@celynsnotes2014

CARDIAC FUNCTION
Anatomy of the Heart The Heart A hollow muscular organ that is approximately the size of a fist Weighs 325 g in men and 275g in females Approximately 12 cm in length Enclosed in a double-layered fibrous membrane (sac) called the PERICARDIUM Layers of pericardium : Visceral pericardium Parietal pericardium Myocardium Contains striated muscle fibers that alternate between contraction and relaxation Fibers composed of cardiac-specific contractile proteins called actin and myosin and regulatory proteins called TROPONINS These fibers also contain a number of ezymes such as myosin, creatine kinase (CK) and lactate dehydrogenase (LDH) that have been used as markers of cardiac injury Two of the troponins, the cardiac forms of troponins I and T have become the DEFINITIVE BIOMARKERS OF CARDIAC INJURY A typical cardiac cycle consists of two intervals known as: SYSTOLE The blood pressure in the aorta is typically about 120mmHg DIASTOLE The blood pressure falls to about 70mmHg

At rest, the heart pumps between 60 and 80 times per minute. The cardiac cycle is tightly controlled by the cardiac conducting system, which initiates electrical impulses and carries them, via a specialized conducting system, to the myocardium ELECTROCARDIOGRAM ECG records changes in electrical potential Is a graphic tracing of the variations in electrical potential caused by the excitation of the heart muscle The surface ECG is a recording of the electrical potential as detected at the body surface ECG is 1. 2. 3. 4. used to identify: Anatomic Metabolic Ionic Hemodynamic changes

The clinical sensitivity and specificity of ECG abnormalities for detecting acute coronary syndromes are influenced by a wide spectrum of physiological and anatomical changes and the clinical situation. Under normal circumstances, the pattern of each cardiac cycles electrical potential changes (each complex) is similar to that of every other cycle, and includes three major components. The P wave atrial depolarization The QRS complex ventricular depolarization The ST segment and T wave repolarization

A routine ECG is composed of 12 leads.

Notes by: Carol Chan

@celynsnotes2014 Six are called limb leads (I, II, III, aVR, aVL,a nd aVF) - because they are recorded between arm and leg electrodes Six are called precordial or chest leads (V1, V2, V3, V4, V5, V6) - They are recorded across the sternum and left precordium. The valves ensure that blood flows in a single direction through the heart, and because there is a slight (~0.1 second) delay after the SA node fires and before the AV node is stimulated, each chamber is able to empty completely before becoming closed off. In addition, for brief periods of time, the cells of the SA and AV nodes are insensitive, or refractory, to incoming electrical signals. These changes in potential for stimulation, during which charged ions are passing into or out of cells to re-establish resting voltages, give the heartbeat its regularity. The coupling of electrical timing with muscular contraction is simultaneously powerful and intricate. But the intimacy of these processes with the bodys circulation means that even the slightest defect in function can have severe consequences on overall health. Electrical impulses generated by the sinoatrial (SA) node, a bundle of nerve cells embedded in the muscle of the right atrium, stimulate the muscles of both the right and left atria (or upper chambers of the heart) to contract, thereby pushing blood into the ventricles (or lower chambers). The famous lub-dub sound of the beating heart is a function of the different heart valves. The lub is created by the closing of valves between the atria and ventricles, and the dub by the closing of valves between the ventricles and the pulmonary artery and aorta. The wave of neuronal excitation created by the SA node passes to the atrioventricular (AV) node, which lies between the atria and ventricles. Once stimulated, the AV node fires off a contractile signal to the ventricular muscles. The ventricles then force blood away from the heart, with blood exiting via either the pulmonary artery, which runs from the right

Each LEAD records the same electrical impulse but in a different position relative to the heart. Areas of pathology shown on the ECG can be localized by analysing differences between the tracing in question and what is known to be normal in the 12 different leads.

