Heart Failure Flashcards
What is heart failure?
When heart muscle doesn’t pump blood as well as it should
Heart tries to compensate by increasing size and thickness but loses flexibility (stiff)
What are common symptoms of heart failure?
Dyspnea, fluid retention, fatigue
What is the difference between arteries and veins?
Arteries carry blood away from the heart
Veins carry blood towards the heart
Why are there pulmonary symptoms in heart failure?
Left ventricle muscle is too weak to pump oxygenated blood to body, blood back flows into left atrium, and then into pulmonary veins and lungs –> pulmonary edema (SOB)
What is a crucial biomarker of heart failure?
BNP (B type or brain natriuretic peptide)
- it regulates BP by promoting vasodilation
- encourage natriuresis (excrete sodium in urine) and diuresis
- goal is to decrease BP (triggered by stretching of ventricle)
Is heart failure a dynamic disease?
Yes. Disease trajectory changes over time. Periods of remission
What are common causes of heart failure?
Hypertension, ischemic heart diseases, valvular heart disease
How does hypertension cause heart failure?
Heart has to pump harder to overcome pressure (afterload), extra workload leads to left ventricular hypertrophy (thickening) -> stiffening
How does ischemic heart disease cause heart failure?
Disease reduces healthy blood flow and oxygen supply to heart muscle (damage)
If muscle dies, scarring occurs, worsen function of muscles
How does valvular heart disease lead to heart failure?
Back flow can lead to volume overload or pulmonary congestion
How do you classify heart failure?
- Reduced ejection fraction (HFrEF)= LVEF ≤ 40%
- Mildly reduced ejection fraction (HFmEF)= LVEF 41-49%
- Preserved ejection fraction (HFpEF)= LVEF≥ 50%
- Improved ejection fraction (HFimpEF)= Baseline ≤ 40% + 10 point increase + second measurement >40%
What are the two compensatory mechanisms in heart failure?
Ventricular hypertrophy (initial adaptive response to overcome pressure. Heart muscle thickens to keep up)
Ventricular dilation (heart muscle becomes overstretched due to volume overload)
What is the difference between HFrEF and HFpEF?
HFrEF is a decreased pump function issue (systolic) whereas HFpEF is a myocardial relaxation issue (diastolic)
HFrEF has dilatation whereas HFpEF does not
HFpEF instead has possible hypertrophy and normal/mildly abnormal LVEF
Treatment is limited for HFpEF
What are the 3 types of drugs that can cause heart failure exacerbation?
- Sodium or fluid retaining drugs
- Androgen, corticosteroids, minoxidil, NSAIDs, high dose salicylates, pregabalin, thiazolidinediones - Negative inotropes
- Antiarrhythmic except amiodarone or dofetilide
- Beta blockers
- Itraconazole
- Non-DHP CCB - Cardiotoxic drugs
- Alcohol
- Amphetamine
- Cancer therpay
- Clozapine
- Cocaine
If there are no clear signs/symptoms of HF, what marker can help?
BNP or NT-proBNP
What are the BNP biomarker values?
HF unlikely: BNP<100
HF possible: BNP 100-400
HF very likely: BNP >400
What are the NT- proBNP biomarker values?
Age <50
HF unlikely: NT-proNBP<300
HF possible: NT-proNBP 300-450
HF very likely: NT-proNBP>450
Age 50-75:
HF unlikely: NT-proNBP<300
HF possible: NT-proNBP 300-900
HF very likely: NT-proNBP> 900
Age >75
HF unlikely: NT-proNBP<300
HF possible: NT-proNBP 300-1800
HF very likely: NT-proNBP >1800
What test should be done after diagnosis?
Echo to find LVEF and ventricular size
What are some non-pharm advice?
- No more than 1 alcoholic drink/day
- Restrict sodium (<2-3g/day)
- Restrict fluid intake (<1.5-2L/day)
How should patients monitor weight (edema)?
