Heart Failure PDF

Heart Failure Basics Jason Ryan, MD, MPH Heart Failure Impaired ability of the heart to pump blood Hallmark: Low cardiac output ↓ CO Heart Failure Tank H20 Tank Pump Heart Failure Tank H20 Tank Pump Heart F...

Heart Failure Basics Jason Ryan, MD, MPH Heart Failure Impaired ability of the heart to pump blood Hallmark: Low cardiac output ↓ CO Heart Failure Tank H20 Tank Pump Heart Failure Tank H20 Tank Pump Heart Failure Tank H20 Tank Pump Heart Failure Tank H20 Tank Heart Heart Failure Blood Tank Tank Heart Heart Failure Blood Tank Tank Heart Heart Failure Lungs & Veins Heart Heart Failure Pathophysiology “Failing” chambers → Increased pressures Pressures rise in cardiac chambers Heart Failure Pathophysiology Left ventricular failure → ↑ LV pressure LV systolic pressure: depends on contractility (can be low) LVEDP = always high in left heart failure Hallmark of left heart failure Less blood pumped out → more left behind → more pressure Stiff ventricle (diastolic HF) → high pressure Heart Failure Pathophysiology ↑ LVEDP → ↑ LA pressure ↑ pulmonary capillary pressure Dyspnea Pulmonary edema Aorta LV LA Heart Failure Pathophysiology ↑Pc Heart Failure Pathophysiology ↑ pulmonary capillary pressure → ↑ PA pressure ↑ PA pressure → ↑ RV pressure ↑ RV pressure → ↑ RA pressure Right atrial pressure = central venous pressure High pressure in venous system ↑ jugular venous pressure (neck veins) Capillary leak → pitting edema Heart Failure Signs/Symptoms Physiologic effects of lying flat (supine) Increased venous return Redistribution of blood volume From lower extremities and splanchnic beds to lungs Little effect in normal individuals Impaired ventricle cannot tolerate changes Worsens pulmonary congestion and breathing Heart Failure Signs/Symptoms Left heart failure Dyspnea especially on exertion Paroxysmal nocturnal dyspnea (wake up SOB) Orthopnea (can’t breathe lying flat) Right heart failure Increased jugular venous pressure Lower extremity edema Liver congestion (rarely can cause cirrhosis) “Backward failure” Heart Failure Right Heart Failure Most common cause R heart failure: Left heart failure Occasionally right heart failure occurs in isolation Normal left atrial pressure High pulmonary artery, right ventricular, right atrial pressure Usually secondary to a lung process Pulmonary hypertension COPD. This is often called “cor pulmonale” Heart Failure Signs/Symptoms Low flow signs/symptoms (“forward failure”) Loss of appetite Weight loss (cachexia) Confusion Cool extremities “Narrow pulse pressure” Seen only with very low cardiac output (systolic HF) Not seen in diastolic heart failure Heart Failure Lung Findings Classic finding is rales Fluid filled alveoli “pop” open with inspiration Chest X-ray shows congestion Lungs/CXR can be clear in chronic heart failure ↑lymphatic drainage Heart Failure Lung Findings Heart failure cells Hemosiderin (iron) laden macrophages Brown pigment in macrophages Zorkun/Wikipedia Heart Failure Signs/Symptoms Elevated jugular venous pressure (normal 6-8cmH2O) Look for height of double bounce (cause by a and v waves) Heart Failure Hepatojugular Reflux Pressure on abdomen raises JVP 1-3cm normally With failing RV, increase is greater Heart Failure Signs/Symptoms Lower extremity pitting edema Increased capillary hydrostatic pressure Fluid leak from capillaries → tissues Gravity pulls fluid to lower extremities ↑Pc James Heilman, MD Heart Failure Abnormal Heart Sounds S3 (associated with high left atrial pressure) S4 (associated with stiff left ventricle) Displaced apical impulse – enlarged heart S1 S2 S4 S1 S2 S3 Heart Failure Pathophysiology All forms of heart failure lead to ↓ cardiac output Activates two physiologic systems Activation of sympathetic nervous system Activation of renin-angiotensin-aldosterone system All RAAS hormone levels will rise Both systems lead to two key effects: Increased peripheral vascular resistance (vasoconstriction) Retention of sodium/water (kidneys) Heart Failure Total Peripheral Resistance Cardiac output falls → vasoconstriction Angiotensin II, sympathetic nervous system TPR always high Blood pressure often high but may be low Depends on combined changes CO and TPR