Cardiovascular System – 2024 PDF

PHM 143 Cardiovascular System – 2024 Heather Kertland, BScPhm, PharmD, BCCP [email protected]  Learning Objectives State the basic mechanisms of disease, including the pathophysiology and biochemical changes and how diagnostic investigations can confi...

PHM 143 Cardiovascular System – 2024 Heather Kertland, BScPhm, PharmD, BCCP [email protected]  Learning Objectives State the basic mechanisms of disease, including the pathophysiology and biochemical changes and how diagnostic investigations can confirm the presence of – Hypertension – Atherosclerosis (angina, myocardial infarction) – Heart Failure – Arrhythmias Integrate above knowledge in order to interpret findings in a specific patient scenario and explain the disease state process to patients  Mortality Statistics 2022 # of deaths Other 16043 COVID-19 16151 Suicide 3839 Renal 4042 Liver 4520 Diabetes 7557 # of deaths Accidents 18365 Influenza 5985 Respiratory 12462 Heart/CVD 71272 Cancer 82412 0 20000 40000 60000 80000 100000 Stats Canada 2023 Cardiovascular cause of death in Canada Number of Deaths 40000 35000 30000 25000 20000 15000 10000 5000 0 Number of Deaths  Coronary Heart Disease mortality Stats Can  Cardiovascular System Stroke Arrhythmia Coronary artery disease/myocardial infarction Congenital Heart disease Venous thromboembolism Rheumatic heart disease (deep vein thrombosis/pulmonary embolism) Pericardial disease Heart Failure /Cardiomyopathy Aortic diseases Vascular disease Peripheral arterial disease https://twsmassage.wordpress.com/2016/01/11/benefits-for-the-circulatory-system/  Terminology Cardiovascular (CV) – Coronary heart disease, stroke, peripheral arterial disease Coronary Heart Disease(CHD)/Coronary artery disease (CAD) – Disease of the coronary arteries (angina, myocardial infarction) Cerebrovascular Disease – Disease of the blood vessels supplying the brain (stroke) Vascular Disease – Diseases of the aorta and peripheral arteries (aortic aneurysm, intermittent claudication)  Major Cardiovascular Risk Factors Modifiable Non-modifiable Hypertension Age Smoking Sex Cholesterol Family history* Diabetes Left ventricular *family history = 1° relative, male < 55 yrs, female < 65 years hypertrophy (LVH)  Cardiovascular Risk Factors Major Minor Age Obesity (Body mass index [BMI] > 25 Sex kg/m2) Smoking Sedentary lifestyle Hypertension Elevated triglyceride Diabetes mellitus Excess alcohol intake Left ventricular hypertrophy (LVH) Poor diet Increased Total/LDL cholesterol Thrombogenic factors Low HDL cholesterol Inflammation/Inflammatory Family history of premature coronary conditions artery disease* Rheumatoid arthritis Inflammatory bowel disease HIV *family history = 1° relative, male < 55 yrs, female < 65 years 3 4 You are in front of the dispensary looking at the various non-prescription products and to answer questions customers may have. Someone calls you over to the blood pressure machine. The machine is telling them their blood pressure is 156/94. They are wondering if this is okay or should they be worried?  Learning Objectives 1. Define normal blood pressure and hypertension 2. Describe how blood pressure is regulated 3. State the proposed mechanism of essential hypertension 4. List causes of secondary hypertension  Hypertension Isolated systolic hypertension ≥ 140 and < 90 25% of the adult population in Canada are hypertensive Arterial Blood Pressure  Blood vessels Kumar, Vinal et al Robbins Basic Pathology 2017  Blood pressure regulation Kumar, Vinal et al Robbins Basic Pathology 2017  Blood pressure regulation Kidney, adrenal gland, myocardium/heart release substances – Vascular tone – Sodium/fluid balance Kidney – Renin – released when: Low blood pressure in the afferent artery of the kidney High levels of catecholamines Low sodium levels is the distal convoluted tubule – – Renin – cleaves angiotensinogen to angiotensin I which is converted to angiotensin II by Angiotensin Converting Enzyme (ACE) Smooth muscle cell contraction Increases aldosterone release from adrenal gland (which causes sodium resorption) Causes sodium resorption Heart – Natriuretic peptides released when increased pressure/volume sensed – Inhibit sodium resorption  Blood Pressure regulation Kumar, Vinal et al Robbins Basic Pathology 2017 Causes of hypertension  Mechanism of essential hypertension Reduced renal excretion of