> 0.5 kg/day on consecutive days or 2kg in 3 days -> refer
What vaccines should be recommended to HF patients?
Influenza, pneumococcal, SARS-COV2
What is the NYHA Functional Classification?
Class I= No sx with ordinary activity
Class II= Sx occurs with ordinary activity
Class III= Sx occurs with less than ordinary activity
Class IV= Sc occurs at rest with minimal activity
Fluid overload generally worsens as HF progresses, what agent is the cornerstone of management?
Diuretics
Does this agent decrease mortality?
No. Does not modify course of HF, only alleviates symptoms
What is the danger of over diuresis?
Exacerbate renal dysfunction and impact the tolerance of other HF drugs that actually improve HF outcomes
What type of diuretic is usually used?
Potent loop diuretic like furosemide
When do we prefer IV or PO furosemide?
IV is good if rapid diuresis is needed or if patient isn’t responding to PO (Ex: resistance or poor absorption due to GI edema)
When should we time administration of diuretics?
Early in the day to avoid night time/ sleep disturbance
When do we consider adding intermittent low-dose thiazide?
Refractory volume overload. Agent of choice is usually metolazone.
Addition of thiazide can counteract reabsorption of sodium from chronic loop diuretic use. Close monitoring required due to risk of fatal dehydration and electrolyte imbalance
What’s the relationship between pulmonary congestion and peripheral edema?
Peripheral edema commonly resolves after pulmonary congestion clears
What electrolyte needs to be monitored?
Hypokalemia, hypomagnesemia, hyponatremia risk
Which of the above electrolytes need closer monitoring. Why?
Potassium must be ≥4mmol/L.
Any lower would increase the risk of digoxin toxicity and fatal ventricular arrhythmias
What are the quadruple therapy agents used to treat heart failure with reduced ejection fraction?
- ARNI or ACE/ARB
- Beta blocker
- Mineralocorticoid receptor antagonist (MRA)
- SGLT2i
Quadruple therapy should be started ______ and titrated to _________ or _________ __________ doses .
Goal is to optimize doses in ____ - ____ months.
early
target or maximally tolerated
3-6
What does ARNI stand for?
Angiotensin receptor/neprilysin inhibitor
What is the ARNI combo we use for heart failure?
Valsartan/Sacubitril (Entresto)
The ARNI vs enalapril trial was of great success. What were the trial entry criteria?
- Asymptomatic LV dysfunction
or - Severe HFrEF
or - New HFrEF
or - Cannot tolerate the equivalent of enalapril 10mg BID
What are two reasons why ACEi is often used instead of ARNI?
Cost and if patients doesn’t fit trial criteria
How quickly do you titrate ACEi to target doses?
Titrate every 7-14 days
a) What parameters do you need to monitor before starting ACEi?
b) Which parameter can you expect to change following initiation?
a) Serum creatinine, potassium, and BP
b) Serum creatinine (up to 30% increase is expected and acceptable)
How do you manage a SCr increase greater than 30% following initiation of ACEi?
Check for other causes of worsening renal function. A common reason with HF is hypovolemia from excessive diuresis.
If no other cause is found, reduce dose or discontinue ACEi.
What parameters have ACEi been shown to improve?
- Improve symptoms
- Reduce risk of hospitalization
- MI and death in patients
What are four side effects to monitor for after starting ACEi?
cough, angioedema, hyperkalemia, renal dysfunction
Which of those side effects can be mediated by switching to an ARB?
Cough or angioedema
Why does ACEi cause hyperkalemia?
- ACEi blocks the conversion of angiotensin I to angiotensin II
- Angiotensin II stimulates release of aldosterone
- Aldosterone acts on kidney to promote sodium reabsorption and potassium excretion
∴ ACEi decreases angiotensin II, aldosterone, and therefore potassium excretion
How does ACEi decrease blood pressure?
