Heart Failure and Angina Medication

Heart Failure

Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) (HF)

A clinical syndrome characterized by the inability of the cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics to meet the metabolic demands of the body:

• Due to abnormal heart function and associated neurohormonal abnormalities
• Leads to circulatory congestion and/or inadequate tissue perfusion
• Results from the body’s attempt to compensate for heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)

Decreased cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics activates the sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification and RAAS RAAS A blood pressure regulating system of interacting components that include renin; angiotensinogen; angiotensin converting enzyme; angiotensin i; angiotensin ii; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to angiotensin II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal vascular smooth muscle, leading to retention of salt and water in the kidney and increased arterial blood pressure. In addition, angiotensin II stimulates the release of aldosterone from the adrenal cortex, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down bradykinin, a powerful vasodilator and component of the kallikrein-kinin system. Adrenal Hormones:

• Ensures brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and cardiac perfusion, but leads to the vicious cycle of chronic neurohormonal activation
• ↑ Vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure → ↑ afterload Afterload Afterload is the resistance in the aorta that prevents blood from leaving the heart. Afterload represents the pressure the LV needs to overcome to eject blood into the aorta. Cardiac Mechanics → further ↓ in cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics
• ↓ Renal perfusion → ↑ aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia → ↓ diuresis → ↑ overload
• ↑ Catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones → promote arrhythmias and ↑ O₂ consumption
• ↑ Angiotensin II Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the c-terminal by angiotensin converting enzyme. The amino acid in position 5 varies in different species. To block vasoconstriction and hypertension effect of angiotensin II, patients are often treated with ace inhibitors or with angiotensin II type 1 receptor blockers. Renal Sodium and Water Regulation + norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS → pathologic cardiac remodeling ( hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation, fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans, and cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death)

Types:

• Systolic heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR):
  • Impaired myocyte contractility and dilated heart → reduced left ventricular (LV) ejection fraction Ejection fraction Cardiac Cycle and stroke volume Stroke volume The amount of blood pumped out of the heart per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume. Cardiac Cycle
  • Also known as reduced ejection fraction Ejection fraction Cardiac Cycle heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) (HFrEF)
• Diastolic heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR):
  • Inadequate relaxation and filling of the hypertrophied heart but normal myocyte contractility
  • Preserved ejection fraction Ejection fraction Cardiac Cycle despite low stroke volume Stroke volume The amount of blood pumped out of the heart per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume. Cardiac Cycle
  • Also known as preserved ejection fraction Ejection fraction Cardiac Cycle heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) (HFpEF)
• Left-sided heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR):
  • Most common form of heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
  • Fluid may build up in the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy and cause dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea and pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema.
• Right-sided heart failure Right-Sided Heart Failure Ebstein’s Anomaly:
  • Often occurs along with left-sided heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
  • Fluid builds up in the abdomen, legs, and feet, resulting in peripheral edema Peripheral edema Peripheral edema is the swelling of the lower extremities, namely, legs, feet, and ankles. Edema.

Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) classification:

• NYHA functional classification:
  • Class I: no limitations Limitations Conflict of Interest in physical activity
  • Class II: comfortable at rest but slight limitation during moderate/prolonged physical activity
  • Class III: comfortable only at rest. Daily activities, such as dressing up, result in marked limitations Limitations Conflict of Interest of physical activity.
  • Class IV: symptomatic even at rest
• American Heart Association classification American Heart Association classification Heart Failure:
  • Stage A: high risk for heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) but without structural heart disease, objective evidence of cardiovascular disease, or symptoms of heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
  • Stage B: structural heart disease/objective evidence of minimal cardiovascular disease but without signs or symptoms of heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
  • Stage C: structural heart disease/objective evidence of moderate-to-severe cardiovascular disease with prior or current symptoms of heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
  • Stage D: refractory heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)/objective evidence of severe cardiovascular disease requiring specialized interventions

General therapy

Address the associated conditions or causes:

• Ischemic heart disease Ischemic heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease
• Valvular heart disease
• Cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Cardiomyopathy: Overview and Types
• Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
• Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus
• Arrhythmias (e.g., atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation)
• Obstructive sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea
• Hyperlipidemia
• Others:
  • Advise smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation.
  • ↓ Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity and weight

Pharmacologic management depends on the type of heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR):

