Cardiovascular Dysfunction, Heart Failure and Hypertension Cardiac Anatomy Pathophysiology and Pharmacology 2011 JOHN RAMJAN 4 chambers

of the heart Left and right atria Left and right ventricle 4 valves Tricuspid Pulmonary Mitral or bicuspid Aortic Veins to the heart Vena cava Pulmonary veins Arteries away from the heart Pulmonary artery Aorta Electrical system Sinoatrial node Atrioventricular node Bundle of His Right bundle branch Left bundle branch Left anterior bundle branch Right posterior bundle branch Perkinje fibres Arterial flow to the heart muscle Left coronary artery Left anterior descending artery Circumflex artery Right coronary artery Cardiac Physiology Specialised muscle cells innervated by autonomic system but Cardiac cycle maintained by nodes without needing neural direction Heart beat depends on electrical impulses called action potentials These cause depolarisation and repolarisation Action potential phases 0-depolarisation: rapid Na+ entry into cell 1-early repolarisation: slow entry of Ca+ into cell 2-Plateau: continued slow entry of Na+ and Ca+ 3-K+ leaves cell 4-Return to resting potential

Myocardial Dysfunction: General Clinical Manifestations

Cardiac Apex, HR, volume, quality, arrhythmia BP changes, postural, anxiety Temp Heart sounds, bruits (humming vessel) Venous pressure i.e. jugular Point of maximal impulse (LV) at 4/5th ICS Pain Respiratory SOB, dyspnea on exertion, orthopnea, nocturnal asthma, pain, coughing, haemoptysis Brain Disorientation, visual or hearing impairments, reflexes Renal Oliguria Gastro Anorexia, constipation, ascites Hepatic Enlargement and tenderness Skin Colour, temperature, peripheral pulses, peripheral oedema, nails, stasis ulcers Cardiac Pharmacology Drugs affect both heart and vascular system Drugs are used to treat Heart failure Arrhythmias Ischaemic heart disease Hypertension Dyslipidaemia Shock and hypotension Wide variety of drugs for various conditions Inotropes Antiarrhythmic Drugs Class I: Sodium channels blockers Class II: -adrenoceptor blockers Class III: Potassium channel blockers Class IV: Calcium channel blockers Diuretics Hydrochlorothiazide, spironolactone ACE inhibitors Captopril Centrally-acting drugs Clonidine Vasodilators Hydralazine Lipid lowering drugs Statins Niacin

Coronary Artery Disease (CAD) Any vascular disorder that narrows or occludes the coronary arteries Atherosclerosis is the most common cause Plaques Stable (lipid-poor, thick fibrous cap) Unstable (lipid-rich, thin fibrous cap) Disease leads to myocardial ischemia and possible infarction Risk Factors for CAD Same as those for atherosclerosis LDL, hypertension, smoking, diabetes, obesity/sedentary lifestyle Nontraditional risk factors Serum markers (C-reactive protein etc), hyperhomocysteinemia, infection Myocardial Ischemia Imbalance between coronary blood supply and myocardial demand Result in a transient coronary occlusion. No tissue damage Types Stabile angina (Angina pectoris) Recurrent predictable substernal chest discomfort of 3-5 minutes, possible radiation into neck, left arm or shoulder, lower jaw pain relieved with rest +/or nitrate drugs (GTN) Prinzmetal angina Unpredictable, at rest, due to vasospasm Silent ischemia Asymptomatic ischemia (nerve damage post MI) Evaluation ECG during pain and exercise Thallium scan to detect region of diminished activity Coronary angiography, angioplasty, stent

Treatment Organic nitrates Nitroglycerin Nitrate converted to nitric oxide Calcium Channel Blockers (class IV) Diltiazem, Nifedipine -Blockers (class II) Propranolol, metoprolol Coronary artery bypass grafts (CABG) Glyceryl trinitrate Action Absorbed by epithelial cells and converted to NO which increases cGMP messenger causing dilation More venous than arterial dilation Reduces cardiac preload Causes collateral coronary dilation Adverse effects Reflex tachycardia, hypotension, syncope, headache

Practice points Transdermal, sublingual, buccal, IV Tolerance can develop Patch off periods Dont get any on yourself! Acute Coronary Syndromes Sudden coronary obstruction from formation of a thrombus over a ruptured or ulcerated atherosclerotic plaque Unstable angina At rest, > 30 min, not relieved by sublingual nitrates, frequency Myocardial infarction Sudden and extended obstruction of the myocardial blood supply Results in myocyte necrosis and cell death Types of Myocardial Infarction Subendocardial infarction In myocardium beneath endocardium Transmural infarction Full thickness of myocardium Infarct may be anterior, inferior, posterior or lateral depending on which coronary artery is occluded 12-lead ECG can help localise the affected area through identification of ST segment and T wave changes and later q wave formation in certain leads

Changes Post MI Myocyte hypertrophy and loss of contractile force Arrhythmias, related to site and extent of MI, temporary or permanent Repair post MI Degradation of damaged cells, proliferation of fibroblasts and synthesis of scar tissue Collagen matrix weak, mushy and vulnerable to re-injury in first 10 -14 days post MI Tough inelastic scar complete at 6 weeks Complications of MI Arrhythmias LVF results in pulmonary congestion NB complications are the signs and symptoms of cardiac failure Cardiogenic shock if >40% LV infarcted Pericarditis 2-3 days post Aneurysm Heart Failure Definition Cardiac dysfunction which results in inadequate perfusion of tissues with bloodborne nutrients

Causes of Heart Failure Impaired Cardiac Function MI, cardiomyopathies, valve disorders, congenital, constrictive pericarditis Excess work demands Systemic hypertension or pulmonary disease (cor pulmonale), blood volume (IV fluids), perfusion needs (thyrotoxicosis, anemia)

Types of Heart Failure Failure of one side of the heart leads to right or left sided heart failure However, long term heart failure will eventually involve both sides

Right Heart Failure Most commonly caused by hypoxic pulmonary disease Congestion of blood in venous system Peripheral, sacral oedema, liver and spleen engorgement, ascites of peritoneal cavity, congestion of gastrointestinal tract Left heart failure There is a decrease in cardiac output Subsequent ventricular hypertrophy, ventricular remodeling and thus contractibility Pulmonary congestion Impaired gas exchange causing cyanosis, hypoxia Pulmonary oedema with orthopnea, nocturnal dyspnea, cough with frothy sputum

Heart Failure Treatment Pharmacological treatments Inotropes Diuretics Vasodilators Inotropes

Increase force of contraction All increase intracellular cardiac Ca++ concentration E.g.: Digitalis (cardiac glycoside) Dobutamine (-adrenergic agonist) Milrinone (phosphodiesterace inhibitor)

Digoxin Increase force of contraction (positive inotropic) without increase in oxygen consumption Increases intracellular Ca++ Slow heart rate (negative chronotropic) Slow impulse via AV node Absorbed via GI/ IV Excreted by kidneys loading dose (digitalizing) to speed up therapeutic level Narrow therapeutic index Therapeutic drug monitoring required Neurohumoral Compensatory Mechanisms

Increase HR Pumps more blood from heart and increases circulation. Hypertrophy of the heart Increases pump strength by contracting more forcefully. Eventually these contribute to disease by causing walls of heart to enlarge Treatment aimed at interrupting neurohumoral pathways