BP = CO X TPR Heart Failure Sodium/Water Retention ↓ cardiac output ↓ Effective Circulating Volume ↑ RAAS ↑ SNS ↑ ADH ↑ Na/H2O ↑ Total Body Water Heart Failure Other Hormones ANP (Atrial natriuretic peptide) Atrial stretch (pressure/volume) → ANP release Vasodilator (↓TPR) Constricts renal efferents/dilates afferents ↑ diuresis Opposite effects of RAAS system Afferent Efferent Heart Failure Other Hormones ANP released by atrial myocytes BNP (brain natriuretic peptide): Ventricles Both rise with volume/pressure overload Both counter effects of RAAS system BNP sometimes used for diagnosis in dyspnea High levels suggest heart failure Low levels suggest other causes of dyspnea ANP/BNP RAAS Nesiritide Recombinant BNP Vasodilation ↓ afterload, ↑CO Failed to show benefit in clinical trials Heart Failure Diagnosis Most common: typical signs/symptoms Elevated BNP level Heart catheterization Increased LVEDP = left heart congestion/failure Increased RA, RVEDP = right heart congestion/failure BruceBlaus Systolic and Diastolic Heart Failure Jason Ryan, MD, MPH Heart Failure Systolic and Diastolic Systolic Heart Failure Diastolic Heart Failure Ejection fraction is reduced EF is normal (55-65%) Heart Failure Systolic and Diastolic Same congestive signs/symptoms Dyspnea, orthopnea, paroxysmal nocturnal dyspnea Rales, ↑ JVP, pitting edema Exception: Low flow symptoms in systolic only Cool extremities Cachexia Confusion 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 Concentric Hypertrophy Pressure overload Chronic ↑↑ pressure in ventricle: HTN, Aortic stenosis Decreased compliance (stiff ventricle) Often seen in diastolic heart failure Normal Increased myocyte size LV Size ↓ LV Size Sarcomeres in parallel Increased wall thickness  LV Pressure LV Pressure LV Vol LV Vol Systolic Heart Failure Diastolic Heart Failure ↓ Contractility ↓ LV Compliance ↓ Lusitropy Systolic Heart Failure ↓ Cardiac output Problem in SYSTOLE Can’t get blood out LV Pressure ↓ Stroke volume SV = EDV – ESV ↑ ↑ ESV (↓ contractility) ↑ EDV (↑ESV + VR) ↑ LVEDP LV Vol Systolic Heart Failure ↓ Contractility Frank-Starling Curve Normal Stroke ↓ Contractility Volume Preload (LVEDV) Diastolic Heart Failure ↓ Cardiac output Problem in DIASTOLE Can’t get blood in LV Pressure Small ↓ stroke volume ↓ EDV (↓ filling) ↑↑ LVEDP (stiff ventricle) LV Vol Diastolic Heart Failure ↓ LV Compliance ↓ Lusitropy Systolic vs. Diastolic Normal Systolic/Dilated Diastolic EDV 100 200 90 ESV 40 160 40 SV/CO 60 40 50 EF % 60 20 56 Systolic Heart Failure Most common cause: Myocardial infarction Myocytes replaced by scar tissue “Ischemic” cardiomyopathy Many causes of “non-ischemic” cardiomyopathy About 50% idiopathic Many other causes: viral, familial, peri-partum, chemotherapy toxicity, HIV, alcoholic, sarcoidosis, tachycardia-mediated Diastolic Heart Failure Exact cause unknown Many cases have concentric hypertrophy Many associated conditions Age, diabetes, hypertension Terms: Heart failure preserved EF HFpEF Diastolic dysfunction Nonischemic Cardiomyopathy Viral May follow upper respiratory infection Many associated viruses Coxsackie Influenza, adenovirus, others Virus enters myocytes Causes myocarditis → cardiomyopathy Myocarditis phase may go undiagnosed Pixabay/Public Domain No specific therapy for virus Nonischemic Cardiomyopathy Peri-partum 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 Wikipedia/Public Domain Many autosomal dominant X-linked, autosomal recessive also described 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 Markedly reduced LVEF Increase CK, MB, Troponin; EKG changes Looks like anterior MI (but no coronary disease) Usually recovers 4-6 weeks Jheuser/Wikipedia Alcohol Chronic consumption can cause cardiomyopathy Believed to be due to toxic metabolites Can recover with cessation of alcohol Pixabay/Public Domain High Output Heart Failure Heart in overdrive Severe anemia Thyroid disease John Liu/Flikr Thiamine (B1) vitamin deficiency (beriberi) A-V fistulas (post-surgical) Exact mechanism unclear Decreased LV filling time Defining characteristic: HIGH cardiac output Heart failure symptoms in absence of low output ↑JVP, pulmonary edema Restrictive Cardiomyopathy Jason Ryan, MD, MPH