EKG Interpretation - Cardiology Slides PDF

EKG Interpretation Jason Ryan, MD, MPH EKG Determining Heart Rate 3 – 5 big boxes between QRS complexes 300 150 100 75 60 50 QRS Axis SA AV LBB His Purkinje RBB Fibers Q...

EKG Interpretation Jason Ryan, MD, MPH EKG Determining Heart Rate 3 – 5 big boxes between QRS complexes 300 150 100 75 60 50 QRS Axis SA AV LBB His Purkinje RBB Fibers QRS Axis -90o -30⁰ +180o 0o Normal QRS Axis -30 and +90 degrees +90o QRS Axis Left Axis Deviation -90o LBBB Ventricular Rhythm -30⁰ +180o 0o Normal QRS Axis -30 and +90 degrees +90o QRS Axis Left Axis Deviation -90o LBBB Ventricular Rhythm Right Axis Deviation RBBB RVH -30⁰ +180o 0o Normal QRS Axis -30 and +90 degrees +90o Determining Axis -90o (-) Lead F (+) Lead I (-) (+) -30⁰ +180o 0o Normal Axis -30 to +90 +90o Axis Quick Method First, glance at aVr It should be negative If upright: limb lead reversal Normal Axis Quick Method If leads I and II are both positive, axis is normal Lead I Axis 0 to 90° Lead II Axis Quick Method For left axis deviation: All you need is lead II Lead I Axis -30 to -90° Lead II Axis 0 to -30° Lead II Physiologic Left Axis Axis Quick Method For right axis deviation: All you need is lead I Negative = RAD Lead I Axis 90 to 180° Lead II Axis Quick Method Look at aVr: Make sure its negative Look at I, II: If both positive, axis is normal If II is negative: LAD If I is negative: RAD Normal Phys Left Left Right Lead I Lead II Step 1: Find the p waves Are p waves present? Sinus p waves Originate in sinus node Upright in leads II, III, F Step 2: Regular or Irregular Distance between QRS complexes (R-R intervals) Regular Irregular Steps 1 & 2 Sinus Rhythm P waves present, regular rhythm Sinus rhythm Rare: atrial tachycardia, atrial rhythm No p waves, irregular rhythm Atrial fibrillation – irregularly irregular Atrial flutter with variable block Atrial Fibrillation Steps 1 & 2 Sinus rhythm with PAC P waves present, irregular rhythm Sinus rhythm with PACs Multifocal atrial tachycardia Sinus with AV block Mobitz I AV Block (Wenckebach) Mutifocal Atrial Tachycardia Steps 1 & 2 No p waves, regular rhythm Hidden p waves: retrograde Supraventricular tachycardias (SVTs) Ventricular tachycardia AV Nodal Reentrant Tachycardia (AVNRT) Step 3: Wide or narrow Narrow QRS (< 120 ms; 3 small boxes) His-Purkinje system works No bundle branch blocks present Wide QRS Most likely a bundle branch block Ventricular rhythm (i.e. tachycardia) QRS Interval Normal QRS Right Bundle Left Bundle Branch Block Branch Block Ventricular Tachycardia Ventricular Tachycardia AV Dissociation Fusion Fusion and Capture Beats Capture Step 4: Check the intervals PR (normal < 210 ms; ~5 small boxes; ~1 big box) Prolonged in AV block, drugs QT (normal < 1/2 R-R interval) Prolonged with ↓ Ca Shortened with ↑ Ca Prolonged by antiarrhythmic drugs, other drugs Can lead to torsades de pointes Step 5: ST segments T wave abnormalities Inverted: ischemia Peaked: Early ischemia, hyperkalemia (↑K) Flat/U waves: hypokalemia (↓K) ST depression Subendocardial ischemia Common in UA/NSTEMI ST elevation Transmural ischemia STEMI Peaked T waves Hyperkalemia Early ischemia: “hyperacute” Precedes ST elevation Normal T waves Peaked T waves U waves T U Can be normal Also seen in hypokalemia T U PAC and PVC ACLS and Tachycardias Jason Ryan, MD, MPH Cardiac Arrest Sudden cessation of cardiac activity with hemodynamic collapse Usually associated with one of four underlying cardiac rhythms Ventricular Tachycardia Pulseless Electrical Activity Ventricular Fibrillation Asystole ACLS Advanced cardiac life support Clinical algorithm for treatment of life-threatening cardiac emergencies Applied to unresponsive patients Public Domain ACLS Advanced cardiac life support Unresponsive, pulseless patient → call for help Start chest compressions (CPR) Apply oxygen Attach monitor and defibrillator Wikipedia common ACLS Advanced cardiac life support Is the rhythm shockable? YES if ventricular tachycardia or fibrillation NO if PEA or asystole Ventricular Tachycardia Pulseless Electrical Activity Ventricular Fibrillation Asystole ACLS Advanced cardiac life support Reversible Causes Hypovolemia Hypoxia Acidosis Hypo/hyperkalemia Hypothermia Myocardial infarction Tension pneumothorax Cardiac tamponade Pulmonary embolism Stable Ventricular Tachycardia Pulse intact Patient remains awake No evidence of hemodynamic compromise (hypotension, chest pain) Intravenous amiodarone Alternatives: lidocaine or procainamide Do not perform cardioversion while patient is conscious Ventricular Tachycardia Polymorphic Ventricular Tachycardia Subtype of ventricular tachycardia Continuously varying QRS complex morphology Caused by multiple foci of QRS complexes within the ventricle Unstable rhythm that often leads to cardiac arrest Almost always caused by myocardial ischemia Polymorphic Ventricular Tachycardia Monomorphic Ventricular Tachycardia Torsades de Pointes Polymorphic ventricular tachycardia that occurs with prolonged QT segment Specific subtype of polymorphic ventricular tachycardia Urgent defibrillation indicated in hemodynamically unstable patients For patients with recurrent episodes: IV magnesium sulfate Torsades de Pointes Prolonged Qt Interval Out-of-Hospital Cardiac Arrest Time to resuscitation: strongest predictor of survival Short time: good survival Long time: poor prognosis Other poor prognostic signs Initial PEA or asystole Prolonged CPR > 5 minutes Advanced age Pxhere/Public Domain Tachycardias Unstable Patients Hemodynamic instability: hypotension, chest pain or respiratory distress Often associated with tachycardia Tachycardia may be cause or consequence of hemodynamic instability Key distinction: wide versus narrow QRS complex  QRS Interval Normal QRS Ventricular Tachycardia Right Bundle Branch Block Left Bundle Branch Block Wide Complex Tachycardias Rapid heart rate with wide QRS complex (> 120 ms) Differentiation based on ECG Ventricular tachycardia Ventricular Tachycardia SVT with aberrancy (LBBB, RBBB) Sudden onset/unstable WCT: shock Sinus Tachycardia with LBBB Narrow Complex Tachycardias Rapid heart rate with narrow/normal QRS complex ( 100 bpm Cardiomyopathy Caused by untreated, rapid atrial fibrillation “Tachycardia-induced cardiomyopathy” ↓ LVEF Systolic heart failure Atrial Fibrillation Thrombus in Left Atrial Appendage Atrial Fibrillation Cardiac Embolism Brain (stroke) Gut (mesenteric ischemia) Spleen ConstructionDealMkting Atrial Fibrillation Risk Factors Age ~10% of patients > 80 < 1% of patients < 55 More common in women Most common associated disorders: HTN, CAD Anything that dilates the atria → atrial fibrillation Heart failure Valvular disease Key diagnostic test: Echocardiogram Hyperthyroidism Commonly leads to atrial fibrillation Reversible with therapy for thyroid disease Atrial fibrillation therapies less effective Key diagnostic test: TSH Atrial Fibrillation Triggers Often no trigger identified Binge drinking (“holiday heart”) Increased catecholamines Infection Surgery Pain Public Domain Atrial Fibrillation Treatment Rate control Control of heart rate Ideally < 110 bpm Rhythm control Restoration of sinus rhythm Anticoagulation Rate Control Beta Blockers Calcium Channel Blockers Digoxin Rate Control Slow AV node conduction Beta-blockers Usually β1-selective agents Metoprolol, Atenolol Hyperthyroid patients: propranolol Calcium channel blockers Verapamil, Diltiazem Digoxin Increases parasympathetic tone to heart Propranolol Rhythm Control Goal: restore sinus rhythm Cardioversion Cardioversion Electrical Deliver “synchronized” shock at time of QRS Administer anesthesia Deliver electrical shock to chest All myocytes depolarize Usually sinus node first to repolarize/depolarize Pollo/Wikipedia Cardioversion Chemical Administration of antiarrhythmic medication Often Ibutilide (class III antiarrhythmic) Less commonly used due to drug toxicity Cardioversion Spontaneous Often occurs after hours/days Cardioversion Risk of Stroke Chemical/electrical cardioversion may cause stroke 48 hours required for thrombus formation Symptoms < 48 hours: cardioversion safe Symptoms > 48 hours (or unsure) Anti-coagulation 3 weeks → cardioversion Transesophageal echocardiogram to exclude thrombus Exception: Hypotension/shock Emergent cardioversion performed Rhythm Control Antiarrhythmic medications Administered before/after cardioversion Class I drugs Flecainide, propafenone Class III drugs Amiodarone, sotalol, dofetilide AFFIRM trial: no mortality difference between rate and rhythm control Stroke Prevention Warfarin Aspirin Requires regular INR monitoring Less effective Goal INR usually 2-3 Only used if risk of stroke is very low Less risk of bleeding Rivaroxaban, Apixaban Factor Xa inhibitors Dabigatran Direct thrombin inhibitor Anticoagulation Anticoagulation MUST be administered Does not matter whether atrial fibrillation persists, or sinus rhythm restored Studies show similar stroke risk for rate control versus rhythm control Stroke Risk CHADS VASC Score CHF (1 point) HTN (1 point) Diabetes (1 point) Stroke (2 points) Female (1 point) Age 65-75 (1 point) Age > 75yrs (2 points) Vascular disease (1 point) Score >2 = Warfarin or other anticoagulant Score 0 -1 = Aspirin