Heart Failure

Question 1

What is the definition of Cardiac Output?

Answer 1

Cardiac output is the amount of blood pumped by left ventricle into the aorta per minute

Question 2

What is the formula for Cardiac output?

Answer 2

CO = Stroke volume (SV) x Heart Rate (HR)

Question 3

List 3 factors that can affect cardiac output

Answer 3

1) Preload (volume)
2) Afterload (resistance)
3) Heart function- contractility, heart rate

Question 4

What is the definition of cardiac failure?

Answer 4

1) Failure of the heart to pump at sufficient rate to service the metabolic requirements of the tissues OR
2) The ability to do so only at elevated filling pressures (after compensation)

Question 5

What is the threshold for HF with reduced ejection fraction (HFrEF)? And list 3 common causes for HFrEF.

Answer 5

Threshold: EF< 40%
Common causes:
1) AMI
2) Long-standing increase in afterload
3) Arrhythmias
4) Cardiac myopathies

Question 6

What is the threshold for HF with preserved ejection fraction (HFpEF)? Explain how HF symptoms can still occur despite preserved ejection fraction.

Answer 6

EF > 50%
Diastolic dysfunction -> failure of heart to relax adequately -> reduced suction force that draws blood from the atria into the ventricles -> slower/inadequate filling at the expense of higher pressures in the pulmonary venous system (more pronounced during exercise as heart has to handle an increased preload) -> coupled with reduced diastolic time for filling -> inability to handle preload -> backpressure effect on the lungs -> increased pulmonary venous pressure -> breathlessness

Question 7

Right HF leads to backpressure on (1), and leads to what symptoms (2)?

Answer 7

1) Systemic veins
2) Edema, peripheral venous congestion

Question 8

Left HF leads to backpressure on (1)? and leads to what symptom? (2)

Answer 8

1) Lungs
2) breathlessness

Question 9

What is Ejection Fraction (EF)?

Answer 9

EF is the fraction of end-diastolic volume pumped out during systole

Amount of blood pumped out of the ventricle/ total amount of blood in ventricle after diastole = EF

Question 10

What is the normal range for ejection fraction (EF)?

Answer 10

55-70%/ 0.55-0.7

Question 11

Ejection fraction of less than ? is indicative of heart failure?

Answer 11

0.4 / 40%

Question 12

HFpEF is primarily a (?) dysfunction?

Answer 12

Diastolic dysfunction leading to backpressure effects

Question 13

HFrEF is primarily a (?) dysfunction?

Answer 13

Systolic dysfunction leading to backpressure effects

Question 14

How may a HF patient present with “forward” failure effects?

Answer 14

1) Low BO
2) Tire easily

CO insufficient to sustain metabolic requirements -> tire easily
CO low -> low BP (note: in pts with HTN, BP can still be high)

Question 15

How may a HF patient present with symptoms as a result of backpressure effects? List down the symptoms respective to right and left heart.

Answer 15

Left heart:
1)Breathlessness due to pulmonary edema (backpressure on pulmonary venous system)
2) Orthopnea- breathlessness when patients lie down flat, as the heart cannot deal with increased volume of blood coming back -> increased backpressure
3) Paroxysmal nocturnal dyspnea: breathlessness does not occur immediately, happens suddenly and at night. This is due to loss of sympathetic compensation during sleep, hence heart is no longer beating harder and faster, leading to increased venous return -> backpressure effect

Right heart:
1) Peripheral edema (ankles, sacral area): usually starts at the ankles if patient is mobile; pitting ankle can also occur in left HF as kidneys are activated to increase fluid reabsorption
2) Enlarged liver and spleen

Question 16

What are the effects of compensation (both acute and long-term)?

Answer 16

Acute: increased sympathetic activation -> increased HR, contractility, sweating (sweat glands innervated by SNS)

Long-term: RAAS activated to reabsorb fluid -> decreased urine output, congestion in the venous system and peripheral edema

Question 17

List the 4 different New York Heart Association (NYHA) classification of HF and its corresponding symptoms

Answer 17

Class I: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea

Class II: Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea

Class III: Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea

Class IV: Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.

Question 18

What are the 5 main classes of medications indicated for HFrEF?

Answer 18

1) ARNi/ARBs/ACE-i +
2) Beta blockers +
3) MRA (mineralocorticoid receptor antagonist) +
4) SGLT2 inhibitors
5) +/- loop diuretics

Question 19

What are the 2 medications that can used as an alternative to RAASI for HFrEF if patient is renally impaired?