sodium Increased vascular resistance – Chronic changes in vascular wall Genetic factors – ACE gene/aldosterone gene Environmental factors – Excessive Na intake, stress, smoking, physical inactivity, obesity  Drug induced hypertension Method Drug Increasing volume retention Glucocorticoid (steroids), sex hormones, non-steroid anti-inflammatory (NSAIDS) Activation of sympathetic nervous system Pseudoephedrine, phenylpropanolamine, cocaine, venlafaxine, amphetamine Activation of renin-angiotensin- Lead aldosterone system Direct vasoconstriction Cyclosporin, tacrolimus, Mixed ERAs (erythropoietin) Anti-vascular endothelial growth factor Sunitinib (oral chemotherapy) Unknown Acetaminophen, lithium, paclitaxal Role for Pharmacists  Key points Normal blood pressure < 120/80 mmHg Hypertension is common Concerned about the end organ damage Majority of individuals have essential hypertension Understanding how blood pressure is regulated will help you understand how drugs may impact blood pressure Drugs can cause/exacerbate blood pressure Many opportunities for pharmacist’s to impact the care of patients diagnosed with hypertension  Wayne 66 year old male Complains to his family doctor that when he walks up 2-3 flights of stairs he starts to feel this heaviness in his chest Heaviness stops when he stops climbing He has started to avoid taking the stairs  Atherosclerosis “Hardening of the arteries”  Learning Objectives 1. Describe the formation of an atherosclerotic plaque and the process of thrombus formation 2. Compare and contrast the underlying pathophysiology of an acute coronary syndrome and stable angina 3. Differentiate angina from other pain 4. Describe the tests (including blood work) that are used in the diagnosis of acute coronary syndrome and stable angina 5. State the complications of an acute coronary syndrome/myocardial infarction  The artery https://en.wikipedia.org/wiki/Artery  Endothelium Regulates vascular tone, platelet activity and leukocyte adhesion Nitric oxide (NO) Decreased NO availability with smoking, hypertension – Decreased production – Increased degradation Promotes pro-inflammatory state Endothelial dysfunction  Atherosclerotic Plaque Formation Nature Review Disease Primer https://doi.org/10.1038/ s41572-019-0106-z Nature Review Disease Primer https://doi.org/10.1038/ s41572-019-0106-z  Atheromatous Plaque Kumar, Vinal et al Robbins Basic Pathology 2017 Courtesy of J Butany Arterial blood flow Clinical manifestations of atherosclerosis  Cardiac Anatomy https://www.texasheart.org/heart-health/heart-information-center/topics/the-coronary- arteries/  Terminology Acute Coronary syndromes (ACS) – acute atherosclerotic plaque rupture – Myocardial infarction (heart attack) Non-ST segment/ST segment – Unstable angina Stable angina (Chronic coronary syndrome) – Atherosclerotic plaque narrowing > 70% coronary artery  Myocardial Infarction /Acute Stable angina Coronary Syndrome https://www.drugs.com/health-guide/angina.html  Acute Coronary Syndrome N Engl J Med 2012;366:54-63.  Figure 1 Sequelae of vascular injury Adhesion Activation Aggregation Yousuf, O. & Bhatt, D. L. (2011) The evolution of antiplatelet therapy in cardiovascular disease Nat. Rev. Cardiol. doi:10.1038/nrcardio.2011.96 vWF = von Wilderbrand factor, TxA2 = thromboxane ADP = adenosine diphosphate  Figure 1 Mechanism of thrombus formation Franchi, F. & Angiolillo, D. J. (2014) Novel antiplatelet agents in acute coronary syndrome Nat. Rev. Cardiol. doi:10.1038/nrcardio.2014.156  Signs and symptoms of cardiac ischemia Angina (chest pain) – Heaviness, tightness, squeezing – Sub-sternal – Radiation to jaw, arm, elbow – Others – nausea, vomiting, shortness of breath Stable angina – occurs at reproducible amounts of work, improves with rest Acute coronary syndrome – at rest  Natural History – Acute Coronary Syndromes CL = culprit lesion, NCL – non-culprit lesion Major adverse cardiac event: cardiovascular death, cardiac arrest, myocardial infarction, hospitalization for unstable angina or N Engl J Med 2011;364:226-35. progressive angina  Romeo 62 year old male developed intermittent chest burning after dinner, took some antacids and went to bed Am - burning returned but he went to work where the burning got worse in intensity and was now continuous – his co-workers convinced him to go to the emergency department  Electrocardiogram (ECG) RA= right