or no therapy Atrial Fibrillation Summary New Onset Atrial Fibrillation Unstable Patient Emergent Cardioversion Echocardiogram TSH Rate Control Anticoagulation Rhythm Control Beta-Blockers Aspirin Cardioversion Calcium Blockers Warfarin Antiarrhythmic drugs Digoxin Other drugs Pulmonary Vein Isolation Surgical Therapy for Atrial Fibrillation Atrial Flutter Atrial Flutter Symptoms Symptoms Generally the same as atrial fibrillation May be asymptomatic Palpitations, dyspnea, fatigue Treatment Generally the same as atrial fibrillation Rate or rhythm control Rate-slowing drugs Cardioversion Anticoagulation based on stroke risk Atrial Flutter Ablation Bradycardia Jason Ryan, MD, MPH Bradycardia Pulse < 60/min Sinus bradycardia: slow SA node depolarization AV Block: blocked conduction through AV node Sinus Bradycardia Complete AV Block Bradycardia Symptoms Often asymptomatic Symptoms with severe/persistent forms only Fatigue Exercise intolerance Dizziness Syncope Sinus Bradycardia Sinus rate < 60/min Often an incidental finding Drugs: beta-blockers, calcium channel blockers Well-trained athletes Sinus Bradycardia Sinus Bradycardia Usually no treatment required Rare, severe cases treated with: Atropine (muscarinic antagonist) Dopamine or epinephrine (beta-1 agonists) Pacemaker implantation Sinus Bradycardia Sinus Node Dysfunction Sick Sinus Syndrome Bradycardia due to abnormal SA node function Usually due to age-related changes Slow or absent SA node function after atrial fibrillation conversion “Conversion pause” Treatment: pacemaker implantation Atrial Fibrillation Conversion Pause AV Block Slowed or blocked conduction atria → ventricles Can cause prolonged PR interval Can cause non-conducted p wave Non-conducted P wave Prolonged PR Interval  AV Node HIS Bundle Bundle Branches Purkinje Fibers R SA AV T HIS P Bundle Q Bundle Atrial S Branches Depolarization Ventricular Depolarization Purkinje Fibers AV Block Symptoms Often incidentally noted on EKG Especially milder forms with few/no non-conducted p waves Can cause bradycardia symptoms Occurs when many or all p waves not conducted Fatigue, dizziness, syncope Symptomatic AV block often treated with a pacemaker AV Blocks Anatomy Caused by disease in AV conduction system AV node → HIS → Bundle Branches → Purkinje fibers Divided into two causes SA AV node disease HIS-Purkinje disease AV HIS Bundle Bundle Branches Purkinje Fibers AV Blocks Anatomy AV node disease Usually less dangerous Conduction improves with exertion (sympathetic activity) SA HIS-Purkinje disease More dangerous AV Usually does not improve with exertion Often progresses to complete heart block Often requires a pacemaker HIS Bundle Bundle Branches Purkinje Fibers AV Blocks Four Types Type 1 Prolongation of PR interval only All p waves conducted Type II Some p waves conducted Some p waves NOT conducted Two sub-types: Mobitz I and Mobitz II Type III No impulse conduction from atria to ventricles 1st degree AV Block Prolonged PR (normal < 200-210 ms) Block usually in AV Node Beta-blockers Calcium channel blockers Well-trained athletes Treatment: Usually none 2nd degree AVB Mobitz I/Wenckebach Block usually in AV Node Progressive PR prolongation Grouped Beating RR intervals NOT regular Similar causes as 1st degree AV block Treatment: Usually none 2nd degree AVB Mobitz I/Wenckebach Block usually in AV Node Progressive PR prolongation Grouped Beating RR intervals NOT regular Similar causes as 1st degree AV block Treatment: Usually none 2nd degree AVB Mobitz II Block usually in the HIS-Purkinje System Often seen with bundle branch block Usually symptomatic Dizziness, syncope Treatment: Pacemaker 3rd degree AVB Block usually in the HIS-Purkinje System Regular RR intervals excludes Wenckebach Usually symptomatic Dizziness, syncope Treatment: Pacemaker 3rd degree AVB Block usually in the HIS-Purkinje System Regular RR intervals excludes Wenckebach Usually symptomatic Dizziness, syncope Treatment: Pacemaker Cannon a waves See in complete heart block (3rd degree) Caused by atrial contraction with closed tricuspid valve Visible as large venous pulsations Lyme Disease Spirochete infection with Borrelia burgdorferi Stage 2: Lyme carditis Varying degrees of AV block 1st, 2nd, 3rd AV block improves with antibiotics Image courtesy of Wikipedia/Public Domain Causes of AV Block Drugs Beta-blockers, calcium channel blockers Digoxin Athletes At rest: sinus bradycardia plus slow AV node conduction Fibrosis and sclerosis of conduction system Flikr/Public Domain Pacemaker Treatment for sinus node dysfunction Also “high-grade” AV block Usually Mobitz II or 3rd degree Often in patients with symptoms (syncope, dizziness) Coronary Artery Disease Jason Ryan, MD, MPH Coronary Artery Disease Narrowing of coronary artery Caused by atherosclerosis Asymptomatic until ~75% artery lumen occluded Chest pain (angina) May also cause dyspnea, other symptoms Freestocks.org Asymptomatic Stable Unstable Angina STEMI Angina NSTEMI Major Risk Factors CAD Equivalents Diabetes Diabetes Chronic kidney disease CKD Hypertension Hyperlipidemia (LDL) Age (M > 45, F > 55) Family History of premature CAD (1° relative, M < 55, F < 65) Smoking (quitting smoking → significantly ↓ risk) Obesity, sedentary lifestyle Stable Angina Plaque occluding ~75% or more of coronary artery Causes “typical” chest pain Pressure-like chest pain Occur with exertion Relived by rest or nitroglycerine EKG at rest: normal Symptoms at rest: absent Diagnosis: symptoms or stress testing Stress testing key when diagnosis uncertain Stress Testing Patient must be asymptomatic Goal: provoke ischemia and detect ischemia Provocation: exercise always preferred Detection: EKG changes (ST-depressions) Nuclear imaging (usually Technetium) Echocardiography Wikipedia/Public Domain  Pharmacologic Stress Testing Pharmacologic nuclear (induce coronary steal) Regadenoson Dipyridamole Adenosine Persantine Contraindication: reactive airway disease/wheezing Dobutamine stress echocardiography Risk of arrhythmias Stress Testing Identifies ischemia due to “flow-limiting” stenosis (usually >75%) Non-flow-limiting lesions not detected Acute MI may occur despite negative stress test Angiography Stable Angina Management Preventative therapy (↓ risk of mortality and myocardial infarction) Aspirin Statin Anti-angina therapy (goal: ↓ O2 demand) Beta-blockers or calcium-channel blockers (↓ heart rate/contractility) Nitroglycerine (↓ preload) Coronary stent implantation Coronary artery bypass grafting (CABG) surgery COURAGE Trial: medical therapy has similar outcomes to stent implantation Coronary Stents Percutaneous Coronary Intervention (PCI) About 600,000 stents/year implanted US Wikipedia/Public Domain CABG Coronary Artery Bypass Grafting “Bypass Surgery” Left Internal Mammary Artery (LIMA) Graft Saphenous (leg) Vein Grafts Radial (arm) Artery Grafts Patrick J. Lynch/Wikipedia Stable Angina: Typical Case 65-year-old man with chest pain while walking Relieved with rest Presents to ED: EKG normal Biomarkers normal Stress test Walks on treadmill→ chest pain, EKG changes Cardiac catheterization performed 90% LAD artery blockage Stent placed → angina resolved Stent Complications Restenosis Slow, steady growth of scar tissue over stent “Neo-intimal hyperplasia” Re-occlusion of vessel Rarely life-threatening Slow, steady return of angina Most stents coated “drug-eluting stents” Metal stent covered with polymer Polymer impregnated with drug to prevent tissue growth Sirolimus Stent Complications Thrombosis Acute closure of stent Same as STEMI: life-threatening event Dual anti-platelet therapy for prevention Associated with missed medication doses Stent Thrombosis Prevention “Dual antiplatelet therapy” Typically one year of: Aspirin Clopidogrel, prasugrel or ticagrelor (P2Y12 receptor antagonists) After one year, stent metal no longer exposed to blood Scar tissue and endothelial growth Risk of thrombosis is lower (but not zero) Most patients take aspirin only Variant (Prinzmetal) Angina Episodic vasoconstriction of coronary vessels Episodes usually at rest Midnight to early morning Sometimes symptoms improve with exertion Associated with smoking Diagnosis: usually based on history Variant (Prinzmetal) Angina Treatment Quit smoking Calcium channel blockers, nitrates Dihydropyridine CCB: amlodipine Vasodilators Dilate coronary arteries, oppose spasm Avoid propranolol Nonselective beta blocker Can cause unopposed alpha stimulation Symptoms may worsen Pixabay/Public Domain Acute Coronary Syndromes Plaque rupture → thrombus formation Subtotal occlusion Unstable angina Non-ST elevation myocardial infarction Total occlusion (100%) Subtotal Occlusion ST-elevation myocardial infarction (STEMI) Subendocardial Ischemia Transmural Ischemia Total Occlusion Unstable Angina and NSTEMI Unstable angina Ischemic symptoms occurring with increasing frequency or at rest Negative biomarkers NSTEMI Positive biomarkers Ischemic EKG changes (other than ST-elevation) may occur in both UA/NSTEMI ECG Changes ST depressions T-wave inversions UA/NSTEMI Cardiac Biomarkers Biomarkers spill into blood with cardiac injury Most common marker used: Troponin I or T Increase 2-4 hours after MI Stay elevated for weeks CK-MB also