Answer 19

1) Hydralazine
2) Isosorbite Dinitrate (can be used as an add-on)

Question 20

What are the 3 classes of medications that can be used for optimisation of doses of RAASI and pulse/heart rate in HFrEF pts?

Answer 20

1) Beta blockers: target pulse rate < 70 bpm
2) Ivabradine: BP neutral, used when someone cannot tolerate BB or cannot push BP lower any more, used as an adjunct to reduce HR further
3) Digoxin (if AF): ivabradine cannot be used in AF patients as there is controversy over new onset of AF; digoxin is used on top of BB in AF

Question 21

What are the cornerstones of therapy in patients with HFpEF?

Answer 21

1) Manage root causes: e.g. heart valve, amyloidosis
2) Aggressive management of comorbidities: e.g. HTN, AF
3) Recent evidence with Empagliflozin and Sacubitril Valsartan

Question 22

What is the MOA of Sacubitril/Valsartan?

Answer 22

Sacubitril: pro-drug, upon activation to sacubitrilat, acts as a neprilysin inhibitor, preventing the breakdown of natriuretic peptides, leading to prolonged duration of favourable effects of these peptides against the pathogenesis of HF. (Neprilysin also breaks down Ang II, hence inhibition of neprilysin leads to accumulation of Ang II)

Valsartan: ARB, blocks the RAAS system to block the effect of excess angiotensin II

Question 23

Why cant sacubitril be used together with ACE-inhibitors? What is the washout period when switching ACE-I and sacubitril/valsartan and why is there a need for a washout period?

Answer 23

Neprilysin also breaks down bradykinin. Hence sacubitril inhibition on neprilysin leads to a build-up of bradykinin. Usage with ACE-inhibitors will lead to an increased risk of angioedema.

Washout period: 36 hours- to lower the risk of angioedema

Question 24

What are the 2 main types of SGLT2 inhibitors that is used in HF?

Answer 24

1) Empagliflozin
2) Dapagliflozin

Question 25

When should SGLT2 inhibitors be commenced for HF patients? (List down the 6 criteria)

Answer 25

1) Can be started right after decompensation/ when patient is stable (how to tell if patient is stable: refer to points 3-6)
2) No increase in diabetic ketoacidosis
3) No IV inotrope or IV vasodilators within 2 days
4) Must have discontinued IV diuretic and
5) Chronic oral loop diuretic prescribed and/or administered
6) SBP >/= 100mmHg

Question 26

What are the 3 beta-blockers used for HF?

Answer 26

1) Bisoprolol
2) Carvedilol
3) Metoprolol XL

(ONLY these 3 can be used in HF)

Question 27

For ACE-I use in HF patients, list down:
1) When to initiate?
2) Monitoring parameters?
3) Follow up

Answer 27

1) Probably during admission, when stable
2)Renal Panel/ SCr + K, BP, urea
3) 1w after initiation and after last adjustment; follow Q4-monthly; do not double dose at < 2 weekly intervals

Question 28

For ARNi use in HF patients, list down:
1) When to initiate?
2) Monitoring parameters?
3) Follow up

Answer 28

1) Consider during admission when stable, but probably outpatient. Consider reducing diuretic dose; if on ACEi, wash out for 36h first
2) Renal Panel/ SCr + K, BP, urea
3) 1w after initiation and after last adjustment; follow Q4-monthly; do not double dose at <2 weekly intervals

Question 29

For BB use in HF patients, list down:
1) When to initiate?
2) Monitoring parameters?
3) Follow up

Answer 29

1) During admission, when stable: use of BB can suppress CO and may precipitate fluid overload when used in unstable patients
2) BP, pulse rate, clinical status
3) Do not double dose at <2 weekly intervals; do not uptitrate if in overload; may add ivabradine if PR not at goal; add digoxin if concomitant AF

Question 30

For MRA (e.g. spironolactone) use in HF patients, list down:
1) When to initiate?
2) Monitoring parameters?
3) Follow up

Answer 30

1) Post MI + EF < 40% + HF sx/DM, probably during admission
2) Renal panel / SCr + K, urea, BP, gynecomastia (spironolactone)
3) 1w after initiation, 4w after adjustment; up-titrate: 4-8 weeks, can be longer for stable patients

Question 31

For loop diuretics use in HF patients, list down:
1) When to initiate?
2) Monitoring parameters?
3) Follow up

Answer 31

1) Anytime when congested
2) Renal panel/ SCr+K, BP, urea, input/output, body weight
3) After initiation and adjustment, can be given PRN, watch KCl replacement; follow-up appointment: 2-4 weeks; may add metolazone (sequential blockade effects, complementary effects)

Question 32

For SGLT2i use in HF patients, list down:
1) When to initiate?
2) Monitoring parameters?
3) Follow up

Answer 32

1) Consider during admission when stable, but probably outpatient
2) Renal panel/ SCr, BP, Euglycemia ketoacidosis, genitourinary tract infections
3) Follow up after initiation and adjustment; follow-up appt:2-4 weeks, can be longer for stable patients

Question 33

Why is there a need for close monitoring of RAASi agents when acutely diuresing HF patients?