• HFrEF:
  • Diuretics
  • Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) (unless unstable in acute exacerbation of HF)
  • Renin-angiotensin system inhibitors (ACE inhibitor, ARB, or angiotensin receptor-neprilysin inhibitor Angiotensin Receptor-Neprilysin Inhibitor Renin-Angiotensin-Aldosterone System Inhibitors ( ARNi ARNi Renin-Angiotensin-Aldosterone System Inhibitors))
  • SGLT2 inhibitors SGLT2 inhibitors Non-insulinotropic Diabetes Drugs ( dapagliflozin Dapagliflozin Non-insulinotropic Diabetes Drugs)
  • Hydralazine + nitrate
  • Mineralocorticoid receptor antagonists Mineralocorticoid receptor antagonists Drugs that bind to and block the activation of mineralocorticoid receptors by mineralocorticoids such as aldosterone. Potassium-sparing Diuretics ( MRAs MRAs Drugs that bind to and block the activation of mineralocorticoid receptors by mineralocorticoids such as aldosterone. Potassium-sparing Diuretics)
  • Digoxin Digoxin A cardiotonic glycoside obtained mainly from digitalis lanata; it consists of three sugars and the aglycone digoxigenin. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. Cardiac Glycosides
• HFpEF:
  • ARNis (or ARBs) and MRAs MRAs Drugs that bind to and block the activation of mineralocorticoid receptors by mineralocorticoids such as aldosterone. Potassium-sparing Diuretics: may decrease hospitalizations in select individuals
  • SGLT2 inhibitors SGLT2 inhibitors Non-insulinotropic Diabetes Drugs: may reduce hospitalizations
  • Diuretics: for volume overload (while carefully avoiding volume depletion Volume depletion Volume status is a balance between water and solutes, the majority of which is Na. Volume depletion refers to a loss of both water and Na, whereas dehydration refers only to a loss of water. Volume depletion can be caused by GI losses, renal losses, bleeding, poor oral Na intake, or third spacing of fluids. Volume Depletion and Dehydration)
  • Other therapies based on associated conditions
  • Avoid organic nitrates Nitrates Nitrates are a class of medications that cause systemic vasodilation (veins > arteries) by smooth muscle relaxation. Nitrates are primarily indicated for the treatment of angina, where preferential venodilation causes pooling of blood, decreased preload, and ultimately decreased myocardial O2 demand. Nitrates, digoxin Digoxin A cardiotonic glycoside obtained mainly from digitalis lanata; it consists of three sugars and the aglycone digoxigenin. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. Cardiac Glycosides, and phosphodiesterase (PDE) 5 inhibitors.

Pharmacologic Management of HF

The medications used for the chronic management of HF (often HFrEF) to control and reduce symptoms, prevent progression, and for mortality Mortality All deaths reported in a given population. Measures of Health Status benefit are listed below.

The following medications are used for the secondary therapy of HF:

Acute Exacerbation of HF and Precautions in Pharmacotherapy

Acute decompensated HF

• Caused by several differential medical conditions such as:
  • MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction
  • Arrhythmias such as atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation
• May be complicated by:
  • Severe pulmonary congestion 
  • Severe cardiogenic shock Cardiogenic shock Shock resulting from diminution of cardiac output in heart disease. Types of Shock
• Most cases occur in the context of underlying chronic heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) and are potentially fatal.
• The goal of pharmacotherapy is to reduce volume overload, tailoring additional management to individual causes and comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus.

