Heart Failure Flashcards
What is heart failure?
abnormal heart function
-any cardiac structural or functional disorder leading to inadequate CO &/or elevated ventricular filling pressures
-impairs the ability of the ventricles to fill (diastolic) with or eject (systolic) blood
complex clinical syndrome with signs and symptoms of:
-reduced CO and/or unable to meet metabolic demands or only able to maintain CO with abnormally high cardiac pressure
-pulmonary or systemic congestion at rest or with stress
Briefly describe the epidemiology of heart failure.
100,000 Canadians diagnosed each year
700,000+ living with HF in Canada today
higher mortality rates than certain cancers
50% will die within 5yrs
True or false: HF prognosis is worse than many cancers
true
What is a strong predictor of mortality for heart failure?
number of HF hospitalizations
-with each acute event, myocardial injury may contribute to progressive LV dysfunction
What is the pathophysiology of heart failure?
cardiac output is decreased
-persistent=long term activation of compensatory responses
myocardial injury–>compensatory responses in an attempt to maintain CO
How is heart rate controlled?
by the autonomic nervous system
What is stroke volume?
the volume of blood ejected per heartbeat, which is dependent on preload, afterload, and contractility
Differentiate preload, contractility, and afterload.
preload:
-stretching of the muscle fibers in the ventricle
-stretching results from blood volume at the end of diastole
contractility:
-inherent ability of the myocardium to contract normally
-influenced by preload (greater stretch=forceful contraction)
afterload:
-pressure that the ventricular muscles must generate to overcome the higher pressure in the aorta to get blood out of the heart
What is the Frank-Startling Law?
ability of the heart to alter the force of contraction based on changes in preload
increased ventricle volume=increased contractility=increased SV
if the heart is overstretched, it loses its ability to return force
-normal: more filling, greater force
-mild-moderate LV dysfunction: more filling, no more force
-severe LV dysfunction: more filling, less force
In general, what does pharmacotherapy target for heart failure?
the neurohormonal model
-NE, ANG II, aldosterone, vasopressin, cytokines
can slow progression, and reduce risk of morbidity & mortality
What are the compensatory responses seen in heart failure due to decreased cardiac output?
increased preload (via Na and water retention)
vasoconstriction
tachycardia & increased contractility (SNS)
ventricular hypertrophy & remodeling
What are the beneficial and detrimental effects of increased preload as a compensatory response in HF?
beneficial effects:
-optimize stroke volume via Frank-Starling mechanism
detrimental effects:
-pulmonary & systemic congestion
What are the beneficial and detrimental effects of vasoconstriction as a compensatory response in HF?
beneficial effects:
-maintain BP during reduced CO
-shunt blood from nonessential organs to brain and heart
detrimental effects:
-increased myocardial oxygen demand
-increased afterload decreases SV
What are the beneficial and detrimental effects of tachycardia & increased contractility as a compensatory response in HF?
beneficial effects:
-maintain CO
detrimental effects:
-increased myocardial oxygen demand
-shortened diastolic filling time
-precipitation of ventricular arrhythmias
What are the beneficial and detrimental effects of increased ventricular hypertrophy & remodeling as a compensatory response in HF?
beneficial effects:
-maintain CO
-reduces myocardial wall stress
-decreases myocardial oxygen demand
detrimental effects:
-increased risk of myocardial cell death
-myocardial ischemia
-arrhythmia
-fibrosis
-diastolic &/or systolic dysfunction
What are the common etiologies for heart failure?
tachyarrhythmia
valve disease
known or risk factors for CAD
LVH
Describe the universal definition for heart failure.
symptoms and/or signs of HF caused by structural and/or functional cardiac abnormality
-structural heart disease: LVH, valvular heart disease
-abnormal cardiac function: reduced left/right ventricular systolic function, increase filling pressures, abnormal diastolic function
elevated natriuretic peptide levels
-NT proBNP >125pg/ml
-BNP >50pg/ml
objective evidence of cardiogenic pulmonary or systemic congestion
-diagnostic modalities or hemodynamic measurements
What are the typical symptoms of heart failure?
breathlessness
orthopnea
paroxysmal nocturnal dyspnea
reduced exercise tolerance
fatigue
ankle swelling
What are some of the less typical symptoms of heart failure?
nocturnal cough
wheezing
bloated feeling
loss of appetite
syncope
What are the gold standard biomarkers in heart failure?
B-type natriuretic peptide (BNP)
NT proBNP
Where and when would the natriuretic peptides be produced?
synthesized & released from the ventricle in response to pressure or volume overload
What occurs when plasma concentrations of natriuretic peptides are elevated?
increased natriuresis, diuresis & attenuate RAAS & SNS activation
Can the natriuretic peptides alone be used to diagnose heart failure?
good for ruling out HF, not to establish HF on its own
should not be used independent of signs/symptoms & other diagnostics
Which natriuretic peptide is used for heart failure?
either can be used (similar)
-dependent on local lab
absolute values & thresholds are not interchangeable
What is a clinically meaningful change in natriuretic peptide levels?
