Heart Failure Flashcards
What are the NYHA classes?
- Class 1: no limitations of physical activity, no symptoms of CHF
- Class 2: Slight limitations of moderate or prolonged physical activity, comfortable at rest
- Class 3: Marked limitations of physical activity, comfortable at rest
- Class 4: confined to bed, discomfort during any form of physical activity, symptoms at rest
Contraindicated medications in heart failure
- NSAIDs: Worsen renal perfusion, reduce the effect of diuretics, may trigger acute cardiac decompensation
- Calcium Channel Blockers (verapamil, diltiazem): negative inotropic effect, worsen symptoms and prognosis - combination with B blockers is contraindicated
In heart failure, which are the medications that improve prognosis vs improve symptoms
Prognosis:
(a) Aldosterone antagonists - spironolactone, eplerenone
(b) B blockers - bisoprolol, nebivolol, carvedilol, metoprolol XR
(c) ACEi
Symptoms
(a) Diuretics
(b) Digoxin
Note:
- metoprolol, nebivolol and bisoprolol are B1 cardioselective
- carvedilol is non=selective beta blocker with additional a-blocking action
Side effects of ACE inhibitors
CATCHH
- Cough secondary to increased bradykinin
- Angioedema due to increase bradykinin
- Teratogen
- Increased creatinine/reduce GFR
- Hyperkalaemia
- Hypotension
- Used with caution in bilateral renal artery stenosis because ACEi will further ↓ GFR causing renal failure
Digoxin
- Used in patients with concomitant AF + heart failure (symptomatic LV systolic dysfunction) or remains symptomatic despite other therapy
- No mortality benefit
- Enhances contractility, reduces cardiac enlargement, improves symptoms, slows AV node
- Mechanism of Action: A cardiac glycoside that inhibits Na+/K+- ATPases in cardiomyocytes.-
Digoxin and half life
- Aim trough concentration 0.5-0.8 micrograms/L, avoid levels >1.2 micrograms/L to minimise risk of toxicity
- In patients with normal kidney fx, the half-life of digoxin is at least 24 hours
- Following initiation/change in digoxin dose, it takes at least 5 days (five half-lives) to achieve a steady state (when the concentration of the drug stays consistent)
Digoxin toxicity
• Cardiac
- ST depression with ‘reverse tick’
- Bradyarrhythmias – slow AF, 2nd-3rd degree AV block
- Junctional and atrial tachycardia
- VT –> VF –> asystole
• GI: nausea, vomiting, abdominal pain, diarrhea
• Visual: blurred vision, yellow/green discolouration, haloes
• CVS: palpitations, syncope, dyspnoea
• CNS: confusion, dizziness, delirium, fatigue
• Hyperkalaemia
Entresto
- Entresto (sacubitril + valsartan) - ARB + angiotensin receptor neprolysin inhibitor (ARN)
- Used in patients with persistent HFrEF (<35%)
Add to therapy if NYHA II-IV and LVEF <40% after 3-6 months of optimal therapy - ACEi must be stopped at least 36 hours before starting entresto
- Monitor hypotension, kidney impairment, hyperkalaemia
- Sacubitril: pro drug, further metabolised to the neprilysing inhibitor
What does neprilysin normally degrade?
Neprylisin is a neutral endopeptidase which normally degrades severe endogenous vasoactive peptides including natriuretic peptides, bradykinin and adrenomedullin, angiotensin II
What does neprilysin normally degrade?
Neprylisin is a neutral endopeptidase which normally degrades severe endogenous vasoactive peptides including natriuretic peptides, bradykinin and adrenomedullin
Ivabradine
- Indication
- MOA
- SE
INDICATIONS in HF (SHIFT Trial)
- LVEF ≤ 35%
- Sinus, HR ≥ 70-75
- On stable background HF therapy including beta blockers if tolerated
- One hospitalisation for HF ≤ 12 months
MOA
- direct sinus node inhibitor, selectively inhibits the If channel (funny ion channels) in the pacemaker cells of the SA node → prolongs slow depolarisation (phase 4) → slows heat rate which in turn lowers cardiac workload and myocardial oxygen demand
SE
- Visual changes
- Bradycardia
- AF
- HTN
Indications for implantable cardiac defibrillator (ICD)
Primary Prophylaxis
- CHF with EF <35% and >1 month after MI or >3 months after CABG
- EF < 35% and HF NYHA I-III
Secondary Prophylaxis
- History of sudden cardiac arrest, VF
Indications for cardiac resynchronisation therapy
Dyssynchronous myocardial contraction evidenced by broad QRS
- CHF with EF < 35%
- QRS >120ms, broad complex, LBBB
- NHYA II-IV
- Sinus rhythm
- Optimal medical therapy for at least 3 months
Why should iron be corrected in heart failure?
To improve symptoms and quality of life and reduce admissions
no mortality benefit
Cardiac transplantation indications
- End stage CHF (NYHA IV)
- EF < 20%
- No other viable treatment options
Eligibility
- Smoking cessation
- BMI (weight < 100)
- Nil malignancy
- Compliance with treatment
Dobutamine
- MOA: B1 Agonist, direct acting inotropic agent (contraction of the heart)
- increases inotropy and chronotropy and reduces left ventricular filling pressure, functions to increase heart contractility and cardiac output. It is not a vasopressor.
