Cardiac Injury Markers PDF

Cardiac Injury Markers Dr. Önder Şirikçi  Muscle Cells Creatine phosphate acts as a storage / reserve form of ATP. An equilibrium concentration of ATP, ADP and CP are maintained by Creatine kinase and myokinase enzymes Heart: Efficient and Durable...

Cardiac Injury Markers Dr. Önder Şirikçi  Muscle Cells Creatine phosphate acts as a storage / reserve form of ATP. An equilibrium concentration of ATP, ADP and CP are maintained by Creatine kinase and myokinase enzymes Heart: Efficient and Durable Pump Most disease processes result from ischemia; coronary arteries are vulnerable to atherosclerosis As a result, cardiac function deteriorates and dysfunctional states arise Acute ischemic heart disease Heart Failure  Clinical Abbreviations ACS Acute coronary syndrome ASCVD Atherosclerotic cardiovascular disease (also referred to as coronary heart disease [CHD], ischemic heart disease [IHD], and others) CVD Cardiovascular disease (comprising ASCVD, HF, stroke, and hypertension) HF (Congestive) heart failure MI (Acute) myocardial infarction NSTEMI Non–ST-elevation myocardial infarction STEMI ST-elevation myocardial infarction UA Unstable angina Atherosclerosis Obstructive plaques begin as nonobstructive fatty streaks triggered by uptake of oxLDL particles by macrophages, which migrate to intima. FS forms a lipid core (mainly cholesterol esters) surrounded by macrophages and inflammatory cells and covered with a cap of endothelialized connective tissue. Inflammatory cells and mediators play a role in the evolution of the lesion Advanced lesions also contain new blood vessels and calcium deposits.  Atherosclerosis Plaques have a dynamic role in ACS rather than being a passive irreversible barrier to blood flow. The balance of inflammatory mediators, shear forces, and other factors can cause the fibrous cap of the plaque to strengthen or weaken. Erosion / rupture of the cap expose thrombogenic material, leading to deposition of platelets and eventually enlargement of the lesion. Rupture of the plaque may cause thrombosis and occlusion to result in ACS. Plaque vulnerability gains attention since statins diminish the risk of ACS without a decrease in stenosis.  Acute Coronary Syndromes The major cause of ACS is atherosclerosis, which contributes to significant narrowing of the artery lumen and a tendency for plaque disruption and thrombus formation  Acute Coronary Syndromes (ACS), Acute Myocardial Infarction (AMI) Why is myoglobin the fist indicator to rise in AMI 75 % of O2 requirement is supplied by blood, myoglobin provides local storage of O2 Damage due to thrombotic occlusion superimposed on coronary atherosclerosis. Interrupted blood supply inadequate myocardial O2 supply death of myocytes and necrosis. In addition, a substantial number of cells die as the result of apoptosis.  Which statment is correct Cell Damage about cell damge Free radicals lead to futher damge but not initiate a Plasma membrane integrity require energy (ATP). Processes that damge The irreversible point of cell impair ATP production deprive the cell of oxidizable substrates or by injury is when the membrane is imapaired restricting the access to oxygen (ischemia or anoxia) and disrupts cell Enzyme leaks do not membrane. contintude an irreversible damge Efflux of potassium with influx of sodium accumulation of H2O and All true swelling of cells. Calcium entry stimulate intracellular enzymes; cell damage and disruption of the cell membrane. Free radicals formed may cause further damage. The membrane becomes leaky; in irreversible injury, the cell will die, but enzyme leak may also occur without the occurrence of irreversible injury.  Congestive Heart Failure Ineffective pumping of the heart Heart failure with reduced ejection fraction (HFREF) Heart failure with preserved ejection fraction (HFPEF); increased stiffness of the cardiac muscle High-output HF (those related to valvular heart disease) Prognosis depends on disease severity; patients are staged with the New York Heart Association (NYHA) functional classifications I to IV. Correlation between LVEF and subjective symptoms is poor, staging criteria is subjective; patients with CHF often go undiagnosed and untreated early in their disease or are misdiagnosed because of conditions such as pulmonary disease.  