[Web Module] Cardiovascular System - Drugs for Heart Failure

What is heart failure?

A cardiac condition marked by the inability of the heart's ventricles to pump enough blood to satisfy the body's demand for oxygen

What causes a decreased oxygen supply in heart failure?

Increased blood volume (fluid retention), increased venous pressure (decreased venous compliance), and increased ventricular compliance leads to increased preload.

Increased preload can lead to a failure of the left side of the heart, resulting in blood backing into the lungs, resulting in a pulmonary edema.

A pulmonary edema can lead to congestion and reduced gas exchange in the lungs, resulting in a decreased oxygen supply and shortness of breath.

What causes increased preload in heart failure?

-Increased blood volume from fluid retention (RAA pathway, ADH, Aldosterone)

-Increased venous pressure from decreased venous compliance

-Increased ventricular compliance - resulting in the heart filling up more

What does increased preload lead to in heart failure?

Especially if left side of heart is impacted, blood is backed into the lungs, which causes a pulmonary edema and congestion, leading to decreased gas exchange and decreased oxygen supply. This causes the hallmark SOB symptoms in heart failure

What is compliance?

The ability of a chamber or vessel to stretch and expand. Increased compliance means that the chamber/vessel has more elasticity, while decreased compliance means that the chamber/vessel is more stiff

What causes increased cardiac workload in heart failure?

Decreased contractility of the heart and decreased cardiac output (SV * HR) leads to decreased blood pressure.

The body activates compensatory mechanisms, which worsens the heart failure.

A) Decreased blood pressure leads to decreased blood flow to the kidneys, which results in ADH and the RAA pathway being activated.

ADH and RAA act to increased sodium and water retention, which leads to increased blood volume, fluid accumulation and an edema, especially in the limbs due to gravity. The increased blood volume results in greater cardiac workload due to increased preload

The RAA pathway also causes vasoconstriction, resulting in increased peripheral resistance, which results in greater cardiac workload due to increased afterload

B) The body increases heart rate as a compensatory mechanism for decreased blood pressure, leading to increased cardiac output and increased cardiac workload

What does decreased blood pressure lead to in heart failure?

Decreased blood pressure leads to activation of compensatory mechanisms to increased blood pressure, leading to worsening of the heart failure

A) Blood flow is decreased to the kidneys, resulting in release of ADH and activation of the RAA pathway, resulting in sodium and water retention -> leading to increased blood volume and edemas, and increased peripheral resistance, leading to increased afterload. Both of these increased cardiac workload on the heart

B) Heart rate is increased, leading to increased cardiac workload on the heart

What causes decreased blood pressure in heart failure?

-Decreased contractility of the heart

-Decreased cardiac output of the heart

What are predisposing risk factors for heart failure?

-Hypertension

-Cardiovascular disease

-Congenital heart disease

-Myocardial infarction

-Mitral stenosis

-Diabetes Mellitus

Other cardiomyopathies

Leads to an overall increase in myocardial oxygen demand

What is preload?

Degree to which muscle fibers stretch before the heart contracts in systole

Increased by more blood flow to the heart

What is afterload?

The pressure that the heart must work against to eject blood during contraction

Increased by greater vascular resistance or blood pressure

What occurs to cardiac myocytes leading to a heart failure?

Increased cardiac workload on the heart causes the walls of the ventricles to grow more thicker (aka hypertrophy) to compensate, leading to a decreased ability to pump blood and greater oxygen demand of the heart

What symptoms are prominent in left sided heart failure?

Leads to backup of blood back to the lungs, leading to pulmonary edema and SOB

What symptoms are prominent in right sided heart failure?

Leads to back up of blood in the peripheries, leading to peripheral edemas, more prominent in the limbs due to gravity

What causes decreased cardiac output in heart failure?

Cardiac output is controlled by stroke volume and heart rate.

Decreased heart rate is caused by decreased function of the SA node, can be the result of increased age

Decreased stroke volume is caused by systolic and/or diastolic function

What is stroke volume?

The amount of blood pumped out of the left ventricle to the rest of the heart.

It is regulated by:

A) Preload - how much blood is able to flow into the heart

B)Afterload - how well the heart contracts to eject this blood

What is the Frank Starling mechanism?