arm, LA = left arm, RL = right leg, LL = left leg V1 – V6 – chest leads 12 ‘pictures’ of the heart Chest leads = horizontal plane Diagnostics - Electrocardiogram  Acute Coronary Syndrome (ACS) ECG findings ECG obtained quickly - ST segment elevation ACS – ST segment elevation – Thrombus occluding the artery Non-ST segment elevation – ST segment depression – T wave inversion – Thrombus that narrows artery 90 – 99% Provisional diagnosis of acute coronary syndrome Chest pain symptoms consistent with angina ECG showing ST segment elevation or depression or T wave inversion  Diagnostics - Laboratory tests Confirm an acute coronary syndrome A = myoglobin B = troponin T, I or C C = creatine kinase (CK) D = creatine kinase – MB subfraction Pharmacotherapy: A Pathophysiologic Approach 11th ed  Complications of a myocardial infarction Plumbing – Recurrent myocardial infarction due to reocclusion Electrical – Arrhythmias Tachyarrhythmia Bradyarrhythmia Mechanical – Heart failure – Left ventricle free wall rupture – Ventricular septal defect – Acute valve dysfunction Courtesy of J Butany Courtesy of J Butany  Wayne 66 year old male Complains to his family doctor that when he walks up 2-3 flights of stairs he starts to feel this heaviness Heaviness stops when he stops climbing Has started to avoid taking the stairs Stable angina MVO2 – myocardial oxygen consumption Blood Flow Diagnostic tests for coronary artery disease Exercise stress test – ECG – Blood pressure – Symptoms Drugs to mimic stress For diagnosis Symptoms management JAMA  SPECT (common name MIBI) (single photon emission computer tomography) - Combined with stress test - Myocardial perfusion imaging - Nuclear scan (Thallium -201, technetium-99 sestimibi [MIBI]) Curr ProblCardiol2017;42:316–366.  Coronary Angiography - Radio opaque contrast media  Other Cardiac CT + angiography Magnetic Resonance Imaging (MRI) Positron emission tomography (PET)  Summary Hypertension is a risk factor for CVD – myocardial infarction, stroke, dementia……… Atherosclerosis contributes significantly to morbidity and mortality – Stable angina – Acute coronary syndromes Diagnostic tests will vary depending upon presentation – Electrocardiogram is used for both presentations Questions  Heart Failure Stephen is 66 year old male, had a myocardial infarction 2 years ago, now complains of shortness of breath even when he walks up one flight of stairs and swollen ankles. His breathing is worrisome so he goes to the emergency department Cynthia is a 72 year old female who has hypertension x 20 year. When speaking with her doctor she complains of fatigue which has worsened over past 6 weeks and some coughing that won’t go away  Learning Objectives 1. Define reduced, preserved and mid-range heart failure and why it is important to know which one your patient has 2. Describe the compensatory mechanisms that result due to a decreased cardiac output 3. State how drugs can cause or exacerbate heart failure 4. Given a patient scenario, identify the signs and symptoms of heart failure  Heart Failure What is “heart failure”? The syndrome of pulmonary and systemic congestion, caused by failure of the heart to pump enough blood to meet the metabolic needs of the body and its resulting compensatory responses …syndrome that can result from any structural or functional impairment of ventricular filling or ejection of blood (ACC/AHA guidelines 2013)  Mortality and morbidity # 1 reason for hospitalization for those 65 years or older 1 year mortality – 20% 5 year survival rate - 42% Cost to the health care system $2.8 billion Nature Review Disease Primer https://doi.org/10.1038/ s41572-019-0106-z  Etiology Reduced Ejection Fraction (Systolic) Dysfunction – Reduced muscle mass (infarction) – Dilated cardiomyopathy (viral, idiopathic, ETOH) Preserved Ejection Fraction (Diastolic) dysfunction – Ventricular stiffness (hypertension, ischemia) – Valve disease (mitral stenosis) – Pericardial disease  Cardiac Function Cardiac output (CO) = HR (heart rate) x SV (stroke volume) stroke volume influenced by: preload afterload contractility Compensatory Response to Decreased CO Tachycardia (and Increased contractility) Via sympathetic nervous system activation (SNS) Benefits – increase CO, Harmful – activated, increased myocardial oxygen demand (MVO2), shortened diastolic filling time, increased risk of cell death Compensatory