Diagnosis of Heart Disease Electrophysiologic methods (ECG) Severe MIs, involving transmural damage to the myocardium, disrupt electrical flow and cause the appearance of changes known as ST-segment elevations and the later appearance of Q-waves (STEMIs). Lesser amounts of damage may cause ECG alterations that are not sufficiently specific for diagnosis or may cause no ECG change whatsoever (NSTEMIs). Catheterization and angiography; Invasive, it can identify restrictions to coronary blood flow; it says nothing about the biology of the plaque lesions. Imaging; CT can noninvasively image the accumulation of calcium in atherosclerotic lesions (the “calcium score”), but can not predict the future behavior of lesions. Clinical laboratory tests  Laboratory Diagnosis of Heart Disease Measurement of proteins in sera of patients that are present in cardiac myocytes indicate recent damage to cardiac muscle (mainly for the diagnosis of ischemic events (acute coronary syndromes [ACSs]). Many Which one of the biomarkers different markers have been used in the past, at present the most below can be used for risk important marker is cardiac troponin (cTn). assessment of ASCVD ? Meaasurement of substances that are damaging to the coronary arteries, or associated with atherosclerotic cardiovascular disease (ASCVD), to Which of the bio markers below is used for assess risk and select appropriate preventive measures. (lipids, presentance and severity of heart failure? homocysteine (Hcy) and C-reactive protein (CRP). Measurement of natriuretic peptides released from myocardium, particularly B-type natriuretic peptide (BNP) and the inactive fragment, NT- pro-BNP, reflects the presence and severity of heart failure.  Ideal Cardiac Biomarker Specific High myocardium/serum ratio, not present in non-cardiac tissue Differentiation of cardiac pathology (acute versus chronic, necrosis, hypertrophy, rhythm) Sensitive Marker of ‘early,’ reversible cardiac event, early release after injury Amount released should be proportional to extent of injury Predictive Robust Rapid, simple, accurate and inexpensive detection, Have a convenient diagnostic time window Non-invasive / accessible  A Cardiac Biomarker Should… …ascertain the diagnosis,  help the decision to admit the for the appropriate level of care and/or intervention in patients with chest pain, suspected ACS and those with acute exacerbations of heart failure  help the decision to send the patient home …help risk stratification Metabolic Changes During a Coronary Event We will see cardic bimaker cell relase only after irreversible dmage due to leaking of enzymes in that stage Release of Myocardial Cell Constituents That is why you would see adenosine first then CK.Mk becuase metablites leake first due to their smaller size  ACS Sequence and Timing All Ischemia Some Ischemia, some Necrosis All Necrosis ED Presentation Plaque Rupture Amount of Tissue Onset of Pain Discharge Time -12 to 0 12 to 0 hrs 24 hrs Ischaemia marker Necrosis marker Cardiac Dysfunction marker Evolution of Biochemical Cardiac Markers Myoglobin assay RIA for BNP RIA for and proANP proBNP CK – MB CK-MB cTnl assay Electrophoresis POCT for myoglobin CK- mass assay for CK and LD MB, cTnI AST in AMI CK in Immuno assay for RIA for cTnT assay AMI proBNP ANP IMA Genetic Markers 1950 1960 1970 1980 1990 2000 2005 Time [years] Timeline history of assay methods for markers of cardiac tissue damage and myocardial function. AST: aspartate aminotransferase ANP: atrial natriuretic peptide CK: creatine kinase BNP: brain natriuretic peptide LD: lactate dehyydrogenase POCT: point-of-care testing cTn: cardiac-specific troponin IMA: ischaemia-modified albumin Biomarkers of Myocardial Injury (from reversible mild injury to necrosis)  “Cardiac enzymes”; AST (SGOT), ALT (SGPT) Which one of the statement Ladue and coworkers noticed that in patients with suspected or below is correct about AST confirmed MI, serum transaminase levels rose sharply after an MI. It can be found in liver smooth Transaminases are abundant in liver, smooth muscle, skeletal muscle, muscle and skeletal muscle Activities fall in to normal range and other tissues besides cardiac muscles, therefore offer poor in 4 to 5 daya sensitivity and specificity for cardiac diagnosis. It can reflect the extant of cardic damge The extent to which reversible cell