The more blood that is returned from the veins, or preload, is directly proportional to the amount of stretch of the ventricles to compensate for this increased blood flow to eject it

What causes diastolic dysfunction in heart failure?

Increased preload and hypertrophy -> stiffening of the ventricles (decreased compliance) leads to the inability of the ventricles to compensate for the increased cardiac demand, resulting in decreased stroke volume.

Incomplete relaxation of the ventricles (aka reduced lusitropy) leads to decreased capacity of the ventricles to pump out blood, leading to decreased stroke volume.

What is lusitropy?

Issues with the ventricles not completely relaxing during diastole, which decreases the capacity of the ventricles to pump out blood, and can lead to decreased stroke volume and heart failure

What causes systolic dysfunction in heart failure?

Loss of heart contractility, either by loss of muscle tissue from a myocardial infarction or alterations in cellular signal transduction, leads to systolic dysfunction, resulting in increased preload from compensatory mechanisms (RAA + ADH pathways).

Systolic dysfunction also leads to blood being left in the ventricles after systole (ejection fraction), leading to increased cardiac workload.

The heart will compensate by increasing muscle mass (aka hypertrophy), or increase compliance, allowing more blood into the chambers, both of which are unfavorable as it leads to increased oxygen demand and reduced mechanical efficiency

What are common symptoms of heart failure?

Dyspnea (SOB)

Orthopnea (SOB while laying down)

Paroxysmal nocturnal dyspnea (SOB while sleeping)

Fatigue (increased cardiac workload)

Weakness (increased cardiac workload)

Exercise intolerance (increased cardiac workload)

Dependent edema (swelling of lower limbs)

Cough (pulmonary edema)

Weight gain (Water retention)

Abdominal distention (Fluid collection in peritoneum)

Nocturia (Urination at night)

Cool Extremities (Poor blood flow to extremities)

What are severe/less common symptoms of heart failure?

Cognitive impairment (Poor blood flow to brain -> increased in elderly patients)

Altered mentation or delirium (Poor blood flow to brain -> increased in elderly patients)

Nausea (Abdominal distention)

Abdominal discomfort (Abdominal distention)

Oliguria (Decreased in urine output -> renal failure)

Anorexia

Cyanosis (Poor tissue oxygenation)

What are the most common symptoms of heart failure?

Increased SOB (Pulmonary edema)

Edemas (Fluid retention)

What are common drug classes prescribed to treat heart failure?

Adrenergic blockers (Decrease HR + BP)

ACE inhibitors (Decreased BP and Fluid retention)

Direct Vasodilators (Decreased TPR + Edemas)

Loop Diuretics (Decreased Fluid retention)

ARNIs (Decreased BP + Fluid retention)

MRAs (Decreased Fluid retention

Ivabradine (Decreased HR)

Cardiac glycosides (Decreased HR and Increased contractility

Phosphodiesterase Inhibitors (Increased contractility)

How are adrenergic blockers used to treat heart failure?

Inhibition of b1 receptors causes lowered HR which reduces CO and cardiac demand

Inhibition of a1 receptors causes lowered BP which decreases afterload and cardiac demand

How are direct vasodilators used to treat heart failure?

Includes Hydralazine and Isosorbide Dinitrate, which work synergistically together

Hydralazine causes vasodilation on arterioles, which reduces total peripheral resistance and BP, which decreases afterload and cardiac demand

Isosorbide Dinitrate causes vasodilation on veins, which decreases venous pressure, decreasing fluids following into tissues, resulting in lower edema formation and relieves both pulmonary and systemic edemas

What is the role of Hydralazine in direct vasodilators for treating heart failure?

Hydralazine causes vasodilation on arterioles, which reduces total peripheral resistance and BP, which decreases afterload and cardiac demand

What is the role of Isosorbide Dinitrate in direct vasodilators for treating heart failure?