used Increase 4-6 hours after MI Normalize within 2-3 days Very good for re-infarction Treatment of UA/NSTEMI Thrombotic and ischemic syndrome (like STEMI) No “ticking clock” (unlike STEMI) Subtotal occlusion Some blood flow to distal myocardium No emergency angioplasty No benefit to thrombolysis Aspirin Beta-blocker Heparin Angioplasty (non-emergent) Typical UA/NSTEMI Course Presents to ER with chest pain Biomarkers elevated Absence of ST-segment elevations Obtain EKG in all chest pain patients Medical Therapy Aspirin Give aspirin to chest pain patients with possible NSTEMI Metoprolol Heparin drip Admitted to cardiac floor Hospital day 2 → angiography 90% blockage of LAD → Stent UA/NSTEMI Treatment Long-term therapy Goal: ↓ mortality and recurrent infarction Aspirin Statin Beta-blocker for prevention of recurrent disease Strong indication in STEMI Weak indication NSTEMI/UA Used for prevention in NSTEMI only STEMI Jason Ryan, MD, MPH STEMI ST-Elevation Myocardial Infarction Angina at rest with ST-segment elevation Biomarkers elevated after 4-6 hours Leads go together ST Elevations - Anterior Leads go together ST Elevations - Anterior Leads go together ST Elevations - Lateral Leads go together ST Elevations - Lateral Leads go together ST Elevations - Inferior Leads go together ST Elevations - Inferior Posterior STEMI Anterior ST depressions with standard leads V7 ST-elevation in posterior leads (V7-V9) V8 V9 Left Main Occlusion Special Complications Inferior MI Right ventricular infarction Occurs in inferior STEMI (II, III, aVF) Loss of right ventricular contractility Elevated jugular venous pressure Decreased preload to left ventricle → hypotension Diagnosis: right-sided chest leads Avoid nitroglycerine Treatment: IV fluids (↑ preload) Special Complications Inferior MI Sinus bradycardia and heart block Inferior wall ischemia RCA: SA node 60%, AV node 90% Special Complications Anterior MI Cardiogenic shock Usually occurs with large anterior STEMIs Hypotension Tachycardia Pulmonary edema Respiratory distress Treatment of STEMI “Time is muscle” Coronary artery occluded by thrombus Longer occlusion → more muscle dies More likely the patient may die More heart failure symptoms More future hospitalization for heart disease n=1791 Medical emergency Treatment of STEMI Main objective is to open the artery “Revascularization” Option 1: Emergency angioplasty Mechanical opening of artery Stent placemnt Should be done < 90min Option 2: Thrombolysis Alteplase, TPA Should be done < 30min “Door to balloon” or “door to needle” Treatment of STEMI Time matters Medical therapy is supportive Given while working to open artery This is a thrombotic problem Aspirin to inhibit platelet aggregation Heparin to inhibit clot formation This is also an ischemic problem Beta-blockers to reduce O2 demand Nitrates to reduce O2 demand Cautions Beta-blockers Inferior MI Bradycardia and AV block can develop Nitrates Occlusion of RCA can cause RV infarct RV infarction → ↓ preload Nitrates ↓ preload→ hypotension Other STEMI Treatments Clopidogrel ADP receptor blocker Inhibits platelets Eptifibatide IIB/IIIA receptor blocker Inhibits platelets Bivalirudin Direct thrombin inhibitor Inhibits clot formation Typical STEMI Course Arrival in ER with chest pain 5:42 pm EKG done 5:50 pm STEMI identified Cardiac cath lab activated for emergent angioplasty Meds given in ER Aspirin Metoprolol Nitro drip Heparin bolus Transport to cath lab 6:15 pm Artery opened with balloon 6:42 pm DTB time 60 minutes (ideal < 90min) Typical STEMI Course Arrival in ER with chest pain 5:42 pm EKG done 5:54 pm STEMI identified Meds given in ER Aspirin Metoprolol Nitro drip Heparin bolus tPA given based on weight 6:07 pm IV push Door to needle time 25 min (ideal < 30) Complications of Ischemia First 4 days Arrhythmia 5 – 10 days Free wall rupture Tamponade Papillary muscle rupture VSD (septal rupture) Weeks later Dressler’s syndrome Aneurysm LV Thrombus/CVA Cause of Death 0 – 4 days after MI Sudden Cardiac Death Most common cause among older patients: myocardial infarction Ventricular tachycardia → ventricular fibrillation → cardiac arrest Cause of Death 5-10 days after MI Free wall rupture Best Test: Usually fatal – sudden death Transthoracic Echocardiogram May lead to tamponade Papillary muscle rupture Acute mitral regurgitation (holosystolic murmur) Heart failure, respiratory distress More common inferior MIs Septal rupture – VSD Loud, holosystolic murmur (thrill) Hypotension, right heart failure (↑ JVP, edema) Ventricular Aneurysm Weeks to months after MI More common anterior infarction Risk of thrombus → stroke, peripheral embolism Causes persistent ST elevations Patrick J. Lynch, medical illustrator/Wikipedia Ventricular Aneurysm Weeks to months after MI Ventricular Pseudoaneurysm 1 to 2 weeks after MI Rupture contained by pericardium/scar tissue Not a true aneurysm No endocardium or myocardium May rupture Presents as chest pain or dyspnea Often seen in the inferior wall Occurs earlier (< 2 weeks) than true aneurysm Dressler’s Syndrome Weeks to months after MI Form of pericarditis Chest pain Friction rub Immune-mediated (details not known) Diagnosis: clinical Treatment: NSAIDs or steroids Fibrinous Pericarditis Occurs days after MI Sometimes called “post-MI” pericarditis Not autoimmune Extension of myocardial inflammation Dressler’s occurs weeks after MI Sometimes called “post cardiac injury” pericarditis Rarely life-threatening Diagnosis: clinical Evaluation of Chest Pain Must consider: STEMI, aortic dissection and pulmonary embolism Best first test: EKG to evaluate for STEMI Additional testing considerations: CT scan (PE or dissection) Cardiac biomarkers (NSTEMI) D-dimer Public Domain Heart Failure I Jason Ryan, MD, MPH Heart Failure Definition Clinical syndrome Impaired ability of left ventricle to fill or eject blood Heart Failure Types Heart failure with reduced ejection fraction HFrEF Systolic heart failure Problem ejecting blood from left ventricle Usually caused by a dilated cardiomyopathy Heart failure with preserved ejection fraction HFpEF Diastolic heart failure Problem filling left ventricle with blood Diastolic Heart Failure Systolic Heart Failure EF is normal (55-65%) Ejection fraction is reduced Volume Status Euvolemic Hypervolemic Volume overloaded Wet Hypovolemic Volume depleted Dry Most heart failure symptoms from volume overload Volume Status Assessed by physical exam Rales, edema, jugular venous pressure Unrelated to ejection fraction LVEF of 20% can be dry LVEF of 70% can be wet Wikipedia/Public Domain Heart Failure Volume Overload Symptoms Normal Pulmonary Edema Dyspnea Orthopnea Paroxysmal nocturnal dyspnea Classic finding is rales Fluid filled alveoli “pop” open on inspiration Chest X-ray shows congestion Increased Pressures Increased left atrial pressure Pulmonary capillary wedge pressure Increased pulmonary artery pressure Increased right atrial pressure NYHA Classification Class Symptoms I Asymptomatic II Symptoms with moderate exertion III Symptoms with activities of daily living IV Symptoms at rest S3 Gallop Signs/Symptoms Classic finding associated with increased LA pressure Indicates volume overload state Normal finding in children, pregnant women S4 S1 S2 S3 Heart Failure Signs/Symptoms Elevated jugular venous pressure (normal 6-8cmH2O) Look for height of double bounce Hepatojugular reflux Heart Failure Signs/Symptoms Lower extremity pitting edema Increased capillary hydrostatic pressure Fluid leak from capillaries → tissues Gravity pulls fluid to lower extremities James Heilman, MD/Wikipedia EKG and Echocardiogram EKG Exclude ischemia as precipitating cause Q waves suggest prior infarction Evaluate for arrhythmia (atrial fibrillation) Transthoracic echocardiogram Used to distinguish HFpEF from HFrEF Critical to determine therapy Brain Natriuretic Peptide BNP ANP (atrial natriuretic peptide) released by atrial myocytes BNP (brain natriuretic peptide) released by ventricles Serum levels rise with volume/pressure overload Both counter effects of RAAS system BNP sometimes used for diagnosis in dyspnea Highly sensitive for diagnosis of heart failure High levels seen in most cases of heart failure but also many other disorders Low levels strongly suggest other causes of dyspnea ANP/BNP RAAS Right heart catheterization Pulmonary Artery Catheterization Increased PCWP = left heart congestion/failure PCWP = pulmonary capillary wedge pressure Increased RA, RVEDP = right heart congestion/failure BruceBlaus Heart Failure Diagnosis History Physical examination Chest X-ray Transthoracic echocardiogram EKG BNP level Right heart catheterization Cor Pulmonale Isolated right heart failure Hypertrophy Dilation Decreased contractility Caused by long standing pulmonary hypertension Lung disease (e.g., COPD) Primary pulmonary hypertension Cor Pulmonale Dyspnea with right heart failure Elevated jugular venous pressure Lower extremity edema Hepatomegaly Absence of rales Treatment: Usually aimed at underlying disease (COPD, etc.) High Output Heart Failure Exact mechanism unclear Decreased LV filling time Defining characteristic: HIGH cardiac output Heart failure symptoms in absence of low output ↑JVP, pulmonary edema Heart in overdrive