Notes by: Carol Chan

@celynsnotes2014 ventricle to the lungs, or the aorta, which extends from the left ventricle and connects to arteries leading to the various other parts of the body. Edema Cyanosis Fatigue Diminished cardiac function Pulmonary insufficiency Lack of sleep

Dyspnea 3 basic types: A. Cardiac occurs when something is weakened or something obstructs the flow of blood through the heart B. Pulmonary shortness of breath as a result of lung disease C. Psychological occurs as a result of anxiety or panic attacks Chest Pain Second most common symptom of heart disease Not all is due to heart attack, it may originate from other chest structures, a chest muscle, strained cartilage, or when organs below the chest have become irritated (blocked gallbladder, ulcerated stomach, inflamed pancreas, or acid reflux) Angina pectoris Also known as angina, is chest pain from the heart Described as griping or crushing central chest pain felt around or deep within the chest. Pain may radiate from the neck or jaw, less commonly to the back or abdomen, and is associated with pain in one (usually the left) or both arms. It is most often caused by ischemia (restriction of blood supply to the heart) due most commonly to coronary artery disease. It is worsened by exercise or relieved by rest Notes by: Carol Chan

PHYSIOLOGIC CONDITIONS OF THE HEART Cardiovascular Disease A debilitating condition Responsible for deaths of many Timely and accurate diagnosis is essential 7 symptoms of Heart Disease SYMPTOM Dyspnea Chest pain Palpitations Syncope Most common cause Symptom Diminished heart failure Coronary artery disease Extra heartbeats Disturbance in heart rhythm of

@celynsnotes2014 2 types of Angina: 1. Stable (reversible) Presents as pain and discomfort in the chest only when engaged in moderate activity (running or walking). Once the activity is removed, the pain subsides. A formed plaque enclosed in a fibrous cap may be seen 2. Unstable (progressive) Presents with pain and discomfort unpredictably at rest. The plaque ruptures, allowing blood clots to precipitate and further decrease the lumen of the coronary vessel Extremely painful, does not respond well to standard treatment and progresses rapidly toward AMI Palpitation Term used to describe the awareness one has of their own heartbeat. Not the pounding one feels as result of heavy exertion rather, it has been described as a fluttering beating or a thumping, flip-flopping, skipped heartbeat The most common cause is due to heightened awareness because of anxiety or tension It is frustrating for the patient and physician because they often subside before they can be evaluated Syncope Term used to indicate fainting or the sudden loss of consciousness May be caused by a number of conditions that result in the deprivation of oxygen and blood to the brain. The most common type is VASOVAGAL in nature (simple faints) and is not the result of serious disease. Most common cardiovascular cause is an irregular heartbeat (arrhythmia) Without warning, the patient falls to the ground with a slow or absent pulse and, after a few seconds, recovers. Edema Refers to the swelling of tissue around the ankles, legs, eyes, chest wall, or abdominal wall due to the retention of water or lymph fluid in the cells of tissues. It is nearly always considered abnormal and a potential sign of disease Edema associated with heart disease is often absent in the morning (as fluid is reabsorbed while lying down) and is progressively worse during the day. Cyanosis Term used to describe a bluish discoloration of the skin and is caused by an increased amount of nonoxygenated hemoglobin in the blood due to dyspnea The discoloration is most apparent in the fingernail beds and around the lips 2 types of cyanosis: 1. Central cyanosis Due to an inherited form of heart disease where venous and arterial blood

Notes by: Carol Chan

@celynsnotes2014 mixes together because of a congenital opening between the left and right sides of the heart Or due to an anatomically defective heart where there is a common mixing chamber. 2. Peripheral cyanosis Is the type commonly caused by exposure to cold temperatures where the body attempts to conserve heat by restricting the capillaries of the skin and slowing blood flow PATHOLOGIC CONDITIONS OF THE HEART CONGENITAL CARDIOVASCULAR DISEASE Congenital Cardiovascular defects (CCVDs) are abnormalities arising from the abnormal formation of the heart or its major blood vessels Defects can involve: a. Interior walls of the heart b. Valves inside the heart c. Arteries and veins that carry blood to the heart or out of the body Estimated that 4 to 50 live born infants per 1000 are born with a congenital heart defect Signs and symptoms: 1. Cyanosis 2. Pulmonary hypertension 3. Clubbing of fingers 4. Embolism 5. Reduced growth 6. Syncope Etiology of CCVDs Unknown Most appear multi-factorial etiology based on an interaction between genetic predisposition and environmental influences Factors associated with development of CCVDs include: 1. Maternal rubella infections 2. Maternal alcohol abuse 3. Drug treatment 4. Radiation 5. Certain genetic and chromosomal abnormalities CCVDs include: Tetralogy of Fallot Transposition of the great arteries Atrioventricular septal defects Coarction of the aorta Hypoplastic left heart syndrome Ventrical septal defects (VSDs)