Medications

• Diuretics:
  • IV administration of loop diuretics Loop diuretics Loop diuretics are a group of diuretic medications primarily used to treat fluid overload in edematous conditions such as heart failure and cirrhosis. Loop diuretics also treat hypertension, but not as a 1st-line agent. Loop Diuretics such as:
    • Furosemide Furosemide A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for edema and chronic renal insufficiency. Loop Diuretics
    • Torsemide Torsemide A pyridine and sulfonamide derivative that acts as a sodium-potassium chloride symporter inhibitor. It is used for the treatment of edema associated with congestive heart failure; chronic renal insufficiency; and liver diseases. It is also used for the management of hypertension. Loop Diuretics
    • Bumetanide Bumetanide A sulfamyl diuretic. Loop Diuretics
  • Individuals on diuretic therapy for the treatment of chronic HF will require higher doses of IV medications.
  • Due to different effects, the following parameters are monitored:
    • Renal function (may worsen)
    • Electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes (may be depleted)
    • Hemodynamic effects ( hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension can occur)
• Vasodilator therapy may be required to reduce LV filling pressures and afterload Afterload Afterload is the resistance in the aorta that prevents blood from leaving the heart. Afterload represents the pressure the LV needs to overcome to eject blood into the aorta. Cardiac Mechanics:
  • Nitroprusside Nitroprusside A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins. Nitrates (causing arterial and venous dilation, decreasing both LV filling and systemic vascular resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing) is useful to treat:
    • Severe hypertension Severe hypertension A confirmed blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic. Uncontrolled Hypertension
    • Acute mitral regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
    • Acute aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
  • Nitrates Nitrates Nitrates are a class of medications that cause systemic vasodilation (veins > arteries) by smooth muscle relaxation. Nitrates are primarily indicated for the treatment of angina, where preferential venodilation causes pooling of blood, decreased preload, and ultimately decreased myocardial O2 demand. Nitrates:
    • Preload Preload Cardiac Mechanics reduction, particularly if the individual is hypertensive
    • Reduces LV filling via venodilation Venodilation Venous Function
    • Contraindicated in individuals with hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension or those prescribed a phosphodiesterase inhibitor
• Inotropic medications that may be used to manage cardiogenic shocks:
  • Dobutamine Dobutamine A catecholamine derivative with specificity for beta-1 adrenergic receptors. Sympathomimetic Drugs is a beta-1 adrenergic agonist.
  • Dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS is a dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors agonist with beta-adrenergic effects at low doses and alpha-adrenergic effects at high doses.
  • Milrinone Milrinone A positive inotropic cardiotonic agent with vasodilator properties. It inhibits camp phosphodiesterase type 3 activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the inotropic potency of amrinone. Phosphodiesterase Inhibitors is a PDE3 inhibitor.
• The use of beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) in an acute setting depends on severity:
  • Hold medication in cases of severe decompensation.
  • Continue in cases of mild decompensation, if tolerated.

Use these drugs with caution in individuals with HF

• Calcium-channel blockers:
  • Especially drugs from the nondihydropyridine class
  • May cause an overall negative inotropic effect Negative Inotropic Effect Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers)
• Antiarrhythmics (class III agents such as sotalol Sotalol An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias. Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers), ibutilide Ibutilide Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers), dofetilide Dofetilide Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers)):
  • Can produce a proarrhythmic effect
  • In heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR), medications increase the risk for torsades de pointes Torsades de pointes A malignant form of polymorphic ventricular tachycardia that is characterized by heart rate between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long qt intervals exceeding 500 milliseconds or bradycardia. Torsades de pointes may be self-limited or may progress to ventricular fibrillation. Ventricular Tachycardia.
• Thiazolidinediones Thiazolidinediones Thiazoles with two keto oxygens. Members are insulin-sensitizing agents which overcome insulin resistance by activation of the peroxisome proliferator activated receptor gamma (ppar-gamma). Non-insulinotropic Diabetes Drugs:
  • Can promote fluid retention
  • Can precipitate and worsen the progression of HF
• Metformin Metformin A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. Non-insulinotropic Diabetes Drugs: associated with the risk of lactic acidosis Lactic Acidosis Oxazolidinones
• Some chemotherapeutic agents are cardiotoxic:
  • Anthracyclines Anthracyclines Organic compounds that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine. Antitumor Antibiotics
  • Cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants
  • Trastuzumab Trastuzumab A humanized monoclonal antibody against the ErbB-2 receptor (HER2). As an antineoplastic agent, it is used to treat breast cancer where HER2 is overexpressed. Targeted and Other Nontraditional Antineoplastic Therapy
  • Bevacizumab Bevacizumab An anti-vegf humanized murine monoclonal antibody. It inhibits vegf receptors and helps to prevent pathologic angiogenesis. Targeted and Other Nontraditional Antineoplastic Therapy
• PDE5 inhibitors ( sildenafil Sildenafil A phosphodiesterase type-5 inhibitor; vasodilator agent and urological agent that is used in the treatment of erectile dysfunction and primary pulmonary hypertension. Phosphodiesterase Inhibitors, vardenafil Vardenafil A piperazine derivative, phosphodiesterase 5 inhibitor and vasodilator agent that is used as a urological agent in the treatment of erectile dysfunction. Phosphodiesterase Inhibitors, tadalafil Tadalafil A carboline derivative and phosphodiesterase 5 inhibitor that is used primarily to treat erectile dysfunction; benign prostatic hyperplasia and primary pulmonary hypertension. Phosphodiesterase Inhibitors):
  • Vasodilators Vasodilators Drugs used to cause dilation of the blood vessels. Thromboangiitis Obliterans (Buerger’s Disease)
  • ↑ Risk of hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension if used with nitrates Nitrates Nitrates are a class of medications that cause systemic vasodilation (veins > arteries) by smooth muscle relaxation. Nitrates are primarily indicated for the treatment of angina, where preferential venodilation causes pooling of blood, decreased preload, and ultimately decreased myocardial O2 demand. Nitrates

