1.1k Coronary Artery Disease

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MEDICINE II 1.1K CORONARY ARTERY DISEASE: ACUTE & CHRONIC CORONARY SYNDROMES

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OBJECTIVES To discuss the pathophysiology, different clinical presentations and physical findings in coronary artery disease. To discuss the basic methods in diagnosing CAD To enumerate the management strategy in treating patients with CAD.

PATHOPHYSIOLOGY OF MYOCARDIAL ISCHEMIA

Coronary artery disease (CAD) generally refers to atherosclerosis of the coronary arteries that may results in significant obstruction to coronary blood supply leading to myocardial ischemia Myocardial ischemia refers to a condition in which there is an imbalance between the oxygen supply and oxygen demand of the myocardium usually due to a severe fixed or dynamic obstruction of the myocardial blood supply, or an increase in myocardial oxygen requirements, or both.

SPECTRUM OF CORONARY ARTERY DISEASE

PATHOGENESIS OF ATHEROSCLEROTIC PLAQUE Endothelial Dysfunction and Inflammation CLINICAL MANIFESTATIONS OF CHRONIC CORONARY ARTERY DISEASE  Symptoms  Physical examination  Biochemical tests  ECG  Other ancillary tests

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The Fatty Streak

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The Ruptured Plaque

ANGINA PECTORIS Angina pectoris is a discomfort of the chest or adjacent areas caused by myocardial ischemia Usually brought on by exertion or stress Constricting, crushing, heavy, squeezing in character Retrosternal in location but may radiate to other areas of the chest, ulnar surface of the arms, more commonly the left arm, epigastrium, and mandible Begins gradually and reaches its maximum over a few minutes before dissipating May be associated with dyspnea, faintness and easy fatigability

Symptoms Not Suggestive of Angina Pectoris  Pleuritic pain; brought on by respiratory movement or cough  Pain located in the middle or lower abdomen  Pain localized with one finger  Pain reproduced by movement or palpation of the chest wall  Constant pain lasting for days  Very brief episodes of pain lasting a few seconds  Pain radiating to the lower extremities Grading of Angina Pectoris Canadian Cardiovascular Society Classification Ordinary physical activity does not cause angina; angina occurs with strenuous, rapid, or prolonged exertion. Slight limitation of ordinary physical activity; angina occurs after walking > 2 blocks on the level or climbing > 1 flight of ordinary stairs at a normal pace and under normal conditions. Marked limitation of ordinary physical activity; angina occurs on walking 1 to 2 blocks on the level and climbing 1 flight of stairs at a normal pace and under normal conditions. Inability to carry on any physical activity without discomfort; angina may be present at rest.

I II

III IV

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DIFFERENTIAL DIAGNOSIS OF CHEST PAIN Angina pectoris Myocardial infarction

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1.1K CORONARY ARTERY DISEASE: ACUTE & CHRONIC CORONARY SYNDROMES

Aortic dissection Pulmonary embolism Acute pericarditis Acute pleuritis Severe pulmonary hypertension Gastroesophageal reflux Esophageal motility disorders Biliary colic Cervical radiculitis Costochondritis

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CORONARY FLOW RESERVE (STRESS) R1 = driving pressure of large epicardial arteries R2 = coronary arteriolar resistance R3 = wall tension in the subendocardium

PHYSICAL EXAM IN CHRONIC CAD Many patients with CAD have normal physical findings General: corneal arcus, xanthomas, xanthelasma, retinal arteriolar changes, elevated BP, diagonal earlobe crease, diminished arterial pulses and bruits Cardiac examination: During an episode of angina pectoris, one may detect a S3, paradoxical splitting of S2, transient systolic murmurs, and pulmonary rales. A displaced left ventricular impulse suggests ventricular dysfunction BIOCHEMICAL TESTS IN CHRONIC CAD Lipid profile  total cholesterol  low density lipoprotein (LDL)  high density lipoprotein (HDL)  triglycerides Fasting blood glucose Other biochemical markers:  Lipoprotein Lp(a)  Homocysteine level  High sensitivity C- reactive protein ELECTROCARDIOGRAM (ECG) IN CHRONIC CAD Resting ECG is normal in ≈ 50% of patients with chronic stable angina pectoris Most common ECG findings in chronic CAD are non-specific ST-T wave changes with or without Q waves Various arrhythmias, especially ventricular premature beats may be seen

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EXERCISE ECG Most widely used test to diagnose CAD Usually performed on a treadmill or bicycle Gives information not only on the presence or absence of ECG evidence of ischemia but also on exercise capacity, blood pressure and heart rate responses to exercise ECG findings of horizontal or downsloping ST segment depression is indicative of myocardial ischemia Accuracy of ECG diagnosis may be limited in patients with abnormal baseline ECG Treadmill exercise test Bicycle ergometry ABNORMAL STRESS ECG