Tetralogy of Fallot results from lowoxygenation of blood due to the mixing of oxygenated and deoxygenated blood in the left ventricle via the VSD and preferential flow of the mixed blood from both ventricles through the aorta because of the obstruction to flow through the pulmonary valve. This is known as a right- to-left shunt.

Notes by: Carol Chan

@celynsnotes2014 Common cause of Blue baby syndrome VENTRICULAR SEPTAL DEFECTS (VSD) Are the most common type of CCVD encountered this type of defect is commonly referred to as a hole in the heart There is a large opening, between the ventricles of the heart Because of the structural defect, blood flows through the defect from the left to the right ventricle, resulting in oxygenated blood entering the pulmonary artery. This extra blood, in addition to pulmonary flow from the vena cava, increases blood flow to the lungs and subsequently increases pulmonary venous return into the left atrium and ultimately into the left ventricle. This increased volume results in LEFT VENTRICULAR DILATATION and the HYPERTROPHY. It increases the end-diastolic pressure and then pulmonary venous pressure. Finally, as blood is shunted through the VSD away from the aorta, cardiac output decreases, and compensatory mechanisms are stimulated to maintain increased catecholamine secretion and salt and water retention by means of the renin angiotensin system Genetic test to assist in diagnosis of CCVD Fluorescence in situ hybridization (FISH) DNA mutation analysis HEART FAILURE Formerly referred to as CHF Known as a condition of the aging population, affecting 10 of every 1000 persons over the age of 65 years. Of those hospitalized, 80% are over the age of 65 It is a clinical syndrome that results from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. When the left side of the heart is unable to pump, excess fluid accumulates in the lungs. As a result, PULMONARY EDEMA and reduced output of blood to systemic circulation Kidneys respond by retaining excess fluid, making HF worse. When the right heart is unable to pump, excess fluid accumulates in systemic circulation and generalized edema occurs NEW YORK HEART ASSOCIATION STAGING FAILURE Stagin Symptom Limitation Objectiv g s s e Evidence Class I None None No evidence of CVD Class II Mild Some during exercise and walking Marked OF HEART Comment s

Class III

Severe

Ordinary PA does not cause symptoms Objective Comfortabl evidence e at rest; of minimal ordinary PA CVD results in symptoms Objectivel May be y evidence comfortabl of e at rest; moderatel less than y severe ordinary CVD activity results in symptoms Notes by: Carol Chan

@celynsnotes2014 Class IV Severe even at rest Severe Objective evidence of severe CVD Unable to carry on activity without discomfort Causes of Heart Failure CAUSE Coronary artery disease Cardiomyopathies Inflammatory heart disease TYPES Dilated cardiomyopathy Restrictive cardiomyopathy Hypertrophic cardiomyopathy Cardiac infections Immunologic injury to myocardium Valvular incompetence

ACC/AHA CLASSIFICATION OF SYSTEM FOR HEART FAILURE STAGE DESCRIPTION A No identified structural/functional abnormalities; no signs and symptoms of HF; Patients at high risk for developing HF due to presence of conditions* associated with the development of HF B Structural heart diseases noted; no signs or symptoms of HF C Underlying structural heart disease; current or prior symptoms of HF D Advanced structural heart disease; marked symptoms of HF at rest despite medical therapy *hypertension, DM, coronary artery disease, family history May result from disorders of the walls of the heart (pericardium, myocardium, endocardium) or from disorders of the great vessels, however most HF cases are due to left ventricular dysfunction. The most common cause of HF are: Coronary artery disease Cardiomyopathies Inflammatory heart disease Valvular disease Cardiac arrhythmias