- ACEi blocks conversion of angiotensin I to angiotensin II
- Angiotensin II is a vasoconstrictor
- Angiotensin II also stimulates release of aldosterone which promotes sodium reabsorption
How does ACEi cause angioedema?
- ACE (angiotensin converting enzyme) usually breaks down bradykinin
- Bradykinin increases vascular permeability and vasodilation.
- ACEi increases bradykinin and leads to capillary leakage and fluid buildup
How does ACEi cause dry cough?
- ACEi leads to more bradykinin and substance P
- These both promote the production of prostaglandins, which may exacerbate the cough reflex
How does ACEi help with heart failure?
- ACEi blocks conversion of angiotensin I to II.
- Angiotensin II causes vasoconstriction
- This also leads to less aldosterone and less sodium retention
What is the dosing for ACEi for HF?
(enalapril, lisinopril, perindopril, ramipril, trandolapril)
Enalapril (I= 1.25-2.5mg BID, T= 10 mg BID)
Lisinopril (I= 2.5-5mg QD, T= 20-35mg QD)
Perindopril (I= 2mg QD, T= 8mg QD)
Ramipril (I=1.25-2.5mg BID, T= 5mg BID)
Trandolapril (I= 1mg QD, T= 4mg QD)
If starting an ARNI, should we use BNP or NT-proBNP to monitor clinical outcomes?
NT-proBNP
Neprilysin inhibition leads to accumulation of NP which makes BNP inaccurate.
How does the ARNI combo affect the bioavailability of valsartan?
Sacubitril enhances bioavailability of valsartan.
Valsartan 51mg potentiates to 80mg.
As per current Canadian HF guidelines, when do we recommend Entresto over ACEi/ARB?
- Patient with HFrEF who remain symptomatic despite treatment
or - Newly diagnosed HFrEF admitted to hospital
What is the washout period when switching between ARNI and ACEI?
36 hours
Do you need a washout period for ARB to ARNI?
No
How often should dose be titrated with ARNI?
Titrate every 2-4 weeks
What is dosing schedule of Entresto?
Initial: 51/49mg BID
Target: 103/97 mg BID
26/24mg BID is an option for those at risk of hypotension or not at target dose for ACEi/ARB
What parameters have beta blockers been shown to improve?
- Improve symptoms
- Reduce the risk of hospitalization
- Death in patients
Which beta blockers are used in HF?
First line= bisoprolol, carvedilol
Second line= metoprolol tartrate, as data is extrapolated from metoprolol succinate (unavailable in Canada)
*There has been more mortality and hospital admission with metoprolol tartrate (controversial point though)
What are the target doses of the beta blockers?
Bisoprolol (I=1.25mg QD, T= 10mg QD)
Carvedilol (I= 3.125mg BID, T= 25mg BID)
Metoprolol (I= 6.25mg BID, T= 100mg BID)
How quickly do you titrate beta blockers?
Titrate every 2-4 weeks
When should we not initiate or increase doses of beta blockers in heart failure?
When patient is acutely decompensated (negative inotropic effect can worsen HF) or if bradycardic
What’s an important counselling point for new starts of beta blockers?
May feel temporarily worse during initiation and up-titration but will benefit from long term reductions in HF outcomes
Can you stop beta blockers abruptly?
No, rebound tachycardia
What parameters have mineralocorticoid receptor antagonists been shown to improve?
Reduce mortality and morbidity
What are the two MRA options?
Spironolactone and eplerenone
When should we not use MRA?
Baseline potassium >5 mmol/L or CrCl <30 mL/min
What are the monitoring parameters after starting MRA?
SCr and potassium on day 3 and 7. Monthly for 3 months and then every 3 months.
When differentiates eplerenone from spironolactone?
Eplerenone does not have anti-androgen effects, so no gynecomastia, impotence, or irregular menstruation.
Does eplerenone have a similar risk of hyperkalemia and renal dysfunction as spironolactone?
