Heart Failure 2024 Student PDF

Heart Failure Victoria Miller, PharmD, BCPS [email protected]  Classify heart failure (HF) syndrome types Classify using guideline terminology Objectives Differentiate between common underlying Diffe...

Heart Failure Victoria Miller, PharmD, BCPS [email protected]  Classify heart failure (HF) syndrome types Classify using guideline terminology Objectives Differentiate between common underlying Differentiate etiologies of HF for Describe the pathophysiology of HF as it relates to the RAAS system, sympathetic Describe nervous system, and endogenous peptide All Heart Failure systems Lectures Identify Identify signs and symptoms of HF Classify a given patient by NYHA Classify Classification and ACC/AHA Stages 2  Discuss the goals of therapy for a patient with Discuss acute and/or chronic HF Objectives Discuss nonpharmacologic management of Discuss patients with HF for All Heart Failure Develop an evidence-based pharmacologic treatment and monitoring plan for a patient Lectures Develop with acute or chronic HF with reduced ejection fraction Develop an evidence-based pharmacologic Develop treatment and monitoring plan for a patient with HF with preserved ejection fraction 3 Heart Failure Guidelines 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001063#F8 2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure With Preserved Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee https://www.jacc.org/doi/10.1016/j.jacc.2023.03.393 4 Epidemiology 5 Incidence Affects ~6.2 million people in the United States Relative incidence is slightly higher in women compared to men Hospitalizations have declined slightly in the last decade (~800,000 admissions per year) Estimated costs for managing chronic and acute HF are in the billions of dollars per year 6 Prognosis Five-year mortality rate for chronic HF is >50% Average hospital LOS is ~4-6 days Up to 30-60% of patients are readmitted within 6 months of initial discharge date 7 Racial and Ethnic Disparities Non-Hispanic Black patients have the highest death rate per capita Age-adjusted mortality rate for HF ◦Non-Hispanic Black patients: 92 per 100,000 individuals ◦Non-Hispanic White patients: 87 per 100,000 individuals ◦Hispanic patients: 53 per 100,000 individuals 8 Possible Reasons for Disparities Higher prevalence of cardiovascular risk factors (HTN, DM, obesity, chronic kidney disease) Genetic susceptibility Access to care Socioeconomic factors Social determinants of health Implicit biases in healthcare providers and systems 9 10 Heart Failure Definitions 11 Heart Failure Inadequate ability of the heart to pump enough blood ◦Cannot meet blood flow or metabolic demands of the body Results from any structural or functional cardiac disorder that impairs the ability of the ventricle to eject or fill with blood “Congestive heart failure” 12  Systolic dysfunction and/or diastolic dysfunction can result in a similar decrease in cardiac output 13 https://www.heartplace.com/post/advanced-heart-failure-medical-management Ventricular Dysfunction Reflects involvement of either the right or left ventricle (or both) Right-sided HF ◦Often manifests as systemic congestion Left-sided HF ◦Often manifests as pulmonary congestion 14 Ejection Fraction 15  Classification by Left Ventricular Ejection Fraction (LVEF) Type of HF According to LVEF Criteria HFrEF (HF with reduced EF) LVEF 50% HFimpEF (HF with improved EF) Previous LVEF 40% 16 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001063#F8  Reduced vs Preserved HFrEF HFpEF Predominant abnormality in Predominant abnormality in systolic function diastolic function (sometimes) Ejection fraction is reduced Ejection fraction often normal 17 https://www.lexpharma.com/pipeline/sotagliflozin/about-heart-failure