Isosorbide Dinitrate causes vasodilation on veins, which decreases venous pressure, decreasing fluids following into tissues, resulting in lower edema formation and relieves both pulmonary and systemic edemas

What are phosphodiesterase inhibitors? (Use, Mechanism of Action, Route of Administration, Monitoring)

Use

Used for acute/crisis management of heart failure

Mechanism of Action

Increases heart contractility, which increases stroke volume and blood supply

Route of Administration

IV

Monitoring

ECG monitoring

What are cardiac glycosides? (Use, Mechanism of Action, Caution)

Use

Used for treatment of heart failure, only used in severe cases or when other pharmacological agents do not work

Mechanism of Action

Decreases heart rate, which increases heart contractility, leading to increased stroke volume and blood supply

Caution

Narrow therapeutic index, can easily lead to adverse effects

How is Ivabradine used to treat heart failure?

Used when beta blockers are either contraindicated for the patient, or the maximum dosage has been prescribed

Lowers heart rate by inhibiting the SA node, thus resulting in decreased cardiac workload

How are potassium sparing diuretics used to treat heart failure?

aka mineralocorticoid receptor antagonist

aka aldosterone antagonist

Inhibits binding of aldosterone to it's receptor, resulting in increased Na+ and water excretion and decreasing K+ excretion, leading to decreased water retention

They are weaker than loop diuretics, however, they are associated with reduced mortality rates in patients with heart failure

How are angiotensin receptor neprilysin inhibitors used to treat heart failure?

Consists of valsartan and sacubitril

Valsartan inhibits angiotensin II receptors, which inhibits vasoconstriction and inhibits sodium and water retention via RAA pathway inhibition, resulting in decrease blood pressure and water retention

Sacubitril inhibits neprilysin, which is responsible for breaking down natriuretic peptides.

Increased natriuretic peptides cause diuresis and reverse effects of the SNS and RAA on heart function in patients with heart failure, thus decreasing blood pressure, heart rate and water retention

What is the role of valsartan in ANRIs for treating heart failure?

Valsartan inhibits angiotensin II receptors, which inhibits vasoconstriction and inhibits sodium and water retention via RAA pathway inhibition, resulting in decrease blood pressure and water retention

What is the role of sacubitril in ANRIs for treating heart failure?

Sacubitril inhibits neprilysin, which is responsible for breaking down natriuretic peptides.

Increased natriuretic peptides cause diuresis and reverse effects of the SNS and RAA on heart function in patients with heart failure, thus decreasing blood pressure, heart rate and water retention

How are ACE inhibitors used to treat heart failure?

ACE inhibitors inhibit ACE enzyme in the RAA pathway, leading to decreased blood pressure, resulting in lower cardiac workload, and decreased fluid retention due to RAA inhibition

How are loop diuretics used to treat heart failure?

Loop diuretics increased urine output, which decreases blood volume and leads to decreased preload, lowering the cardiac workload

What is the overall pharmacology protocol for treating patients with heart failure?

Provide individualized pharmacotherapy based on the patient's symptoms and severity of heart failure (NYHA classification)

What patient education should be provided for patients with heart failure?

Diet

-Reduce salt intake

-Reduce saturated fat intake and include plenty of high fibrous foods (vegetables and fruits) to lower CAD, which contributes to increased heart failure risk

-Fluid restrictions

Physical activity

-Perform stress test to determine activity tolerance

-Perform exercises as tolerated

Monitoring

-Daily weight monitoring to assess effectiveness of prescribed diuretics

-Consult with pharmacist for the use of other drugs or herbal supplements due to possible drug-drug interactions

What is the importance of performing weight monitoring for patients with heart failure?

Patients should keep a daily weight record if they are prescribed diuretics to detect onset of fluid retention

Daily weight gain can be a sign of increased fluid retention, and can lead to worsening heart failure and hospitalization if it is not promptly treated

What monitoring should occur for patients prescribed with ACE or ARB therapy?

Monitor for hypotension during first dose

Monitor CBC for neutropenia during first year of therapy

Monitor for hyponatremia and hyperkalemia

What monitoring should occur for patients prescribed with beta blocker therapy?

Use caution for patients with diabetes and hepatic impairments

What monitoring should occur for patients prescribed with MRA therapy?

Monitor for hyperkalemia

Monitor for impaired renal function

Monitor for hormonal dysfunction

What monitoring should occur for patients prescribed with diuretic therapy?

Monitor for weight gain

Monitor for potassium levels + other electrolytes

Monitor for blood glucose levels