Cardiac Function

1. Cardiac Function Lecture 21

2. The Heart • The heart is a muscular organ responsible for pumping blood through the blood vessels by repeated, rhythmic contractions. • Size of human fist • Weighs 250-350 g • The primary function of the heart is to pump blood in order to generate and sustain an arterial blood pressure necessary to provide adequate perfusion of organs.

3. Pathologic Conditions Of The Heart • Cardiovascular disease (CVD) is a condition that affects an estimated 80 million adults in the US. • CVD is responsible for the deaths of approximately 2,400 Americans daily. • Timely and accurate diagnosis is essential, • But even today, this is difficult due to the lack of tests available to provide information quickly enough to be beneficial to those presenting with chest pain.

4. Role of Laboratory • The laboratory has been used primarily: • to assess cardiac disease, such as acute myocardial infarctions (AMIs), • and offer body chemistry information to aid supportive cardiac therapy. • Use of laboratory results still supports diagnosis of AMI but also assesses risk for future cardiac disease

5. Role of Laboratory • This is performed through analysis of body chemistry metabolites, such as: • total cholesterol, • high-density lipoprotein • cholesterol, • and high-sensitivity C-reactive protein. • Risk factor assessment enables health-care professionals to educate the patient and to start activities that will reduce risk for an AMI.

6. Common Symptoms of Heart Disease • Dyspnea ضيق التنفس • Chest pain • Cyanosis الزرقة • Palpitationsالخفقان • Fatigueالتعب • Edema

7. Heart Diseases • Congenital heart disease or Congenital Cardiovascular Defects (CCVDs) • Abnormalities arising from the abnormal formation of the heart or its major blood vessels • There are a number of genetic tests available that may assist in the diagnosis of CCVDs • Congestive heart failure • Clinical syndrome that results from any disorder that impairs the ability of the ventricle to fill with or eject blood

8. Heart Diseases • Hypertensive heart disease • a general term used to describe heart diseases caused by direct or indirect effects of elevated BP • Hypertension is defined as persistent systolic blood pressure (BP) of at least 140 mm Hg and/or diastolic pressure of at least 90 mm Hg • Data have established that death from ischemic heart disease and stroke increases progressively and linearly • every 20 mm Hg systolic or 10 mm Hg diastolic increase in BP, there is a doubling of mortality from ischemic heart disease and stroke.

9. Heart Diseases • Acute Coronary Syndromes • A general term used to describe the following series of events: • Angina ((الذبحة الصدرية, reversible tissue injury, myocardial infarction (MI), and extensive tissue necrosis. • The major cause of ACS is atherosclerosis

10. Heart Diseases • Infective heart disease • Infectious agents have been associated with a variety of heart diseases • The most common heart diseases caused by infectious agents are: • rheumatic heart disease, • infective endocarditis, • and pericarditis.

11. Diagnosis of Heart Disease • Single diagnostic laboratory test that assess cardiac function does not exist • The ideal marker for heart disease should have the following criteria: • It should be absolutely heart specific. • It should be highly sensitive to detect even minor heart damage. • It should be able to differentiate reversible from irreversible damage. • In acute myocardial infarction "AMI" the marker should estimate infarct size and prognosis. • The marker should be stable, rapid and easy to perform and cost effective.

12. Laboratory Diagnosis of AMI • Enzymes • Creatine kinase "CK" • Involved in the transfer of energy in muscle metabolism. • Isoenzymes CK-BB, CK-MB & CK-MM • CK-MB "CK2" isoenzyme is the most specific for cardiac muscle eventhough it accounts for only 20% for total CK activity in the heart.

13. Laboratory Diagnosis of AMI- CK enzyme • Total CK activity in early AMI has great specificity "80%". • CK-MB takes 4-6 h from onset of chest pain before it can be detected in significant levels. • Peak levels occur at 12-24 h, it returns to normal in 2-3 days. • Calculation of a relative index (CK-MB mass assay/total CK × 100) may be used as an indicator of MI. • Allows the distinction between increased total CK due to myocardial damage and that due to skeletal or neural damage. • A relative index exceeding 3 is indicative of AMI.

14. Laboratory Diagnosis of AMI- CK enzyme • CK-MB mass assay • It measures the protein concentration of CK-MB rather than its catalytic activity. • Laboratory procedures are based on immunoassay techniques using monoclonal antibodies. • It is more sensitive and have fewer interferences than activity-based assays. • Mass assays can detect an increased serum concentration of CK-MB about 1 h earlier than activity-based assay.

15. Cardiac Proteins • Myoglobin • It is more sensitive than CK and CK-MB activities during the first hours after chest pain onset. • It starts to rise within 2-4 h and is detectable in all AMI patients between 6-9 h from chest pain onset. • It returns to baseline levels within 18-24 h. • If conc. remain within the reference range 8 hours after the onset of chest pain, AMI can essentially be ruled out.

16. Cardiac Proteins - Myoglobin • Myoglobin is rapidly cleared by the kidneys as it is small in size • Myoglobin should not be used for early diagnosis of AMI in patients with renal disease because of its decreased clearance.

