ISCHAEMIC HEART DISEASE 3 H.A. MWAKYOMA, MD

Aims and Objectives Ischaemic heart disease Chest pain Definition, manifestations, epidemiology, aetiology, pathophysiology, risk factors and prevention, relevance to dentistry Chest pain Differential diagnosis Acute myocardial infarction Assessment, treatment, complications Cardiopulmonary resuscitation

Ischaemic heart disease Definition An imbalance between the supply of oxygen and the myocardial demand resulting in myocardial ischaemia. Angina pectoris symptom not a disease chest discomfort associated with abnormal myocardial function in the absence of myocardial necrosis

Ischaemic heart disease Definition--- cont-- Supply Atheroma, thrombosis, spasm, embolus Demand Anaemia, hypertension, high cardiac output (thyrotoxicosis, myocardial hypertrophy)

Myocardial Ischemia Results when there is an imbalance between myocardial oxygen supply and demand Most occurs because of atherosclerotic plaque with in one or more coronary arteries Limits normal rise in coronary blood flow in response to increase in myocardial oxygen demand

Ischemic Heart Disease What is Ischemic Heart Disease (IHD)? Ischemic heart disease results when blood flow to the myocardium is insufficient to meet the demands of the heart. IHD results in: Angina pectoris (cardiac chest pain) High risk for ACS High risk for developing congestive heart failure (CHF)

IHD Ischemic Heart Disease: Basic Physiology IHD results when coronary oxygen supply does not meet the oxygen demand of the myocardium, so decreased supply or increased demand may be responsible.

IHD: Oxygen Supply Ischemic Heart Disease: Oxygen Supply Myocardial O2 supply is determined by two factors: O2 carrying capacity of the blood 2) Coronary blood flow

IHD: Oxygen Supply Ischemic Heart Disease: O2 Carrying Capacity The carrying capacity of the blood is determined by the hemoglobin content and the ability of the lungs to effectively oxygenate the hemoglobin. Anemic people (those with low hemoglobin levels) are more likely to experience symptoms related to IHD. Athletes frequently inject Epogen (erythropoietin), a drug that increased hemoglobin production, in order to enhance performance.

IHD: Oxygen Supply Ischemic Heart Disease: Coronary Flow The coronary blood flow is dependant on many factors including: Coronary perfusion pressures (related to diastolic BP) Coronary vascular resistance External compression of the coronary arteries Intrinsic regulation of vasodilation/vasoconstriction Local metabolites and endothelial factors Nervous system innervation of the coronaries

IHD: Oxygen Demand Ischemic Heart Disease: Oxygen Demand Oxygen demand is determined by three factors: Myocardial wall stress (afterload + preload) Heart rate (chronotropy) Contractility (inotropy)

IHD: Oxygen Demand Ischemic Heart Disease: Wall Stress The higher the stress on the walls of the heart, the higher the myocardial oxygen demand. This is explained by the “Law of LaPlace”: Wall stress = pressure X radius_ 2 X wall thickness Note: Since the LV is the largest part of the heart, the LV wall stress, LV pressure, LV radius, and LV wall thickness is used in the above equation.

IHD: Oxygen Demand Ischemic Heart Disease: LV Pressure The LV pressure is determined by the “afterload” (a.k.a. systemic vascular resistance or SVR). Conditions that increase afterload include systemic hypertension and aortic valve stenosis. Afterload is decreased with antihypertensive therapy and as a long-term response to exercise. LV Wall stress =LV pressure X LV radius_ 2 X LV wall thickness

IHD: Oxygen Demand Ischemic Heart Disease: LV Thickness The LV thickness is the heart’s natural response to increased preload and afterload as a compensatory mechanism to try to maintain a normal LV wall stress and thus myocardial oxygen demand. As the LV wall thickness increases, wall stress per gram of myocardium decreases by a factor of 2. LV Wall stress = LV pressure X LV radius_ 2 X LV wall

IHD: Oxygen Demand Ischemic Heart Disease: Heart Rate (HR) The HR also determines myocardial oxygen demand. Larger amounts of oxygen is required when the heart rate is high, thus tachycardia can lead to increased oxygen demand and ischemia if the HR is high enough and if it is sustained for long periods of time. Conversely, slowing the heart rate decreases the myocardial oxygen demand. This is the reason behind using -blockers when myocardial ischemia is present

IHD: Oxygen Demand Ischemic Heart Disease: Contractility The strength of contraction of the myocardium, termed contractility or inotropy, also determines oxygen demand. Things that increase contractility include SNS stimulation (from epinephrine induced 1 receptor agonism) or inotropic medications (such as dobutamine). Thinks that decrease contractility include -receptor blockers, again contributing to their role in decreasing myocardial oxygen demand.