> 30%
What does an echocardiogram provide information on?
size and shape of heart
pumping capacity (ejection fraction)
location and extent of damage tissues
pressure estimates
What are the classifications of heart failure?
HF stages: acute/decompensated vs chronic vs advanced
left ventricular ejection fraction
NYHA classification: severity of symptoms & functional status
Differentiate chronic HF, acute/decompensated HF, and advanced HF.
chronic:
-persistent & progressive
acute/decompensated HF:
-gradual or rapid changes in HF signs/symptoms
-results in need for urgent therapy
advanced HF:
-frequent decompensations
-mechanical devices
-transplantation
-palliative therapies
What is the ejection fraction?
compares the amount of blood in the heart to the amount of blood pumped out
Differentiate between a normal EF, borderline EF, and reduced EF.
normal: 50-70%
borderline: 41-49%
reduced: <40%
Describe LVEF >50%.
HF-pEF: HF with preserved EF
-diastolic dysfunction
-problems with heart stiffness/ventricular relaxation & filling
-slow onset
-elderly, females, DM, AF, HTN
Describe LVEF 41-49%.
HF-mEF: HF with mid-range or mildly reduced EF
Describe LVEF <40%.
HF-rEF: HF with reduced EF
-systolic dysfunction
-problems with the heart pump/ventricular contractility
-usually after an acute CAD event
What is HFimpEF?
HF with improved EF
-had HF-rEF
-baseline LVEF >40% & >10% increase in EF
-second measurement of LVEF >40%
Describe the New York Heart Association Classification of HF.
Class I: asymptomatic
-no limitation of physical activity
-ordinary physical activity does not cause symptoms
Class II: mild
-slight limitation of physical activity
-comfortable at rest
-ordinary physical activity causes symptoms
Class III: moderate
-marked limitation of physical activity
-comfortable at rest
-less than ordinary activity causes symptoms
Class IV: severe
-severe limitation and discomfort with physical activity
-symptoms present at rest
What are the standard therapies for HFrEF?
ARNI or ACEI/ARB
beta-blocker
MRA
SGLT2 inhibitor
Which ACEIs and ARBs are approved for HF?
ACEI:
-captopril
-enalapril
-lisinopril
-ramipril
-trandolapril
ARB:
-candesartan
-valsartan
ARNI=sacubitril/valsartan
Which beta-blockers are approved for HF?
bisoprolol
carvedilol
metoprolol
Which MRAs are approved for HF?
eplerenone
spironolactone
Which SGLT2 inhibitors are approved for HF?
dapagliflozin
empagliflozin
What are the benefits of the standard therapies for HFrEF?
decreased risk of mortality
decreased risk of HF hospitalizations
improve HF symptoms
Describe the desired titration for the standard therapies of HFrEF.
strive to initiate within 3-6 months after diagnosis and titrate to target or maximally tolerated doses
Provide a quick summary of RAAS.
drop in BP or drop in fluid volume–>renin release from kidney
renin activates angiotensinogen–>ANG I
ACE acts on ANG I–>ANG II
ANG II
-acts on adrenals to release aldosterone (reabsorb H20+Na)
-causes vasoconstriction
net result=increased preload and afterload
What is the MOA of ACEI?
blocks conversion of ANG I to ANG II
increased bradykinin
What are the benefits of ACEIs in HFrEF?
decrease the risk of all-cause mortality
decrease the risk of HF hospitalizations
What is the difference in dosing of ramipril for hypertension compared to heart failure?
OD for HTN
BID for HF
What is the dose titration for ACEI in HF?
double dose q1-3wks
List the starting dose and target dose for each ACEI in HF.
enalapril:
-start: 1.25-2.5mg BID
-target: 10mg BID/20mg BID in NYHA IV
lisinopril:
-start: 2.5-5mg daily
-target: 20-35mg daily
perindopril:
-start: 2-4mg daily
-target: 4-8mg daily
ramipril:
-start: 1.25-2.5mg BID
-target: 5mg BID
trandolapril:
-start: 1-2mg daily
-target: 4mg daily
What are the contraindications to ACEI?
bilateral renal artery stenosis
history of angioedema
pregnancy
What are some cautions for ACEIs?