Restrictive Heart Disease Something “infiltrates” the myocardium Granulomas (Sarcoid) Amyloid protein (Amyloidosis) Heart cannot relax and fill SEVERE diastolic dysfunction MarkBuckawicki/Wikipedia Restrictive Heart Disease LVEF = normal Left ventricular volume = normal (not dilated) Restricted filling = ↑ atrial pressure Dilated left and right atria Classic imaging findings: Normal left ventricular function/size Bi-atrial enlargement Restrictive Heart Disease Clinical Features Dyspnea Prominent right heart failure Markedly elevated jugular venous pressure Lower extremity edema Liver congestion May lead to cirrhosis (“nutmeg liver”) David Monniaux/Wikipedia Restrictive Heart Disease Classic signs Kussmaul’s sign Inspiration causes rise in JVP Restrictive Heart Disease Rhythm Disturbances Myocardial infiltration may disrupt electrical activity Arrhythmias (sudden death) AV block Ventricular Tachycardia 3rd Degree Heart Block Restrictive Heart Disease Major Causes Amyloidosis Amyloid protein deposits in heart Various forms (primary, secondary, etc.) Ed Uthman, MD Restrictive Heart Disease Classic signs Can see thickened myocardium Low voltage on EKG Classic finding in amyloidosis and Fabry’s disease Restrictive Heart Disease Major Causes Sarcoidosis Granuloma formation Usually involves lungs Extra-pulmonary organs include heart Restrictive Heart Disease Major Causes Fabry disease Lysosomal storage disease Deficiency of α-galactosidase A Accumulation of ceramide trihexoside Mediran/Wikipedia Restrictive Heart Disease Major Causes Hemochromatosis Iron excess Commonly causes dilated cardiomyopathy Rarely may cause restrictive Tomihahndorf Restrictive Heart Disease Major Causes Post-radiation Acutely: May cause inflammation Fibroblast recruitment Extra-cellar matrix deposition Collagens and fibronectin Dina Wakulchik/Wikipedia Restrictive Heart Disease Major Causes Pericarditis may occur acutely after therapy Long term effects Pericardial disease Coronary artery disease Valvular disease Conduction abnormalities Restrictive cardiomyopathy Fibrous tissue accumulation Diastolic dysfunction Restrictive Heart Disease Major Causes Loeffler’s syndrome Hypereosinophilic syndrome High eosinophil count Eosinophilic infiltration of organs Bobjgalindo/Wikipedia Skin (eczema) Lungs (fibrosis) Restrictive Heart Disease Major Causes Primary HES Neoplastic disorder Stem cell, myeloid, or eosinophilic neoplasm Secondary HES Bobjgalindo/Wikipedia Reactive process Eosinophilic overproduction due to cytokines Occurs in parasitic infections (ascaris lumbricoides) Some tumors/lymphomas Idiopathic HES Restrictive Heart Disease Major Causes Eosinophilic infiltration of myocardium Common mode of death Acute phase Myocarditis (often asymptomatic) Bobjgalindo/Wikipedia Chronic phase Endomyocardial fibrosis and myocyte death Can see restrictive heart disease Thrombus formation common (embolic stroke) Restrictive Heart Disease Major Causes Endocardial fibroelastosis Endocardial thickening (innermost myocardium) Infants in first year of life Thick myocardium Proliferation of fibrous (collagen) and elastic fibers Restrictive cardiomyopathy Avsar Aras Acute Heart Failure Jason Ryan, MD, MPH Heart Failure Acute vs. Chronic Acute Chronic Congested/Swollen Euvolemic Pulmonary Edema Clear lungs Pitting Edema No pitting edema ↑JVP JVP flat Acute Exacerbations Causes #1: Dietary indiscretion High salt intake #2: Poor medication compliance LukeB20161933/Wikipedia Pixabay/Public Domain Dietary Indiscretion ↑Na Intake Plasma Na = 140meq/L ↑Plasma Osmolarity ↑ADH ↑Free Water ↑Volume Normal ↓RAAS Plasma [Na] ↓ADH ↑Urine Output Acute Exacerbations Causes Infection/trauma/surgery Activation of sympathetic nervous system Ischemia (rare) Decreased cardiac output NSAIDs Inhibit cyclooxygenase (COX) → ↓ prostaglandins Prostaglandins maintain renal perfusion Result: Less renal perfusion → salt/water retention Acute Heart Failure Therapy Often treated in the hospital Goal: Symptom relief Contrast with chronic HF: reduce mortality/hospitalizations Often same therapies for diastolic versus systolic Loop Diuretics Na K 2Cl Ascending Limb Loop Diuretics Loop Diuretics Furosemide, Bumetanide, Torsemide, Ethacrynic