9 - Heart Failure (Anti-RAAS)

Define heart failure

occurs when the heart is unable to pump enough blood to meet the oxygen requirements of the body; chronic & progressive

Define ejection fraction.

the percent of blood ejected from the ventricle

What is the normal left ventricular ejection fraction value?

55-75%

What is necessary to differentiate between types of heart failure?

left ventricular ejection fraction

Define acute decompensated heart failure (ADHF).

sudden worsening of baseline symptoms that occurs when cardiac output is further decreased and/or volume overload occurs; requires hospitalization & aggressive management

What are the common causes of HF?

1. coronary heart disease

2. hypertension

What are the clinical manifestations of HF?

• dyspnea - breathlessness

• fluid retention (pulmonary and/or peripheral)

• poor perfusion (exercise intolerance/fatigue)

What are the determinants of cardiac output?

heart rate, stroke volume

What are the determinants of stroke volume?

preload, afterload, FOC

Define preload.

the end-diastolic pressure determining the stretch of the ventricular walls, determined by the volume of blood in the ventricle at end-diastole

Define afterload.

pressure that the ventricle must overcome by contraction to pump blood forward, determined by systemic vascular resistance

Define the Frank-Starling relationship

the ability of the heart to alter the force of contraction depends on changes in preload

T/F: left ventricular end-diastolic pressure≅preload.

true

Explain the Frank-Starling relationship in a normal heart.

as the volume of blood filling the ventricle increases, it stretches the myocardium and leads to increased stroke volume

• a small increase in preload results in a large increase in SV & CO

Explain the Frank-Starling relationship in heart failure.

preload is already increased because of compensatory mechanism; further increase does not further increase SV, but instead produces volume overload

What anti-RAAS agents are used for chronic heart failure?

• ACE inhibitors

• ARBs

• angiotensin receptor-neprilysin inhibitors (ARNIs)

What are the 4 major cardiovascular actions of angiotensin II via AT1 receptor?

1. vasoconstriction

2. aldosterone release

3. cardiac remodeling

4. norepinephrine release

What is the benefit of ACEIs in HF?

decreases angII production, resulting in:

• decreased preload & afterload → increased SV & CO

• decreased pulmonary & peripheral congestion

• decreased cardiac remodeling

What is the clinical outcome of ACEIs in HF?

decrease mortality

Which ACEI is best for treatment of HF?

no data indicating differences in any agent

What are the ADE of ACEIs?

• acute kidney injury

• hyperkalemia

• angioedema

• dry cough

Explain the mechanism by which ACEIs cause AKI.

patients with HF can have reduced renal perfusion, causing constriction in the efferent arteriole to maintain glomerular pressure for filtration.

• inhibition of RAAS → dilation of renal efferent arterioles

• decreased glomerular pressure/filtering → AKI

worsened with conditions/drugs reducing renal blood flow

How should kidney function be monitored when on an ACEI?

monitor serum creatinine closely during the first 1-2 weeks

What is the MOA of ARBs?

selectively block AT1 receptors

What is the clinical outcome of ARBs?

decreased mortality

Which ARBs are beneficial in HF?

1. losartan

2. candesartan

3. valsartan

T/F: combination of ARBs & ACEI proves greater benefit

false, it increases risk

What are the ADE of ARBs?

same as ACEI with the exception of cough & angioedema

What is the effect of HF on enodgenous natriuretic peptides?

increases in preload/afterload result in atrial/ventricular distension, increasing production of natriuretic peptides: B-type & A-type

• beneficial effects diminish with tolerance

• neprilysin enzyme breaks down natriueretic peptides, bradykinin, and other vasoactive peptides

What is the purpose of natriuretic peptides?

increases natriuresis, arterial vasodilation, and venous vasodilation, resulting in decreased preload and afterload, increasing CO

What is the MOA of valsartan/sacubitril?

• sacubitril is an inactive prodrug converted to sacubitrilat

• the combination inhibits neprilysin while blocking RAAS

What is the clinical outcome of valsartan/sacubitril?

decreases mortality; superior to enalapril

What are the ADE of valsartan/sacubitril?

• same as ACEI/ARBs

• cough (less than enalapril)

What are the contraindications of valsartan/sacubitril?

• angioedema history

• concomitant use of ACEI - needs 36hr washout period