BIOCHEMICAL INVESTIGATIONS IN THE DIAGNOSTICS OF CARDIOVASCULAR DISORDERS. As. MARUSHCHAK M.I.

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1 BIOCHEMICAL INVESTIGATIONS IN THE DIAGNOSTICS OF CARDIOVASCULAR DISORDERS As. MARUSHCHAK M.I.

2 Heart attack symptoms

3 Acute MI

5 Measurement of cardiac enzyme levels Measure cardiac enzyme levels at regular intervals, starting on admission and continuing until the peak is reached or until 3 sets of results are negative. Biochemical biomarkers are useful for both diagnosis and prognostication

6 This plot shows changes in cardiac markers over time after the onset of symptoms. Peak A is the early release of myoglobin or creatine kinase isoenzyme MB (CK-MB) after acute myocardial infarction (AMI). Peak B is the cardiac troponin level after infarction. Peak C is the CK- MB level after infarction. Peak D is the cardiac troponin level after unstable angina. Data are plotted on a relative scale, where 1.0 is set at the myocardial- infarction cutoff concentration. Courtesy of Wu et al (1999). ROC = receiver operating characteristic.

7 Laboratory Diagnosis of Myocardial Infarction

8 Measurement of CK-MB levels CK-MB, the isoenzyme specific to the heart muscle, was the principal biomarker of cardiac injury until troponin supplemented it. In the setting of myocardial infarction, plasma CK-MB concentrations typically rise about 4-6 hours after the onset of chest pain. They peak within hours and return to baseline levels within hours. Serial measurements obtained every 6-8 hours (at least 3 times) are warranted until peak values are determined.

9 Clinical settings other than acute coronary syndrome, such as trauma, heavy exertion, and skeletal muscle disease (eg, rhabdomyolysis) may elevate CK-MB values. The area under the concentration-time curve for CK-MB created with serial measurements of blood enzyme levels provides a reliable estimate of the size of the infarct. Determination of subforms of CK-MB (CK-MB2 that is more specific to heart muscle) may improve the sensitivity of this test.

10 Measurement of troponin levels Troponin is part of the contractile apparatus of the myocyte associated with tropomyosin and actin and myosin filaments. Troponin has 3 subunits: TnT, TnI, and TnC. TnI and TnT are normally not detectable in the blood. Measurement of troponin level has both diagnostic and prognostic value. Positive troponin levels are virtually diagnostic of myocardial infarction in the most recent revisions of the ACC/AHA guidelines, as they are without equal in terms of combined specificity and sensitivity in diagnosing myocardial infarction. Elevated troponin levels might help in identifying patients who might greatly benefit from aggressive antiplatelet and other adjunctive therapy. Troponin levels are typically measured serially along with CK values.

11 Measurement of myoglobin levels Myoglobin is not cardiac specific, but it may be detected as early as 2 hours after myocardial necrosis starts. Myoglobin results should be supplemented with other more specific cardiac biomarkers, such as CK-MB or troponin. Myoglobin values have a high negative predictive value when blood is sampled in the first 4-8 hours after onset.

12 Lactate dehydrogenase Enzyme isoforms LDH-1 (4H) - in the heart LDH-2 (3H1M) - in the reticuloendothelial system LDH-3 (2H2M) - in the lungs LDH-4 (1H3M) - in the kidneys LDH-5 (4M) - in the liver and striated muscle

13 Time from Onset Microscopic Morphologic Finding in MI 1-3 Hours Wavy myocardial fibers 2-3 Hours Staining defect with tetrazolium or basic fuchsin dye 4-12 Hours Hours Hours 3-7 Days Coagulation necrosis with loss of cross striations, contraction bands, edema, hemorrhage, and early neutrophilic infiltrate Continuing coagulation necrosis, pyknosis of nuclei, and marginal contraction bands Total loss of nuclei and striations along with heavy neutrophilic infiltrate Macrophage and mononuclear infiltration begin, fibrovascular response begins Days Fibrovascular response with prominent granulation tissue 7 Weeks Fibrosis

14 Histologic section of the myocardium showing a cross- section of coronary artery affected by atherosclerosis and myocyte hypertrophy

15 Histologic section of an autopsy myocardial specimen from a patient with long-standing hypertension and associated coronary artery disease. The slide shows myocardial hypertrophy, contraction bands (typical of left ventricular hypertrophy), and "car box" nuclei.

16 Progressive build-up of plaque in coronary artery

Myocardial Infarction

Myocardial Infarction MI = heart attack Defined as necrosis of heart muscle resulting from ischemia. A very significant cause of death worldwide. of these deaths, 33% -50% die before they can reach the