Causes of HF 18 Common Causes Ischemic heart disease Myocardial infarction (MI) Hypertension (HTN) Valvular heart disease (VHD) 19 Other Nonischemic Causes Endocrine or Familial Chemotherapy and metabolic (thyroid, cardiomyopathy or Rheumatologic and other cardiotoxic acromegaly, inherited and autoimmune medications pheochromocytoma, genetic heart diabetes, obesity) disease Myocarditis Heart rhythm-related Infiltrative cardiac (infectious, toxin or (tachycardia- disease (amyloid, Peripartum medication, mediated, PVCs, RV sarcoid, cardiomyopathy immunological, pacing) hemochromatosis) hypersensitivity) Stress Substance abuse cardiomyopathy (alcohol, cocaine, (Takotsubo) methamphetamine) 20 Medication-Related Causes Medications may cause or exacerbate HF: ◦Direct myocardial toxicity ◦Negative inotropic or chronotropic effects ◦Exacerbating HTN ◦Delivering large amounts of sodium ◦Drug-drug interactions that limit beneficial effects of HF medications 21  Medication Examples Direct Myocardial Toxicity Worsen Heart Failure Certain chemotherapy agents NSAIDs ◦Doxorubicin Ketamine ◦Paclitaxel Thiazolidinediones ◦5-fluorouracil ◦Cyclophosphamide/ifosfamide DPP-4 inhibitors Amphotericin B Class I antiarrhythmics ◦Flecainide Lithium ◦Disopyramide Stimulants (amphetamines) Class III antiarrhythmics TNF-alpha inhibitors ◦Sotalol Dronedarone Non-dihydropyridine CCB’s 22 Pathophysiology 23 Cardiac Output Volume of blood ejected per unit of time (L/min) Major determinant of tissue perfusion Cardiac output = HR x SV Heart rate – controlled by autonomic nervous system (SNS  stimulation of beta receptors  increase in heart rate) Stroke volume – determined by preload, afterload, and contractility 24  Definitions Preload (LVEDP) Afterload (SVR) Measure of ventricular filling pressure at Resistance to ventricular ejection the end of diastole Pressure that the heart must overcome to Volume of blood in the left ventricle just open the aortic valve and push blood prior to systole volume out into the systemic circulation Preload = Air going into balloon Afterload = Knot on balloon that air must force its way past 25 26 https://www.researchgate.net/figure/Effect-of-changes-in-myocardial-contractility-on-the-Frank-Starling-curve-The-curve_fig1_282437873 27 28 Compensatory Mechanisms Index event can be acute or slow onset 29 Compensatory Mechanisms 1. Sympathetic nervous system 2. Frank-Starling mechanism 3. Vasoconstriction 4. Ventricular hypertrophy and remodeling 30 1. Sympathetic Nervous System Tachycardia and increased contractility occur in response to a decrease in cardiac output Primarily due to norepinephrine release Downside: Impairs Increased Causes or diastolic Decreases myocardial Increased heart rate worsens and stroke oxygen ischemia systolic volume demand functions 31 2. Frank-Starling Mechanism Augmentation of preload is rapidly activated in response to decreased cardiac output Renal perfusion will be decreased due to lower cardiac output and redistribution of blood away from nonvital organs Results in activation of the renin-angiotensin- aldosterone system (RAAS) ◦Helps maintain blood pressure and increase renal sodium and water retention 32 33 Downside of RAAS in HF Patients Chronically failing hearts usually exhaust preload reserves Increases in preload will increase SV only to a certain point Further increases in preload lead to pulmonary or systemic congestion 34 3. Vasoconstriction Increased vasoconstriction occurs in HFrEF to redistribute blood away from nonessential organs ◦Increases afterload Several neurohormones likely contribute (NE, Ang II, endothelin-1, neuropeptide I, urotensin II, and arginine vasopressin) Downside: Impedes forward Heightens Further ejection of blood compensatory decreases