.
INFARCTION PRESENTS AS A CIRCUMSCRIBED
AREA OF ISCHEMIC, COAGULATIVE NECROSIS
(CELL DEATH). ON GROSS EXAMINATION, THE
INFARCT IS NOT IDENTIFIABLE WITHIN THE FIRST
BIOMARKERS OF PLAQUE
DESTABILIZATION AND
MYOCYTE RUPTURE
Myeloperoxidase (MPO), a
component of neutrophil granules,
is abundantly released from
unstable atherosclerotic plaques
and plays a critical role in
myocardial inflammation and
oxidative stress.
When used alone, MPO does not
seem to be appropriate for AMI
diagnosis.
However, when combined with TnI
and CK-MB, MPO appears to
improve the early diagnostic
accuracy of AMI.
Biomarkers, including lipid markers
(lipoprotein A, apolipoproteins A and B),
endothelial cells- (endocan) and platelet-
(mean platelet volume, mean platelet
volume-toplatelet count ratio, beta-
thromboglobulin, platelet miR-126) related
markers have been
proposed as AMI biomarkers.
Non-coding RNAs, including microRNAs
(miRNAs), circular RNAs, and long
noncoding
RNAs (lncRNAs), act as strong, tissue- and
cell-specific epigenetic regulators of
cardiac gene expression, homeostasis, and
function, and have recently emerged as
promising biomarkers in a wide variety of
cardiovascular diseases.
 MYOCARDITIS
• Also known as Inflammatory Cardiomyopathy, is an Acquired
Cardiomyopathy due to inflammation of the cardiac muscle.
• Myocarditis is most often due to a viral infection. Other causes include
bacterial infections, certain medications, toxins and autoimmune disorders. A
diagnosis may be supported by an electrocardiogram (ECG), increased
troponin, heart MRI, and occasionally a heart biopsy.
• An ultrasound of the heart is important to rule out other potential causes such
as heart valve problems.
• LABORATORY STUDIES USE TO EVALUATE SUSPECTED
MYOCARDITIS MAY INCLUDE THE FOLLOWING:
1. Complete Blood Count: Leukocytosis (may demonstrate eosinophilia).
2. Erythrocyte Sedimentation Rate Level (and that of other acute phase
reactants [e.g., C-Reactive Protein])
3. Rheumatologic Screening
4. Cardiac Enzyme Levels (e.g., Creatine Kinase or Cardiac Troponins)
5. Serum Viral Antibody Titers
6. Viral Genome Testing in Endomyocardial Biopsy
7. Electrocardiography
• Cardiac Enzymes and Natriuretic Peptide: Elevated Creatine Kinase or Cardiac
Troponins (in Fulminant Myocarditis, an elevated Serum Cardiac Troponin [CTN] is
almost always present, but the absence of its elevation does not rule out Myocarditis.)
• Elevated cardiac enzymes are an indicator for cardiac myonecrosis. Cardiac troponin
(troponin I or T), in particular, is elevated in at least 50% of patients with biopsy-proven
myocarditis.

MYOCARDITIS. HEMATOXYLIN AND EOSIN

STAINING. HIGH POWER. TOXOPLASMOSIS
(NUMEROUS PURPLE GRANULAR-LIKE
STRUCTURES WITHIN A MYOCYTE) IS
• Antimyosin scintigraphy (using antimyosin antibody injections) can identify myocardial
inflammation with high sensitivity (91-100%) and negative predictive power (93-100%)
but has low specificity (31-44%) and low positive predictive power (28-33%).
• Positron emission tomography (pet) scanning has been used in selected cases (e.g.,
sarcoidosis) to assess the degree and location of inflammation.
• Gadolinium-enhanced magnetic resonance imaging (MRI) is used for assessment of the
extent of inflammation and cellular edema, although it is still nonspecific.
• Delayed-enhanced MRI has also been used to quantify the amount of scarring that occurred
following acute myocarditis.
• Endomyocardial biopsy (EMB) is the criterion standard for the diagnosis of myocarditis.
However, endomyocardial biopsy has limited sensitivity and specificity, as inflammation
can be diffuse or focal.
 HEART FAILURE
• Heart failure develops when the heart, via an abnormality of cardiac function (detectable
or not), fails to pump blood at a rate commensurate with the requirements of the
metabolizing tissues or is able to do so only with an elevated diastolic filling pressure.
• Symptoms result from a structural and/or functional abnormality of the heart, that
disrupts its filling with blood or its ejecting of it during each heart beat.
• Careful evaluation of the patient's history and physical examination (including signs of
congestion, such as jugular venous distention) can provide important information about
the underlying cardiac abnormality in heart failure. However, other studies and/or tests
may be necessary to identify structural abnormalities or conditions that can lead to or
exacerbate heart failure.
• Endomyocardial biopsy is indicated only when a specific diagnosis is suspected that
would influence therapy in patients presenting with heart failure.
• CLINICAL PRACTICE GUIDELINES ON THE DIAGNOSIS AND
MANAGEMENT OF HEART FAILURE BY THE EUROPEAN SOCIETY OF
CARDIOLOGY (ESC) WERE PUBLISHED IN AUGUST 2021.
RECOMMENDATIONS INCLUDE THE FOLLOWING:
1. HFPEF (Heart Failure with Preserved Ejection Fraction) diagnosis requires evidence of
cardiac structural or functional abnormalities as well as elevated plasma NP (natriuretic
peptide) concentrations consistent with LV diastolic dysfunction and increased LV filling
pressures. A diastolic stress test is recommended if these markers are equivocal.
2. Basic tests such as serum urea and electrolytes, creatinine, full blood count, and liver and
thyroid function tests are recommended to differentiate HF from other conditions, to
provide prognostic information, and to guide potential therapy.
• Genetic testing should be considered in individuals who
have a clinical diagnosis of ARVD based on the diagnostic
criteria.
• A case can be made to offer genetic testing to all with a
clinical diagnosis of ARVD with a negative family history
based on the high rate of reduced penetrance thus far
identified with the ARVD genes.
• Molecular genetic testing is available on a clinical basis for
TGFB3, RYR2, TMEM43, DSP, PKP2, DSG2, DSC2, and
JUP.
LIVER FUNCTION TESTS
In severe cases of acute right
ventricular (RV) or left ventricular
(LV) failure, frank jaundice may
occur.
Acute hepatic venous congestion can
result in severe jaundice, with a
bilirubin level as high as 15-20
mg/dL, elevation of AST to more
than 10 times the upper reference
range limit, elevation of the serum
alkaline phosphatase level, and
prolongation of the prothrombin
time.
RENAL FUNCTION TESTS
Patients with severe heart
failure, particularly those on
large doses of diuretics for long
periods, may have elevated BUN
and creatinine levels indicative
of renal insufficiency owing to
chronic reductions of renal blood
flow from reduced cardiac
output.