John Liu/Flikr Severe anemia Thyroid disease Thiamine (B1) vitamin deficiency (beriberi) A-V fistulas Heart Failure II Jason Ryan, MD, MPH Heart Failure Treatment Acute heart failure Volume overloaded Goal: improve symptoms of dyspnea, pulmonary congestion Chronic heart failure Euvolemic Goal: prevention of hospitalizations, mortality Acute Heart Failure Goal: reduce left atrial pressure and remove fluid Improves pulmonary edema Most commonly used drug class: loop diuretics Furosemide, torsemide Increased urine output Reduce intracardiac pressures Improve pulmonary edema and lower extremity edema Main adverse effect: hypokalemia Other adverse effects: acute renal failure, hypotension Also cause some venous dilation: ↓ left atrial pressure Acute Heart Failure Nitroglycerine Venous dilation → pool volume in venous system Reduces left atrial pressure Improves dyspnea Afterload reducers Nitroglycerine Hydralazine, ACE-inhibitors Increased cardiac output → improve renal perfusion → diuresis Hydralazine Captopril Chronic Heart Failure HFpEF No specific therapies Control blood pressure, blood sugar Chronic diuretics often used (furosemide) HFrEF Many specific therapies shown to reduce hospitalizations and mortality Treatments aimed at prevention of cardiomyopathy progression Chronic Systolic Heart Failure Goal: reduce hospitalizations and mortality Guideline directed medical treatment (GDMT) Beta-blockers (metoprolol, carvedilol, bisoprolol) ACE-inhibitors (captopril, lisinopril) Aldosterone antagonists (spironolactone, eplerenone) Neprilysin inhibitors (sacubitril → increases ANP) Ivabradine (inhibits SA node → ↓ heart rate) Nitrates/hydralazine (combination therapy) Most drugs disrupt chronic activation of SNS and RAAS Prevent cardiac remodeling (progression of LV dysfunction) ICD Implantable Cardiac Defibrillator Annual risk SCD > 20% some studies Most due to ventricular tachycardia ICD Implantable Cardiac Defibrillator Improve mortality in appropriate patients Indications: Aborted sudden cardiac death LVEF < 35% Biventricular Pacemakers Cardiac Resynchronization Therapy (CRT) Out of Synch After Pacemaker Biventricular Pacemakers Cardiac Resynchronization Therapy (CRT) Improve mortality in appropriate patients Indications: Left bundle branch block (wide QRS; > 120ms) LVEF < 35% QRS > 120ms Downward in lead V1 Heart Failure Treatment Pathway Acute Heart Failure Furosemide Nitroglycerine Rx Afterload reducers Chronic Heart Failure Diastolic Systolic Heart Failure Heart Failure No specific therapy Drugs ICD Bi-V Pacer Advanced Heart Failure Severe form of HFrEF Severely reduced cardiac output Fatigue Hypotension Cool extremities Confusion Decreased appetite (cardiac cachexia) Advanced Heart Failure Treatments Inotropes (associated with ↑ mortality) Dobutamine Milrinone Digoxin (oral) Left ventricular assist devices (LVADs) Heart transplantation Acute Exacerbations Causes #1: Dietary indiscretion High salt intake #2: Poor medication compliance LukeB20161933/Wikipedia Pixabay/Public Domain Acute Exacerbations Causes Infection/trauma/surgery Activation of sympathetic nervous system Ischemia (rare) Decreased cardiac output Arrhythmias (A fib) NSAIDs Inhibit cyclooxygenase (COX) → ↓ prostaglandins Prostaglandins maintain renal perfusion Result: Less renal perfusion → salt/water retention Typical Acute Heart Failure Course ER presentation: Dyspnea, edema, sleeping in chair Admitted to hospital Nitro drip to relieve dyspnea IV Furosemide to remove fluid Hospital Day 2 Weight down 4 kg, feels better Nitro drip stopped Changed to oral furosemide Hospital Day 3: Discharge More Complex Heart Failure Course ER presentation: Dyspnea, edema, sleeping in chair Known LVEF 10% Admitted to hospital Nitro drip to relieve dyspnea IV Furosemide to remove fluid Hospital Day 2 Poor urine output, Cool extremities, Cr rises 1.1→1.4 Dobutamine drip started More Complex Heart Failure Course Hospital Day 3-5 Good urine output Weight loss 4 kg Breathing improves Hospital Day 6 Dobutamine stopped Furosemide drip stopped Hospital Day 7 Oral furosemide given Hospital Day 8: Discharge Noninvasive Ventilation Positive pressure ventilation Administered through mask not ETT Used in acute respiratory failure Often effective for pulmonary edema Often avoids intubation Patient must be awake, alert, cooperative Classic case HF patient in respiratory distress Tachypnea, hypoxemia NIV → improved respiratory status Wikipedia/Public Domain Functional Mitral Regurgitation Caused by left ventricular dilatation Mitral valve leaflets pulled apart Can cause holosystolic murmur at cardiac apex May resolve with diuresis Hyponatremia Occurs in severe heart failure RAAS activation → ADH release → water retention Poor renal perfusion → decreased water excretion Poor prognostic indicator Venous Stasis Edema Common in the elderly Caused by poor venous drainage Unrelated to heart No dyspnea Normal lung exam Normal jugular venous pressure Treatments: Leg elevation Compression stockings Diuretics rarely work May lead to skin ulcers/infection Drugs to Avoid in Heart Failure Metformin May cause lactic acidosis Thiazolidinediones (glitazones) Pioglitazone, rosiglitazone Cause fluid retention Calcium channel blockers Negative inotropes NSAIDs Cause fluid retention Public Domain Cardiomyopathy Jason Ryan, MD, MPH Dilated Cardiomyopathy Systolic heart failure with LV cavity dilation “Eccentric” hypertrophy Volume overload (chronic retention of fluid in cavity) Longer myocytes Sarcomeres added in series Normal LV Size Dilated LV Increased myocyte size Sarcomeres in series Normal wall thickness Dilated Cardiomyopathy Symptoms Depend on volume status Volume overload → acute systolic heart failure Dyspnea Pitting edema Severely reduced LVEF Fatigue Cachexia Confusion Dilated Cardiomyopathy Diagnosis: Transthoracic echocardiography Treatment: Guideline directed medical treatment (GDMT) Beta-blockers ACE inhibitors Aldosterone antagonists Neprilysin inhibitors Defibrillators Bi-ventricular pacemakers Ejection fraction is reduced Dilated Cardiomyopathy Most common cause: myocardial infarction Ischemic cardiomyopathy Myocytes replaced by scar tissue Focal hypokinesis (e.g., anterior wall) Many causes of “non-ischemic” cardiomyopathy About 50% idiopathic Many other causes Global hypokinesis Nonischemic Cardiomyopathy Viral May follow upper respiratory infection Many associated viruses Coxsackie Influenza, adenovirus, others No specific therapy for virus Pixabay/Public Domain Nonischemic Cardiomyopathy Peripartum Late in pregnancy or early post-pregnancy Exact cause unknown (likely multifactorial) Women often advised to avoid future pregnancy Øyvind Holmstad/Wikipedia Nonischemic Cardiomyopathy Chemotherapy Usually after treatment with anthracyclines Antitumor antibiotics Doxorubicin and daunorubicin Daunorubicin Doxorubicin (Adriamycin) Nonischemic Cardiomyopathy Familial Mutations Often sarcomere proteins Beta-myosin heavy chain Alpha-myosin heavy chain Troponin Many autosomal dominant X-linked, autosomal recessive also described Wikipedia/Public Domain Nonischemic Cardiomyopathy Tachycardia-mediated Constant, rapid heart rate for weeks/months Leads to depression of LV systolic function Reversible with slower heart rate Nonischemic Cardiomyopathy Takotsubo/Apical ballooning Stress-induced cardiomyopathy Occurs after severe emotional distress and high catecholamines Markedly reduced LVEF Increase CK, MB, Troponin; EKG changes Looks like anterior MI (but no coronary disease) Usually recovers 4-6 weeks Diastole Systole Alcohol Chronic consumption can cause cardiomyopathy Believed to be due to toxic metabolites Can recover with cessation of alcohol Pixabay/Public Domain Restrictive Cardiomyopathy Something “infiltrates” the myocardium Amyloid protein (Amyloidosis) Heart cannot relax and fill SEVERE diastolic dysfunction Presents as diastolic heart failure Treatment: diuretics Also treat underlying cause MarkBuckawicki/Wikipedia Restrictive Cardiomyopathy LVEF = normal Restricted filling = ↑ atrial pressure Dilated left and right atria Classic imaging findings: Normal left ventricular function/size Bi-atrial enlargement Restrictive Cardiomyopathy Normal Restrictive Cardiomyopathy Restrictive Cardiomyopathy Clinical Features Dyspnea Prominent right heart failure Markedly elevated jugular venous pressure Lower extremity edema Liver congestion May lead to cirrhosis Restrictive Cardiomyopathy Classic signs Kussmaul’s sign Inspiration causes rise in JVP Restrictive Cardiomyopathy Major Causes Amyloidosis Sarcoidosis Fabry disease (lysosomal storage disease) Hemochromatosis (rare) Post-radiation Loeffler’s syndrome (hypereosinophilic syndrome) Ed Uthman, MD Endocardial fibroelastosis (babies) Hypertrophic Cardiomyopathy Cardiomyopathy of myocyte hypertrophy Concentric hypertrophy Pathologic hypertrophy Not due to stress Absence of HTN or athlete’s heart Diagnosis: Echocardiography Genetic testing LVEF normal with increased wall thickness Hypertrophic Cardiomyopathy Normal Hypertrophic Cardiomyopathy Hypertrophic Cardiomyopathy Genetic disorder caused by gene mutations About 50% cases familial (50% sporadic) Autosomal dominant Variable expression Significant variation in