CO from ventricle responses 35 4. Ventricular Hypertrophy and Remodeling Key components in pathogenesis of progressive myocardial failure Ventricular hypertrophy: ◦Increase in ventricular muscle mass Ventricular remodeling: ◦Changes in both myocardial cells and the extracellular matrix that result in changes in the size, shape, structure, and function of the heart 36  Normal LVH https://www.mayoclinic.org/diseases-conditions/left-ventricular-hypertrophy/symptoms-causes/syc-20374314#dialogId64169744 https://www.sciencephoto.com/media/257807/view/x-ray-of-heart-with-left-ventricular-enlargement 37 https://www.researchgate.net/figure/Six-months-follow-up-chest-X-ray-showing-nearly-normal-size-of-heart_fig5_7754844 Downsides of Ventricular Hypertrophy and Remodeling Changes in size, shape, and function further depress the mechanical performance of the heart Increases regurgitant flow through mitral valve Continues the progression of remodeling  Further decreases diastolic and systolic function Onset of remodeling usually precedes development of HF symptoms *Ventricular hypertrophy and remodeling can occur in any condition that causes myocardial injury 38 Additional Downsides! Substances (such as NE and Ang II, etc) are activated systemically and locally and initiate a signal transduction cascade that causes remodeling ◦Harmful effects on the heart and are also toxic to other organs 39 Neurohormonal Model of Heart Failure 40  Neurohormonal Model Initiating event Decreased CO “HF state” Systemic disease mediated by neurohormones and other factors Myocyte injury, oxidative stress, inflammation, extracellular matrix remodeling 41 Angiotensin II Binds to AT1 receptors in vasculature  potent vasoconstrictor Facilitates release of NE and arginine vasopressin Promotes sodium retention by stimulating aldosterone release Stimulates ventricular hypertrophy, remodeling, myocyte apoptosis, oxidative stress, inflammation, and alterations in myocardial extracellular matrix 42 Norepinephrine Central role in tachycardia, vasoconstriction, and increased contractility Excessive SNS activation causes β1-receptor downregulation and loss of sensitivity to receptor stimulation Increases the risk of arrhythmias, causes necrosis and apoptosis of myocardial cells, contributes to hypertrophy and remodeling 43 Aldosterone Increases sodium and fluid retention Also has direct effects on the heart ◦Interstitial cardiac fibrosis ◦Increases stiffness of the myocardium Decreases systolic function, impairs diastolic function, causes vascular remodeling and a systemic proinflammatory state, and increases ventricular remodeling and HF progression 44 Arginine Vasopressin (AVP) Pituitary peptide hormone that regulates renal water excretion and plasma osmolality Plasma concentrations are elevated in HF ◦Volume overload and hyponatremia ◦Increased arterial vasoconstriction ◦Stimulation of remodeling 45 Natriuretic Peptides B-type natriuretic peptide (BNP) ◦Synthesized and released from the ventricle in response to pressure or volume overload (stretch) Benefits in HF ◦Increase natriuresis and diuresis ◦Attenuate activation of the RAAS and SNS Commonly performed lab for diagnosis and monitoring of HF 46 Sodium-Glucose-Cotransporter-2 (SGLT2) Highly expressed in renal proximal tubule and reabsorbs more than 90% of filtered glucose that is coupled with Na+ ions Inhibiting this cotransporter will increase sodium excretion ◦Natriuresis and diuresis 47 Signs and Symptoms 48 Common Symptoms Dyspnea Orthopnea Paroxysmal nocturnal dyspnea Exercise intolerance Fatigue Swollen ankles (or other parts of body) 49 Dyspnea Comparison Orthopnea Paroxysmal Nocturnal Dyspnea (PND) Difficulty breathing when Difficulty breathing during lying down sleep (abrupt onset) Relieved