IHD: Syndromes Ischemic Heart Disease: Syndromes Ischemia heart disease results from one of four possible ischemic syndromes: Chronic stable angina (always from atherosclerosis) Acute coronary syndromes (usually from atherosclerosis) Variant or Pritzmetal’s Angina (not from atherosclerosis) Silent ischemia (usually from atherosclerosis)

IHD: Syndromes

Ischemic Heart Disease Classification = mainly 4 types Myocardial infarction (MI) Sudden cardiac death Angina pectoris Chronic IHD with heart failure

IHD: Stable Angina Ischemic Heart Disease: Stable Angina Stable angina refers to myocardial ischemia that occurs with exertion and is relieved with rest. This occurs universally from atherosclerosis and results from significant flow-limiting stenosis of the coronary arteries that causes ischemia only when oxygen demand is increased, such as during exertion.

IHD: Stable Angina Ischemic Heart Disease: Symptoms Symptoms include typical cardiac chest pain lasting less than 10 minutes which is often described as: “pressure-like” or “tightness” or “heaviness” or “indigestion” in the chest Located substernally radiating to the left arm, neck, jaw, or shoulder (see next slide). Levine sign: When a patient makes a fist on their chest to describe their chest pain.

IHD: Stable Angina

IHD: Stable Angina Ischemic Heart Disease: Symptoms While many people are familiar with the classic description of cardiac chest pain, many atypical presentations of cardiac pain may occur. These include: Sharp or burning pain instead of pressure-like. Radiation to the shoulders, right chest/arm, or back. Describing the feeling as a “discomfort”, not pain.

IHD: Stable Angina Ischemic Heart Disease: SNS Effects The sympathetic nervous system (SNS) is activated during ischemia due to pain, emotion, and sometimes due to the baroreceptor response (if hypotension is present). Signs of SNS activation include: Cold sweat (diaphoresis) 2) Palpitations 3) Cold and clammy skin due to vasoconstriction 4) A feeling of impending doom

IHD: Stable Angina Ischemic Heart Disease: PNS Effects The parasympathetic nervous system (PNS) is activated in order to attempt to compensate for the increased SNS activity. Signs of PNS activation include: Nausea and vomiting Weakness Note: Since -blockers can hinder SNS symptoms, PNS symptoms may predominate in people on -blockers.

IHD: Stable Angina Ischemic Heart Disease: Atypical Symptoms Many “atypical” presentations of angina occur and are much more common in women. They include: Dizziness or lightheadedness alone Weakness alone Fever alone Nausea and vomiting alone Syncope or “passing out”

IHD: Stable Angina Ischemic Heart Disease: Diagnosis The diagnosis of IHD is based on 3 steps: Suspicion of disease based on CAD risk factors and symptoms. Screening via EKG and/or cardiac stress testing. Confirmation of CAD via coronary angiography in people with positive stress tests. Note: Step 2 may be skipped in people who are considered “high risk” for CAD.

IHD: Stable Angina Ischemic Heart Disease: Diagnosis - EKG EKG findings during myocardial ischemia include ST segment depression and T wave inversion (not ST elevation, which is seen in acute myocardial infarction). In stable angina, these findings should not be seen at rest. In unstable angina, these findings may be seen at rest. Normal Horizontal ST Downsloaping ST T Wave ST Depression Depression Inversion Elevation

IHD: Stable Angina Ischemic Heart Disease: Screening Cardiac stress testing is the preferred method of screening for CAD. Each stress test has a diagnostic modality and a means of inducing stress to the heart. Based on findings during cardiac stress testing, a coronary angiogram may or may not be recommended.

IHD: Stable Angina Ischemic Heart Disease: Screening The three most common diagnostic modalities during stress testing are: Continuous EKG monitoring Echocardiography Nuclear imaging

IHD: ACS Ischemic Heart Disease: ACS Acute coronary syndrome (ACS) occurs when severe myocardial ischemia occurs for prolonged periods of time. The pain is similar to that of stable angina, however it typically lasts for more than 10 minutes and is not relieved with rest. ACS includes three distinct types (see next lecture): Unstable Angina (UA) 2) Non-ST elevation MI (NSTEMI) 3) ST elevation MI (STEMI)

IHD: Variant Angina Ischemic Heart Disease: Variant Angina Variant or “Pritzmetal’s” angina is a relatively rare syndrome that occurs due to severe vasoconstriction of the coronary arteries leading to myocardial ischemia due to decreased coronary flow. The etiology is unclear, but may relate to dysfunctional endothelial cells present in early atherosclerosis. Variant angina is more common in females, occurs most often in early morning hours (upon awakening), and results in ST elevation on EKG (not ST depression).

