Lecture 18: Physiology/ Pharmacology/ Management of heart failure Flashcards
What is heart failure characterized by?
Impaired cardiac pumping such as the heart is unable to pump adequate amount of blood to meet metabolic needs.
What can heart failure result from?
Any structural or functional cardiac disorder that impairs the ability of the ventricle to eject blood or to fill with blood.
What are other words for heart failure?
- Chronic heart failure
- Congestive cardiac failure
- Congestive heart failure
What are the signs and symptoms of heart failure?
- Shortness of breath
- Excessive tiredness
- Leg swelling
What are the underlying causes and risk factors for heart failure?
- Ischemic heart disease
- Hypertension
- Myocardial infarction
- Valvular heart disease
- Congenital heart disease
- Dilated cardiomyopathy
What is congestive heart failure?
Left sided failure
- its the most common form
- Blood backs up through the left atrium into the pulmonary veins
How is cardiac output calculated?
heart rate x stroke volume
What is stroke volume?
The volume of blood pumped from each ventricle
What is stroke volume affected by?
- Preload
- Afterload
- Ventricular contractility
What happens when preload increases?
- End diastolic volume increases
- Resulting in an increase stroke volume
What happens when afterload increases?
- End systolic volume increaeses
- Resulting in a decreased stroke volume
What happens if contractility is increased?
- End systolic volume is reduced, resulting in an increse in stroke volume
How does heart rate affect cardiac output?
The higher the heart rate, the higher the cardiac output
How does excessivly high heart rate affect cardiac output?
Diastolic filling time begins to fall, causing stroke volume and cardiac output falls
What is preload?
The amount of fibre stretch in the ventricles at the end of diastole (so before the next contraction)
What is preload directly related to?
Ventricular filling
What does a higher end diastolic volume imply?
Higher preload
What does preload increase with?
- increase in blood volume
- Vasodilation
What does preload decrease with?
- Loss in blood volume
What is starlings law?
Describes the relationship between preload and cardiac output
How does the stretch of the cardiac muscle fibers affect the force of contraction?
The greater the stretch, the greater the force of contraction
What does excessive preload result in?
Excessive stretch, reduced contraction, reduced systolic volume/ cardiac output
What is afterload?
The resistance against which the ventricle must pump
What is the effect of excessive afterload?
Difficult to pump blood so reduced systolic volume and cardiac output
What causes an increase in afterload?
- Hypertension
- Vasoconstriction
What causes a decrease in afterload?
Vasodilation
What is contractility of the heart?
Ability of the heart muscles to contract
What causes a decrease in heart contractility?
- Infarcted tissue: no contractile strength
- Ischemic tissue: reduced contractile strength
What causes an increase in heart contractility?
Positive inotropes (medications that increase contractility, such as digoxin, sympathiomimetics
What are the mechanisms that attempt to increase cardiac output when the heart pump fails?
- Sympathetic nerve stimulation
- Myocardial hypertrophy
- Hormonal response
What is sympathetic nerve stimulation?
- Release of epinephrine/ norepinephrine
What does release or epinephrine/ norepinephrine result in?
- Increased heart rate
- Increased contractility
- Peripheral vasoconstriction (incraeses afterload)
What is myocardial hypertrophy?
Walls of the heart thicken to provide more muscle mass so stronger contraction
What is the hormonal response to increase cardiac output?
- Reduced cardiac output decreased renal perfusion which is interpretated by juxtaglomerular apparatus as hypovolemia
- Kidneys release renin - this stimulates conversion of angiotensin I to angiotensin II
- Angiotensin II causes aldosterone release, resulting in Na and water retention (via antidiuretic hormone secretion) and increasing fluid volume in the venous return to the atria
- Angiotensin II also causes peripheral vasoconstriction
How can excess compensatory mechanisms worsen heart failure?
- Vasoconstriction increases the resistance against which the heart has to pump (increases afterload), so may decrease cardiac output
- Na and water retention increase fluid volume, this increases preload. Too much stretch means a decreased strength of contraction and decreased cardiac output
- Excessive tachycardia means a decreased diastolic filling time so decreased ventricular filling so a decrease SV and cardiac output
What is the cycle of heart failure?
- Decreased blood pressure and decreased renal perfusion
- Stimulates the release of renin, allows the conversion of angiotensin I to angiotensin II. Angiotensin II stimulates aldosterone secretion which causes retention of Na and water, increasing filling pressure
- LV dysfunction causes decreased cardiac output
What is acute heart failure?
An emergancy situation in which a patient was stable before the onset of heart failure; seen in acute heart injury such as MI
What is chronic heart failure?
Long term syndrome in which a patient exhibits syndromes over a long period of time, usually as a result of a preexisting cardiac condition
What drugs are used in chronic congestive heart failure?
- ACE inhibitor
- Aldosterone antagonist
- Beta blocker
- Diuretics
- Vasodilators
- New drugs eg Neprilysin antagonist
What is at the core of the pathophysiology of heart failure?
RAAS
- Its modulation is central to altering the disease in patients with reduced ejection fraction
How do ACE inhibitors work in heart failure patients?
- ACE inhibitors block the conversion of angiotensin I to angiotensin II
- Relax block vessels, lower arteriolar resistance and increase venous capacity, decrease cardiac output, stroke work and volume
- Lowers resistance in blood vessels in the kidneys; and leads to increased natriuresis
- Reduces secretion of aldosterone, reducing reabsorption of sodium
What is natriuresis?
Excretion of sodium in the urine
How do beta blockers work in heart failure patients?
- Metoprolol, bisopralol, carvedilol
- Reduce excessive sympathetic stimulation which causes : -
↳ Tachycardia increase myocardial oxygen demand
↳ Cardiac effects caused catecholamines remodeling by catecholamines - Reduce heart rate decrease force of contraction
What is aldosterone?
A steroid hormone produced by adrenal cortex is essential for sodium conservation mainly via mineralocorticoid receptors in the distal tubules and
collecting ducts of the nephron .
What do aldosterone antagonist do?
Reduce sodium and water retention which decreases intravascular volume by releasing fluid from the body.
What are the pharmacological effects of aldosterone antagonists?
↳ Reduce preload
↳ Reduce afterload
↳ Relieve symptoms of congestion
What diuretics are used in heart failure patients?
Loop diuretics (furosemide, bumetanide)
Where do loop diuretics act?
Ascending limb of the loop of Henle in the kidney
What do loop diuretics do?
inhibit sodium, chloride and potassium reabsorption , so that there is less osmotic driving force for water has to leave the collecting duct system.
What does a decrease in intravascular volume lead to?
- Reduces preload
- Improves LV function by reducing venous return
What are vasodilators used in heart failure?
Hydralazine combined with isosorbide dinitrate - smooth muscle relaxants
What are natriuretic peptides?
Peptides released by the heart in response to elevated wall strength from increased preload and afterload
What is the effect of netriuretic peptide release?
Promote vasodilation and natriuresis
What is neprilysin?
An enzyme that cleaves natriuretic peptides reducing their beneficial effects in a failing heart
What are neprilysisn inhibitors?
Used to prevent the breakdown of natriuretic peptides maintaining their ability to decrease intravascular volume and vasodilation