upon changing to Patient wakes up gasping an upright position Often 1-2 hours after falling Occurs when awake or asleep asleep “How many pillows do you sleep on?” 50 Signs of Heart Failure Jugular venous distension (JVD) Cardiomegaly S3 gallop Peripheral edema Pulmonary edema Pleural effusions Hepatomegaly/ascites “Have you gained more than 2 pounds in one day or 5 pounds in one week?” 51  Jugular Venous Distention https://www.medicalnewstoday.com/articles/320320#what-is-jugular-vein-distention 52 Pulmonary Edema vs Pleural Effusions Video: Crackles 53  Peripheral Edema https://www.cormedicalgroup.com/conditions/edema/ https://www.medicalnewstoday.com/articles/321773#symptoms 54 http://www.med-health.net/images/10437462/image001.jpg  Symptom severity does not directly correlate with degree of LV dysfunction 55 Diagnosis 56  Echocardiogram Standard Assesses abnormalities in cardiac structure and function Includes evaluation of pericardium, myocardium, and heart valves Quantifies the LVEF (%) Transthoracic (TTE) vs transesophageal (TEE) https://myheart.net/articles/heart-function-including-ejection-fraction-ef/ 57 Contributing Diagnostic Methods Review of signs/symptoms, medical history, medications BNP >35 pg/mL or NT-proBNP >125 pg/mL Chest x-ray and 12-lead ECG 58  “Blunting of the costophrenic angles” https://www.reliasmedia.com/articles/144361-volume-overload-acute-decompensated-heart-failure-in-the-emergency-department https://radiopaedia.org/cases/normal-frontal-chest-x-ray 59 Staging and Classification 60  ACC/AHA Stages of HF X https://www.ahajournals.org/doi/10.1161/CIR.0000000000001063#F1 61 New York Heart Association (NYHA) Classification Ex: Can shovel snow, ski, play basketball Ex: Walking up stairs results in symptoms of HF Ex: Bathing or dressing results in symptoms of HF Ex: Symptoms of HF occur at rest Classification is only for symptomatic patients (Stage C or D) Patients can move back and forth between classes 62 Practice Question A patient who has HTN, DM, and left ventricular hypertrophy on chest X ray (no current or previous s/s of HF) would be classified as: A. ACC/AHA Stage A B. ACC/AHA Stage B C. ACC/AHA Stage C D. ACC/AHA Stage D 63 Practice Question Which one of the following stages and classifications applies to this patient scenario? Patient with history of DM and HFrEF who is currently experiencing peripheral edema. The patient can walk up one flight of stairs with no symptoms but was unable to shovel the snow at his home this past weekend. A. ACC/AHA Stage B, NYHA Class III B. ACC/AHA Stage C, NYHA Class II C. ACC/AHA Stage C, NYHA Class III D. ACC/AHA Stage D, NYHA Class I 64 Treatment 65 Goals of Therapy Improve the patient’s quality of life Relieve or reduce symptoms Prevent or minimize hospitalizations Slow progression of the disease Prolong survival Increasing emphasis on PREVENTION of heart failure 66 Drug Classes/Medications* 1. ACE inhibitors (ACEI) 2. Angiotensin II receptor blockers (ARB) 3. ARB/Neprilysin inhibitor (ARNI) 4. β-blockers 5. Aldosterone antagonists 6. Sodium-glucose cotransporter Type 2 (SGLT2) inhibitors 7. Diuretics 8. Isosorbide dinitrate + hydralazine 9. Ivabradine 10. Digoxin 11. Soluble guanylate cyclase stimulator *All dosing charts in these slides are specifically for HF patients 67 Generic Brand Initial Dosing Target Dosing Captopril Capoten 6.25 mg TID 50 mg TID Enalapril Vasotec 2.5 mg BID 10-20 mg BID Fosinopril Monopril 5-10 mg once daily 40 mg once daily Lisinopril Prinivil or Zestril 2.5-5 mg once daily 20-40 mg once daily Perindopril Aceon 2 mg once daily 8-16 mg once daily Quinapril Accupril 5 mg BID 20 mg BID Ramipril Altace 1.25-2.5 mg once daily 10 mg once daily Trandolapril Mavik 1 mg once daily 4 mg once daily ACE Inhibitors 