Advanced Pharmacotherapy I - Heart Failure Lecture Notes PDF

Advanced Pharmacotherapy I Heart Failure & Its Management Lecture 1 University of Sharjah COP Doctor of Pharmacy Fall 2024 Mohd Shara, Pharm.D., Ph.D, FACN  Lecture Objectives Upon completion of the chapter, the reader wi...

Advanced Pharmacotherapy I Heart Failure & Its Management Lecture 1 University of Sharjah COP Doctor of Pharmacy Fall 2024 Mohd Shara, Pharm.D., Ph.D, FACN  Lecture Objectives Upon completion of the chapter, the reader will be able to: Classify heart failure (HF) syndrome types into HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), HF with mid-range ejection fraction (HFmrEF), and HF with recovered ejection fraction (HFrecEF). Differentiate between the common underlying etiologies of HF, including ischemic, nonischemic, and idiopathic causes. Describe the pathophysiology of HF as it relates to neurohormonal activation of the renin-angiotensin- aldosterone system, sympathetic nervous system, and endogenous counterregulatory vasodilatory peptide systems. Identify signs and symptoms of HF and classify a given patient by New York Heart Association Functional Classification and American College of Cardiology/American Heart Association Heart Failure Stage. Discuss and modify the goals of therapy for a patient with acute and/or chronic HF. Create a strategy for the nonpharmacologic management of a patient with HF that includes patient education. Develop an evidence-based pharmacologic treatment and monitoring plan for a patient with chronic HFrEF. Design a pharmacologic treatment and monitoring plan for a patient with acute HF. Formulate a therapeutic management plan for a patient with HFpEF.  Heart Failure (HF) Heart failure (HF) is a syndrome defined as the inability of the heart to pump enough blood to meet the metabolic demands of the body. lowered cardiac output (CO) Generally, it involves a weakened heart muscle (most often the left ventricle) caused by a variety of illnesses. May or many not involve fluid overload (congestion) HF will present as acute (new onset HF) or chronic HF currently decompensated High output failure (excessive CO, due to unusually high metabolic demand beyond a normal heart capacity) will not be discussed here  HF can be due to structural or functional disease and affecting the ventricles' ability to fill properly (diastolic failure) and more often eject enough blood – can be classified based on the cardiac cycle – systole and diastole, therefore: – Ventricular Systolic HF (ejection problem) – Ventricular Diastolic HF (relaxation or filling problem) Ejection fraction (EF): The ejection fraction is the volume present at the end of diastole, and it's pushed into the aorta during systole (contraction of the ventricles). Both systolic and diastolic HF results in ↓ CO & HF symptoms with some differences – Systolic dysfunction is more common  A normal healthy ejection fraction is ~ 55-65%, however the normal cutoff for HF diagnosis EF is < 40%, technically, normal EF is ≥ 40% - however, most healthy people are well above that ~ 2/3 of patients have components of both systolic & diastolic Isolated diastolic occurs in about 1/3-1/2 of patients & based on impaired ventricular filling without HF symptoms as left ventricular ejection fraction (LVEF) is ≥ 50% – If isolated diastolic patients have HF symptoms, it’s called HF with preserved EF. Long standing HTN is the leading cause of this HF type HF can be right, left side or both (based ventricle involved) – Right sided HF is characterized by systemic congestion – Left sided HF is characterized by pulmonary congestion  Causes of Heart Failure 1. Related to Ischemia/Myocardial infarction (~70% of all HF) 2. Hypertension most common cause of diastolic dysfunction (~30% of HF) 3. Dilated cardiomyopathies 4. Valve disease (may be correctable) 5. Drug-induced: – Cardiotoxic drugs: Doxorubicin, Daunomycin, Cyclophosphamide See table 7-1 for a complete list of causes, see table 7-3 for causes of exacerbation & precipitation of HF  Epidemiology The most frequent Hospital discharge diagnosis in the elderly – Patients > 65 yrs. Slightly higher in females A most frequent cause of hospitalization among those with CAD and other comorbid conditions such as DM and renal insufficiency Prognosis is relatively poor, 5 years mortality rate >50% - that’s worse than cancer – Sudden cardiac death is the most common cause, in ~ 40% of patients Sudden cardiac death most often means a dangerous arrhythmia such as ventricular fibrillation (VF), potassium and Mg++ depletion increases this risk  Increasing incidence, cases increased from 500,000 to 960,000 new cases per year (US) over the past decade Overall, 5-year survival rate ≈ 50% 1-year survival rate NYHA-FC IV 50% 5-year mortality rate NYHA-FC IV 90% Higher rate in Gulf countries compared to US  Cardiac Physiology CO = HR X SV, amount of blood ejected per unit time SV: the amount of blood ejected from the heart during systole (contraction of the ventricles) and depends on Preload, Afterload and Contractility Preload: ventricular filling pressure. Forces acting on the venous side to affect myocardial wall tension. Blood return to the heart Afterload: Ventricular tension during systole, arterial impedance Frank-Starling Curve: Myocardial workload Vs Preload. When the demand increases, the heart muscle responds by increasing its output. The force of ventricular contraction (and therefore CO) proportionally increases as the degree of stretch (diastole) increases. Frank-Starling Curve Frank-Starling Curve FIGURE 7.1 Relationship between cardiac output (shown as cardiac index) and preload (shown as pulmonary capillary wedge pressure). System resistance and HF  Compensatory mechanisms RAAS The body responds to decreased CO via several mechanisms to compensate for the CO loss – Decreased blood flow to the periphery to conserve blood for heart and brain – Decreased blood flow to the kidneys results in activation of the RAAS Increased synthesis of Angiotensin II → synthesis and release of aldosterone → Increased Sodium and water retention → ↑ intravascular volume → ↑ Preload → ↑ CO Failing heart does not respond (Frank-Starling) to preload reduction and the increased volume further decompensates the heart  Precipitating and Exacerbating factors in HF A stable patient on optimal therapy is in a “compensated” state until he/she decompensate most often leading to an Emergency Room (ER) visit and sometimes a 4-6 day hospitalization. Reversible causes should be identified ASAP: Steps should be taken to address the causes – Most frequently, Volume overload due to: Medication or Dietary non-compliance Complicating illness (CAD, pneumonia, etc.)  Compensatory mechanisms: tachycardia & increased afterload Activation of the SNS –Increases the HR to affect an increase in the CO –SV does not increase significantly in HF, CO increase is mainly due to HR. This transient increase in CO due to ↑ HR is not effective and leads to arrhythmias and increased oxygen demand & worsening of ischemia in the long term –The Vasoconstriction from ↑ SNS → ↓ SV and CO  Compensatory mechanisms: Cardiac hypertrophy and remodeling Increased ventricular muscle mass due to higher pressure or fluid overload The increase in mass in HF is an abnormal growth that is able to maintain or increase CO temporarily but leads to worsening of HF and further damage to cardiac myocytes in the long term  Clinical Presentation – Symptoms of left-sided failure: Dyspnea (DOE) Orthopnea (pulmonary congestion) Paroxysmal nocturnal dyspnea (PND) – Symptoms of right-sided failure: Fluid retention Gastrointestinal bloating Fatigue – Left-sided failure will eventually lead to failure on both sides  Clinical Presentation & Evaluation Polyuria, nocturia, cough, weakness-exercise intolerance, tachypnea, tachycardia..... Lab tests: – BNP – ECG – Serum Creatinine – CBC – CXR – Echocardiogram (