Cardiac conduction dysfunctions/arrhythmias Congenital cardiovascular disease ACUTE CORONARY SYNDROMES Is a general term used to describe the following continuum of events: Angina Reversible tissue injury Unstable angina Myocardial infarction (MI) Extensive tissue necrosis SYMPTOMS: Chest pain Referred pain (pain referred to the arm, jaw, neck, back, or abdomen) Nausea Vomiting Dyspnea Diaphoresis Lightheadedness

Notes by: Carol Chan

@celynsnotes2014 Lowering serum LDL cholesterol values has been shown to reduce the incidence of coronary artery disease and the progression of atherosclerosis. HYPERTENSIVE HEART DISEASE HIGH BLOOD PRESSURE Defined as persistent systolic blood pressure (BP) of at least 140 mmHg and/or diastolic pressure of at least 90 mmHg, or BP that is controlled to guidelinerecommended levels using antihypertensive medication. Contributing factors: Obesity Physical inactivity Unhealthy nutrition The FRAMINGHAM HEART STUDY also reported that systolic BP values of 130-135 mm Hg and diastolic BP values of 85-80 mmHg are associated with a more than twofold increase in risk for CVD. Is a general term used to describe heart diseases, such as left ventricular hypertrophy, coronary artery disease, cardiac arrhythmias, and CHF, caused by direct or indirect effects of elevated BP Most important Factor for BP determination: PERIPHERAL RESISTANCE PERIPHERAL RESISTANCE Increases the workload of the left ventricle, eventually resulting in hypertrophy and dilatation. Problem with the left ventricle affects the mitral valve, which allows a regurgitation of blood to the left atrium.

The clinical laboratory plays a critical role in diagnosis, management, identification, and risk stratification of these events ATHEROSCLEROSIS Thickening and hardening of the artery walls caused by deposits of cholesterol-lipid-calcium plaque in the lining of the arteries It is an inflammatory disorder, not a cholesterol issue, as there are many mechanisms that lead to the cellular injury, such as bacterial infection, hyperlipidemia, glycosylated products seen in diabetes mellitus, and pro-inflammatory cytokines, among others. Results in the narrowing of the arteries and a tendency for plaque disruption and thrombus formation. ISCHEMIA reduced blood supply to the heart Nine factors predispose individuals to atherosclerosis: Age, sex, family, history, dyslipidemia, smoking, hypertension, sedentary lifestyle, diabetes mellitus Premonaupal women appear to be less at risk for the development of atherosclerosis compared to men due to the higher levels of high density lipoprotein (HDL) cholesterol found in this subset of women, however, when estrogen levels drop at menopause, the difference between men and women disappears. It is a more common finding in adults over the age of 40 and is found almost universally in older persons in the western world. DYSLIPIDEMIA, specifically elevations in triglycerides and LDL cholesterol and reductions in HDL cholesterol, have been shown to have a strong association with the development of atherosclerosis

Notes by: Carol Chan

@celynsnotes2014 Over time, it results in increased pressure and dilatation in the left atrium As many as 39% of the affected children may develop degrees of pancarditis associated with valve insufficiency, HF, pericarditis and even death Diagnosis proposed by Dr. T. Duckett Jones in 1944 and has been modified four times with the updated diagnostic recommendation published in 1992. Diagnosis is divided into two levels of criteria: MAJOR and MINOR The diagnosis requires the presentation of two major or one major and two minor criteria addition to evidence of a recent streptococcal infection. (refer to table Jones Criteria for Dx of Rheumatic Heart Disease)

CLASSIFICATION OF HYPERTENSION FOR ADULTS CLASSIFICATION BLOOD PRESSURE (mmHg) Normal <120 systolic; <80 diastolic Prehypertension 120 139 systolic or 80 89 diastolic Stage 1 hypertension 140 159 systolic or 90 99 diastolic Stage 2 hypertension 160 systolic; 100 diastolic By the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure The category prehypertension is not a disease category, but a designation used to identify those at an increase risk for the development of hypertension.

