angina-srdíčko Treatment of ischemic heart disease – coronary artery disease (CAD) Regina Demlova angina-srdíčko angina-srdíčko Ischemic heart disease Group of diseases with the presence of myocardial ischemia, which occurs on the basis of the pathological process in the coronary vessels. Reducing the flow in coronary arteries>>> ischemia angina-srdíčko myokarditida2 koronární cévy 2 angina-srdíčko Ischemic heart disease The cause •Organic - atherosclerosis (95%), thrombus, embolism, arteritis, etc. •Functional - coronary spasm •Combined Atherosclerotic plaque>> reduce the flow>> ischemia angina-srdíčko angina-AS angina-ucpání2 angina-ucpání3 angina-ischémie Ischemic heart disease unstable AP nonQIM QIM (cTnI < 0,4 ug/l) (cTnI >0,4 ug/l) (cTnI > 0,4ug ) angina-srdíčko Risk factors: •Should not be influenced - age, gender, family history •Should be influenced - hypertension, hyperlipoproteinaemia, smoking, stress, obesity, physical inactivity, dietary habits Ischemic hearth disease kouření obezita-muž angina-srdíčko Classification: •acute (unstable) - acute myocardial infarction, unstable angina, sudden death •chronic (stable) - angina pectoris (exertional, mixed, variant), silent ischaemia, arrhythmic forms • Ischemic hearth disease angina-srdíčko Angina pectoris: •Most frequent clinical manifestations of IHD - caused by the myocardial ischemia, in which the patient has chest pain (stenocardia). • Imbalance between myocardial oxygen supply and demand Ischemic hearth disease angina-srdíčko Angina pectoris Main cause: •atherosclerotic plaque in coronary artery lumen stenosis lower than 50% - insignificant lumen stenosis above 50% - a significant lumen stenosis above 95% - critical angina-AS angina-srdíčko Angina pectoris Classification of severity: I. stenocardia provoked by extraordinary exertion II. stenocardia provoked more than usual exertion III. stenocardia provoked by regular exertion stenocardia IV. stenocardia provoked by minimal exertion or at rest angina-srdíčko Angina pectoris Clinical picture: constringent pain with / without feeling a lack of breath, pain with the propagation to the back, neck, shoulders, upper extremities. Usually it is a link to the previous load (walking, stress, food, ....) Typically takes a few minutes and gradually subsides after removal causing torque. • angina-bolest3 angina-bolest angina-bolest2 angina-srdíčko Angina pectoris Diagnosis: History - family, personal, pharmacological, social.. Problems - duration, time from first occurrence of pain, frequency, repetition, connection to the load, etc. Complete clinical examination, exclusion of non-cardiac etiology problems (nerve, muscle, gastrointestinal, pulmonary, other ... ..) Laboratory signs - Troponin-I, CK-MB • angina-srdíčko Angina pectoris Diagnostic procedures: angina-změny ekg ECG – at rest and during exercise, 24-hour ambulatory monitoring, during of angina found in a typical case of ECG changes (depression / ST segment elevation), between angina symptoms ECG is negative. ekg2 Ergometer stress test ergometrie angina-pozadí angina-srdíčko Angina pectoris Diagnostic procedures: • Echocardiography: at rest and during the exercise • Coronary angiography – used to directly view the coronary field using a contrast agent injected into coronary arteries, allowing accurate identification of narrowing or occlusion vessel, its significance, may be determined by the residual flow of the affected artery koronarografie koronárky2 angina-srdíčko Treatment of CAD Objective: •to improve the quality of life •to improve patient prognosis • Methods: 1st: stopping or slowing progress of atherogenesis 2nd: improve the flow of ischemic myocardium 3rd: prevention of vascular thrombus occlusion angina-srdíčko Treatment of CAD •nonpharmacologic - lifestyle changes • •pharmacological - drug therapy • •intervention - PTCA with / without stent - surgical revascularization angina-srdíčko Treatment of CAD Non-pharmacological: Motion mode - aerobic (running, swimming, cycling, ....) Dietary measures - change in eating habits (limit saturated fats, increase the proportion of unsaturated fats, fish, vegetables, fruits) Abstinence of smoking, alcohol in moderation Mental relaxation - sports, culture, yoga, psychotherapy Control of diabetes and hypertension 319788 cien-dieta joga tonometr-30 premium angina-srdíčko Treatment of CAD Interventions: • Percutaneous transluminal coronary angioplastic (PTCA) • The principle consists from delivery of a catheter (thin tube - at the end of the cylindrical balloon) into the narrowed or closed coronary artery and the balloon expands narrow blood vessels. The next step may be followed by stent (metallic reinforcement) in place of the previous narrowing. • Critical stenosis of the left coronary artery solved successfully by PTCA with stent implantation. PTCA2 n na peripheral or coronary stents (a scaffold) placed into narrowed, diseased peripheral or coronary arteries that slowly releases a drug to block cell proliferation. n nThe stent is usually placed within the peripheral or coronary artery by an Interventional cardiologist or Interventional Radiologist during an angioplasty procedure. n Drug-eluting stents – DES nCypher sirolimus nTaxus paclitaxel nBiomatrix, Nobori biolimus nXience everolimus nEndevour tacrolimus n Drug-eluting stents – DES angina-srdíčko Treatment of CAD Methods of interventional treatment: • Surgical revascularization Coronary artery bypass is the process of restoring the flow of blood to the heart. The surgical procedure places new blood vessels around existing blockages to restore necessary blood flow to the heart muscle. Critical stenosis of the left coronary artery bypass solved successfully by surgery. bypass bypass2 bypass3 angina-srdíčko Treatment of CAD Methods of pharmacological treatment: 1st: stopping or slowing progress of atherogenesis 2nd: improve the flow of ischemic myocardium 3rd: prevention of vascular thrombus occlusion angina-srdíčko Methods of pharmacological treatment: 1st: stopping or slowing progress of atherogenesis 1. control of risk factors: - correction of BP – antihypertension th. - corrections of lipids – hypolipidemics - DM – glucose control - antidiabetics angina-srdíčko Methods of pharmacological treatment: 2nd: improve the flow of ischemic myocardium smooth muscle relaxation of coronary artery stenosis slowing the heart rate - a reduction of metabolic demands reduction of myocardial contractility - improving coronary perfusion nitrates, beta-blockers, Ca-channel blockers, If-channel blockers angina-srdíčko Methods of pharmacological treatment: 1. 3rd: Prevention of vascular thrombus occlusion Antiplatelet/anticoagulants, such as aspirin or warfarin angina-srdíčko Treatment of CAD Methods of pharmacological treatment: 1st: stopping or slowing progress of atherogenesis 2nd: improve the flow of ischemic myocardium 3rd: prevention of vascular thrombus occlusion Hypolipidemics nStatins: inhibition of HMGCoA (3-OH-3 CH3 glutaryl coenzyme A) reductase. nFibrates: activate lipoprotein lipase, reduces VLDL and increase HDL nEzetimibe: blocks absorption of Cholesterol in the intestine nNiacin: blocking the breakdown of adipose tissue (inhibition of lipolysis) nResin: inhibiting resorption of bile acids angina-srdíčko Treatment of CAD Methods of pharmacological treatment: 1st: stopping or slowing progress of atherogenesis 2nd: improve the flow of ischemic myocardium 3rd: prevention of vascular thrombus occlusion angina-srdíčko Methods of pharmacological treatment: 2nd: I . improve the flow and perusion of ischemic myocardium - smooth muscle relaxation of coronary artery stenosis II . Reduce its metabolic demand - slowing the heart rate reduction of myocardial contractility • •I+II : nitrates, Ca-channel blockers •II : beta-blockers + If-channel blockers • Nitrates nNitroglycerin was synthesized by the chemist Ascanio Sobrero in 1847 nNitroglycerin is converted to nitric oxide in the body by mitochondrial aldehyde dehydrogenase nNO - nitric oxide - identical to the 'endothelium-derived relaxing factor' (EDRF) - is a natural vasodilator ( stimulation of guanylate cyclase of smooth muscle - relaxation-vasodilatation) NO guanylate cyclase → ↑cGMP ↑ ↓ relaxation - vasodilitation Endothelial cell Smooth muscle Nitrates = nitric oxid Enzymatic step – reaction with tissue sulfhydryl (-SH) groups angina-srdíčko Nitrates •Effects: local x systemic • LOCAL: the direct effect on coronary artery tone - dilation of coronary arteries SYSTEMIC: venorelaxation – consequent reduction in central venous pressure – reduce preload Relaxation of lareger muscular arteries – reduce afterload angina-srdíčko Nitrates • •Adverse reactions: • •headache, orthostatic hypotension, • •onset of tolerance (possibly partly because of depletion of free –SH groups), mainly longer-acting drugs angina-srdíčko Nitrates • •Representatives: • Nitroglycerin (glyceryl trinitrate) - rapidly inactivated by hepatic metabolism -well