severity of symptoms Many variations in location/severity of hypertrophy Wikipedia/Public Domain Hypertrophic Cardiomyopathy Clinical Features Many patients asymptomatic Many symptoms from LVOT obstruction Left ventricular outflow tract Hypertrophic Cardiomyopathy Clinical Features Heart failure Diastolic dysfunction LVOT obstruction Chest pain (angina) Increased O2 demand Hypertrophic Cardiomyopathy Clinical Features Sudden cardiac death Abnormal myocytes → ventricular arrhythmias Most common cause SCD in young patients Syncope Arrhythmias may lead to syncope LVOT obstruction Mitral regurgitation Systolic anterior motion (SAM) Hypertrophic Cardiomyopathy Clinical Features EKG: Left ventricular hypertrophy (LVH) Normal Hypertrophic Cardiomyopathy Hypertrophic Cardiomyopathy Clinical Features Systolic ejection murmur Usually left lower sternal border Caused by outflow tract obstruction Sounds just like AS unless you do maneuvers Other associated abnormal heart sounds S4 Holosystolic murmur of MR Paradoxical split S2 S1 S2 Hypertrophic Cardiomyopathy Maneuvers For any HCM maneuver, think about size of LV ↑ LV size → ↓ murmur ↓ LV size → ↑ murmur Hypertrophic Cardiomyopathy Maneuvers Valsalva Patient bears down as if having a bowel movement Or blows out against closed glottis Increase thoracic pressure → compression of veins → ↓ VR Less VR → Less preload → Smaller LV cavity Obstructing septum moves further into the outflow tract Murmur INCREASES in intensity Hypertrophic Cardiomyopathy Maneuvers Squatting Forces blood volume stored in legs to return to heart Preload rises → size of LV increases → less obstruction Murmur DECREASES in intensity Raising the legs Increases venous return Murmur DECREASES in intensity Standing Opposite mechanism of leg raise Murmur INCREASES in intensity Wikipedia Aortic Stenosis Both HCM and AS cause a systolic ejection murmur Opposite effects of maneuvers in aortic stenosis Less preload → less flow → quieter AS murmur Hypertrophic Cardiomyopathy Associations Maternal diabetes Infants: transient hypertrophic cardiomyopathy Usually thickening of interventricular septum Resolves by a few months of age Friedreich Ataxia Autosomal recessive CNS disease Cause of death Øyvind Holmstad/Wikipedia Wikipedia/Public Domain Hypertrophic Cardiomyopathy Treatment Beta-blockers and calcium channel blockers ↓ contractility ↓ outflow gradient Surgery Myomectomy Alcohol septal ablation Eliminates outflow obstruction Cautious diuretics for pulmonary edema ↓ preload → hypotension Implantable cardiac defibrillators (ICDs) ARVD Arrhythmogenic right ventricular dysplasia Genetic disorder Cardiomyopathy of right ventricle → arrhythmias Associated with sudden cardiac death in young adults EKG: epsilon wave Diagnosis: cardiac MRI Heart Murmurs Jason Ryan, MD, MPH Heart Murmurs Cardiac sound heard with stethoscope Caused by turbulent blood flow May be normal or pathologic Wikipedia/Public Domain Murmurs Grading I - barely audible on listening carefully II - faint but easily audible III - loud and easily audible, no thrill IV - loud murmur with a thrill V –heard with scope barely touching chest VI - audible with scope not touching the chest  LUSB Pulmonic Stenosis RUSB PDA Aortic Stenosis A P LSB Aortic Regurg T Apex M Mitral Regurg Pulm Regurg HCM Mitral Stenosis MVP LLSB Tricuspid Regurg VSD Innocent/Functional Murmurs Caused by normal flow of blood Common in children Also young, thin patients Generally soft murmurs No signs/symptoms of heart disease Stills murmur Pulmonic flow murmur Venous hum Systolic Murmurs Occur when heart contracts/squeezes Between S1-S2 Flow murmur (benign) Aortic stenosis Mitral regurgitation Pulmonic stenosis Tricuspid regurgitation Hypertrophic cardiomyopathy Ventricular septal defect (VSD) Diastolic Murmurs Occur when heart relaxes/fills Between S2-S1 Aortic regurgitation Mitral stenosis Pulmonic regurgitation Tricuspid stenosis Murmur Evaluation Test of choice: transthoracic echocardiography Visualize valves Measure flow velocities Aortic Stenosis Murmur Systolic crescendo-decrescendo murmur Also called an “ejection murmur” S1 S2 Aortic Stenosis Severe Disease Findings Late-peaking murmur Slow flow across stenotic valve Soft/quiet S2 Stiff valve can’t slam shut Pulsus parvus et tardus Weak and small carotid pulses Delayed carotid upstroke HCM Hypertrophic Cardiomyopathy Same murmur as aortic stenosis Differentiated by maneuvers Valsalva Decreases venous return/preload Increases HCM murmur Decreases AS murmur HCM Aortic Regurgitation Aortic insufficiency, aortic incompetence Decrescendo, blowing diastolic murmur S1 S2 Mitral Regurgitation Holosystolic murmur heard best at the apex 5th intercostal space, mid-clavicular line S1 S2 Holosystolic (Pansystolic) Mitral Stenosis Diastolic rumbling murmur preceded by opening snap Loud S1 Systole Diastole Systole Diastole Diastolic Rumble S1 S2 OS (Murmur) Mitral Stenosis No left sided S3, S4 in mitral stenosis Time to opening snap associated with severity High left atrial pressure in severe disease Higher left atrial pressure → ↓ time to opening snap Short time to opening snap seen in severe disease Tricuspid/Pulmonic Disease Valve lesions sound like left-sided counterparts Heard in different locations Carvallo’s Sign Tricuspid regurgitation gets louder during inspiration Mitral regurgitation gets softer during inspiration Inspiration draws blood volume to lungs Louder right sided murmurs Softer left-sided murmurs Exhalation does the opposite rIght-sided murmurs increase with Inspiration lEft-sided murmurs increase with Exhalation PDA Patent Ductus Arteriosus Continuous, “machine-like” murmur S1 S2 S1 S2 Maneuvers Performed at bedside with patient May increase or decrease murmur Used to make diagnosis Davidjr74/Wikipedia Maneuvers Preload/Venous Return Increase preload/venous return Leg raise – blood falls back toward heart Squatting – blood in legs forced back toward heart Decrease preload/venous return Valsalva- ↑ intra-thoracic pressure→ vein compression →↓ VR Standing – Blood falls toward feet, away from heart Most murmurs INCREASE with more preload except: HCM MVP Maneuvers Afterload Increase Afterload Hand grip - clench fist Decrease Afterload Amyl Nitrate - vasodilator Amyl Nitrate Maneuvers Afterload Backward Disorders AR, MR, VSD Louder with more afterload Forward Disorders MS, AS Softer with more afterload MVP, HCM Softer Increased LV cavity size Heart Sounds Jason Ryan, MD, MPH S1 and S2 S1 S2 Normal heart sounds Each has two components One from left-sided valves (aortic, mitral) MV TV AV PV One from right-sided valves (tricuspid, pulmonic) S1 usually “single” Two components close together Cannot distinguish separate sounds S2 can be “split” Two components far enough apart to be audible Wikipedia/Public Domain Physiologic S2 splitting S1 S2 Exhalation MV TV AV PV S1 S2 Inspiration MV TV AV PV Increased venous return delays P2 by 40-60 ms Single to split with inspiration Persistent S2 splitting RBBB or Pulmonary Hypertension S1 S2 Exhalation PeRsistent = Right-sided delay MV TV AV PV S1 S2 Inspiration AV PV MV TV Delayed PV closure even during exhalation Fixed S2 splitting Atrial septal defect S1 S2 Atrial Septal Defect Fixed split S2 Systolic Ejection Murmur LSB Exhalation MV TV AV PV S1 S2 Inspiration AV PV MV TV Flow across ASD → increased right-sided flow Paradoxical S2 splitting Delayed closure of aortic valve S1 S2 Exhalation MV TV PV AV S1 S2 Inspiration MV TV PV AV Paradoxical Splitting Electrical causes → delayed LV activation LBBB RV pacing Mechanical causes → delayed LV outflow LV systolic failure Aortic stenosis Hypertrophic cardiomyopathy ParadoxicaL = Left-sided delay Loud P2 S1 S2 Loud pulmonic component of S2 Pulmonary hypertension Forceful closure of pulmonary valve Normally P2 not heard at apex MV TV AV PV If you hear it here, it’s “loud” S3 and S4 Pathologic/abnormal heart sounds Occur in diastole during filling of left ventricle Low-pitched sounds heard best with bell S3: Early filling sound S4: Late filling sound S1 S2 S4 S1 S2 S3 Tama988/Wikipedia S3 Commonly seen in acute heart failure High LA pressure → rapid early filling of LV → S3 Associated with ↑ LAP & ↑ LVEDP Very specific sign of high left atrial pressure May be heard in normal hearts Young patients (< 30), pregnant women Vigorous LV relaxation Wikipedia/Public Domain S3 Louder in left lateral decubitus position Loudest at apex Rama/Wikipedia S4 Heard in patients with stiff left ventricle Long-standing hypertension Hypertrophic cardiomyopathy Diastolic heart failure Rapid late filling of LV due to atrial kick Not heard in atrial fibrillation Atrial Fibrillation Systolic Clicks Click Click S1 S2 S1 S2 Ejection Click Non-Ejection Click Early in systole Late in systole BEFORE carotid pulse AFTER carotid pulse Bicuspid Aortic Valve Mitral Valve Prolapse Pulmonic stenosis Mitral Valve Prolapse Classic Patients Young women Billowing of mitral valve leaflets above annulus Marfan syndrome Common cause of mitral regurgitation Causes a systolic click Don’t confuse with opening snap of mitral stenosis (diastole) Normal MVP Mitral Valve Prolapse Systole Diastole Click S1 Murmur S2 Murmur intensity increases with Valsalva Cardiovascular