INFECTIVE HEART DISEASE Most common heart diseases caused by infectious agents: Rheumatic heart disease Infective endocarditis Pericarditis RHEUMATIC HEART DISEASE A serious complication of rheumatic fever It is hypothesized to result from an autoimmune response Rheumatic fever is a disease that primarily affects children and young adults as a result of complications from infection with group A hemolytic streptococci.

INFECTIVE ENDOCARDITIS Infection of endocardial surface of the heart caused by several microorganisms and fungi Streptococci and staphylocci are common bacterial causes in which the organism attaches to the endocardium, invades the valves and forms vegetations that interfere with the function of the valves. Acute occurs with a sudden onset of spiking fevers, chills and drowsiness Subacute presents in a vague and insidious manner with low-grade fevers, fatigue, anorexia, splenomegaly PERICARDITIS Condition of inflammation of the pericardium, the membrane that surrounds the heart

Notes by: Carol Chan

@celynsnotes2014 May be caused by infections (bacteria, viral or fungi), autoimmune disorders, or other diseases. The space between the layers of the pericardium contains approximately 20 mL of pericardial fluid. Accumulation of this fluid is the hallmark sign of this condition, and the type of fluid that accumulates will differentiate the cause of pericarditis. Purulent exudates indicate bacterial infections Clear serious fluids are caused by viral infections A serofibrous exudate is associated with severe damage as in rheumatic heart disease It may be defined pathologically as acute, healing or healed. RISK FACTORS Age (men >45 years; women >55 years) Gender: men are more at risk than women Diabetes mellitus (type 1 or 2) High blood pressure Dyslipidemia/hypercholesterolemia (particularly high LDL, low HDL and high triglycerides) Tobacco smoking, including secondhand smoke Short term exposure to air pollution including: carbon monoxide, nitrogen dioxide and sulfur dioxide Family history of ischaemic heart disease or myocardial infarction Obesity (defined by a body mass index or more than 30 kg/m) Lack of physical activity Psychosocial factors including, low socio-economic status, social isolation, negative emotions and stress Alcoholism Oral contraceptive pills Hyperhomocysteinemia/Homocysteinuria The primary tests for diagnosing ACS are electrocardiography (ECG) and laboratory measurement of cardiac markers Cardiac markers are proteins released into the circulation from the damaged heart muscle

DIAGNOSIS OF HEART DISEASE LABORATORY DIAGNOSIS OF MYOCARDIAL INFARCTION MYOCARDIAL INFARCTION Defined as a myocardial necrosis due to prolonged ischemia and it is usually categorized by the size of the infarct Infarct Size: Microscopic (focal necrosis) Small (<10% of the left ventricular myocardium) Moderate (10%-30% of the left ventricular myocardium) Large (>30% of the left ventricular myocardium)

Notes by: Carol Chan

@celynsnotes2014 ACUTE MI Characterized by: Presence of polymorphonuclear leukocytes HEALING MI Characterized by the presence of mononuclear cells and fibroblasts in the absence of polymorphonuclear leukocytes Characterized by scar tissue without cellular infiltration, a process that usually takes 5-6 weeks According to the Expert Concensus Document of the Joint European Society for Cardiology/AHA Science Advisory and Coordinating Committee/ AHA/World Heart Federation Task Force for the Redifinition of Myocardial infarction; the term MI should be used when the evidence of myocardial cell death in a clinical setting with myocardial ischemia. DIAGNOSIS OF AMI Based on: Clinical symptoms Electrocardiographic changes (ECG) Rise and/or fall of highly sensitive biochemical markers The European Society of Cardiology and the ACC (ESC/ACC) consensus report recommended samples are collected at presentation, at 6-9 hours, and again at 12-14 hours if the earlier samples were negative. percentile of the upper reference limit, and evidence of myocardial ischemia, and at least of one of the following: Symptoms of ischemia ECG changes (new ST-T changes or new left bundle-branch block [LBBB]) Development of pathologic Q waves in the ECG Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality Sudden, unexpected cardiac death, involving cardiac arrest, often with symptoms suggestive of myocardial ischemia, and accompanied by presumably new ST elevation, or new LBBB, and/or evidence of fresh thrombus by coronary angiography and/or at autopsy, but death occurring before blood samples could be obtained, or at a time before the appearance of cardiac biomarkers in the blood For percutaneous coronary interventions (PCIs) in patients with normal baseline troponin values, elevations of cardiac biomarkers above the 99th percentile of upper reference limit are indicative of periprocedural myocardial necrosis. By convention, increases of biomarkers greater than 3 times the 99th percentile of upper reference limit have been designated as defining PCI-related MI. For coronary artery bypass grafting (CABG) in patients with normal baseline troponin values, elevations of cardiac biomarkers above the 99th percentile of the upper reference limit are indicative of periprocedural myocardial necrosis. By convention, increases of biomarkers greater than five time the 99th percentile