damage can cause protein leakage It rises 6 to 8 hours after chest pain is not known. All Transaminase Activities in Tissues, Relative To Serum As Unity Transaminase peak value demanstrates extant of cardic demage , it will be elated in cause of rein fraction in 4 days Transaminase Activities in MI AST first becomes abnormal after 6-8 h after the onset of chest pain, peak values are reached 18-24 h. Activities fall to within normal ranges by the 4th- 5th days, provided there is no new infarct. Peak values of AST roughly reflect the extent of cardiac damage, an increase of 4-5 of the normal is usually observed, increases of 10-15 times are usually associated with fatal infarcts. Small elevations do not indicate favorable prognosis. ALT may be marginally increased or normal  Lactate Dehydrogenase; LDH LDH is an enzyme of the glycolytic pathway and requires Zn as co-factor Found in virtually all cells of the body, including RBC; not specific Tetrameric enzyme, made-up of 2 chains; H (heart) and M (musle) joined in any combination [HHHH (LD1), HHHM (LD2), HHMM (LD3), HMMM (LD4), MMMM (LD5)], thus forming 5 isoenzymes. Tissue specific expression of H and M genes determine the proportion Whixh statment is not ture about LD of the isoenzyme. LD1 is specific for heart and RBC, LD5 for liver. Specific It is a dimer with 2 subunit these subints are expressed in proportion to pattern of isoenzymes in different tissue injuries. the isoenzyme LD1 and lD2 are most espific to heart They are activated 10 hours after inital chest pain They remain elevated for 8 days Distribution of LDH Isoenzymes Across Tissues  So transmutases are better to detact rein LDH elevation in MI fractions LDH activity rises above reference ranges approximately 10 hours after the onset of chest pain, peaks between 24 to 48 hours, and remains elevated for six to eight days  Creatine Kinase Requires Mg2+, At neutral pH, CrP has a much higher phosphorylating potential than ATP, which favors the formation of ATP from CrP. Reverse reaction proceeds 2-6 times faster pH 9.0 pH 6.7  Creatine Kinase Dimeric enzyme, made-up of 2 chains; M (musle), B (brain) joined in any combination [BB (brain, CK-1), MB (heart, CK-2), MM (striated mucle, CK-3)] thus forming 3 classical isoenzymes. All three isoenzymes are found in the cytosol, associated with myofibrillar structures A new, fourth isoenzyme, CK-Mt, (immunologically and electrophoretically different) located between inner and outer mitochondrial membranes and accounts for the 15% of total CK in the heart. Catalyzes the conversion of creatine and utilizes adenosine triphosphate (ATP) to create phosphocreatine (PCr) and adenosine diphosphate (ADP).  Creatine kinase is not seen in neurogenic muscle diseases Creatine Kinase because its mainly the engery source of muscle fibers In which disease do we see elavted levels of ? creatine kinase Elevated in all kinds of muscular dystrophy, myositis and muscle destruction and damage, except neurogenic muscle diseases. Other cardiac conditions, including cardioversion, cardiopulmonary bypass, CABG, cardiac transplantation, myocarditis, pericarditis and pulmonary embolism may increase CK and CK-MB levels in addition to MI. In some hypothyroid patients and during childbirth, elevations may be seen  Which on of the statments about creatien kinase is not ture. Clinical Use of Creatine Kinase Ck is a dimeric enzyme expressed in ounter an inner layer of mit memebrane is CK MT how ever normally it has 2 subunits MB. It seen to be evelvatedd in muscular Elevations in Total CK lack specificity. syterphy , myositis and neurological disease of the heart Individuals with lower muscle mass, may have low baseline total CK Ck lacs espasificyt there fore its its activitythat is measured rather that Therefore following CK-MB elevations, as concentration and as the its base line percentage of total CK in 0-6 h of the onset of chest pain have been used. Not enough clinical studies to determine decision limits Isomers may be measured with activity based assays (CK-MB activity; U/L) immunoassays that measure the mass of the enzyme protein present (CK-MB mass; g/L) or by electrophoretic methods Tissue CK Activity and Isoenzyme Composition (expressed as multiples of serum activity) Isoenzymes % Relative CK CK-BB CK-MB CK-MM activity Skeletal Muscle 50,000