Heart Failure Flashcards
Dr. Roane EXAM II
Heart failure definition
the heart is unable to pump blood at a rate with the requirement of the body’s tissues or can do so only at elevated filling pressure
HFrEF (systolic heart failure)
HFpEF (diastolic heart failure)
HFrEF
HFrEF reduced ejection fraction (systolic heart failure) - the heart pushes less blood the normal -> increased HR and contractility
HFpEF
HFpEF perfused ejection fraction (diastolic heart failure) - the pushes out normally, but there is not enough filling volume in the ventricle
Which type of “load” is affected by HFeEF?
Afterload, the heart can’t overcome the pressure present in the aorta -> reduced cardiac output
Which type of “load” is affected by HFpEF?
Preload, not enough ventricular filling during the diastolic phase
ejection fraction is normal
Right side of the heart fails
-not enough blood flow to the lungs
-blood backs up on the systemic venous side
-edema and ascites (fluid in the abdomen) and lower
Left side of the heart fails
-Insufficient blood flow to the systemic circulation
-Fluid backs up in the pulmonary circulation
-Pulmonary edema (cough, dyspnea, pulmonary effusion)
Congestion heart failure
-old term
-general heart failure
-left-sided HF is more common
-pulmonary edema due to “pulmonary congestion”
Frank Starling Curve
Plot between Stroke volume (amount of blood pumped out from both ventricles during systolic phase
and end-diastolic volume - the volume of blood just before the blood gets pumped out
-> in HF the Frank-Starling curve for contractility falls
Causes of HF
-Myocardial infarction, or heart attack: interruption of blood supply -> a portion of the heart muscle dies
-Chronic hypertension: the heart has to work hard against the pressure (afterload is harder)
-Leaky mitral valve: some blood is leaking back into the left ventricle -> more pump work for the heart
-Aortic valve stenosis: aortic valve doesn’t open fully -> more work
-heart tissue got stiff -> preventing normal filling (diastolic reduction)
-others, long-term oxidative stress or genetic cardiomyopathy
What is aortic compliance?
The stretching of the aorta when blood gets pumped out
-Compliance = delta V / delta P
What affects aortic compliance?
-Arteriosclerosis (artery hardening)
-Age
Consequence of CO falling
-Sympathetic outflow
-> increase in ionotropy and chronotropy (HR)
-> Arterial and venous constriction
-activation of RAAS bc renal blood flow and GFR is reduced
Law of Laplace
activated when the heart muscles grow too much
T = P * r
Tension, pressure, radius
as the radius increases, the tension in the wall of the heart increases -> the heart works less efficiently (Wall stress)
-> tissue damage -> tissue fibrosis builds up
How does Angiotensin II react to reduced CO due to heart failure?
vasoconstriction of the arteriole -> increases Afterload
-vasoconstriction of the venous -> increases Preload
-it also stimulates remodeling of the heart (negatively, the heart gets bigger?) and activates sympathetic NS
-it tries to make the heart work harder -> but the heart can’t
Drugs to treat HF
-ACEi, ARBs
-ß-blockers
-Diuretics, CC-blockers
-MRAs
-SGLT2
-Neprilysin inhibitors
-Ionotropic agents
-Nitrates
Drug to treat pulmonary HTN
-Guanylate cyclase activators (riociguat, vericiguat)
-PDE5 inhibitors
Physiology muscle relaxation
GTP is converted to cGMP by Guanylate cyclase (sGC or pGC)
cGMP activates PKG (protein kinase G) -> PKG deactivates MLCK and activates MLCP -> smooth muscle RELAXATION
cGMP is broken down PDE5
Drugs causing muscle RELAXATION
CC-blockers: Ca activates MLCK -> low Ca2+ means less contraction
-Nitrates generate nitric oxide -> NO activates sGC -> conversion of GTP to cGMP -> cGMP activates PKG -> less contraction, more RELAXATION
-Guanylate cyclase activators (riociguat, vericiguat) increase the conversion from GTP to cGMP -> more PKG -> less contraction, more RELAXATION
-cGMP is broken down by PDE5 -> PDE5 inhibitor keep cGMP levels high -> less contraction, more RELAXATION
MOA of MRAs
-prevents Aldosterone from binding to its receptors
-reduces Na+/H2O reabsorption
->reduces body fluid volume
->reduces venous return
->eases the load on the heart
->reduces pathological remodeling
What are aldosterone-induced proteins?
-aldosterone binds to an intracellular receptor (in the cytosol) and forms a complex that activates transcription in the nucleus
-as a result, AIP is produced with a variety of effects, mostly to increase Na+ and water reabsorption -> increase in BP
MRA drugs
-Spironolactone (not entirely specific for aldosterone, but also other steroid receptors like progesterone and androgen)
->Gynecomastia (breast growth in men)
->Dysmenorrhea (irregularities in menstruation)
-Eplerenone (more specific to mineralocorticoid receptors (MRA) -> fewer side effects
-both are K+ sparing: can cause hyperkalemia
How to dose ß-blockers in HF
-HF is an ionotropic disease and ß-blockers are negatively ionotropic
-but they have been shown to work in HF, bc they reduce the work of the heart and promote healing of the tissue (from negative remodeling) and reverse fibrosis!
How to dose ß-blockers in HF
-Carvedilol (non-selective), Bisoprolol, Metoprolol, Nebivolol
-start LOW and go SLOW: double the dose every 4 weeks, giving the heart the time to adjust
Which drug promotes NO-mediated Vasodilation
Nebivolol (ß1-selective)
Where is ANP produced?
What is its effect?
Atrium of the heart (when the atria stretches)
ANP = atrial (heart) natriuretic (Na, in the urine -> urinate Na+) peptide
Where is BNP produced?
Ventricles of the heart (when the ventricles stretch)
Effects of ANP and BNP
-antoganize Angiotensin II
-goes to the kidney and promotes Na+ excretion into the tubules (urine) -> diuretic, lowers BP
How do Neprilysin inhibitors work?
-Neprilysin breaks down ANP and BNP
-inhibition Neprilysin results in greater levels of ANP and BNP -> more Na and water excretion in the urine (diuretic effect)
What causes stretching in the atria and ventricles?
Venous return is too big -> stretching of the ventricles
Q: Why would the venous return be too big?
Ventricular output is too low -> more blood remains in the ventricular -> causing stretch
Neprilysin inhibitor drug
Sacubitril in combination with Valsartan (ARB) -> Entresto
-increases levels of ANP and BNP
-has shown to work better in HFrEF (than in HFpEF)