Any one of the following criteria meets the diagnosis for MI: Rise and/or fall of cardiac biomarkers (preferably troponin) with at least one value above the 99th

Notes by: Carol Chan

@celynsnotes2014 of the upper reference limit plus either new pathologic Q waves or new LBBB, or angiographically documented new graft or native coronary artery occlusion, or imaging evidence of new loss of viable myocardium have been designated as defining CABG-related MI. IDEAL CARDIAC MARKER Rapid and able to measure low concentrations of the marker in serum or plasma samples It would persist in the circulation for several days to provide a late diagnosis time window for patients who arrive late after the event. Features of an Ideal Cardiac Marker: (Bishop) High specificity for myocardial damage in the presence of skeletal muscle injury High sensitivity to detect very minor heart damage Capability to differentiate reversible from irreversible cardiac damage Ability to be used as a monitor of prognosis and therapy Availability of rapid, easy-to-perform, and cost effective quantitative assays Absent or not detectable in patients without myocardial damage Current Guidelines from the NATIONAL ACADEMY OF CLINICAL BIOCHEMISTRY Recommended the use of two biochemical markers to diagnose AMI: 1. A marker increased early after the onset of symptoms (within 6 hours) 2. A definitive marker with a high sensitivity and specificity for myocardial damage that increases within 6-9 hours after symptoms and remains abnormal for several days

Pathologic findings of an AMI Serum glutamineoxaloacetic transaminase (SGOT) -> was replaced by LDH and its isoenzymes and the classic diagnostic LDH flipped ratio, which was replaced by Creatine Kinase (CK) and the MB fraction of CK (CK-MB). ROLE OF CARDIAC MARKER It is defined as a clinical laboratory test useful in cardiac disease, most commonly for detecting AMI or myocardial injury. More useful when patients have non-diagnostic ECGs CM to be clinically useful, it must be released rapidly from the heart into the circulation and provide sensitive and specific diagnostic information

Notes by: Carol Chan

@celynsnotes2014 Creatine kinase (CK) It is a cystosolic enzyme involved with the transfer of energy in muscle metabolism. It is a dimer composed of two subunits, B and M, resulting in three cystosolic isoenzymes, CKMM (CK-3), CK-MB (CK-2), and CK-BB (CK-1) Measurement of total CK not recommended because of the large skeletal muscle distribution and the lack of specificity of the enzyme CK-BB Is of brain origin and is only found in the blood when the blood brain barrier has been damaged. CK-MM It is found primarily from skeletal muscle and heart CK-MB Most specific for the myocardium It is the most valuable tool for the diagnosis of MI because of its relatively high specificity for myocardial damage. It rises within 4-6 hrs after the onset of chest pain, peaks at 12-24 hours, and returns to normal levels within 2-3 days CK-MB activity assays have been replaced by CK-MB mass assays to measure CK-MB. CK-MB mass assays can detect an increased amount of serum CK-MB about 1 hour earlier than activity based assays. Calculation of a relative index (CK-MB mass assay/ total CK x 100) may be used as an indicator of MI. The relative index 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.

ENZYMES Not recommended for routine use in the detection of myocardial damage include: AST LDH LDH isoenzyme determinations Currently in clinical use to detect MI are: CK and its isoenzyme CK-MB (Creatine kinase muscle, brain)

CARDIAC PROTEINS Myoglobin Cardiac troponins Cardiac myosin light chains MYOGLOBIN Heme containing protein that binds oxygen within cardiac and skeletal muscle Molecular weight of 18 kDa It leaks from damaged cells more rapidly than other proteins Following MI, elevated myoglobin may be detectable in plasma before CK-MB or cTn.