Response to Decreased CO Tachycardia (and Increased contractility) Via sympathetic nervous system activation (SNS) Benefits – increase CO, Harmful – activated, increased myocardial oxygen demand (MVO2), shortened diastolic filling time, increased risk of cell death  Increase preload Frank Starling Curve PRELOAD Pharmacotherapy: Pathophysiologic Approach 11th Ed  Increased preload – Na/water retention – Benefits – optimize CO via frank starling Increase SV with increase left ventricular end diastolic pressure/volume [LV EDP (V)] – Harmful Pulmonary and systemic congestion edema  Increase preload Frank Starling Curve PRELOAD Pharmacotherapy: Pathophysiologic Approach 11th Ed  Vasoconstriction – Activation of renin angiotensin aldosterone (RAAS) – increased angiotensin II (AngII) – Benefit – maintain blood pressure, shunt blood – Harmful Increased myocardial oxygen demand (MVO2), further activates compensatory mechanism – stimulates the sympathetic nervous system (SNS)  Afterload Pharmacotherapy: Pathophysiologic Approach 11th Ed  Ventricular hypertrophy – Benefits – maintains CO – Harmful Limited amount of hypertrophy is beneficial  Neurohormonal Activation RAAS – Angiotensin II Vasoconstriction Renal efferent constriction Vessel/myocardial hypertrophy Na retention Increased aldosterone Release of NE from terminals – Aldosterone Na retention Interstitial cardiac fibrosis – Increased college deposition in extracellular matrix Sympathetic Nervous System Norepinephrine Other ?  Etiology of heart failure reduced ejection fraction (HF-rEF) Common Less common Ischemia (myocardial Congenital heart disease infarction, CAD) Infiltrative diseases Hypertension (long – Amyloidosis/sarcoidosis standing, poorly controlled) Inflammatory/infections Tachyarrhythmia – myocarditis Idiopathic cardiomyopathy Drugs – Next slide  Drugs that can cause heart failure (HF-rEF) Chemotherapy – Doxorubicin (Anthracyclines) – Cyclophosphamide – trastuzumab, – Paclitaxel Ergotamine Amphotericin B Alcohol Circulation. 2016;134:e32–e69. Drugs that can exacerbate heart failure Negative inotropes – Diltiazem, verapamil (calcium channel blockers) Sodium retaining/containing – Sodium bicarbonate – Steroids Increased heart rate – Cocaine, sympathomimetics  Classification of HF High output vs low output* Acute vs chronic Systolic vs diastolic (reduced vs preserved) Symptoms Progression  Classification of Heart Failure Ejection fraction - % of blood ejected with each heart beat Normal 60 – 70% Beique L., CPJ 2019  Left Ventricular Function Echocardiogram (echo) Multi-gated acquisition scan (MUGA) Angiogram Cardiac MRI  American Heart Association (AHA) staging At risk for heart failure Heart Failure A: at risk for HF B: structural C: structural D: Refractory but no structural heart disease heart disease heart failure heart disease or without with prior or requiring symptoms symptoms current specialized symptoms interventions Pts with HTN, Previous MI, LV Known heart Marked DM, using remodeling disease + symptoms at cardiotoxins (LVH), valvular symptoms rest on maximal dz therapy Heart Failure classification - symptoms New York Heart Association  How would you classify the following? Stephen- MI 2 years ago complains of shortness of breath even when he walks up one flight of stairs and swollen ankles. His breathing is worrisome so he goes to the emergency department – Echo – ejection fraction 32% Type of heart failure – reduced or preserved Stage A B C D Symptom – NYHA ? Cynthia – hypertension x 20 yrs she complains of some general fatigue which has worsened over past 6 weeks and some coughing – Echo – ejection fraction 54% Type of heart failure – reduced or preserved Stage A B C D Symptoms – NYHA ?  Symptoms Exertional Dyspnea Orthopnea Paroxysmal nocturnal dyspnea (PND) Fatigue and weakness Nocturia  Signs Edema Pallor/cold extremities Sinus tachycardia Rales – when auscultating/listening to the lungs Elevated jugular venous pressure (> 4 cm ASA at 45 degrees) Hepatojugular reflux Hepatomegaly cough  Jugular Venous Pressure (JVP) https://www.youtube.com/watch?v=MZKSkVSbH8k  Edema Edema/Anasarca 1+ 2+ 3+ 4+ 2 mm or less 2 – 4 mm 4 – 6 mm 6 – 8 mm Disappears Disappears in 10 May last more Lasts 10 – 15 rapidly – 15 sec than 1 min min Dependent Dependent extremity looks extremity looks swollen grossly enlarged Lab values - Brain naturetic peptide (BNP) BNP