Answer 33

When acutely diuresing patients, patients will end up with a lot of concentration of electrolytes in the body, serum creatinine can rise/precipitate AKI due to loss of great amount of fluid -> kidney appears to be injured acutely
With RAASi agents, it can reduce efferent arteriolar constriction, hence perfusion in glomerulus decreases and could worsen the stage of AKI

Hence, in state of very bad overload, when aggressively diuresing patients, sometimes RAASI agents are not started, though small doses may be started for vasodilation effect -> caution in renal function, monitor closely

Question 34

List 2 laboratory markers that can increase due to dehydration

Answer 34

1) Serum creatinine
2) Urea

-> caution in AKI

Question 35

What are some key advice that should be given to patients on beta-blockers for HF?

Answer 35

1) Explain expected benefits: Given to improve symptoms, prevent worsening of HF, and increased survival. Symptomatic improvement may develop slowly after starting treatment, sometimes taking 3-6 months or longer

2) Possibility of temporary adverse effects: temporary symptomatic deterioration may occur during initiation or up-titration phase; in the long-term beta blockers improve well being

3) Report deterioration: tiredness, fatigue, breathlessness; can usually be easily managed by adjustment of other medications; DO NOT stop beta blocker without consulting physician

4) Weigh: during initiation or uptitration phase to detect and treat deterioration early, patients should be encouraged to weigh themselves daily (after waking, before dressing, after voiding, before eating), and to increase their diuretic dose should their weight increase persistently (>2 days) by > 1.502kg/day; NOTE: not everyone is capable of self-titration

Question 36

What are some considerations when using beta-blockers in HF patients?

Answer 36

1) Do not start/increase BB when in overt overload
2) If PR<50bpm, halve the dose of BB
3) If PR >70bpm, double the dose of BB
4) If patient experience symptomatic hypotension, consider “sacrificing” other agents instead e.g. nitrates, CCBs instead

Question 37

What are some considerations when using ARNi for HF?

Answer 37

1) Note dizziness/lightheadedness following up-titration; often improves with time, patient shld be reassured
2) Cough: common in HF patients, exclude pulmonary edema when new worsening cough develops; when a troublesome cough develops and can be proved to be due to ARNi and ACEi, substitution of ARB is recommended
3) Rise in Cr and K threshold: an increase of K up to 5.5 is acceptable; if Cr/k/urea rise excessively, investigate causes e.g. K-rich food intake, nephrotoxin/NSAID use, dehydration (review urea as well)

Question 38

When should ivabradine be initiated in HF patients?

Answer 38

1) if PR still > 70bpm
2) Unable to tolerate/optimise BB

Question 39

When should digoxin be initiated in HF patients?

Answer 39

Pulse rate control when concomitant AF

Question 40

When should hydralazine/ isosorbite dinitrate be initiated in HF patients?

Answer 40

• Vaso + venodilator
• Alternative to RASi
• Additional BP control

Question 41

List 5 classes of medications that are associated with increased risk of adverse effects in patients with HF

Answer 41

1) Glucocorticoids: sodium retention
2) NSAIDs: sodium retention and peripheral vasoconstriction, blunted response to diuretics and ACE-inhibitors
3) CCBs (other than amlodipine and felodipine): negative inotropy, neurohumoral activation
4) beta-2 agonists: sympathetic agonist activity, hypokalemia, tachyarrhythmias
5) Trimethoprim-sulfamethoxazole: risk of hyperkalemia/ AKI when taken with ACE/ARBs, risk of hyperkalemia when taken with MRA
6) Itraconazole: negative inotropic effect; also increase serum digoxin conc
7) Na-containing preparations (e.g. fleet phospho soda)
8) Na load QT-prolonging drugs (e.g. haloperidol, erythromycin): proarrhythmia
9) Licorice: mineralocorticoid excess; sodium retention and hypokalemia

Question 42

What are some counselling points for HF patients?

Answer 42

1) Disease modifying role of medicines, onset, ADR
2) Clear communication of how and when to follow up
3) >2kg increase overnight or over 2-3 days
4) Fluid restriction: 800ml-1L, 1.2L when stable
5) Sodium intake and salt substitution