Notes by: Carol Chan

@celynsnotes2014 Peaks about 6 hours after MI and returns to baseline after 24 hours Lack specificity This isoform exists in heart and brain tissue Because of the blood brain barrier, GPBB can be seen as heart muscle specific During the process of ischemia, GPBB is converted into a soluble form and is released into the blood GPBB is one of the new cardiac markers which are discussed to improve early diagnosis in acute coronary syndrome. A rapid rise in blood levels can be seen in myocardial infarction and unstable angina GPBB elevated 1-3 hours after process of ischemia

Ischemia modified albumin (IMA) Low specificity IMA can e detected via the albumin cobalt binding (ACB) tests, a limited available FDA approved assay IMA measures ischemia in the blood vessels and thus returns in minutes rather than traditional markers of necrosis that take hours. ACB test has low specificity therefore generating high number of false positives and must be used in conjunction with typical acute approaches such as ECG and physical exam Pro-brain Natriuretic peptide This is increased in patients with heart failure. It has been approved as marker for acute congestive heart failure. Patients with <80 have a much higher rate of symptom free survival within a year Generally, patients with CHF will have >100 Glycogen phosphorylase isoenzyme BB High sensitivity and specificity early after chest pain Peak: 7 hours Glycogen phosphorylase isoenzyme BB (abbreviation: GPBB) is an isoenzyme of glycogen phosphorylase

CARDIAC TROPONINS Troponin is a complex of three proteins that bind to the thin filament (actin) of cardiac and skeletal muscle. 3 types: Troponin T(TnT)[tropomyosin-binding component] Troponin I (TnI)[the inhibitory component] Troponin C (TnC) [the calcium binding component] It is localized primarily in the myofibrils (94%97%) with a smaller cytoplasmic fraction (3%6%)

Notes by: Carol Chan

@celynsnotes2014 Function of Troponins To bind calcium and regulate muscle contraction Following injury to skeletal or heart muscles, the troponin complex and free troponin subunits are released into the bloodstream. Troponins have been shown to have high sensitivity and specificity for myocardial damage. Troponins rise 4-10 hours after the onset of symptoms, peak 12-48 hours, and remain elevated for 4-10 days. It is the sustained elevation of the troponins that enables them to serve as definitive markers for AMI Blood samples for troponins should be drawn as described for CK-MB at presentation, at 6-9 hours, and again at 12-24 hours if the earlier measurements were not elevated and the clinical suspicion of MI is high. Unlike CK-MB, the serum troponins are not found in the serum of healthy individuals Extremely useful in patients who do not seek medical attention in the 2-3 day window when CK-MB is elevated CTnT begins to rise within a few hours after the onset of chest pain, peeks at 2 days, and can remain elevated for 7-10 days. It increases and reached its peak similarly to TnI, but TnT may show a biphasic release in some MI patients, with a peak occurring during the first 24 hrs after the onset of symptoms and a second peak on approximately the fourth day after admission. TnI

TnT

Is also helpful in monitoring patients after reperfusion treatment It is cardiac specific due to the presence of an additional amino acid residue on the amino-terminal end. It is released in circulation is similar to cardiac TnT and CK-MB and its measurement offers advantages over CK-MB Namely, It is not found in detectable amounts in the serum of patients with multiple injuries, in those engaged in strenuous exercise in patients with renal failure, and in those with acute or chronic skeletal muscle disease. After an AMI, the TnI increases above the reference range between 4 and 6 hours after chest pain onset, peaks at 12-18 hours and returns to within reference limits in about 6 days, depending in AMI. TnI-Ultra (ultrasensitive TnI assay) Has been developed that offers a more sensitive assay for the detection of myocardial injury earlier than the current assays.