gene is activated with increased heart wall stress from volume or pressure BNP: – Stimulates natriuresis and vasodilation – Inhibits renin-angiotensin-aldosterone release – Inhibits SNS activity – Reduces fibrosis Levels are increased in HF Useful to rule in/out heart failure (versus other causes of shortness of breath Can be used to monitor pts long term  Complications of Heart Failure Quality of life Arrhythmias – Atrial fibrillation – Ventricular arrhythmias Stroke and thromboembolism Hospitalizations Death  Summary Heart failure is a syndrome multiple causes drugs can cause and/or exacerbate heart failure HF-pEF versus HF-rEF symptoms ARRHYTHMIAS  Learning Objectives 1. Describe the major ion channels involved in the conduction of an electrical impulse 2. State the proposed mechanism of torsade de pointes and how medications can increase the risk of torsade de pointes 3. Given a patient scenario, identify the signs and symptoms of atrial fibrillation 4. Identify the risk factors for atrial fibrillation 5. State the consequences of atrial fibrillation  Conduction system 60 – 100 bpm 40 – 60 bpm 20 – 40 bpm http://www.cvphysiology.com/Arrhythmias/A007.htm currents and channels of the action potential Channels & antiarrhythmic agents ECG  Pathophysiology of arrhythmias Increased Automaticity Re-entrant Triggered https://ecgwaves.com/topic/mechanisms-cardiac-arrhythmias-automaticity-reentry-triggered-activity/ https://www.imsc.res.in/~sitabhra/research/heart/pacing/index.html  Nomenclature of arrhythmias Normal sinus rhythm (NSR) Location – Sinus, supraventricular, ventricular Speed – Bradycardia (Heart Rate < 60) – Tachycardia (HR >100) – Normal (HR 60 – 100) Activity – Fibrillation – Heart Block Ventricular Fibrillation  Ventricular Fibrillation (V Fib) Life threatening Call 911 CPR Look for Automatic External Defibrillator (AED) Defibrillation Patho: no organized electrical activity  Atrioventricular Node (AV) Block 1st degree, 2nd degree (type I and II), 3rd degree (complete heart block) Increase blockade of electrical conduction thru AV node 1st degree – slowed conduction (PR interval > 200 msec) 2nd degree – occasional non-conducted (dropped) beat (every 3 or 4th ) 3rd degree* – no communication between ventricle and atrium (can be symptomatic) Causes: – Age – Ischemia – Medications Beta-blockers, calcium channel blockers rarely causes 3rd degree heart block at therapeutic doses  Proarrhythmia A medication causes: Exacerbation of a pre-existing arrhythmia – More episodes of ventricular tachycardia (VT) New arrhythmia – Torsade de pointes (TdP)  Torsades de pointes (TdP) (a polymorphic ventricular tachycardia)  Signs and Symptoms of TdP Lightheadedness Loss of consciousness May degenerate into ventricular fibrillation – Becomes life threatening  Cause of torsade? Prolonged QT interval - (Delay in repolarization) + triggering event Can J Cardiol 2005;21:857-64  Causes of QT prolongation Congenital (genetic) DRUGS Mechanism – blocks the potassium channel (delayed rectifier) which results in prolonged repolarization Incidence of Torsade 4 cases per 1 million people annually – Antiarrhythmics 1 – 10% Sotalol 5.4% Ibutilide 4.3% Quinidine 8% – Moxifloxacin 0.001 to 0.0001% – Cisapride 0.001% Eur Heart J 2001:3 (suppl K):K70 - 80 www.crediblemeds.com  Bertie is a 76 year old female who presents with complaints of fluttering in her chest. She feels that her heart is racing. Also, she has had no energy for the past week Pulse is 129 BPM and irregularly irregular Diagnosed with atrial fibrillation  Atrial Fibrillation - Most frequently encountered arrhythmia in practice Atrial rate – 400 – 450 bpm Ventricular response rate (pulse) – 140 – 160 bpm Pulse – Irregularly irregular Symptoms – Palpitations/fluttering, dyspnea, lightheadedness or syncope – Chest pain (typically if pt has angina) – Fatigue Asymptomatic or symptomatic  Risk Factors for a fib Advancing age Hypertension Heart failure with reduced ejection fraction Valvular heart disease (e.g, mitral stenosis/regurgitation) Thyroid disease Obstructive sleep apnea Natural History of atrial fibrillation ESC 2010 Guidelines for atrial fibrillation  Consequences of a fib Symptoms/Quality of Life Thromboembolic risk – clots develop in left atrial appendage – stroke and systemic embolism Heart failure (uncontrolled/rapid heart rate/ventricular response rate) Questions