absorbed from the mouth – is taken as a tbl. under the tongue or sublingual spray – effects within few minutes -Effectiveduration of action app. 30 minutes -Well absorbed through the skin – transdermal patch angina-srdíčko Nitrates • •Representatives: • Isosorbite 2-mononitrate (ISMN) longer acting – half-life app. 4 hours , the same farmacological action I: prophylaxy twice daily (morning, lunch time – to avoid tolerance) Isosorbit 2,5-dinitrate (ISDN) - iv Molsidomin (does not produce tolerance, use of overnight) nProphylaxis of angina n nTreating the patients with unstable angina n nslowing the heart rate and reduction of myocardial contractility • n n n Beta - blockers nCompetitive antagonists (intrinsic activity = 0) or partial agonists (ISA - intrinsic sympathomimetic activity) n nNon-selective or cardioselective (primary blocs of b1 receptors) n n Beta - blockers Non-selective (b1 + b2) propranolol (Cardio)selective (b1) metoprolol Non-selective with ISA (b1 + b2) S ISA pindolol (Cardio)selective (b1) with ISA acebutolol Combining a + b blocade = b-blockers of II.generation labetalol classification Beta blockers Indication: angina pectoris, hearth failure with titration tacharrhytmia, glaukom Contraindication: absolute: AV block (grade 2 or 3), asthma, angina-srdíčko Adverse events -Bronchoconstriction -Bradycardia -Hypoglycaemia -Fatique - angina-srdíčko If blockers –SA node Heart rate is determined by spontaneous electrical pacemaker activity in the sinoatrial node controlled by the If current (f is for "funny", so called because it had unusual properties compared with other current systems known at the time of its discovery) angina-srdíčko If blockers –SA node Ivabradine acts on the If ion current, which is highly expressed in the sinoatrial node. If is a mixed Na+–K If is one of the most important ionic currents for regulating pacemaker activity in the sinoatrial (SA) node. angina-srdíčko Ivabradine (PROCORALAN) • •selectively inhibits the pacemaker If current in a dose-dependent manner. Blocking this channel reduces cardiac pacemaker activity, slowing the heart rate and allowing more time for blood to flow to the myocardium. angina-srdíčko Ivabradine – indication : I: Symptomatic treatment of chronic stable angina pectoris in coronary artery disease adults with normal sinus rhythm. -in adults unable to tolerate or with a contra-indication to the use of beta-blockers - - or in combination with beta-blockers in patients inadequately controlled with an optimal beta-blocker dose and whose heart rate is > 60 bpm. angina-srdíčko Calcium-channel blockers (CCB) •works by blocking voltage-gated calcium channels in cardiac muscle and blood vessels. •↓ intracellular calcium leading to ↓ cardiac contractility •In blood vessels ↓ vascular smooth muscle and therefore ↑ vasodilation. Vasodilation decreases total peripheral resistance. angina-srdíčko Calcium-channel blockers (CCB) •3 chemically distinct classes: • -Phenylalkylamines -Benzothiazepines -Dihydropyrimidines - - Phenylalkylamine: verapamil Preferentially affects Ca-channel in hearth Indications: antiarrhytmics Contraindications: absolute: AV block (grade 2 or 3), heart failure relative: bradycardia below 50/min, concomitant with BB Non DHP CCB Benzithiazepiny : diltiazem Affects both Ca-channel in hearth and in vessels Indications: angina pectoris Contraindications: absolute: AV block (grade 2 or 3), heart failure relative: bradycardia below 50/min, concomitant with BB Non DHP CCB DHP CCB Dihydropyridine CCB Indications: elderly - angina pectoris, coronary disease of lower extremities, atherosclerotic carotid disability Contraindications: relative: tachyarrhythmias, heart failure Calcium-channel blockers (CCB) Class 1st generation 2nd generation Fenylalkylamines Benzothiazepines Dihydropyridines Verapamil Diltiazem Nifedipin Verapamil SR Diltiazem SR Nifedipin GITS Isradipin SRO Felodipin Nitrendipin Nilvadipin Nisoldipin Nimodipin Amlodipin Lacidipin angina-srdíčko Calcium-channel blockers (CCB) ADRs: results from vasodilation and the effect on the conduction system •headache, orthostatic hypotension, palpitations, swollen ankles, •AV block non-DHP in combination with beta-blockers, significant bradycardia angina-srdíčko Combination of antianginous drugs • Nitrates + beta-blockers – a suitable combination • Nitrates + CCB – need BP corrections • Beta-blockers+ CCB – a suitable, but ! AV block non-DHP in combination with beta-blockers, significant bradycardia •