IHD: Variant Angina Ischemic Heart Disease: Variant Angina

IHD: Silent Ischemia Ischemic Heart Disease: Silent Ischemia Myocardial ischemia can occur in the absence of any symptoms! This is common in diabetics who have peripheral neuropathy making it difficult to feel cardiac chest pain. Elderly people may also frequently be asymptomatic during ACS.

Ischaemic heart disease Manifestations Sudden death Myocardial infarction Acute coronary syndrome Stable angina pectoris Heart failure Arrhythmia Asymptomatic

Ischaemic heart disease Epidemiology Commonest cause of death in the Western world. (up to 35% of total mortality) Over 20% males under 60 years have IHD Health in one study showed; 3% of adults suffer from angina 1% have had a myocardial infarction in the past 12 months

Ischaemic heart disease Aetiology

Ischaemic heart disease Aetiology—cont-- Fixed Age, Male, +ve family history Modifiable – strong association Dyslipidaemia, smoking, diabetes mellitus, obesity, hypertension Modifiable - weak association Lack of exercise, high alcohol consumption, type A personality, OCP, soft water (Atherosclerosis)

Ischaemic heart disease Pathophysiology

Ischaemic heart disease Pathophysiology Response to injury hypothesis ATHEROSCLEROSIS Accumulation of cholesterol within the vessel wall intima. Smooth muscle cell proliferation SCLEROSIS Expansion of fibrous tissue INFLAMMATION Chronic inflammatory cells migrate into wall, release cytokines GROWTH FACTORS/INFLAMMATORY MEDIATORS

Ischaemic heart disease Pathophysiology

Ischaemic heart disease Acute coronary syndromes Atherosclerosis Fatal / non-fatal AMI Coronary Artery spasm Unstable angina

Ischaemic heart disease Acute coronary syndromes Fatal AMI Small, fat rich plaques. Plaque RUPTURE. Thrombus in lipid core and on plaques surface. Vessel lumen OCCLUDED. Non-fatal AMI Plaque EROSION rather than rupture. OCCLUSIVE thrombus. Unstable angina Usually mod-severe stenosis. Multiple vessels. Collaterals often formed. Thrombus formation and vasoconstriction. Myocardial infarction may ensue

Ischaemic heart disease Risk factors and prevention

Ischaemic heart disease Risk factors and prevention Family History Smoking Hypertension Diabetes Mellitus Hypercholesterolaemia Lack of exercise PRIMARY PREVENTION

Ischaemic heart disease Relevance to dentistry IHD is common Subjects with IHD have more severe dental caries and periodontal disease – association or causation? Angina is a cause of pain in the mandible, teeth or other oral tissues Stress provokes ACS!

Chest Pain Myocardial ischaemia Site Jaw to navel, retrosternal, left submammary Radiation Left chest, left arm, jaw….mandible, teeth, palate Quality/severity tightness, heaviness, compression…clenched fists

Chest Pain Myocardial ischaemia Precipitating/relieving factors physical exertion, cold windy weather, emotion rest, sublingual nitrates Autonomic symptoms sweating, pallor, peripheral vasoconstriction, nausea and vomiting

Chest Pain Differential diagnosis Cardiac pathology Pericarditis, aortic dissection Pulmonary pathology Pulmonary embolus, pneumothorax, pneumonia Gastrointestinal pathology Peptic ulcer disease, reflux, pancreatitis, ‘café coronary’ Musculoskeletal pathology Trauma, Tietze’s Syndrome

Ischemic Heart Disease MI= Also called Heart attack Incidence = disease of old elderly (45% in 65 yrs. old) young ( 10% in 40yrs. Old), Sex = Male > Female Ethnic = same in African & American Risk factors Major modifiable- DM, HTN, Smoking, Hypercholesterolemia HRT for Postmenopausal females – will not protect the heart

Acute Myocardial Infarction 250,000 deaths per year. 150,000 presentations to hospital. 30% of deaths occur in the first 2 hours. (Cardiac muscle death occurs after 45 mins of ischaemia)

Ischemic Heart Disease Pathogenesis Coronary vessel occlusion Atherosclerosis with thrombus = MC cause ( 90% cases) Others = vasospasm (10%) Most important mechanism = dynamic changes in the plaque (rather than plaque size), Plaque disruption PLTS aggregation thrombus and VC (happens in minutes) Irreversible changes = after 30 minutes of ischemia ATP < 10% of normal Mechanism of cell death = necrosis ( Coagulative