Acid Inhibit Na-K-Cl pump in ascending loop of Henle Result in salt-water excretion Relieve congestion IV better than PO (gut is swollen) Key side effects Hypokalemia Volume depletion (Renal failure; hypotension) Sulfonamide drugs: allergy (except ethacrynic acid) Metolazone Thiazide-like diuretic Inhibits Na-Cl reabsorption distal tubule Gives loop diuretics a “kick” Vigorous diuresis Side effects: additional fluid, K+ loss Nitrates Predominant mechanism is venous dilation Bigger veins hold more blood Takes blood away from left ventricle Lowers LVEDV (preload), LA pressure Less pulmonary edema → improved dyspnea Nitrates Side effects Headache (meningeal vasodilation) Flushing Hypotension Wikipedia/Public Domain Vasodilators “Afterload reduction” ACE inhibitors Hydralazine Cause peripheral vasodilation Reduced afterload → increased cardiac output Nitrates plus Hydralazine Combination therapy for acute and chronic HF Studied in systolic heart failure Reduction in preload (nitrates) and afterload (hydralazine) Acute therapy: Improves symptoms Chronic therapy: Lowers mortality in some studies Largely replaced by ACE inhibitors Some studies suggested benefit in black patients Inotropes Increase contractility Only for systolic heart failure No role in diastolic heart failure (normal contractility) All activate β1 pathways in myocytes Increased HR and contractility Can also active β2 pathways in smooth muscle Vasodilation → hypotension Inotropes Milrinone Phosphodiesterase 3 inhibitor PD3 breaks down cAMP in myocyctes Inhibition → ↑cAMP → contraction Vascular smooth muscle ↑cAMP (β2) → dilation ↑Inotropy ↑Vasodilation Hypotension β1 Contraction cAMP PD3 AMP Myocyte Inotropes Dobutamine Mostly beta-1 agonist Increases heart rate and contractility Weak beta-2 agonist Vasodilation ↑Inotropy ↑Vasodilation Hypotension Similar effects to milrinone β1 Contraction cAMP PD3 AMP Myocyte Inotropes Dopamine Does not cross blood brain barrier (no CNS effects) Peripheral effects highly dependent on dose Low dose: dopamine agonist Vasodilation in kidneys Medium dose: beta-1 agonist Increased heart rate and contractility High dose: alpha agonist Vasoconstriction Inotropes Epinephrine Also dose dependent effects Low dose: beta-1 and beta-2 agonist Increased heart rate & contractility, vasodilation High dose: alpha agonist Vasoconstriction Inotrope Risks Numerous registries and clinical trials demonstrate increased mortality with routine use of inotropes Dangerous drugs used in very sick patients under monitored conditions A 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 4kg, feels better Nitro drip stopped Changed to oral furosemide Hospital Day 3: Discharge A 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 A More Complex Heart Failure Course Hospital Day 3-5 Good urine output Weight loss 4kg Breathing improves Hospital Day 6 Dobutamine stopped Furosemide drip stopped Hospital Day 7 Oral furosemide given Hospital Day 8: Discharge Heart Failure Readmission Recurrence of HF after discharge common Post-discharge follow-up VERY important “Readmissions” a focus of public health policy High risk of readmission within 30 days Highest risk category among Medicare population Acute Heart Failure Most patients require chronic, daily diuretic Helps to maintain euvolemic status Often oral furosemide or other loop diuretic Some patients require daily long acting nitrate Often oral isosorbide mononitrate Acute Heart Failure Rare patients: continued treatment for low output Systolic heart failure only Chronic, IV infusion inotrope (i.e. “home dobutamine”) Left ventricular assist device (LVAD) Heart transplant Digoxin Only available oral inotrope “Dig and diuretic” once the mainstay of HF treatment What changed? Digoxin shown to have no mortality benefit Digoxin not effective for diastolic heart failure About 50% of all cases Digoxin carries significant risk of side effects Digoxin Mechanism Two important cardiac effects #1: Inhibits Na-K-ATPase pump More Na in cell → more Ca++ in cell More Ca++ → more contractility #2 Suppresses AV node conduction (parasympathetic) Can be used to slow heart rate in rapid atrial fibrillation Digoxin Benefits in