Chronic forms of coronary artery disease Sepši Milan sepsim@gmail.com University Hospital Brno, Department of Internal Medicine and Cardiology 2 CAD is the first cause of death 0 1 2 3 4 5 6 7 Ischemic heart disease Cerebrovascular disease Low respiratory tract infections Gastrointestinal infections Perinatal problems COPD Tuberculosis Scarlet fever Car accidents Lung Tumor N.Deaths/milion 6,26 4,38 4,30 2,95 2,44 2,21 1,96 1,06 1,00 0,95 Murray & Lopez. Lancet. 1997;349:1269-1276 3 Pathophysiology Vascular resistance (metabolic control, humoral and neural factors) Coronary blood flow (duration of diastole / pressure gradient) Oxygen demand Oxygen suply • Heart rate • Contractility • Systolic wall stress 4 Timeline Foam Cells Fatty Streak Intermediate Lesion Atheroma Fibrous Plaque Complicated Lesion/ Rupture Adapted from Pepine CJ. Am J Cardiol. 1998;82(suppl 104). From First Decade From Third Decade From Fourth Decade Endothelial Dysfunction 5 Diagnosis • History of patient • Familiar history • Personal history • Sex ( M>F), age • pain • Physical examination • Clinical test • Risk assessment (low, probable, high) 6 Estimate of CAD Probability (Duke Clinical Score) • age, gender and pain type were the most powerful predictors • other predictors • smoking (defined as a history of smoking half a pack or more of cigarettes per day within five years of the study or at least 25 pack-years) • Q wave or ST-T-wave changes • hyperlipidemia (defined as a cholesterol level >250 mg/dL / 6,4 mmol/L) • diabetes (glucose >140mg/dL / 7,8 mmol/L). Of these risk factors, diabetes had the greatest influence on increasing risk.Am J Med 1983;75:771-80 ; Am J Med 1990;89:7-14 Ann Intern Med 1993;118:81-90 7 Estimate of CAD Probability • a 64-year-old man with typical angina has • a ???? % likelihood of having significant CAD • a 32-year-old woman with nonanginal chest pain has • a ???? % chance of CAD N Engl J Med 1979;300:1350-8 94 1 Duke Clinical Score 9 Risk factors • Major independent risk factors • Advancing age • Tobacco smoking • Diabetes mellitus • Elevated total and LDL-cholesterol / Low HDL cholesterol • Hypertension • Conditional risk factors • Elevated serum homocysteine/lipoprotein(a)/serum triglycerides • Inflammatory markers (eg, C-reactive protein) • Prothrombic factors (eg, fibrinogen) • Small LDL particles • Predisposing risk factors • Abdominal obesity • Ethnic characteristics • Family history of premature CAD • Obesity + Physical inactivity • Psychosocial factors 10 Angina pectoris • Typical angina (definite) • 1. Substernal chest discomfort with a characteristic quality and duration that is • 2. Provoked by exertion or emotional stress and • 3. Relieved by rest or nitroglycerin. • Atypical angina (probable) • Meets two of the above characteristics • Noncardiac chest pain • Meets one or none of the typical anginal characteristics. A pain or discomfort in the chest or adjacent areas caused by insufficient blood flow to the heart muscle. J Am Coll Cardiol. 1983;1:574, Letter 11 Pain - description • (1) location • located substernally or just to the left of the sternum. • Less often - over the precordium, rarely only to the apex • Nevertheless - can be located anywhere from the epigastrium to the neck; rarely, it may be located only in the neck, throat, arm, or back. • radiates down the arms / or to the neck, jaw, teeth, shoulders, or back, left side is more common - characteristically down the ulnar aspect of the arm • (2) quality • deep visceral pressure or squeezing sensation, rather than sharp or stabbing or pinprick-like pain. • Angina is almost never sharp or stabbing, and usually does not change with position or respiration. • (3) duration of the discomfort • 10-30 sec plateau and minutes to dissapear • (4) inciting factors • physical activity, emotions, eating, or cold weather • (5) factors relieving the pain 12 Grading of Angina of Effort by the Canadian Cardiovascular Society I. “Ordinary physical activity does not cause … angina,” such as walking and climbing stairs. Angina with strenuous or rapid or prolonged exertion at work or recreation. II. “Slight limitation of ordinary activity.” Walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, or in cold, or in wind, or under emotional stress, or only during the few hours after awakening. Walking more than 2 blocks on the level and climbing more than one flight of ordinary stairs at a normal pace and in normal conditions. III. “Marked limitation of ordinary physical activity.” Walking one to two blocks on the level and climbing one flight of stairs in normal conditions and at normal pace. IV. “Inability to carry on any physical activity without discomfort -- anginal syndrome may be present at rest.” Circulation 1976; 54:522-523 13 Stable / Unstable angina • Stable: duration > 60 days • Unstable angina: rest angina • severe new-onset angina • or prior angina increasing in severity • the acute coronary syndromes of unstable angina and non–ST-segment elevation myocardial infarction were linked • Now. ACUTE CORONARY SYNDROME 14 Silent ischemia • Asymptomatic ischemic episodes • The prevalence : approximates 40 percent in patients with chronic stable angina • ST-segment depression on ECG monitoring • Pathophysiology of Silent Ischemia: ? less severe ischemia? , neuropaty (diabetic) 15 Diagnosis – tests I. • Resting 12-lead ECG (normal in 50% pts) • Q waves, ST segment denivelation • Echocardiography • impaired systolic LV function • regional and global abnormalities 16 17 18 19 Echocardiography – lateral wall Courtesy of: MUDr. Jan Maňoušek 20 Diagnosis – tests II • Exercise ECG stress testing • Ergometry, treadmill , hand-grip • Ecg, BP, heart rate • dificulties in woman • Myocardial Perfusion Imaging • thallium -201 (201Tl); technetium-99m (99mTc) • single-photon emission computed tomography (SPECT) • Stress Echocardiography - dobutamine • (1) decrease in wall motion in one or more LV segments with stress • (2) diminution in systolic wall thickening in one or more segments during stress, and • (3) compensatory hyperkinesis in complementary (nonischemic) wall segments 21 22 23 Comparison of Stress Tests • meta-analysis on 44 articles (published between 1990 and 1997) • Sensitivity Specificity • ECG 52% 71% • Echocardiography 85% 77% • Scintigraphy 87% 64% • exercise echocardiography had significantly better discriminatory power than exercise myocardial perfusion imaging JAMA 1998;280:913-20 24 Diagnosis – coronary angiography • Who? • pain + pathological non-invasive tests • Clinical probability ( smoker, obesity, familiar history, male) • Low LVEF • Other problem: arrhythmias, unstability • rationale is to identify high risk patients in whom coronary angiography and subsequent revascularization might improve survival 25 26 Coronary Angiography 27 Chronic Stable Angina Treatment Objectives • To reduce the risk of mortality and morbid events • To reduce symptoms • anginal chest pain or exertional dyspnea • palpitations or syncope • fatigue, edema or orthopnea 28 Treatment • Non – pharmacological • Revascularisation • Coronary artery bypass grafting (CABG) • percutaneous coronary intervention (PCI, PTCI) • Heart transplantation • Pharmacological • Betablockers • antiplatelet agens • Lipid lowering agens • angiotensin-converting enzyme inhibitor ACEI • Nitroglycerin / nitrates • (Calcium – antagonist) 29 Indications of revascularisation 1. To be candidate for revascularization procedure, one must have symptomatic or objective signs of ischemia. 2. Indications for PTCA or CABG may vary from one center to another according to experience, skills and results. 3. Definite indications for CABG: LM disease and 3 VD with proximal stenosis. 4. Definite indications for PTCA: SVD (apart from ostial LAD), favourable morphology . 30 Procedure • Sheath in femoral, radial or brachial artery • diameter sheath (usually 6F, but also 5 to 8) • guiding catheter • guide wire 0.014 inch • balloon • stent 31 PCI - ACD Courtesy of: MUDr. Roman Miklík, Ph.D. 32 Coronary Artery Bypass Graft Surgery • Coronary artery bypass grafts (CABG): shunt blood from the aorta to the coronary artery, beyond an area of severe narrowing or occlusion • CABGs can be constructed from veins or arteries • Saphenous vein grafts (SVG) are conduits made by harvesting a piece of vein from the patient’s leg and attaching it between the aorta and coronary artery • Arterial bypass grafts involve re-routing an artery from its normal course and attaching it to the coronary artery • Internal Mammary Artery • Gastroepiploic Artery • Radial Artery 33 Current Medical State of SVG Disease • Average lifespan for a vein graft is 5-10 years • 50% of SVGs will be occluded within 10 years • 75% will develop severe narrowing in same period • SVG lesions presenting within the first year after surgery are typically caused by intimal hyperplasia • respond well to balloon dilatation • Late vein graft stenoses are more commonly caused by diffuse atherosclerosis • friable plaque and thrombus tend to fragment and embolize into distal coronary vessels 34 Ischemia Trial 2019 • Patients with stable ischemic ischemic heart disease and moderate to severe ischemia were randomized to routine invasive therapy (n = 2,588) versus optimal medical therapy (n = 2,591) • Duration of follow-up: 3.3 years • Mean patient age: 64 years • Inclusion: Moderate to severe ischemia on noninvasive stress testing • Presented by Judith S. Hochman at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 16, 2019. 