Yes, so no point in using it as substitutes for those reasons
What are the two SGLT2i we use for HF?
Empagliflozin and dapagliflozin
What parameters have SGLT2i been shown to improve?
Decrease morbidity and mortality
When is SGLT2i contraindicated?
Type 1 diabetes, allergy, history of euglycemic ketoacidosis
What are monitoring parameters following SGLT2i initiation?
Fluid status (may cause mild volume depletion)
and renal function (a drop in eGFR <15% is ok)
When is ivabradine used in heart failure?
HF with LVEF ≤35%, NYHA II-III, sinus rhythm, HR ≥77 despite being on optimal beta blocker doses
OR
beta blockers not tolerated
When should ivabradine be avoided?
If patient has afib, 3rd degree AV block
Does ivabradine affect mortality?
Yes, it reduces the risk of mortality
When is digoxin used in heart failure?
For patient with persistent symptoms despite optimal therapy with quadruple agents.
Does digoxin affect mortality?
No
What is usual dosing range for digoxin and serum concentration target?
0.0625-0.25mg
0.6-1.2nmol/L
What are signs of digoxin toxicity?
Confusion, loss of appetite, nausea, vomiting, diarrhea, or vision problems
When do we use nitrates/hydralazine combo in heart failure?
In HF patients who do not tolerate ACEi/ARB or ARNI (renal dysfunction or hyperkalemia)
OR
+add on therapy in Black patients
What is the nitrate/hydralazine combo we use in heart failure?
ISDN/hydralazine
Does ISDN/hydralazine affect mortality?
Yes but only as a combo. Nitrates alone is only good for symptom relief
When is vericiguat used in heart failure?
May be considered in high risk patients hospitalized for HF. Not approved in Canada yet.
What is omega-3’s role in heart failure?
Omega 3 polyunsaturated fatty acid (n-3-PUFA) at low dose (1g/day) may be considered in mild to moderate HF.
*3g/day or more is associated with excessive bleeding
Where does calcium channel blockers come into heart failure?
Avoid non-DHP CCBs like verapamil and diltiazem because of their negative inotropic effects.
Avoid nifedipine and felodipine due to lack of data.
Amlodipine is safe for patients with persistent angina despite beta blockers and nitrates or uncontrolled hypertension despite use of ACEi, MRA, beta blocker, and diuretic.
Caution amlodipine in those with fluid retention.
Do CCBs affect mortality?
No
What’s the role of antiarrhythmics in heart failure?
Only use amiodarone and may be considered to maintain sinus rhythm in those with afib.
Should patients start statins for heart failure?
No. However, it is reasonable to continue them if patient is already receiving them.
What’s the treatment approach for HFpEF?
Treatment does not reduce mortality, so the focus is to control risk factors like hypertension, DM, and ventricular rate in afib).
What drugs are used for HFpEF?
SGTL2i are the only class of medications that have shown improvement in HFpEF.
In Canada, empagliflozin is indicated for HFpEF.
Pregnancy Considerations for HF:
Diuretics
ACEi/ARBs or ARNI
MRAs
Beta blockers
SGLT2i
Ivabradine
Digoxin
Nitrate/Hydralazine
Diuretics= furosemide ok but watch for dehydration
ACEi/ARBs or ARNI = avoid
MRAs= avoid
Beta blockers= metoprolol preferred
SGLT2i=avoid
Ivabradine= avoid
Digoxin= safe but may need higher doses
Nitrate/Hydralazine= ok
Breastfeeding Considerations in HF:
Diuretics
ACEi/ARBs or ARNI
MRAs
Beta blockers
SGLT2i
Ivabradine
Digoxin
Nitrate/Hydralazine
Diuretics= furosemide has limited data
ACEi/ARBs or ARNI= safe
MRAs= spironolactone ok
Beta blockers= metoprolol preferred
SGLT2i= avoid
Ivabradine= avoid
Digoxin= ?
Nitrate/Hydralazine=?