Notes by: Carol Chan

@celynsnotes2014 CARDIAC MYOSIN LIGHT CHAINS (MLCs) Are involved with muscle contractions They were first thought to be unique myocardial proteins, but recent research has determined that MLCs are no more specific for cardiac injury than CK-MB determinations. Although rapid testing of MLCs is available, MLC determination does not offer any advantage over cardiac troponin assays. Therefore, MLC remains of limited clinical significance as a routine cardiac marker. Significant laboratory makers of risk include lipids (cholesterol, triglycerides, and specific lipoprotein fractions), homocysteine (Hcy), and C - reactive protein (CRP) Homocysteine is an amino acid that exacerbates thrombosis CRP is an inflammatory marker that appears to reflect the severity of CHD and may contribute to its pathogenesis MARKERS OF CORONARY RISK Serum Cholesterol LDL fraction (70% of the total circulating cholesterol) HDL fraction (negative risk) Triglycerides major lipid class commonly measured in plasma LIPID PROFILE It is a collective term given to estimate of, typically, total cholesterol, HDL, LDL and triglycerides An extended lipid profile may include VLDL. This is used to identify hyperlipidemia a risk factor for cardiovascular disease

C - reactive protein First isolated in 1930 from the plasma of patients with pneumococcal pneumonia CRP was named because it binds to Cpolysaccharide of the pneumococcus It was later found that the protein appeared in plasma during many infectious or inflammatory conditions CRP was the original acute phase reactant MI is among the acute illnesses associated with elevation of plasma CRP
Recommendations of a Joint Committee of the American Heart Association and the centers of Disease Control and Prevention on CRP testing to assess CHD Risk (Pearson, 2003)

If inflammatory markers are to be used in assessment of CHD risk, CRP is the current analyte of choice Optimally, hsCRP results should be averaged from two specimens drawn about 2 weeks apart. If a level >10 mg/l is identified, there should be a search for an obvious cause of infection or inflammation; that result should be discarded, and another test done 2 weeks late Decision intervals: < 1 mg/l, low risk 1-3 mg/l, intermediate risk; >3 mg/l, high risk

Notes by: Carol Chan

@celynsnotes2014 2. Brain natriuretic peptide (BNP) isolated from porcine brain in humans BNP is produced mainly in the cardiac ventricle so the hormone is now commonly referred to as B-type natriuretic peptide. 3. C- Type natriuretic peptide (CNP) not produced in the heart but in endothelial cells 4. D - Type natriuretic peptide (DNP) isolated from green mamba snake, Dendroaspis angusticeps 5. Urodilatin is a form of ANP produced in the kidneys

Homocysteine (Hcy) This risk marker in some ways parallels that of cholesterol: the regular occurrence of atherosclerosis in persons with massive elevation, due to an inborn error of metabolism Homocystinuria homozygous defect in the enzyme cystathionine-13- synthase due to deficiency in vitamins B6 and B12 Clinical Manifestations of Homocysteinuria: Dislocation of the optic lens Osteoporosis with associated abnormalities Mental retardation Psychiatric disturbance Thromboembolic disease => CHD

skeletal Both ANP and BNP have been investigated with regard to testing for BNP and the other natriuretic peptides down regulate the renin-angiotensin-aldosterone system, decreases sympathetic nerve activity in the heart and kidney, increases renal blood flow, and increase sodium excretion via a direct effect on the renal collecting duct Plasma levels of BNP are less than 100 pg/ml in most healthy individuals The best application of BNP measurement is for diagnostic acutely ill patients presenting to emergency service with shortness of breath Distinguishing Heart Failure from lung disease, such as emphysema BNP test for diagnosis of HF: sensitivity 90%, specificity 76 or

Congestive heart failure Coughing Tiredness Shortness of breath Pleural effusion (excess fluid around lungs) Swelling in abdomen (ascites) Pulmonary edema (excess fluid in lungs) Pumping action of the heart grows weaker Swelling in ankles and legs MARKERS OF CONGESTIVE HEART FAILURE The heart could be an endocrine organ Members of the natriuretic peptide family 1. Atrial natriuretic peptide (ANP) isolated from human heart

Other Conditions Associated with Atherosclerosis Thrombosis Cerebrovascular accident (stroke) Thrombosis in peripheral veins

Notes by: Carol Chan

@celynsnotes2014

Notes by: Carol Chan