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NON-INVASIVE STRESS TESTING Provides useful information to establish the diagnosis and estimate the prognosis in patients with chronic stable angina. Most helpful in patients considered to have a moderate probability of CAD based on clinical symptoms and normal ECG

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CORONARY FLOW RESERVE (REST) R1 = driving pressure of large epicardial arteries R2 = coronary arteriolar resistance R3 = wall tension in the subendocardium

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OTHER FORMS OF NON INVASIVE STRESS TESTING Nuclear Cardiology Techniques  Stress myocardial perfusion imaging 99 99  Uses either thallium, Tc sestamibi, or Tc tetrofosmin  Pharmacologic nuclear stress testing  For patients unable to exercise adequately  May use Dipyridamole, Adenosine, or Dobutamine to “stress” the heart  Positron emission tomography  Useful to detect myocardial viability Stress Echocardiography  Exercise echocardiography  Pharmacologic stress echocardiography Nuclear Gamma Camera Radionuclide Myocardial Perfusion Imaging Stress Echocardiography

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1.1K CORONARY ARTERY DISEASE: ACUTE & CHRONIC CORONARY SYNDROMES

NEWER NON-INVASIVE IMAGING TECHNOLOGIES FOR CAD DIAGNOSIS  Computed tomography (CT)  Electron beam CT coronary calcium scoring  Multi-slice CT coronary angiography  Computed Tomography (CT) Coronary Angiogram  Magnetic resonance imaging  Cardiac Magnetic Resonance Imaging (MRI)

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INVASIVE TESTING IN CAD Cardiac catheterization and coronary angiography  Definitive diagnosis of CAD  Precise assessment of anatomical severity of CAD  Assessment of left ventricular function  Requires the insertion of a catheter in a peripheral artery which is advanced intravascularly to the heart under fluoroscopic guidance Intravascular ultrasonography (IVUS) Coronary Angiogram Intravascular Ultrasound

The Vulnerable Coronary Atherosclerotic Plaque

Pathologic Findings in Acute Coronary Syndrome

ACUTE CORONARY SYNDROMES Acute coronary syndrome  Refers to any constellation of clinical symptoms that are compatible with acute myocardial ischemia  a spectrum of conditions that includes: Unstable angina (UA) Non ST elevation myocardial infarction (NSTEMI); also referred to as non Q wave MI ST elevation myocardial infarction (STEMI); also referred to as Q wave MI  linked by a common pathogenesis, clinical presentation, and therapeutic approach Coronary Angiographic Findings in Unstable Angina / Non ST Elevation MI SPECTRUM OF CORONARY ARTERY DISEASE

PATHOGENESIS OF ACUTE CORONARY SYNDROME Evolution of the Atherosclerotic Plaque Pathologic Findings in Non ST-Elevation Myocardial Infarction

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1.1K CORONARY ARTERY DISEASE: ACUTE & CHRONIC CORONARY SYNDROMES

Coronary Angiographic Findings of A Patient With Anterolateral ST-Elevation Myocardial Infarction

ECG FINDINGS O ST DEPRESSION AND T WAVE INVERSION

Pathologic Findings in Acute Myocardial Infarction (ST-elevation or Q-wave MI) MARKERS OF CARDIAC INJURY Cardiac markers are macromolecular components of cardiac myocytes, consisting mainly of enzymes or contractile proteins, that are released into the circulation during myocardial necrosis or injury. Currently Available Cardiac Markers  Aspartate Aminotransferase (AST)  Lactate Dehydrogenase (LDH) › LD1 isoenzyme  Creatine Kinase (CK) › CK-MB isoenzyme › CK isoforms  Myoglobin  Troponins › Troponin T (cTnT) › Troponin I (cTnI) CLINICAL FEATURES OF ACUTE CORONARY SYNDROME WHO Criteria for the Diagnosis of MI  a clinical history of ischemic-type chest discomfort  changes on serially obtained ECG tracings  rise and fall of serum cardiac markers Principal Presentations of Acute Coronary Syndrome  Rest angina - usually >20 minutes  New-onset angina - at least CCS Class III  Increasing angina - previous angina that has become distinctly more frequent, longer in duration, or lower in threshold (increased by > 1 CCS Class to at least CCS Class III) Acute Coronary Syndrome: ECG Findings  ST elevation with T wave changes with subsequent development of Q wave  New bundle branch block  ST depression or T wave inversion  Nonspecific ST- T changes  Normal ECG