17. Cardiac Proteins • Troponin • The preferred biomarkers for assessment of myocardial necrosis • Complex of 3 proteins that bind to filaments of striated muscle (cardiac & skeletal) • Troponin T (TnT) • Troponin I (TnI) • Troponin C (TnC) • The major function of troponins is to bind calcium and regulate muscle contraction.

18. Cardiac Proteins - Troponin • Troponin T "TnT" • It allows for both early and late diagnosis of AMI. • Serum concentrations of TnT begins to rise within 4-10 hours of chest pain onset and peak by day 2, a plateau lasting from 2-5 days usually follows. • It remains elevated beyond 7 days before returning to reference values. • Unlike CK-MB, the serum troponins are not found in the serum of healthy individuals. • The sensitivity of TnT for detecting AMI is 98% from 12 h – 5 days after chest pain onset. • It is useful for diagnosis of AMI in patients who do not seek medical attention within 2-3 days.

19. Cardiac Proteins - Troponin • Troponin I "TnI" • TnI increases within 4 - 6 hours after chest pain onset, • Peaks at 12-18 hours, and returns to within reference limits in about 6 days • TnT tends to remain elevated longer and maintain higher sensitivity after day 7 after infarct than TnI.

20. Markers of Inflammation and Coagulation Disorders • Inflammation plays a role in atherosclerotic plaque formation, and acute coronary syndrome. • Inflammatory cells, cytokines, and other biomolecules have been considered as potential markers for the assessment of risk for the development of such events • several studies have identified such biomarkers of inflammation over recent years including high-sensitivity C-reactive protein (hsCRP)

21. Markers of Inflammation and Coagulation Disorders • High Sensitivity Assay for CRP ”Hs-CRP” • CRP is an acute-phase reactant produced primarily by the liver. • It increases rapidly with inflammation. • It rises in response to injury, infection, or other inflammatory conditions, it is nonspecific. • CRP may be considered as a risk factor marker for cardiovascular disease.

22. Markers of Inflammation and Coagulation DisordersHigh Sensitivity CRP ”Hs-CRP” • There is evidence that CRP is a reliable predictor of acute coronary syndrome risk. • A positive association between hs-CRP and the prevalence of coronary artery disease. • A mild elevation of baseline levels of hs-CRP among apparently healthy individuals is associated with higher long-term risk for future cardiovascular events.

23. Markers of Congestive Heart Failure "CHF" • Brain-type Natriuretic Peptide "BNP" • BNP is a peptide hormone secreted primarily by the cardiac ventricle. • BNP acts on the renal glomerulus to stimulate urinary excretion of Na (similar to atrial natriuretic peptide) • Plasma concentrations of BNP are increased in diseases characterized by an expanded fluid volume e.g renal failure, primary aldosterodism and CHF. • Patients with a BNP concentration < 20 pmol/L are unlikely to have CHF and those with results above this concentration have a high probability of CHF.

24. Other markers • Glycogen phosphorylase isoenzyme BB • Itis an isoenzyme of glycogen phosphorylase. • This isoform of the enzyme exists in cardiac (heart) and brain tissue. • Improve early diagnosis in acute coronary syndrome. • A rapid rise in blood levels can be seen in myocardial infarction. • Heart Fatty Acid-Binding Protein. • small cytoplasmic protein (15 kDa) released from cardiac myocytes following an ischemic episode

25. Other markers • Homocysteine: • Formed from metabolic demethylation of methionine • Many studies demonstrated the link between high levels of homocysteine and increase risk of CVD • Mechanisms include: • Induce damage to vascular endothelium • Accelerate thrombin formation • Promotion of lipid peroxidation

26. Case Study • Joe is an overweight 57-year-old male who was mowing his lawn when he experienced a sharp chest pain along with pain in his left arm. • His wife rushed him to the hospital, fearing that he was having a heart attack. • In the clinic, the physician examined Joe and sent him for electrocardiogram (ECG) and blood work. • The blood is processed in the clinical laboratory and the serum is tested for troponins, creatine kinase (CK), and creatine kinase isoenzyme MB (CK-MB).

27. Investigations & Comment • All of these cardiac biomarkers are elevated. • There is a high likelihood that Joe had a myocardial infarction. • These results, combined with ECG, history, and physical examination, were used to make the diagnosis of AMI.

28. Case Study • A 62-year-old woman was admitted to the ED by ambulance. Her husband says she fell down some stairs and injured her right leg. • He also reveals that she had some chest pain and discomfort in her left arm a couple of days ago, but did not let him call her physician. • She thought she might have some indigestion and so brushed away her husband’s concerns. • They order a chemistry metabolic profile, a CBC, and right leg x-rays to determine what may be wrong with her. The treating physician also requests cardiac markers on Lindsey.

29. Investigations & Comments • Her troponin level was elevated, indicating that she had experienced an AMI but delayed in seeking diagnosis.

30. Comments • Because of the time frame, troponin was the only cardiac marker that still showed a clear indication that an MI had occurred. • The CK-MB was within normal limits because it returns to normal level after peaking 18 to 24 hours post-MI. • The LD flip was not clear cut, although the LD1 was at the same level as the LD 2, indicating that the LD1 was elevated. • The troponin level is clearly above the upper limit of the reference range and so demonstrates that an MI has occurred.