68 ACE Inhibitors MOA: Blocks the conversion of angiotensin I to angiotensin II  Decreases Ang II and aldosterone HF benefits: ◦Decreases mortality in HFrEF ◦Improves symptoms ◦Slows disease progression ◦Reduces ventricular remodeling Class-wide benefits  No specific ACEI is preferred 69  ACE Inhibitors Common adverse effects ◦Hypotension ◦Renal dysfunction ◦Hyperkalemia ◦Cough (dry, nonproductive) Angioedema ◦Less common but more severe side effect ◦History of angioedema is contraindication for use Increased bradykinin  Cough and angioedema https://www.researchgate.net/figure/Angiotensin-converting-enzyme-ACE-inhibitors-linking-the-angiotensin-and-bradykinin_fig2_323247347 70 ACE Inhibitors Start at low doses with gradual titration to target or maximally tolerated dose ◦Can safely double the dose every two weeks HF symptoms often improve within few days of starting therapy ◦May take weeks to months for full benefits 71 Generic Brand Initial Dosing Target Dosing Candesartan Atacand 4-8 mg once daily 32 mg once daily Losartan Cozaar 25-50 mg once daily 50-150 mg once daily Valsartan Diovan 20-40 mg once daily 160 mg BID ARBs* *Other ARBs exist – these are the only three that are recommended for HF treatment 72 ARBs MOA: Blocks the angiotensin II receptor subtype AT1 (does not affect bradykinin levels) HF benefits: ◦Decreases mortality in HFrEF ◦Improves symptoms ◦Slows disease progression ◦Reduces ventricular remodeling Alternative for patients with ACEI cough or angioedema 73 ARBs Common adverse effects ◦Hypotension ◦Renal dysfunction ◦Hyperkalemia Note that common adverse effects are similar to the ACEI class 74 Generic Brand Initial Dosing Target Dosing Sacubitril-valsartan Entresto 24-26 – 49-51 mg BID 97-103 mg BID FYI: The valsartan in sacubitril-valsartan is more bioavailable than other tablet formulations 26, 51, and 103 mg of valsartan in the sacubitril-valsartan tablets are equivalent to 40, 80, and 160 mg of valsartan in other marketed tablet formulations, respectively ARNI (sacubitril/valsartan) 75  ARNI (sacubitril/valsartan) Overall: Increased vasodilation Increased sodium and fluid excretion Increased bradykinin Clinical Pearl: Why are the two ingredients combined? Increases in Ang levels could offset the vasodilatory effects of sacubitril unless also inhibited by valsartan https://ars.els-cdn.com/content/image/1-s2.0-S2213177920304625-gr1_lrg.jpg 76 ARNI (sacubitril/valsartan) A 36-hour washout period is MANDATORY when switching from an ACEI to an ARNI (or vice versa) Use of sacubitril/valsartan is contraindicated in patients with a history of angioedema, regardless of cause 77 ARNI (sacubitril/valsartan) HF benefits: ◦Decreases mortality in HFrEF ◦Reduces hospitalizations ◦Slows disease progression ◦Improves quality of life Common adverse effects ◦Hypotension ◦Renal dysfunction ◦Hyperkalemia 78 ACEI/ARB/ARNI All three drug classes are contraindicated in pregnancy The three drug classes should not be combined in any way for treatment of HF Monitoring for all three classes: ◦Blood pressure ◦Serum potassium ◦Renal function 79 Practice Question Sacubitril/valsartan is contraindicated in patients with which one of the following? A. Hypokalemia B. Concomitant therapy with bumetanide C. Angioedema with ramipril D. Blood pressure >130/80 mm Hg 80 Generic Brand Initial Dosing Target Dosing Bisoprolol Zebeta 1.25 mg once daily 10 mg once daily Carvedilol Coreg 3.125 mg BID 25 - 50 mg BID Metoprolol succinate ER Toprol XL 12.5 - 25 mg once daily 200 mg once daily β-blockers* *Other β-blockers exist – these are the only three that are recommended for HF treatment 81 β-blockers MOA: ◦Metoprolol and bisoprolol: Selectively blocks β1-receptors ◦Carvedilol: Blocks β1-receptors, β2-receptors, and ⍺1-receptors 