ACUTE CORONARY SYNDROMES

ECG FINDINGS OF ST ELEVATION     

MANAGEMENT OF CORONARY ARTERY DISEASE Lifestyle modification Control coronary risk factors Management of extracardiac contributing factors Pharmacologic therapy Coronary revascularization

NON PHARMACOLOGIC MEASURES IN THE MANAGEMENT OF CORONARY ARTERY DISEASE  Lifestyle modification  Maintain ideal body mass index 2  BMI = weight (kg)/height (m)  Regular, aerobic physical exercise  Minimum of 30-45 mins 4x week  Healthy heart diet  Low salt, low fat, high fiber  Smoking cessation

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CONTROL CORONARY RISK FACTORS Hypertension  Goal is to maintain BP ≤ 130/80  In pts with CAD, beta-blockers, calcium antagonists, or ACE inhibitors preferred Diabetes mellitus

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1.1K CORONARY ARTERY DISEASE: ACUTE & CHRONIC CORONARY SYNDROMES

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Maintain normal fasting and post prandial glucose, and glycosylated hemoglobin; ACE or ARB inhibitors preferred Dyslipidemia  Goals are more stringent in pts with CAD :  Total cholesterol = < 200%  LDL = < 70 mg%  HDL = > 45 mg%  Triglycerides < 150 mg%  Statins are drug of choice

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EXTRA CARDIAC FACTORS WHICH MAY PROVOKE ANGINA Fever Hypertension Anemia Hypoxia Tachyarrhythmias Thyrotoxicosis Illicit drug use

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TREATMENT OF ACUTE CORONARY SYNDROME ACUTE CORONARY SYNDROME : GENERAL MEASURES Hospital admission Oxygen therapy Activity restriction Diet Bowel and bladder care Sedatives and anxiolytics

PHARMACOLOGIC THERAPY OF ACUTE CORONARY SYNDROME  Analgesics  Anti-thrombotic drugs  Unfractionated heparin  Low molecular weight heparin  Glycoprotein IIB/IIIA platelet receptor inhibitor  Thrombolytic agents*  Streptokinase  t-PA  Antiplatelet agents  Aspirin  Clopidogrel (Plavix)  Ticlopidine (Ticlid)  Ticagrelor  Prasugrel  Anti-ischemic drugs  Nitrates – sublingual, oral, topical  Beta-blockers  Calcium channel blockers  Angiotensin converting enzyme inhibitors

EFFECT OF ANTI-ISCHEMIC DRUGS

PHARMACOLOGIC THERAPY OF CORONARY ARTERY DISEASE: ANTIISCHEMIC AGENTS

PHARMACOLOGIC THERAPY OF ISCHEMIC HEART DISEASE: ACE INHIBITORS

PHARMACOLOGIC THERAPY OF ISCHEMIC HEART IDEASE: ANTI PLATELET AGENTS

PHARMACOLOGIC THERAPY FOR AMI: ANALGESICS

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1.1K CORONARY ARTERY DISEASE: ACUTE & CHRONIC CORONARY SYNDROMES

PHARMACOLOGIC THERAPY OF UNSTABLE ANGINA OR NON Q-WAVE MI: HEPARINS

Triage of Patients with Acute ST Elevation MI

Inhibition of Platelet Aggregation By Glycoprotein IIb/IIIa Receptor Antagonists

PHARMACOLOGIC THERAPY OF UA OR NSTEMI: PLATELET GLYCOPROTEIN IIb/IIIa INHIBITORS

Contraindications to Thrombolytic Therapy  Absolute Contraindications  Active internal bleeding (except menses)  Suspected aortic dissection  Recent head trauma or known intracranial neoplasm  History of hemorrhagic CVA  Major surgery or trauma < 2 weeks  Relative contraindications  Blood pressure >180/110  Active peptic ulcer disease  History of CVA  Known bleeding diathesis or current anticoagulant use  Prolonged traumatic CPR  Diabetic hemorrhagic retinopathy  Pregnancy  Prior exposure to STK or APSAC

ANTI-PLATELET & ANTI-THROMBOTIC THERAPY IN ACUTE CORONARY SYNDROME

NON PHARMACOLOGIC THERAPY OF ISCHEMIC HEART DISEASE  Percutaneous Transluminal Coronary Angioplasty (PTCA) with or without coronary stent implantation  Coronary Artery Bypass Grafting (CABG) TREATMENT OF ACUTE CORONARY SYNDROME Q-WAVE (ST-ELEVATION) MI Management of ST Elevation Acute MI

- Coronary Stents

- PTCA With Stenting of the RCA

- Coronary Artery Bypass Grafting (CABG) __________________________________________________________________ END OF TRANX

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