Angina

Angina pectoris Angina pectoris The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation. It is thought to be provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed that supplied by the coronary circulation. Stable and Unstable Angina:

• Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways or discomfort in the chest, often also spreading to the shoulders, arms, and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess/ jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint: Anatomy, which is caused by inadequate blood supply to the heart:
  • Description of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways: retrosternal location, dull/squeezing
  • Provoked by different factors: physical/emotional stress, meals, lying down, drugs
• Stable angina Stable angina Persistent and reproducible chest discomfort usually precipitated by a physical exertion that dissipates upon cessation of such an activity. The symptoms are manifestations of myocardial ischemia. Stable and Unstable Angina is episodic chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways due to transient myocardial ischemia Myocardial ischemia A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary artery disease), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Coronary Heart Disease that results from coronary atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis.
• Unstable angina Unstable angina Precordial pain at rest, which may precede a myocardial infarction. Stable and Unstable Angina is defined as the worsening of previously stable angina Stable angina Persistent and reproducible chest discomfort usually precipitated by a physical exertion that dissipates upon cessation of such an activity. The symptoms are manifestations of myocardial ischemia. Stable and Unstable Angina, or chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways at rest, or pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways not relieved with nitroglycerin Nitroglycerin A volatile vasodilator which relieves angina pectoris by stimulating guanylate cyclase and lowering cytosolic calcium. It is also sometimes used for tocolysis and explosives. Nitrates:
  • Manifests with ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) changes
  • Manifests without elevated troponin levels

Pharmacologic Management of Angina

Pharmacologic agents used initially

• Antiplatelet therapy ( aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs))
• Nitrates Nitrates Nitrates are a class of medications that cause systemic vasodilation (veins > arteries) by smooth muscle relaxation. Nitrates are primarily indicated for the treatment of angina, where preferential venodilation causes pooling of blood, decreased preload, and ultimately decreased myocardial O2 demand. Nitrates:
  • Sublingual nitroglycerin Nitroglycerin A volatile vasodilator which relieves angina pectoris by stimulating guanylate cyclase and lowering cytosolic calcium. It is also sometimes used for tocolysis and explosives. Nitrates (0.4 mg every 5 minutes for a total of 3 doses)
  • Reduce myocardial O₂ demand
  • Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation:
    • Recent use of a PDE5 inhibitor
    • Severe aortic stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS)
    • Hypertrophic cardiomyopathy Hypertrophic Cardiomyopathy Hypertrophic cardiomyopathy (HCM) is the most commonly inherited cardiomyopathy, which is characterized by an asymmetric increase in thickness (hypertrophy) of the left ventricular wall, diastolic dysfunction, and often left ventricular outflow tract obstruction. Hypertrophic Cardiomyopathy
    • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
    • Marked bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias
    • Suspected right ventricular infarct Infarct Area of necrotic cells in an organ, arising mainly from hypoxia and ischemia Ischemic Cell Damage
• IV morphine Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Opioid Analgesics:
  • For severe, persistent chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Effect: reduces sympathetic stimulation resulting from anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
• It is important to note that thrombolytic therapy is not administered to individuals with unstable angina Unstable angina Precordial pain at rest, which may precede a myocardial infarction. Stable and Unstable Angina or NSTEMI.

Further therapy

• Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers)
• Statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins
• Calcium-channel blockers:
  • Adjunctive therapy for individuals with recurrent symptoms
  • May be used in case of rapid atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation (when beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) are contraindicated)
  • Do not use immediate-release nifedipine Nifedipine A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers) (causes reflex sympathetic activation/ tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children).
• Ranolazine:
  • To treat chronic stable angina Stable angina Persistent and reproducible chest discomfort usually precipitated by a physical exertion that dissipates upon cessation of such an activity. The symptoms are manifestations of myocardial ischemia. Stable and Unstable Angina
  • Mechanism: inhibits inward Na⁺ channels Channels The Cell: Cell Membrane in ischemic cardiac muscles → ↓ calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes influx → ↓ ventricular tension and ↓ O₂ demand