82 β-blockers Distinguishing characteristics ◦Carvedilol ◦Should have bigger effect on HTN due to ⍺1-receptor blocking effects ◦Possibly avoid in patients with significant airway disease due to β2-receptor blocking effects ◦Bisoprolol or metoprolol ◦May be preferred in patients with low BP, dizziness, or significant airway disease 83 β-blockers HF benefits: ◦Decreases mortality in HFrEF ◦Reduces hospitalizations ◦Slows disease progression ◦Decreases myocardial oxygen demand ◦Reverse modeling of the heart ◦Returns heart to more normal size, shape, and function 84 β-blockers Common side effects: ◦Bradycardia ◦Fatigue (usually resolves after a few weeks) ◦Hypotension (more so with carvedilol) Should only be initiated in stable patients with no or minimal fluid overload (i.e. do not start during acute decompensation of HF) 85 Generic Brand Initial Dosing Target Dosing Eplerenone Inspra 25 mg once daily 50 mg once daily Spironolactone Aldactone 12.5 – 25 mg once daily 25 – 50 mg once daily Aldosterone Antagonists 86 Aldosterone Antagonists MOA: Blocks the mineralocorticoid receptor (target site for aldosterone) and inhibits cardiac extracellular matrix and collagen deposition HF benefits: ◦Decreases mortality in HFrEF ◦Reduces hospitalizations ◦Decreases cardiac fibrosis and ventricular remodeling Diuretic effects with low doses are minimal 87  Aldosterone Antagonists Possible side effects: ◦Hyperkalemia ◦Gynecomastia https://www.mayoclinic.org/diseases-conditions/gynecomastia/symptoms-causes/syc-20351793 88 Generic Brand Initial Dosing Target Dosing Dapagliflozin Farxiga 10 mg once daily 10 mg once daily Empagliflozin Jardiance 10 mg once daily 10 mg once daily SGLT2 Inhibitors* *Other SGLT2 inhibitors exist – these are the two that are currently preferred for HF treatment 89 SGLT2 Inhibitors MOA: Inhibits glucose and sodium reabsorption in the proximal renal tubule ◦Causes osmotic diuresis and natriuresis and a reduction in arterial pressure HF benefits: ◦Decreases mortality in HFrEF ◦Decreases hospitalizations 90 SGLT2 Inhibitors Possible side effects: ◦Fungal genital infections ◦Urinary tract infections ◦Volume depletion (doses of diuretics may need to be adjusted) Provides HF benefits in both diabetic and non-diabetic patients 91  SGLT2 Inhibitors – FYI https://www.ahajournals.org/doi/10.1161/JAHA.119.013389 92 New Approval – FYI InpefaTM (Sotagliflozin) ◦Combined SGLT1 and SGLT2 inhibitor FDA approved on May 27, 2023 for the treatment of heart failure (all LVEFs and for patients with or without diabetes) ◦Not currently indicated for T2DM treatment SGLT1 inhibition reduces intestinal absorption of glucose and sodium  diarrhea as possible side effect 93 Generic Brand Class Initial Dosing Max Total Duration of Daily Dose Action Bumetanide Bumex Loop 0.5 – 1.0 mg 10 mg 4 – 6 hours once daily or BID Furosemide Lasix Loop 20 – 40 mg 600 mg 6 – 8 hours once daily or BID Torsemide Demadex Loop 10 – 20 mg 200 mg 12 – 16 hours once daily Metolazone Zaroxolyn Thiazide-like 2.5 mg once 20 mg 12 – 24 hours daily Diuretics 94 Diuretics MOA: ◦Loop diuretics – Inhibit the Na-K-2Cl transporter in the ascending loop of Henle ◦Thiazide-like diuretics – block sodium reabsorption in the distal tubule HF benefits: ◦Improve symptoms ◦Improve quality of life ◦Improve exercise tolerance 95  Diuretics Loop diuretics are often the mainstay diuretic in HF Thiazide or thiazide-like diuretics are rarely used alone due to their weaker diuretic effect Loop diuretic + metolazone combination can be used to promote diuresis in patients not responding sufficiently to a loop diuretic alone https://www.cvpharmacology.com/diuretic/diuretics 96 Diuretics Loop diuretics have a ceiling effect in HF ◦Furosemide: ~80 mg in a single dose ◦Bumetanide: ~3 mg in a single dose Additional diuresis can be achieved by dosing the medication more often or combining it with a different diuretic class (like metolazone) Clinical pearl: Furosemide absorption can be significantly affected by intra-abdominal congestion 97 Diuretics Shared side effects of loop and thiazide-like diuretics: ◦Hypokalemia ◦Hyponatremia ◦Hypovolemia ◦Acute kidney injury Additional side effects of thiazide-like diuretics: ◦Hypercalcemia ◦Hyperglycemia 98 Generic Brand Initial Dosing Target Dosing Isosorbide dinitrate Isordil 20 – 30 mg three to four 120 mg total per day times daily in divided doses Hydralazine Apresoline 25 – 50 mg three to four 300 mg per day in times daily divided doses Isosorbide dinitrate + Hydralazine There is also a combination pill containing isosorbide dinitrate and hydralazine (Brand name: Bidil) 99 Isosorbide dinitrate + Hydralazine MOA: ◦Nitrates – increase cGMP in vascular smooth muscle  venous dilation and decreased preload ◦Hydralazine – direct-acting arterial vasodilator HF benefits: ◦Improves symptoms and decreases mortality in HFrEF patients who self-identify as African American ◦May reduce mortality in non-African American patients in certain circumstances 100 Isosorbide dinitrate + Hydralazine Possible side effects: ◦Dizziness ◦Headache ◦GI distress Use is often limited by TID dosing 101 Generic Brand Initial Dosing Target Dosing Ivabradine Corlanor 5 mg BID 7.5 mg BID Ivabradine 102 Ivabradine MOA ◦Selectively inhibits the If current responsible for controlling the depolarization rate of the sinoatrial node  dose dependent slowing of the heart rate HF benefits: ◦Reduces hospitalizations in patients with HFrEF in sinus rhythm 103 Ivabradine Criteria for use: ◦HFrEF ◦Sinus rhythm ◦Resting HR >70 bpm ◦Receiving maximally tolerated dose of beta blocker Possible side effects: ◦Bradycardia ◦Atrial fibrillation ◦Visual disturbances 104  Ivabradine https://www.semanticscholar.org/paper/Ivabradine-(Corlanor)-for-Heart-Failure%3A-The-First-Tse-Mazzola/f1dbcbebe0bc0171fd182ea97959f485ec48682a 105 Practice Question Which one of the following patients meets the ivabradine criteria for use? A. 60 year old male with HFpEF and resting HR of 80 B. 42 year old female with HFrEF and resting HR of 62 C. 54 year old male with HFrEF and resting HR of 77 106 Generic Brand Initial Dosing Target Dosing Digoxin Lanoxin 0.125 – 0.25 Individualized to achieve serum mg daily digoxin level of 0.5-0.9 ng/mL Digoxin 107 Digoxin MOA: ◦⬇ SNS and ⬆PNS in HF patients  decreases HR and enhances diastolic filling HF benefits: ◦May improve symptoms and/or decrease hospitalizations in HFrEF 108 Digoxin Possible side effects: ◦GI (N/V) ◦CNS (halos, photophobia, fatigue, confusion) ◦Various arrhythmias Drug level monitoring ◦Target range: 0.5-0.9 ng/mL ◦Measure levels within six weeks of initiation and every 6-12 months during treatment 109 Generic Brand Initial Dosing Target Dosing Vericiguat Verquvo 2.5 mg once daily 10 mg once daily Vericiguat 110  Vericiguat MOA: soluble guanylate cyclase activator  enhances the effect of nitric oxide to increase cGMP activity Increases in cGMP lead to: Smooth muscle relaxation Vasodilation 111 https://ars.els-cdn.com/content/image/1-s2.0-S2213177917305620-fx1_lrg.jpg Vericiguat HF benefits: ◦May reduce HF hospitalizations and cardiovascular death in select high- risk HFrEF patients (already on GDMT and recent worsening of HF) Possible side effects: ◦Hypotension ◦Anemia (mechanism not completely elucidated) Black box warning – do not use in pregnant patients due to potential for fetal harm Not recommended for use with long-acting nitrates or PDE-5 inhibitors (hypotension risk) 112 Guideline Recommendations HF with reduced ejection fraction (HFrEF) LVEF