Heart Failure PDF

Heart Failure PHARMACOTHERAPY (1) 2023-2024  References Pharmacotherapy; a pathophysiologic approach (Dipiro 12th edition). Chapter 36-CHF Pharmacotherapy; a pathophysiologic approach (Dipiro 12th edition). Chapter 37-ADHF Heidenreich P, Bozkurt B, Aguilar D,...

Heart Failure PHARMACOTHERAPY (1) 2023-2024  References Pharmacotherapy; a pathophysiologic approach (Dipiro 12th edition). Chapter 36-CHF Pharmacotherapy; a pathophysiologic approach (Dipiro 12th edition). Chapter 37-ADHF Heidenreich P, Bozkurt B, Aguilar D, et al. 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. J Am Coll Cardiol. 2022 May, 79 (17) e263–e421. 2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure With Reduced Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee  Definition of HF HF is a complex clinical syndrome with symptoms and signs that result from any structural or functional impairment of ventricular filling or ejection of blood. – asymptomatic stages with structural heart disease or cardiomyopathies are not covered under the above definition as having HF. Such asymptomatic stages are considered at-risk for HF (stage A) or pre-HF (stage B)  ACC/AHA Stages of HF emphasize the development and progression of disease, and advanced stages and progression are associated with reduced survival The ACC/AHA stages of HF are shown. ACC indicates American College of Cardiology; AHA, American Heart Association; CVD, cardiovascular disease; GDMT, guideline-directed medical therapy; and HF, heart failure.  Stages of HF Stages Definition and Criteria Stage A: At Risk for HF At risk for HF but without symptoms, structural heart disease, or cardiac biomarkers of stretch or injury (e.g., patients with hypertension, atherosclerotic CVD, diabetes, metabolic syndrome and obesity, exposure to cardiotoxic agents, genetic variant for cardiomyopathy, or positive family history of cardiomyopathy). Stage B: Pre-HF No symptoms or signs of HF and evidence of 1 of the following: Structural heart disease*  Reduced left or right ventricular systolic function o Reduced ejection fraction, reduced strain  Ventricular hypertrophy  Chamber enlargement  Wall motion abnormalities  Valvular heart disease Evidence for increased filling pressures*  By invasive hemodynamic measurements  By noninvasive imaging suggesting elevated filling pressures (e.g., Doppler echocardiography) Patients with risk factors and  Increased levels of BNPs* or  Persistently elevated cardiac troponin in the absence of competing diagnoses resulting in such biomarker elevations such as acute coronary syndrome, CKD, pulmonary embolus, or myopericarditis Stage C: Symptomatic HF Structural heart disease with current or previous symptoms of HF. Stage D: Advanced HF Marked HF symptoms that interfere with daily life and with recurrent hospitalizations despite attempts to optimize GDMT. BNP indicates B-type natriuretic peptide; CKD, chronic kidney disease; GDMT, guideline-directed medical therapy; HF, heart failure; LV, left ventricular; and RV, right ventricular.  New York Heart Association (NYHA) Classification The NYHA classification is used to characterize symptoms and functional capacity of patients with symptomatic (stage C) HF or advanced HF (stage D). It is a subjective assessment by a clinician and can change over time. Although reproducibility and validity can be limited, the NYHA functional classification is an independent predictor of mortality, and it is widely used in clinical practice to determine the eligibility of patients for treatment strategies. Clinicians specify NYHA classification at baseline after the initial diagnosis and after treatment through the continuum of care of a patient with HF. Although a patient with symptomatic HF (stage C) may become asymptomatic with treatment (NYHA class I), that patient will still be categorized as stage C HF.  NYHA functional classification of HF: Functional Physical Limitations and Symptoms Class Class I Patients with cardiac disease but without limitations of physical activity. Ordinary physical activity does not cause undue fatigue, dyspnea, or palpitation. Class II Patients with cardiac disease that results in slight limitations of physical activity. Ordinary physical activity results in fatigue, palpitation, dyspnea, or angina. Class III Patients with cardiac disease that results in marked limitation of physical activity. Although patients are comfortable at rest, less than ordinary activity will lead to symptoms. Class IV Patients with cardiac disease that results in an inability to carry on physical activity without discomfort. Symptoms of congestive HF are present even at rest. With any physical activity, increased discomfort is experienced.  