Pharmacology I Jason Ryan, MD, MPH Beta-blockers β1-selective antagonists Atenolol, Metoprolol, Esmolol, Bisoprolol Used for hypertension Blockade → ↓ CO → ↓ BP Metoprolol: systolic heart failure Blocks sympathetic stimulation of heart Reduces mortality Beta-blockers β1β2 (nonselective) antagonists Propranolol, Timolol, Nadolol Nadolol, Propranolol: Used in portal hypertension Beta 1 blockade: ↓ CO, ↓ ECV → ↓ BP Beta 2 blockade: ↓ portal blood flow Timolol: Used in glaucoma Beta 1 and Beta 2 → aqueous humor production Propranolol: hyperthyroidism Blocks T4 → T3 conversion Wikimedia Commons/Public Domain Beta-blockers β1β2α1 Labetalol: hypertensive emergency Rapid reduction in blood pressure Carvedilol: systolic heart failure Blocks sympathetic stimulation of heart Reduces mortality Wikimedia Commons/Public Domain Beta-blockers Side effects Fatigue, erectile dysfunction, depression More common with older beta-blockers (propranolol) Hyperlipidemia Mild increase in triglycerides Mild decrease in HDL Effect varies with different beta-blockers Wikimedia Commons/Public Domain Beta-blockers Side effects Caution in diabetes Blockade of epinephrine effects Epinephrine raises glucose levels Blockade → hypoglycemia Blockade of hypoglycemia symptoms ↓ glucose → sweating/tachycardia Symptoms “masked” by beta-blockers Victor/Flikr Beta-blockers Side effects Caution in asthma/COPD Β2-receptors: bronchodilators Β2-blockade may cause a flare Β1-blockers (“cardioselective”) often used Decompensated heart failure Β1-blockers lower cardiac output → worsening of symptoms Commonly used in compensated heart failure Mortality benefit Wikimedia Commons/Public Domain Beta-blockers Overdose Depression of myocardial contractility → shock Bradycardia/AV block Treatment: glucagon Wikimedia Commons/Public Domain Calcium Channel Blockers Three major classes of calcium antagonists dihydropyridines (amlodipine) phenylalkylamines (verapamil) benzothiazepines (diltiazem) Vasodilators and negative chronotropes/inotropes Amlodipine Verapamil Diltiazem Calcium Channel Blockers Dihydropyridines (nifedipine) → vasodilators Main effect: ↓ TPR/BP Amlodipine Non-dihydropyridines (verapamil, diltiazem) Similar to β1-blockers Main effects: ↓HR; ↓ contractility Vascular smooth muscle effects Nifedipine>Diltiazem>Verapamil Verapamil Heart rate/contractility effects Verapamil>Diltiazem>Nifedipine Diltiazem Calcium Channel Blockers Dihydropyridines (amlodipine) Used for hypertension Flushing, headache, hypotension Peripheral vasodilation Key side effect: edema Pre-capillary arteriolar vasodilation Flood capillaries with fluid → edema Amlodipine James Heilman, MD/Wikipedia Calcium Channel Blockers Verapamil, diltiazem Used for hypertension Also used in heart disease Arrhythmias (atrial fibrillation) Verapamil Stable angina (lower oxygen demand) Potential side effect: negative inotropes Contraindicated in heart failure Diltiazem Calcium Channel Blockers Other Side Effects Constipation Most commonly with verapamil Hyperprolactinemia Seen with verapamil Blocks calcium channels CNS → ↓ dopamine release Galactorrhea Leads to hypogonadism Men: ↓ libido, impotence Pre-menopausal women: irregular menses Elya/Wikipedia Calcium Channel Blockers Other Side Effects Gingival hyperplasia Seen in all types CCB Also with phenytoin, cyclosporine Lesion/Wikipedia Vaughan Williams Classification Class I Class II Quinidine Procainamide Ia Lidocaine Beta-blockers Mexiletine Ib Flecainide Propafenone Ic Class III Class IV Amiodarone Sotalol Ca-channel Blockers Dofetilide (Verapamil/Diltiazem) Ibutilide Amiodarone Delayed Repolarization K+ Channel Blockade Class III drug K channel blocker Prolongs Qt interval Also has class I, II, and IV effects Class II, IV: Slow HR ↑ QT Interval Highly effective drug Suppresses atrial fibrillation Suppresses ventricular tachycardia Amiodarone Amiodarone Highly lipid soluble Accumulates in liver, lungs, skin, other tissues Half-life about 58 days Once steady state reached, very long washout Safe in renal disease (biliary excretion) Amiodarone Amiodarone Many potential side effects related to accumulation Less likely at lower dosages Risk accumulates over time Young patients on indefinite therapy at greatest risk Often used in older patients Amiodarone Side Effects Hyper and hypothyroidism Contains iodine Increased LFTs Usually asymptomatic and mild Drug stopped if elevation is marked Skin sensitivity to sun Patients easily sunburn Wikipedia/Public Domain Amiodarone Side Effects Blue-gray discoloration Less common skin reaction “Blue man syndrome” Most prominent on face Corneal deposits Secretion of amiodarone by lacrimal glands Accumulation on corneal surface Abby Crawford/Youtube/Public Domain Appearance of “cat whiskers” on cornea Does not usually cause vision problems See in many patients on chronic therapy Amiodarone Side Effects Pulmonary fibrosis Most common cause of death from amiodarone Foamy macrophages seen in air spaces Filled with amiodarone and phospholipids “Honeycombing” pattern on chest x-ray Public Domain Amiodarone Side Effects When starting amiodarone Chest X-ray Pulmonary function tests (PFTs) Thyroid function tests (TFTs) Liver function tests (LFTs) Sotalol and Dofetilide Commonly used in patients with atrial fibrillation Typical case Recurrent episodes symptomatic atrial fibrillation Sotalol/Dofetilide started Cardioversion to restore sinus rhythm Sinus rhythm persists on therapy Other antiarrhythmics also used in this manner Amiodarone Propafenone Flecainide Ibutilide Intravenous drug Half life of 2 to 12 hours Used for “chemical cardioversion” Class III Antiarrhythmic Drugs Amiodarone, sotalol, dofetilide, ibutilide Major adverse effect: prolongation of Qt interval Increased risk of torsades de pointes Class I drugs Effects on Resting Action Potential Ia Ib Ic ↑QRS ↑QT +/-QRS ↓ QT ↑ QRS +/-QT Class Ia Drugs Quinidine, procainamide Prolong QRS Can also prolong Qt (↓K+ outflow) Quinidine Oral drug Can decrease recurrence rate of atrial fibrillation Associated with increased mortality Procainamide Intravenous drug Slows conduction in accessory pathways (WPW) Used in arrhythmias associated with bypass tracts Procainamide Associated with drug-induced lupus Classic drugs: INH, hydralazine, procainamide Often rash, arthritis, anemia Antinuclear antibody (ANA) can be positive Key features: anti-histone antibodies Resolves on stopping the drug Pixabay/Public Domain Class Ib Drugs Ib Lidocaine, Mexiletine Na channel blockers Most Na channel binding in depolarized state Ischemia → more depolarized myocytes Effective drugs in ischemic arrhythmias More effective at fast heart rates Less time to unbind before Na channels open again +/-QRS ↓ QT Main use: ischemic ventricular tachycardia Fast heart rates Depolarized Na channels Class Ib Drugs Lidocaine, Mexiletine Lidocaine also a local anesthetic Na channel nerve block May cause CNS stimulation Tremor, agitation Tremor in patient on Mexiletine = toxicity Cardiovascular side effects From excessive block of Na channels Bradycardia, heart block, hypotension  Ic Class Ic Antiarrhythmic Drugs Flecainide, propafenone Used for suppression of atrial fibrillation Only used in patients with “structurally normal hearts” Normal LV function ↑ QRS +/-QT No significant valvular disease Major adverse effect: prolongation of QRS interval with exercise Baseline Exercise Antiarrhythmic Drugs Class I and class III agents associated with increased mortality Only used when absolutely necessary Recurrent ventricular tachycardia Highly symptomatic atrial fibrillation Not used for PACs or PVCs Premature Ventricular Contraction Cardiovascular Pharmacology II Jason Ryan, MD, MPH Adenosine AV nodal cells: Activates K+ channels Drives K+ out of cells Hyperpolarizes cells: Takes longer to depolarize Result: Slowing of conduction through AV node Adenosine Short half life – given IV Used to treat supraventricular tachycardias Most common SVT: AV node reentrant tachycardia (AVNRT) Slow and fast circuits in AV node → arrhythmia Adenosine slows AV node conduction → arrhythmia will terminate SVT Break with Adenosine Adenosine Also a vasodilator Causes skin flushing, hypotension Some patients also develop dyspnea, chest pain Effects quickly resolve Must warn patients before administration for SVT Jorge González/Flikr Adenosine Effects blocked by theophylline and caffeine Block adenosine receptors Adenosine Caffeine Theophylline Atropine Muscarinic receptor antagonist Parasympathetic block → ↑ HR and AV conduction Used in bradycardia → ↑ heart rate Also speeds conduction through AV node Useful for bradycardia from AV block Before Atropine After Atropine Atropine Many side effects related to muscarinic block Toxicity: Dry mouth Constipation Urinary retention Confusion (elderly) Wikipedia/Public Domain Digoxin Two cardiac effects #1: Increases contractility Used in systolic heart failure with ↓ LVEF #2: Slows AV node conduction Used in atrial fibrillation to slow ventricular rate Digoxin Increased Contractility Inhibits Na-K-ATPase DIGOXIN X K+ 2 1 Ca+ Na+ ATP Digoxin → Na trapped inside of cell Less Na exchange for Ca (pump 2) Result: More Ca inside of cell Digoxin AV Nodal Slowing Suppresses AV