K+ greater than 5.2mmol/L
SCr greater than 220umol/L
eGFR < 30ml/min
SBP < 90mmHg or symptomatic hypotension
moderate to severe aortic stenosis
What are the drug interactions for ACEI?
increased risk of hyperkalemia:
-K+ supps
-K+ sparing diuretics
-MRA
-renin inhibitors (aliskiren)
-TMP
-NSAIDs
-low salt substitutes high in K+
lithium: increased risk of lithium toxicity
What are the adverse effects of ACEI and the appropriate monitoring for those adverse effects?
hypotension
-monitor bp (there is no target bp in HF)
-symptomatic hypotension
angioedema
-symptoms
dry cough
-document presence/absence before initiating
hyperkalemia
-lab work at baseline & 1-2wks after starting therapy/dose change
-normal range: 3.5-5mmol/L
worsening renal function
-lab work at baseline & 1-2wks after starting therapy/dose change
Describe ACEI-induced angioedema.
ACEI are the leading cause of angioedema but its rare
common symptoms:
-facial, lip, tongue, and upper airway swelling
-develop over several hours
airway compromise is a life-threatening consequence
other sx are self-limiting & resolve within 48-72hrs
What is the MOA of ARBs?
block the angiotensin receptor to prevent ANG II effects
What is the place in therapy of ARBs for HF?
use if ACEI intolerance
-cough
-angioedema
Compare ACEI to ARB in HF.
more evidence with ACEI
no significant differences in rates of hypotension, hyperkalemia or renal dysfunction
do NOT combine eachother due to risk of hypotension, hyperkalemia & renal dysfunction
What is the difference in dosing of valsartan for hypertension compared to heart failure?
OD for HTN
BID for HF
List the starting dose and target dose for the ARBs in HF.
candesartan:
-start: 4-8mg daily
-target: 32mg daily
valsartan:
-start: 40mg BID
-target: 160mg BID
What are the contraindications, cautions, drug interactions, adverse events, monitoring, and titrations for ARBs?
similar to ACEI
What is the MOA of Entresto?
sacubitril:
-inhibits neprilysin (neprilysin breaks down BNP)
valsartan:
-ARB action
What were the benefits found for Entresto from the PARADIGM trial?
further reduced HF hospitalizations and CV death
True or false: Entresto has less symptomatic hypotension compared to an ACEI or ARB
false
Entresto has more symptomatic hypotension
What is the EDS criteria for Entresto?
HF with NYHA class II or III and:
-LVEF <40%
-NYHA class II-III sx despite >4wks of a stable dose of ACEI/ARB in combination with BB, and MRA
-BNP >150pg/ml or NT-proBNP>600pg/ml
-under care of HF specialist
What are the contraindications of Entresto?
concurrent ACEI use (36hr washout period ACEI<–>ARNI)
-washout not required for an ARB
history of ACEI/ARB angioedema
What is a caution for Entresto?
recent symptomatic hypotension
What are the drug interactions, adverse effects, & monitoring parameters for Entresto?
same as ACEI/ARB
What are the doses available of Entresto?
24/26mg=50mg
49/51mg=100mg
97/103mg=200mg
sacubitril/valsartan
What is the starting dose and target dose for Entresto?
start: 50-100mg BID
target: 200mg BID
Describe initiation and titration of Entresto.
> 50% ACEI/ARB target dose: 49/51mg po BID
-double dose in 3-6 wks
<50% ACEI/ARB target dose, risk of hypotension, or ACEI or ARB naive: 24/26mg po BID
-double dose in 6 wks
What is the MOA of beta-blockers in heart failure?
block norepinephrine at the beta-adrenergic receptor
improves myocardial function by prolonging ventricular filling time, resulting in a more productive heartbeat
What is the benefit of beta-blockers in HFrEF?
decrease the risk of all-cause mortality
decrease the risk of HF hospitalizations
List the starting dose and target dose for each beta-blocker in heart failure.
carvedilol: based on body weight
-start: 3.125mg BID
-target: 25mg BID/50mg BID (>85kg)
bisoprolol:
-start: 1.25mg daily
-target: 10mg daily
metoprolol: long-acting formulation preferred
-start: 12.2-25mg daily
-target: 200mg daily
What is the dose titration for beta-blockers in heart failure?
double dose every 2-4 wks
What are the contraindications of beta-blockers?
in absence of pacemaker: 2nd or 3rd degree AV block or HR <50bpm
PR interval greater than 0.24s
severe/uncontrolled asthma
severe PAD
What are cautions for beta-blockers?
NYHA class IV or HF exacerbation within 4 weeks
SBP < 90mmHg or HR < 50bpm
What are the drug interactions for beta-blockers?
risk of bradycardia/AV block
-verapamil, diltiazem, amiodarone, digoxin
risk of hypertensive crisis with clonidine
risk of reduced beta-blocker efficacy with phenobarbital
What are the adverse effects of beta-blockers and the monitoring for these adverse effects?
hypotension
-monitor bp
-symptomatic hypotension
bradycardia
-monitor HR (resting of 50-60=acceptable)
-symptomatic bradycardia
worsening HF symptoms/fatigue
-may get worse before better
-initial inotropic effect
avoid abrupt withdrawal; taper over 1-2 weeks