35 Ischemia Trial ISCHEMIA trial showed that heart procedures added to taking medicines and making lifestyle changes did not reduce the overall rate of heart attack or death compared with medicines and lifestyle changes alone. 36 Treatment • Non – pharmacological • Revascularisation: CABG / PCI • heart transplantation • Pharmacological • antiplatelet agens • Betablockers • ACEI • Calcium – antagonist • Lipid lowering agens • Nitroglycerin / nitrates 37 Treatment – antiplatelet agens • Cyclooxygenase inhibitors • Aspirin (Acetylosalicylic acid) 100 mg daily • Adenosine diphosphate (ADP) receptor inhibitors 6-12 month after MI • Ticagrelor (Brilique) • Prasugrel (Efient) • Clopidogrel 75 mg daily • (Ticlopidine) 38 Treatment - betablockers •Cardioselective •Metoprolol: 100-400 mg •Atenolol: 50-200 mg •Betaxolol 5-40 mg (long half-life) •With intrinsic sympathomimetic activity •Acebutolol 400-1200 mg •Non-selective (with alfa α-blocking activity) •Carvedilol 25-100mg 39 Treatment - betablockers • Freemantle Nick, et al: β Blockade after myocardial infarction: systematic review and meta regression analysis BMJ 1999;318:1730 •Systematic review of randomised controlled trials. •Subjects: Patients with acute or past myocardial infarction. •Intervention: βBlockers compared with control. •Main:outcome measures All cause mortality and non-fatal reinfarction •We identified a 23% reduction in the odds of death in long term trials (95% confidence interval 15% to 31%) REACH Registry (JAMA 2012) • REduction of Atherothrombosis for Continued Health 3 cohorts (44 708 patients): •14 043 patients with known prior MI (31%) •12 012 with known CAD without MI (27%) •18 653 with CAD risk factors only (42%) • endpoint: composite of cardiovascular death, nonfatal MI, and nonfatal stroke •Bangalore S, Steg G, Deedwania P, et al; REACH Registry Investigators. JAMA. 2012;308(13):1340-1349 4040 the same for BB and non BB 41 Treatment : lipid lowering agents 42 Treatment - nitrates • tolerance is a problem • Nitroglycerin 0.4 mg spray (Aborts acute attacks; headaches, hypotension ) • Nitroglycerin 0.4–0.6 mg SL • Nitroglycerin 0.1–0.6 mg/h patches Prophylactic therapy • Isosorbide dinitrate 10–60 mg three times daily • Isosorbide mononitrate 20 mg twice daily Take 7 h apart, slow release form – once daily • Night: molsidomin 2-8 mg (vasodilators) 43 Treatment : ca blockers • Calcium Channel Blockers: • Heart Rate Lowering • Verapamil 120–480mg Heart-rate lowering; AV block, heart failure, constipation • Dihydroperidine Calcium Channel Blockers • Amlodipine 5–10mg Least myocardial depression • Felodipine 5–20mg High vascular selectivity 45 Alternative Diagnoses to Angina for Patients with Chest Pain I • Non-Ischemic CV: aortic dissection, pericarditis • Pulmonary – pulmonary embolus – pneumothorax – Pneumonia, pleuritis • Chest Wall / backbone – Costochondritis, fibrositis, rib fracture – sternoclavicular arthritis – herpes zoster • Gastrointestinal – Esophageal: esophagitis, spasm, reflux – Biliary: colic, cholecystitis, choledocholithiasis, cholangitis – Peptic ulcer / Pancreatitis 46 • Gastrointestinal • Esophageal – esophagitis – spasm – reflux • Biliary – colic – cholecystitis – choledocholithiasis – cholangitis • Peptic ulcer • Pancreatitis Alternative Diagnoses to Angina for Patients with Chest Pain II 47 Variant (Prinzmetal’s) angina • Spasmus of vessels • Provocation during coronarography (ergonovine=ergometrine intra arterially) • Ca blockers (verapamil) 48 49 Treatment • A = Aspirin and Antianginal therapy • B = Beta-blocker and Blood pressure (BP) • C = Cigarette smoking and Cholesterol • D = Diet and Diabetes • E = Education and Exercise •Therapy (risk reduction of new MI) •ASA (clopidogrel / ticlopidin) : -25% •BB risk reduction of new MI: -20% ? •ACEI risk reduction of new MI: -25 •Statins risk reduction of new MI: -30% 50 CAD with heart failure Courtesy of: MUDr. Roman Miklík, Ph.D. 51 CAD with heart failure • Diagnosis: echo, CT scan, coronarography • Therapy: revascularisation • Therapy of heart failure • diuretics • BB • ACEI • ASA • CRT / ICD 52 Arrhythmias - supraventricular • Atrial fibrillation • Th: Beta blockers /propafenone/ verapamilum/ amiodarone • Radiofrequency ablation • Sick sinus syndrome • Atrio ventricular block • Pacemakers (VVI, DDD,CRT) 53 Arrhythmias - ventricular • Ventricular extrasystoly • > 10 per hour • NSVT • Ventricular tachycardia / fibrillation • Sudden cardiac death • Therapy: • ICD • Amiodarone / BB 54 Risk factors (HT, LDL, DM, etc) Atherosclerosis LVH CAD Myocardial ischaemia Coronary thrombosis Myocardial infarction Arrhythmia & Loss of muscle Remodelling Ventricular dilatation Endstage heart disease Heart failure • Revascularisation • ASA +(ADP blockers) • BB / ACEI • Statins • No smoking • Correction of HT and DM 55 Thank You for You attention!