node conduction Increased vagal (parasympathetic) tone Separate effect from blockade of Na-K-ATPase Can be used to ↓ heart rate in rapid atrial fibrillation Continued atrial fibrillation Fewer impulses to ventricle → slower heart rate Effects similar to BB and CCB in AV node Digoxin Toxicity Renal clearance Risk of toxicity in patients with chronic kidney disease Hypokalemia promotes toxicity Caused by many diuretics, especially loop diuretics Digoxin patient on furosemide → toxicity Levels often need to be monitored Digoxin Toxicity Gastrointestinal Anorexia, nausea, vomiting, abdominal pain Hyperkalemia Neurologic Lethargy, fatigue Delirium, confusion, disorientation Weakness Visual changes Alterations in color vision, scotomas, blindness Cardiac arrhythmias Digoxin Toxicity Cardiac Toxicity More Na inside of cell ↑ resting potential atrial/ventricular cells Increased automaticity Extra beats: PACs, PVCs Evidence of AV node block Atrial Tachycardia with AV block Digoxin Toxicity Treatment Digibind Antibody binds digoxin Correct hyperkalemia Sacubitril Neprilysin inhibitor Neprilysin: Degrades atrial/brain natriuretic peptide Inhibition → ↑ANP/BNP Antagonists to RAAS system Vasodilatation Natriuresis (sodium excretion) Diuresis (water excretion) Reduced sympathetic tone ANP/BNP RAAS Sacubitril Entresto: oral combination sacubitril/valsartan Valsartan: angiotensin receptor blocker (ARB) ↓ mortality ↓ hospitalizations ANP/BNP RAAS Sacubitril Studied in combination with valsartan Many side effects similar to ARBs Hypotension Hyperkalemia Angioedema Tissue swelling Rare, feared adverse effect Caused by elevated bradykinin levels Neprilysin degrades bradykinin Cannot be given together with ACE inhibitors Ivabradine Selective sinus node inhibitor Elevated HR → worse prognosis Slows heart rate without ↓ contractility Inhibits SA pacemaker “funny current” (If ) Used in patients on max-dose beta-blocker with ↑HR Limited evidence of ↓ mortality and hospitalizations About 15% of patients experience phosphenes Visual disturbance Rings or spots of bright light Ranolazine Used for refractory angina Inhibits late sodium current Reduces calcium overload → high wall tension Reduces wall tension and O2 demand Late Na influx QT prolongation Na Na Ca Nitrates Used to treat stable angina Converted to nitric oxide → vasodilation Predominant mechanism is venous dilation Bigger veins hold more blood Takes blood away from left ventricle Lowers preload Also arterial vasodilation (art 10 mmHg) = pulsus paradoxus Severe fall = pulse disappears Also seen in asthma and COPD Inspiration normally ↓ left sided flow Exaggerated in lung disease Public Domain Pericardial Tamponade EKG Seen in large pericardial effusions Usually tamponade is present Sinus tachycardia Low voltage – EKG sees less electricity due to effusion Electrical Alternans Tamponade Diagnosis and Treatment Diagnosis: Pulsus paradoxus (clinical evidence of tamponade) Transthoracic echocardiography Treatment: Intravenous fluids (do NOT give diuretics) Pericardiocentesis Surgical pericardial window Tamponade Right heart catheterization Equalization of pressures Occurs when cardiac chambers cannot relax Seen in tamponade and pericardial constriction Tamponade/ Parameter Normal Constriction RA mean 5 20 RV Pressure 20/5 44/20 PCWP Pressure 10 20 LVEDP 10 20 Effusions/Tamponade Causes Pericarditis Cancer metastases to pericardium Trauma Constrictive Pericarditis www.learningradiology.com, courtesy of Dr. William Herring, MD, FACR. Used with permission. Constrictive Pericarditis Fibrous, calcified scar in pericardium Loss of elasticity: stiff, thickened, sticky Can result from many pericardial disease processes Pericarditis Radiation to chest Heart surgery Constrictive Pericarditis Clinical Features Major pathologic process: ventricles cannot fill normally Filling abruptly stops Dyspnea (low cardiac output) Nutmeg Liver Prominent right heart failure (dark spots) Markedly-elevated jugular venous pressure Lower extremity edema Liver congestion May lead to cirrhosis (“nutmeg liver”) Public Domain Constrictive Pericarditis Other Features Pulsus paradoxus uncommon (~20%) High RA, RVEDP, PCWP pressures Equalization of pressures Pericardial knock S1 S2 Pericardial Knock Kussmaul’s Sign Inspiration → ↑ VR → slight fall in mean JVP Kussmaul’s sign = ↑ JVP with inspiration Ventricle cannot accept ↑VR Constrictive pericarditis Restrictive cardiomyopathy ac v RV myocardial infarction Pulsus and Kussmaul’s Pulsus paradoxus: classic sign of tamponade Pulsus in tamPonade Kussmaul’s sign: classic sign of constriction Also seen in restrictive heart disease Kussmaul’s in Konstriction/Restriction Tamponade Constriction Restrictive Pulsus Yes No No Kussmaul’s No Yes Yes Constrictive Pericarditis Diagnosis and Treatment ECG: nonspecific findings Chest X-ray Echocardiography: Poor pericardial visualization Shows normal LVEF Enlarged atria Abnormal filling velocities Cardiac MRI or CT Cardiac catheterization Treatment: pericardiectomy Valvular Heart Disease Jason Ryan, MD, MPH Valvular Heart Disease Stenosis Stiffening/thickening of valve leaflets Obstruction to forward blood flow Regurgitation Malcoaptation of valve leaflets Leakage of blood flow backwards across valve Regurgitant Lesions Acute and chronic forms Acute regurgitation (often from endocarditis) May cause shock Chronic regurgitation No shock Leads to chronic heart failure Valve Disorders Diagnosis and treatment Best initial test: transthoracic echocardiography EKG not helpful but may show signs of chamber enlargement Only severe valvular lesions treated Mostly surgical diseases Surgical repair Valve replacement Bioprosthetic (pig or cow) Mechanical (requires life-long anticoagulation) Valvuloplasty (mitral and aortic stenosis) Valve Disorders Medical treatment Medical therapy used rarely in patients with heart failure Loop diuretics Afterload reduction Vasodilators In theory could improve forward flow in regurgitant valve disease (AR, MR) Clinical trials have shown little benefit of drugs Rheumatic Heart Disease Damage to heart valves by rheumatic fever Often presents years after acute rheumatic fever Many patients do not recall acute symptoms Mitral valve most commonly involved Common in developing countries Limited access to medical care for pharyngitis Often seen in immigrants to US Carcinoid Heart Disease Caused by carcinoid tumors of intestines Secrete serotonin Fibrous deposits tricuspid/pulmonic valves Leads to stenosis and regurgitation Serotonin inactivated by lungs Left-sided lesions rare Serotonin Aortic Stenosis Pathophysiology Fibrotic/calcified aortic valve Increased afterload CDC/Public Domain Aortic Stenosis Hemodynamics LV systolic pressure >> aortic systolic pressure LVSP = 160 mmHg (normal = 120) SBP = 120 mmHg (normal = 120) Gradient = 40 mmHg Aortic Stenosis Clinical features Physical Exam Systolic crescendo-decrescendo murmur at 2nd right intercostal space Often radiates to carotids Severe disease findings Soft, single S2 (restricted leaflet motion) Crescendo-Decrescendo Pulsus parvus et tardus Murmur Symptoms Angina Syncope Left heart failure (worst prognosis) S1 S2 Aortic Stenosis Causes Senile aortic stenosis “Wear and tear” Collagen breakdown Calcium deposition Bicuspid aortic valve Rarely rheumatic heart disease Patrick J. Lynch, medical illustrator CDC/Public Domain Aortic Stenosis Special treatments Transcatheter aortic valve replacement (TAVR) No chest incision Faster recovery Public Domain Aortic Regurgitation Pathophysiology Inadequate closure of leaflets → blood leaks across aortic valve in diastole Increased preload, stroke volume Eccentric hypertrophy eventually leading to heart failure Normal LV Size Dilated LV Increased myocyte size Sarcomeres in series Normal wall thickness Aortic Regurgitation Clinical features Blowing, decrescendo diastolic murmur at lower left sternal border S1 S2 Aortic Regurgitation Clinical features Leaking blood back into LV causes low diastolic BP 120/80 (normal) → 120/40 Low diastolic pressure Wide pulse pressure High cardiac output with low diastolic pressure Wide pulse pressure symptoms “Water hammer” pulses Head bobbing Many, many others (mostly historical) Aortic Regurgitation Causes Dilated aortic root → leaflets pull apart Often from HTN or other aortic aneurysm (Marfan) Rarely from tertiary syphilis (aortitis) Bicuspid aortic valve Turner syndrome Coarctation of the aorta Endocarditis Rheumatic heart disease Almost always with mitral disease Mitral Stenosis Pathophysiology Most cases caused by rheumatic heart disease Stiff mitral valve LA pressure >> LV diastolic pressure Left atrial pressure 20 mmHg (normal = 10) LVEDP 5 mmHg (normal = 10) Gradient = 15 mmHg Left atrium may become massively dilated Commonly causes atrial fibrillation Mitral Stenosis Clinical features Most common symptom: dyspnea ↑ LA pressure → pulmonary congestion Murmur: diastolic rumble with opening snap Mitral Stenosis Special treatments Balloon valvuloplasty Used in rheumatic mitral stenosis Breaks up fibrous tissue Valve must have little/no calcium deposition Wikimedia Commons/Public Domain Mitral Regurgitation Clinical Features Holosystolic murmur at apex Radiates to the