Ischemic Heart Disease MI = Clinical Silent MI = DM, Elderly, Cardiac transplantation recipients, Typical features = Rapid, weak pulse and sweating profusely (diaphoretic), Dyspnea, chest pain Lab= Diagnostic Best markers = Troponins ( T & I), both sensitive and cardio – specific Next best – CK-MB Predictive CRP- >3mg/l – highest risk

Myocardial Infarction Partial or total occlusion of one or more of the coronary arteries due to an atheroma, thrombus or emboli resulting in cell death (infarction) of the heart muscle When an MI occurs, there is usually involvement of 3 or 4 occluded coronary

MI, Atheroma When there is an atheroma, as mentioned before there can be rupture resulting in thrombus formation because of the build up of platelets When there is breakage of the thrombus there is emboli formation An emboli can travel to the brain (cerebral infarct) can remain in the heart (myocardial infarct) or even travel to the extremities cutting off blood supply(Gangrene) As the area beneath the is disrupted atheroma hemorrhages, there can is increased risk of abscess formation and infection

Complications of Myocardial Infarctions Infarction leading to inability of the heart to function properly leading to Heart Failure Angina/Pain Cardiogenic shock Ventricular aneurysm and rupture Embolism Formation Arrhythmias  Myocardial Infarctions can lead to Ventricular Fibrillation (shockable!)

Sudden Death Sudden Death : 250,000 deaths in the US per year are caused by what is referred to as “sudden” cardiac death Sudden Cardiac Death is also known as a “Massive Heart Attack” in which the heart converts from sinus rhythm to ventricular fibrillation In V-Fib, the heart is unable to contract fully resulting in lack of blood being pumped to the vital organs V-Fib requires shock from defibrillator “SHOCKABLE RHYTHM”

MI - Types Transmural Full thickness Superimposed thrombus in atherosclerosis Focal damage Sub-endocardial Inner 1/3 to half of ventricular wall Decreased circulating blood volume( shock, Hypotension, Lysed thrombus) Circumferential

Plaque-Associated Thrombus Heart - Pathology Syndrome Stenoses Plaque Disruption Plaque-Associated Thrombus Stable angina >75% No Unstable angina Variable Frequent Non-occlusive Transmural MI Occlusive Subendocardial MI Widely variable Sudden death severe Often small

MI- chest pain

MI MI -Morphology light microscopy First 12 hrs. after MI – no change Up to 3 days = Coagulative necrosis, neutrophils 1-2 weeks = Granulation tissue ≥ 3 weeks = fine scar ≥ 2 months = dense scar EM – membrane disruption and Mitochondrial densities Special stain = TTC ( Triphenyl Tetrazolium chloride), Detects and stains Mahogany brown with Lactate dehydrogenase Unstained area = infarction Mahogany brown = viable White, glistening= scar Most common and nonspecific change in ischemia = sub-endocardial myocyte vacuolization

Ischemic Heart Disease TTC

MI- MICROSCOPY Up to 3 days duration Neutrophilic infiltrate One-day-old infarct Up to 3 days duration coagulative necrosis Neutrophilic infiltrate 1 -2 weeks >3 weeks Granulation tissue

Ischemic Heart Disease MI –Complications In 75% of Patients with MI Poor prognosis in = elderly, females, DM, old case of MI, Anterior wall infarct – worst, posterior –worse, Inferior wall – best 1. Arrhythmia = Ventr. Fibrillation – MC arrhythmia lead to sudden death in MI patients, before they reach hospital 2. pump failure – LVF, cariogenic shock, if >LV wall infarcts, lead to death ( 70% of hospitalized MI patients) 3.Ventricular rupture = Free or lateral LV wall – MC site, later cause false aneurysm, 4.True aneurysm = rupture is very rare 5.Pericarditis = Dressler’s syndrome ( Late MI complication) 6.Recurrence

Ischemic Heart Disease Sudden cardiac death = unexpected death in one hour due to cardiac causes with or without clinical symptoms Cause – Atherosclerosis ( 90%), others (10%) Romano- Ward syndrome – Long Q-T syndrome ( K+, Na+ channel defects) Mechanism- Most likely due to arrhythmias ( VF) Patients – young athletes, with Pul. HTN, IHD Morphology Prominent finding – increased heart mass Vacuolations in Sub – endocardial myocardium

Ischemic Heart Disease Chronic IHD = also called ischemic cardiomyopathy Patients = post heart transplant receipts, previous MI or CABG pts Cause =compromised ventricular function Morphology =vacuoles, Myocyte Hypertrophy Diagnosis= by exclusion