Heart Failure Useful for systolic HF patients Symptoms despite maximal therapy on other drugs i.e. persistent dyspnea despite good volume status Can be administered for acute heart failure Can be administered long term to maintain CO Digoxin Benefits in Heart Failure Increased cardiac output Improved symptoms and quality of life No established mortality benefit Chronic Heart Failure Jason Ryan, MD, MPH Heart Failure Treatment Pathway Acute Heart Failure Symptom Relief Loop diuretics Nitroglycerine Rx Inotropes Chronic Heart Failure Diastolic Systolic Heart Failure Heart Failure Chronic Heart Failure LOTS of therapies for systolic heart failure Drugs: ACE-inhibitors, beta blockers, aldosterone antagonists Defibrillators Bi-ventricular pacemakers NO direct therapies for diastolic heart failure Guidelines recommendations: treat HTN, diabetes, A. fib Mainstay of therapy: monitor for symptoms, diuretics Systolic Heart Failure Chronic over-activation of two physiologic systems Renin-angiotensin-aldosterone system Sympathetic nervous system (β1 stimulation) Blockade → ↓ mortality and disease progression Renin-Angiotensin System Angiotensinogen ARBs Sympathetic System + Renin Renal Na/Cl resorption AI A2 + ACE Arteriolar vasoconstriction ACE Inhibitors Adrenal aldosterone secretion Net Result Pituitary ADH secretion ↑Salt/Water Retention ↑Preload ↑TPR ↑Afterload RAAS Drugs ACE Inhibitors Captopril, Enalapril, Lisinopril, Ramipril Block conversion AI → AII Angiotensin Receptor Blockers (ARBs) Candesartan, Irbesartan, Valsartan Directly block AII receptor Both classes: ↓ morality, ↓ hospitalizations Side effects Hyperkalemia (↓aldosterone) Renal failure (↓GFR) ACE Inhibitors Unique Side Effects Due to increased bradykinin Dry Cough Occurs in ~10% of patients Angioedema Swelling of face, tongue Can be life-threatening Bradykinin Cough Bradykinin Vasodilation AI X X ACE Inhibitors Inactive A2 Metabolites Beta Blockers Once contraindicated in systolic heart failure Negative inotropes Not used in acute heart failure May worsen cardiac output and symptoms Beta Blockers Three agents beneficial in chronic systolic HF failure Metoprolol (β1) Carvedilol (β1β2α1) Bisoproplol (β1) ↓ morality, ↓ hospitalizations Aldosterone Antagonists Sympathetic System Renal Na/Cl resorption A2 X Spironolactone Arteriolar vasoconstriction Eplerenone Adrenal aldosterone secretion Pituitary ADH secretion Spironolactone, Eplerenone Potassium-sparing diuretics ↑Na/H2O excretion (diuretics) “Spare” potassium Unlike other diuretics, do not increase K+ excretion HYPERkalemia is side effect Reduced mortality Reduced hospitalization rate Spironolactone, Eplerenone Potassium-sparing diuretics Similar structure to testosterone Blocks testosterone effects Gynecomastia in men Eplerenone: No gynecomastia Derivative of progesterone Activates progesterone receptors Eplerenone Amenorrhea in women Testosterone Progesterone Spironolactone Neprilysin Inhibitors Sacubitril 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 Neprilysin Inhibitors Sacubitril Entresto: oral combination sacubitril/valsartan Valsartan: angiotensin receptor blocker (ARB) ↓ morality ↓ hospitalizations ANP/BNP RAAS Neprilysin Inhibitors Side Effects Studied in combination with valsartan Many side effects similar to ARBs Hypotension Hyperkalemia Angioedema Rare, feared adverse effect Neprilysin also degrades bradykinin (like ACE) Angioedema may occur 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 ↓ morality and ↓hospitalizations Chronic Systolic Heart Failure Drug Therapy ACE inhibitors/ARB Beta Blockers Aldosterone antagonists Neprilysin inhibitors Ivabradine ICD Implantable Cardiac Defibrillator Annual risk SCD >20% some studies Most due to ventricular tachycardia ICD Implantable Cardiac Defibrillator Improve mortality in appropriate patients Implantation carries some risk: Bleeding, infection Inappropriate shocks Biventricular Pacemakers Cardiac Resynchronization Therapy (CRT), BiV pacer Out of Synch After Pacemaker Heart Failure Treatment Pathway Acute Heart Failure Lasix Rx Nitroglycerine Inotropes Chronic Heart Failure Diastolic Systolic Heart Failure Heart Failure No specific therapy Drugs ICD Bi-V Pacer