- Side Effects: hypertension, tachycardia, angina, arrythmia - Dobutamine should only be used for LV dysfunction/systolic dysfunction, low EF/cardiogenic shock
Alpha 1 – vasoconstriction
Beta 2 – Smooth Muscle Relaxation
Beta 1 – Heart Specific
Dobutamine Mechanism of Action
Inotrope causing Vasodilation
Predominant Beta 1 Adrenergic Receptor effect Increases inotropy and chronotropy
- reduces left ventricular filling pressure
- reduction in cardiac sympathetic activity
- minimal alpha and beta 2 adrenergic receptor effects = vasodilation
- reflex vasodilation = increased Cardiac Output
Activates Gs protein (activates adenylate cyclase which converts ATP to cAMP –> increases cAMP –> activates protein kinase A –> phosphorylates L-type calcium channel.
Increased intracellular Ca2+ → stimulates sarcoplasmic reticulum calcium release → increased contractility
Levosimendan
MOA
SE
• Mechanism of Action: primarily an inotropic and chronotropic agent rather than a vasopressor. It acts upon beta-1 adrenergic receptors and, unlike dobutamine, has a prominent chronotropic effect. The drug’s high affinity for the beta-2 adrenergic receptor causes vasodilation and a decrease in MAP. Therefore, its utility in hypotensive patients is limited to situations in which hypotension results from bradycardia
Levosimendan is a calcium sensitizer — it increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. Levosimendan exerts its positive inotropic effect by increasing calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium-dependent manner. It also has a vasodilatory effect, by opening adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle to cause smooth muscle relaxation. The combined inotropic and vasodilatory actions result in an increased force of contraction, decreased preload and decreased afterload. Moreover, by opening also the mitochondrial (ATP)-sensitive potassium channels in cardiomyocytes, the drug exerts a cardioprotective effect.
Does not increase O2 requirement.
SE
headache, hypotension, arrhythmias (atrial fibrillation, extrasystoles, Atrial tachycardia, ventricular tachycardia), myocardial ischaemia, hypokalaemia and/or nausea
How do you calculate the mean arterial pressure
MAP, or mean arterial pressure, is defined as the average pressure in a patient’s arteries during one cardiac cycle. It is considered a better indicator of perfusion to vital organs than systolic blood pressure (SBP). True MAP can only be determined by invasive monitoring and complex calculations; however it can also be calculated:
(SBP + 2xDBP)/3. Aim MAP > 60
MOA of Milrinone
Milrinone is a pulmonary vasodilator used in patients who have heart failure. It is a phosphodiesterase 3 inhibitor that works to increase the heart’s contractility and decrease pulmonary vascular resistance.
What are the causes of cardiac transplantation failure?
Cardiac Allograft Vasculopathy
- Frequent long term complication and major cause of death post-transplant causing the coronary arteries to be diseased
- Complex pathophysiology
- Both immunological and non-immunological mechanisms leading to severe intimal proliferation/hyperplasia causing luminal stenosis making it difficult for revascularisation
- Donor endothelium is a major source of host anti-HLA Ab response
- Shares conventional CVD risk factors (DM, lipids, HTN)
2 types of ECMO
Indications
ECMO - venoarterial (VA) and venovenous (VV)
- Both provide respiratory support but only VA ECMO provides haemodynamic support
Peripherally: speed of implantation
Centrally: post CABG
Indications for VA ECMO
- Refractory cardiogenic shock
- Cardiac arrest
- Failure to wean from cardiopulmonary bypass after cardiac surgery
Bridge to:
- Cardiac transplantation
- Placement of ventricular assist device
- Myocardial recovery
- Neurological recovery
Management of acute heart failure
- Nitrate, frusemide, morphine
- Inotropes
Dobutamine
Dopamine
Milrinone
Levosimendan
Increased mortality regardless of agent
- Non drug therapies CPAP/BIPAP Intra-aortic balloon pump Impella ECMO
What do you use as a marker in entresto? BNP or NT-ProBNP
NT-ProBNP
BNP: biological active
Shorter half life
NT-ProBNP: not biologically active, longer half life
Circulating levels of BNP may increase meaningfully early after initiation of sacubitril/valsartan. In comparison, NT-proBNP is not a substrate of neprilysin inhibition, and thus may lead to less clinical confusion when measured within 8 to 10 weeks of drug initiation.
What is BNP?
• B-type natriuretic peptide (BNP) is a hormone produced mainly by the left ventricular myocardium in response to strain (ventricular overload)
• Elevated BNP
○ Heart failure
○ Any cause of left ventricular dysfunction, eg: myocardial ischaemia or valvular disease
○ Reduce excretion in patients with CKD
- Can increase with age, females, post menopausal
• Reduced BNP
Treatment with diuretics, ACEi, ARBs
