Heart Failure and Cardiac Output Quiz

Pharmacological Management of Congestive Heart Failure

• Congestive heart failure (CHF) is a condition where the heart struggles to pump enough blood to meet the body's needs. It can result from systolic or diastolic dysfunction. Systolic dysfunction refers to a weakened heart unable to pump blood effectively. Diastolic failure involves the inability of the ventricles to properly fill during the relaxation phase (diastole).
• Learning outcomes for pharmacological management of heart failure include identifying major drug groups used for treatment, understanding the mechanisms of action of digitalis and its toxic effects, clinical implications of diuretics, vasodilators, ACE inhibitors and other drugs, strategies used in treatment.

What is Heart Failure?

• Heart failure is a condition where the heart isn't able to pump enough blood to meet the body's needs. This can be due to either the heart not pumping enough blood (systolic heart failure) or not filling up properly with blood (diastolic heart failure).
• In both cases, fluid backs up into the lungs, causing congestion, which is why it's often called congestive heart failure.
• Heart failure results from any structural or functional issue of the heart that impairs its ability to fill or eject blood.

Heart Failure (HF) Factors

• Factors contributing to heart failure include:
  • Pulmonary hypertension
  • Myocardial infarction
  • Valvular heart disease
  • Dilated cardiomyopathy
  • Chronic systemic hypertension

Cardiac Output

• Cardiac output (CO) is the volume of blood the heart pumps per minute. It's calculated as heart rate (HR) multiplied by stroke volume (SV).
• Normal cardiac output is about 5 liters per minute.

Ejection Fraction

• Ejection fraction (EF) is the percentage of blood the heart pumps out of the left ventricle with each beat.
• A normal ejection fraction is around 50-70%. Values below 40% often indicate heart failure.

Definitions

• Stroke Volume (SV): The amount of blood pumped by the heart with each contraction.
• Cardiac Output (CO): The total volume of blood pumped out of the heart per minute (SV x heart rate).
• Preload: The volume of blood in the left ventricle at the end of diastole, primarily determined by the venous return of blood to the heart.

Cardiac Output Example

• In a healthy adult, the heart might beat 70 times per minute and pump out 70 ml of blood per beat, resulting in a cardiac output of 4900 ml/min (approximately 5 liters/min).
• The stroke volume is only a fraction of the total volume in the ventricle. The other portion stays in the ventricle until the next beat.

Cardiac Output Example - Ejection Fraction

• Ejection fraction can be calculated by dividing the stroke volume by the total volume in the ventricle before each beat.
• When the ejection fraction is 40% or less, it suggests systolic heart failure.

Compensatory Responses During Heart Failure

• Heart failure triggers compensatory responses. For example, the body releases renin to increase blood pressure and retain sodium and water, often leading to edema.

Cardiac Remodeling

• Cardiac remodeling is the structural and functional changes in the heart due to heart failure.
• These changes include hypertrophy (enlarging) of heart muscle cells, necrosis (cell death), and fibrosis (scar tissue formation).

Compensated vs. Decompensated HF

• Compensated heart failure (acute): Adaptive mechanisms restore cardiac output.
• Decompensated heart failure (acute): Failure of adaptive mechanisms leads to worsening symptoms like dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, fatigue and peripheral edema.

Goal of Heart Failure Treatment

• Primary goals of heart failure treatment include alleviating symptoms, slowing disease progression and improving survival.

Therapeutic Strategies in HF

• Treatment strategies for heart failure include fluid limitation, low sodium diets, treatment of co-morbidities, appropriate diuretic doses, and avoiding drugs that may worsen the condition (e.g., Nonsteroidal anti-inflammatory drugs (NSAIDs), certain calcium channel blockers, and some anti-arrhythmics).

Phosphodiesterase Inhibitors

• Amrinone and milrinone are selective phosphodiesterase III inhibitors. These medications increase intracellular cAMP, improving cardiac contractility and promoting relaxation of vascular smooth muscle.

Other Inotropic Drugs

• Dopamine and dobutamine are inotropic agents. Used in acute heart failure situations.

Beta-Blockers

• Beta-blockers are used to reduce morbidity and mortality in chronic stable heart failure. They prevent the damaging effects of norepinephrine on the heart and reduce heart rate and renin release. Examples include carvedilol, bisoprolol, and metoprolol.

ACE Inhibitors

• ACE inhibitors, such as captopril, enalapril, ramipril, and lisinopril, are used to reduce afterload and preload to normalize blood pressure.

Angiotensin Receptor Blockers (ARBs)

• Angiotensin receptor blockers (ARBs), such as losartan, candesartan, valsartan, and telmisartan, block the angiotensin II receptor. They are often used in patients who cannot tolerate ACE inhibitors.

Aldosterone Receptor Blockers

• Aldosterone antagonists (e.g. spironolactone and eplerenone) are used in severe heart failure to reduced fluid retention.

Digoxin

• Digoxin is a cardiac glycoside used in heart failure and certain arrhythmias.
• Digoxin enhances the vagal tone, decreasing heart rate and myocardial oxygen demand.

Pharmacodynamics of Digoxin

• In therapeutic doses, Digoxin partially inhibits Na+/K+ ATPase which leads to increased intracellular sodium leading to increased cytoplasmic calcium levels, thus increasing the force of contraction. Its mechanism of action elevates cAMP levels in myocardial cells, leading to better contraction and relaxation.
• Digoxin has a long half-life, accumulating in cardiac muscle. Requires dose adjustment in renal dysfunction.
• Digoxin and other drugs that slow AV conduction should be used with caution together.

Adverse Effects of Digoxin

• At therapeutic doses, Digoxin is generally well-tolerated.
• Higher doses or patient factors can lead to adverse effects such as anorexia, nausea, vomiting, blurred vision (yellowish), and various cardiac arrhythmias.

Management of Digoxin Toxicity

• If digoxin toxicity is suspected, administering potassium supplements or digoxin antibodies is required

DD Interactions

• Digoxin toxicity is worsened by hypokalemia which further increases the risk of arrhythmias. Conversely, hyperkalemia reduces its effectiveness.

Uses of Digoxin

• Digoxin is used to treat congestive heart failure and cardiac arrhythmias, particularly atrial fibrillation and other supraventricular arrhythmias.

Adverse Effects of Digoxin (Cardic/Extracardiac)

• Extra-cardiac: Nausea, vomiting, vomiting, restlessness, disorientation, visual disturbance, gynecomastia
• Cardiac: Bradycardia, Pulsus bigemini, atrial extrasystole, atrial flutter, ventricular extrasystole, tachycardia, partial heart block, complete heart block

Treatment of Digoxin Toxicity

• If toxicity is suspected, stopping digoxin, checking potassium levels, and administering potassium supplements are first steps.

Other Treatment Considerations

• PharmacoKinetics: Understanding how the drug is absorbed, distributed, metabolized, and excreted (ADME) is crucial for proper dosing and management.
• Patient-Specific Considerations: Factors like renal function, other medications, and overall health status strongly influence treatment decisions.