Classification of Heart Failure ACCF/AHA Stages of HF NYHA Functional Classification A At high risk for HF but None without structural heart disease or symptoms of HF. B Structural heart disease but I No limitation of physical activity. Ordinary without signs or symptoms physical activity does not cause symptoms of HF. of HF. C Structural heart disease I No limitation of physical activity. Ordinary with prior or current physical activity does not cause symptoms of HF. symptoms of HF. II Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF. III Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF. IV Unable to carry on any physical activity without D Refractory HF requiring symptoms of HF, or symptoms of HF at rest. specialized interventions.  Classification of HF by LVEF Type of HF According to LVEF Criteria HFrEF (HF with reduced EF)  LVEF ≤40% HFimpEF (HF with improved EF)  Previous LVEF ≤40% and a follow-up measurement of LVEF >40% HFmrEF (HF with mildly reduced EF)  LVEF 41%–49%  Evidence of spontaneous or provokable increased LV filling pressures (e.g., elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement) HFpEF (HF with preserved EF)  LVEF ≥50%  Evidence of spontaneous or provokable increased LV filling pressures (e.g., elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement) LVEF is considered important in the classification of patients with HF because of differing prognosis and response to treatments and because most clinical trials select patients based on ejection fraction (EF). RCTs with evidence of survival benefit in patients with HF have mainly enrolled patients with HF with an LVEF ≤35% or ≤40%, often labeled HF with reduced ejection fraction (HFrEF)  Classification and Trajectories of HF Based on LVEF Patients with HFrEF who improve their LVEF to >40% are considered to have HFimpEF and should continue HFrEF treatment. There is limited evidence to guide treatment for patients who improve their LVEF from mildly reduced (41%-49%) to ≥50%. It is unclear whether to treat these patients as HFpEF or HFmrEF. Trajectory of LVEF can be important, and a significant reduction in LVEF over time is a poor prognostic factor.  Epidemiology and Causes of HF HF is a growing health and economic burden, in large part because of the aging population In the United States, approximately 115 million people have hypertension, 100 million have obesity, 92 million have prediabetes, 26 million have diabetes, and 125 million have atherosclerotic CVD (1). These are known risk factors with high relative risk and population attributable risk for development of HF. Therefore, a large proportion of the U.S. population can be categorized as being at-risk for HF or stage A HF. With the increasing ability to detect myocardial injury and with an increasing awareness of cardiotoxicity and injury patterns including inflammation, pre-HF or stage B HF will likely continue to increase. The common causes of HF include: – ischemic heart disease and myocardial infarction (MI), – hypertension, – valvular heart disease (VHD). Other Potential Nonischemic Causes of HF Chemotherapy and other cardiotoxic medications Rheumatologic or autoimmune Beyond classifications of Endocrine or metabolic (thyroid, acromegaly, pheochromocytoma, diabetes, obesity) EF and staging in HF, Familial cardiomyopathy or inherited and genetic heart disease clinicians should seek the Heart rhythm–related (e.g., tachycardia-mediated, PVCs, RV pacing) cause of HF because Hypertension appropriate treatment Infiltrative cardiac disease (e.g., amyloid, sarcoid, hemochromatosis) may be determined by the Myocarditis (infectious, toxin or medication, immunological, hypersensitivity) Peripartum cardiomyopathy cause Stress cardiomyopathy (Takotsubo) Substance abuse (e.g., alcohol, cocaine, methamphetamine) Self-Reading  Selected Drugs That May Precipitate or Exacerbate Heart Failure Negative inotropic effect Antiarrhythmics (disopyramide, dronedarone, flecainide, propafenone, sotalol) β-Blockers (eg, propranolol, metoprolol, carvedilol) Calcium channel blockers—nondihydropyridine type (verapamil, diltiazem) Itraconazole Cardiotoxic Self-Reading Alkylating agents (eg, cyclophosphamide, ifosfamide, melphalan) Amphetamines (eg, cocaine, methamphetamine) Anthracyclines (eg, doxorubicin, daunorubicin, epirubicin, idarubicin) Antiarrhythmics (eg, disopyramide, dronedarone, flecainide, propafenone, sotalol) Antimetabolites (eg, fluorouracil, capecitabine, fludarabine, decitabine) Antimicrotubules (eg, docetaxel, paclitaxel) BCR-ABL inhibitors (eg, bosutinib, dastinib, imatinib, ponatinib) BRAF inhibitors (eg, dabrafenib) Carbamazepine Chimeric antigen receptor (CAR) T-cell therapy (eg, tisagenlecleucel, axicabtageneciloleucel) Daunomycin Ethanol Hormonal therapy (eg, aplalutamide, bicalutamide, darolutamide, nilutamide) Human epidermal growth factor receptor (HER/EGFR) inhibitors (eg, lapatinib, osimertinib) Human epidermal growth factor receptor 2 (HER2) inhibitors (eg, pertuzamab, trastuzumab ) Immune checkpoint inhibitors (eg, nivolumab, ipilimumab, pembrolizumab) Immunomodulators (eg, lenalidomide, pomalidomide, thalidomide) MEK inhibitors (eg, binimetinib, cobimetinib, trametinib) Mitomycin Mitoxantrone Mitomycin Vascular endothelial growth factor (VEGF) inhibitors (eg, axitinib. bevacizumab, cabazantobinib, lenvatinib, pazopanib, sorafenib, sunitinib, vandetanib Miscellaneous (eg, entrectinib, fedratinib, ripretinib, tretinoin) Sodium and water retention Androgens and estrogens Cyclooxygenase-2 (COX-2) inhibitors Rosiglitazone and pioglitazone Glucocorticoids Nonsteroidal anti-inflammatory drugs (NSAIDs) Pioglitazone and rosiglitazone Salicylates (high dose) Sodium-containing drugs (eg, carbenicillin disodium, ticarcillin disodium) Uncertain mechanism Dipeptidyl peptidase-4 (DPP-4) inhibitors (eg, saxagliptin) TNF-α inhibitors (eg, adalimumab, infliximab, etanercept)  Prognosis Despite earlier diagnosis and aggressive medical management of HF, the prognosis is poor. Factors affecting the prognosis of patients with heart failure include, but are not limited to, age, gender, LVEF, renal function, blood pressure, heart failure etiology, and drug or device therapy. The quality of life is adversely affected by progressive functional disability. A greater consequence is the high mortality rate. – 5 year mortality rate is 50% (AHA/ACC 2013) – 80% of men and 70% of women under age 65 who have CHF will die within 8 years – Median survival following onset is 1.7 years for men and 3.2 years for women American Heart Association. 2006 Heart and Stroke Statistical Update. Dallas, Tex.: American Heart Association, 2005 Massie BM, Shah NB. Am Heart J 1997;133:703-712  Pathophysiology of HF Self-Reading Watch the video by Osmosis regarding congestive heart failure (CHF)—systolic, diastolic, left side, right side, and symptoms. https://www.youtube.com/watch?v=ypYI_lmLD7g This video provides an overview of the pathophysiology of heart failure due to both systolic and diastolic dysfunction. It also explains how heart failure symptoms relate to the underlying pathophysiology. A thorough understanding of heart failure pathophysiology and symptoms is key for students understanding how pharmacotherapy affects symptoms and improves overall outcomes. This will assist students in understanding the COLLECT and ASSESS steps in the patient care process.  Pathophysiology of HF May involve Self-Reading – The right ventricle, – The left ventricle – Or both, The majority of patients with HF have symptoms due to an impairment of left ventricular function. Regardless of the etiology of heart failure, the underlying pathophysiologic process and principal clinical manifestations (fatigue, dyspnea, and volume overload) are similar and appear to be independent of the initial cause.  Compensatory Mechanisms in HF The manifestations of  CO Self-Reading – The major direct consequence  exercise tolerance Rapid muscular fatigue – The Other manifestations result from The attempts by the body to compensate for the intrinsic cardiac defect in an attempt to maintain CO and oxygenation of vital organs. An understanding of the potential benefits and adverse consequences of the compensatory mechanisms is essential to understanding the signs, symptoms, and treatment of HF What are the compensatory mechanisms of the body? Compensatory mechanisms Self-Reading  Compensatory Mechanisms: Myocardial Hypertrophy Self-Reading The most important intrinsic compensatory mechanism – The increase in muscle mass helps to maintain cardiac performance in the face of adverse effects such as pressure or volume overload, loss of functional tissue (e.g. MI) or decrease in the contractility. However, after initial beneficial effect, there will be: – Ischemic changes – Impairment of diastolic filling – Alteration of ventricular geometry  HF Models Older paradigms Self-Reading – cardiorenal model problem viewed as excess Na+ & H2O diuretics main therapy – cardiocirculatory model (viewed as being due to both reduced pumping capacity of the heart and systemic vasoconstriction) problem viewed as impaired CO main therapies are positive inotropes, vasodilators Current paradigm: neurohormonal model – initiating event (MI or long standing HTN) leads to decreased CO (HF state) – becomes progressive systemic disease mediated by neurohormones & autocrine/paracrine factors – not a full explanation: drug therapies that target neurohormonal imbalances slow progression but do not stop disease progression The neurohormonal model of heart failure and therapeutic insights it provides Self-Reading  SGLT2 role in HF The sodium-glucose-cotransporter-2 (SGLT2) is highly expressed in the renal proximal tubule and is responsible for reabsorbing more than 90% of filtered glucose that is coupled with Na+ ions. The SGLT2 inhibitors (eg, empagliflozin, dapagliflozin) lower blood glucose by increasing urinary glucose (and sodium) excretion resulting in diuresis and natriuresis. Clinical trials reported that these agents also reduce the risk of cardiovascular events in patients with HF, including hospitalizations, even in patients without diabetes, suggesting that mechanism(s) other than simply lowering blood glucose are important. Although the exact beneficial mechanisms remain uncertain, these agents reduce inflammation, oxidative stress, and sympathetic nervous system activity as well as improve cardiac remodeling and myocardial energetics. The impressive outcomes with these medications in patients with HF further support the notion of HF as a disorder driven by multiple systemic mechanisms.  