axilla S1 S2 Mitral Valve Prolapse Primary mitral regurgitation Also called degenerative or myxomatous Billowing of mitral valve leaflets above annulus Causes a systolic click Don’t confuse with opening snap of mitral stenosis Systolic murmur from MR Increases with standing or Valsalva Decreases with squatting Mitral Regurgitation Secondary causes Ischemia → damage to papillary muscle Left ventricular dilation Dilated cardiomyopathy Leaflets pulled apart “Functional” MR Hypertrophic cardiomyopathy Systolic anterior motion (SAM) Mitral Regurgitation Secondary causes Endocarditis Rheumatic heart disease Congenital Cleft mitral valve Endocardial cushion defect Down syndrome Tricuspid Regurgitation Holosystolic murmur at left sternal border Small amount of TR normal (“physiologic TR”) Pathologic causes Functional TR from RV enlargement Endocarditis - classically IV drug users Carcinoid Ebstein’s anomaly S1 S2 Tricuspid Stenosis Very rare valve disorder Diastolic murmur at left lower sternal border Caused by rheumatic heart disease (with mitral disease) Tricuspid regurgitation more common Carcinoid heart disease Pulmonic Stenosis Congenital defect in children Fused commissures with thickened leaflets Carcinoid heart disease Systolic crescendo-decrescendo murmur at left upper sternal border Wikipedia/Public Domain Pulmonic Regurgitation Most common cause: repaired Tetralogy of Fallot Repair of RVOT obstruction damages valve Endocarditis (rare) Tetralogy of Fallot Rheumatic heart disease (rare) Diastolic decrescendo murmur at left upper sternal border Endocarditis Prophylaxis Antibiotics prior to dental work or surgical procedures Sometimes indicated in patients with valve disease Indicated in patients with prior endocarditis Endocarditis Indicated only after valve replacement with prosthetic valves NOT indicated for patients with unrepaired valve disease Wikipedia/Public Domain Hyperlipidemia Jason Ryan, MD, MPH Lipid Measurements Total Cholesterol LDL HDL Triglycerides LDL Cholesterol “Bad” cholesterol Associated with CV risk < 100 mg/dl very good > 200 mg/dl high Evidence that treating high levels reduces risk HDL Cholesterol “Good” cholesterol Inversely associated with risk < 45mg/dl low Little evidence that raising low levels reduces risk Triglycerides Normal TG level < 150mg/dl Levels > 1000 can cause pancreatitis Elevated TG levels modestly associated with CAD Little evidence that lowering high levels reduces risk Hyperlipidemia Elevated total cholesterol, LDL or triglycerides Risk factor for coronary disease and stroke Modifiable – often related to lifestyle factors Sedentary lifestyle Saturated and trans-fatty acid foods Lack of fiber Secondary Hyperlipidemia Selected Causes of Hyperlipidemia Alcohol Pregnancy Beta-blockers HCTZ Thyroid disease Nephrotic syndrome Hyperlipidemia Treatment Lifestyle modification recommended for all patients Healthy diet, weight loss, quit smoking Major clinical decision is related to statin therapy Wikimedia Commons Hyperlipidemia Treatment Moderate-intensity statins Many choices Atorvastatin 10 to 20 mg/day Rosuvastatin 5 to 10 mg/day Simvastatin 20 to 40 mg/day High-intensity statins Atorvastatin 40 to 80 mg/day Rosuvastatin 20 to 40 mg/day Wikimedia Commons Hyperlipidemia Treatment Indication Statin CAD, Stroke or PAD High-intensity LDL > 190 mg/dL High-intensity Diabetics > 40 years old Moderate- or High-Intensity ASCVD Risk > 7.5% over 10 years Moderate- or High-Intensity Hyperlipidemia Treatment Hyperlipidemia Treatment Treatment goal usually < 100 mg/dL For patients with known vascular disease goal often < 70 mg/dL Signs of Hyperlipidemia Most patients have no signs/symptoms Physical findings occur in patients with severe ↑ lipids Usually familial syndrome Wikipedia/Public Domain Signs of Hyperlipidemia Xanthomas Plaques of lipid-laden cells Appear as skin bumps or on eyelids Tendinous Xanthoma Lipid deposits in tendons Common in Achilles Corneal arcus Wikipedia/Public Domain Lipid deposit in cornea Ring around iris Klaus D. Peter, Gummersbach, Germany Min.neel/Wikipedia Familial Dyslipidemias Type Type I Dyslipidemia Hyperchylomicronemia ↑↑↑ triglycerides ( > 1000; milky plasma appearance) LPL deficiency or dysfunction Recurrent pancreatitis Enlarged liver, xanthomas Treatment: very low-fat diet Reports of normal lifespan No apparent ↑risk atherosclerosis Type II Dyslipidemia Familial Hypercholesterolemia Autosomal dominant Few or zero LDL receptors Very high LDL ( > 300 heterozygote; > 700 homozygote) Tendon xanthomas, corneal arcus Severe atherosclerosis (can have MI in 20s) Type III Dyslipidemia Familial Dysbetalipoproteinemia Mutations of apolipoprotein E gene Poorly lipid particle cleared by liver Accumulation of chylomicron remnants and VLDL Collectively know as β-lipoproteins Elevated total cholesterol and triglycerides Usually mild (TC > 300 mg/dl) Xanthomas Premature coronary disease Type IV Dyslipidemia Hypertriglyceridemia Autosomal dominant VLDL overproduction or impaired catabolism ↑TG (200-500) ↑VLDL Associated with diabetes type II Often diagnosed on routine screening bloodwork Increased coronary risk/premature coronary disease Lipid-Lowering Therapy Statins Niacin Fibrates Absorption blockers Bile acid resins PCSK9 Inhibitors Omega-3 fatty acids  3-hydroxy-3-methylglutaryl-coenzyme A Statins HMG-CoA Lovastatin, Atorvastatin, Simvastatin HMG-CoA reductase inhibitors ↓cholesterol synthesis in liver ↑LDL receptors in liver Major effect: ↓ LDL decrease Some ↓TG, ↑HDL HMG-CoA Excellent outcomes data (↓MI/Death) Reductase Adverse effects: Hepatotoxicity (↑ AST/ALT) Muscle problems Mevalonate Statin Muscle Problems Myalgias Weakness, soreness Normal CK levels Myositis Like myalgias, increased CK Rhabdomyolysis Weakness, muscle pain, dark urine CKs in 1000s Acute renal failure → death ↑ risk with some drugs (gemfibrozil, P450 inhibitors) Wikipedia/Public Domain P450 Most statins metabolized by liver P450 system Examples: atorvastatin, simvastatin and lovastatin Exceptions: ravastatin and rosuvastatin Potential interactions with other drugs P450 inhibitors increase ↑ risk LFTs/myalgias Cyclosporine Macrolide antibiotics Azole antifungal agents HIV protease inhibitors Grapefruit juice Citrus_paradisi/Wikipedia Niacin Complex, incompletely understood mechanism Overall effect: LDL ↓↓ HDL ↑↑ ↓ HDL breakdown Often used when HDL is low Niacin Major side effects is flushing Stimulates release of prostaglandins in skin Face turns red, warm Can blunt with aspirin (inhibits prostaglandin) prior to Niacin Fades with time Pixabay/Public Domain Niacin Hyperglycemia Insulin resistance (mechanism incompletely understood) Avoid in diabetes Hyperuricemia Victor/Flikr James Heilman, MD/Wikipedia Fibrates Gemfibrozil, clofibrate, bezafibrate, fenofibrate Activate PPAR-a Modifies gene transcription ↑ activity lipoprotein lipase ↑ liver fatty acid oxidation Gemfibrozil Major overall effect → TG breakdown Used for patients with very high triglycerides Fibrates Gemfibrozil, clofibrate, bezafibrate, fenofibrate Myositis Rhabdomyolysis associated with gemfibrozil Caution when used with statins ↑ LFTs Cholesterol gallstones Absorption blockers Ezetimibe Blocks cholesterol absorption Works at intestinal brush border Blocks dietary cholesterol absorption Highly selective for cholesterol Does not affect fat-soluble vitamins, triglycerides Public Domain Absorption blockers Ezetimibe Result: ↑ LDL receptors on liver Modest reduction LDL Some ↓ TG, ↑ HDL Weak data on hard outcomes (MI, death) ↑ LFTs Diarrhea Bile Acid Resins Cholestyramine, colestipol, colesevelam Old drugs; rarely used Prevent intestinal reabsorption bile Cholesterol → bile → GI tract → reabsorption Resins lead to more bile excretion in stool Liver converts cholesterol → bile to makeup losses Modest lowering LDL Miserable for patients: bloating, bad taste Can’t absorb certain fat-soluble vitamins Cholesterol gallstones Omega-3 Fatty Acids Found in fish oil Consumption associated with ↓ CV events Reduce VLDL production Lowers triglycerides (~25 to 30%) Modest ↑ HDL Commercial supplements available (Lovaza) GI side effects: nausea, diarrhea, “fishy” taste docosahexaenoic acid (DHA) PCSK9 Inhibitors Alirocumab, Evolocumab FDA approval in 2015 PCSK9 → degradation of LDL receptors Alirocumab/Evolocumab: Antibodies Inactivate PCSK9 ↓ LDL-receptor degradation ↑ LDL receptors on hepatocytes ↓ LDL cholesterol in plasma Wikipedia/Public Domain PCSK9 Inhibitors Alirocumab, Evolocumab Given by subcutaneous injection Results in significant LDL reductions ( > 60%) Major adverse effect is injection site skin reaction Used when hyperlipidemia persists despite statins Downside: cost Hypertension Jason Ryan, MD, MPH Hypertension Diagnosis of hypertension requires more than one measurement Stage SBP DBP Normal 180 or >120 Etiology Most (90%) is primary (“essential”) HTN Cause not clear Remainder (10%) secondary Most associated with chronic kidney disease Hyperaldosteronism Renal artery stenosis Pheochromocytoma White coat hypertension Elevated BP in clinic only Public Domain Hypertension Risk Factors Family history High salt intake Alcohol Obesity Physical inactivity Wikipedia/Public Domain Hypertension Association