Factors Precipitating/Exacerbating HF Hospitalization for HF exacerbation consumes large amounts of healthcare dollars and significantly impairs the patient’s quality of life. Appropriate therapy can often maintain patients in a “compensated” state, indicating that they are relatively symptom-free. However, there are many aggravating or precipitating factors that may cause a previously compensated patient to develop worsened symptoms necessitating hospitalization. Often, these precipitating factors are reversible or treatable, thus thorough evaluation for their presence is imperative. – Cardiac events are a frequent cause of worsening HF (CAD, Afib, HTN) – Noncardiac events (Pulmonary infections , PE, DM, CKD, hypothyroidism, and hyperthyroidism) – Nonadherence with prescribed HF medications or with dietary recommendations (eg, sodium intake and fluid restriction) – Many drugs can precipitate or exacerbate HF Engaging a pharmacist in HF care is recommended to – assist with identifying inadequate HF therapy, – detecting medication nonadherence, – avoiding drug-drug interactions or other medication-related causes of HF.  CLINICAL PRESENTATION: Heart Failure Symptoms Signs Specific for Heart Failure Common – Jugular venous distention – Dyspnea, particularly on exertion – Cardiomegaly, lateral displacement of the – Orthopnea apical impulse – Paroxysmal nocturnal dyspnea – Hepatojugular reflux – S3 gallop – Exercise intolerance – Cheyne-Stokes respiration (advanced HF) – Fatigue Less Specific for Heart Failure – Swollen ankles of other parts of the body – Peripheral edema (lower extremities, sacral, – Bendopnea scrotal) – Pulmonary rales Less Common – Pulmonary edema – Cough – Weight gain (>2 kg/week) – Wheezing – Weight loss with muscle wasting/cachexia (advanced HF) – Nocturia – Pleural effusion – Anorexia, poor appetite, early satiety – Tachycardia/irregular pulse – Nausea – Tachypnea – Bloating – Hepatomegaly/ascites – Weight gain or loss – Cool extremities – Oliguria – Dizziness or syncope – Narrow pulse pressure – Depression – Cardiomegaly – Reduced cognitive function (especially in – Peripheral edema the elderly) – Hepatomegaly – Venous stasis changes  Notes on S&S of HF The primary manifestations of both HFrEF and HFpEF are: – dyspnea and fatigue, which lead to exercise intolerance, and – fluid overload, which can result in peripheral edema and pulmonary congestion. The presence of these signs and symptoms may vary considerably from patient to patient such that some patients have dyspnea but no signs of fluid retention, whereas others may have marked volume overload with few complaints of dyspnea or fatigue. However, many patients have both dyspnea and volume overload. Clinicians should remember that symptom severity often does not correlate with the degree of LV dysfunction It is also important to note that symptoms can vary considerably over time in a given patient even in the absence of changes in ventricular function or medications. It is difficult to attribute a specific sign or symptom as caused by either right or left ventricular failure.  CLINICAL PRESENTATION: Heart Failure Laboratory tests BNP > 35 pg/mL for ambulatory patients or > 100 pg/mL for patients hospitalized or with decompensated HF NT-proBNP >125 pg/mL for ambulatory patients or > 300 pg/mL for patients hospitalized or with decompensated HF An electrocardiogram may be normal or it could show numerous abnormalities including acute ST-T wave changes from myocardial ischemia, atrial fibrillation, bradycardia, left ventricular hypertrophy Serum creatinine: It may be increased due to hypoperfusion. Preexisting renal dysfunction can contribute to volume overload. Complete blood count is useful to determine if HF is due to reduced oxygen- carrying capacity Chest x-ray: Useful for detection of cardiac enlargement, pulmonary edema, and pleural effusions Echocardiogram: Used to assess LV size, valve function, pericardial effusion, wall motion abnormalities, and ejection fraction Hyponatremia: Serum sodium 1 year, an ICD is recommended for primary prevention of sudden cardiac death (SCD) to reduce total mortality. 6. In patients with LVEF ≤40%, beta blockers should be used to prevent 1 C-LD symptomatic HF. 3: 7. In patients with LVEF