Heart failure Flashcards
What is heart failure and what are some causes
the failure of the heart to pump blood to meet the circulatory needs
may be due to failure of heart muscles or values. can be chronic or acute. can lead to hypertension, ischaemic heart disease, cardiomyopathies, and lead to adaptation of the heart muscles
precipitated by pregnancy anaemia, hyper- or hypothyroidism, and fluid retaining drugs such as glucocorticoids and NSAIDs. increased fluid volume increases the workload on the heart
Neurohormonal adaptations occur to compensate, such as through sympathetic activation and through the RAAS. this cycle however then leads to further impairment of the heart function - myocyte dysfunction. the increased aldosterone can lead to fibrosis and stiffening of the heart
Chronic heart failure + diagnosis and goals of treatment
left-sided failure is the most common form. is associated with pulmonary oedema - congestion in pulmonary circulation.
Sees fatigue, poor exercise tolerance, cold peripheries, hypotension, reduced urination, weight loss, and breathlessness (from pulmonary oedema).
Diagnosis based on symptoms, echocardiogram, and chest X-rays (would see cardiomegaly - enlarged heart, and pulmonary oedema).
Poor prognosis - median survival in mild-moderate is only 5 years.
Goals of treatment are to identify the cause, reduced cardiac workload, increase CO, counteract maladaptation, relieve symptoms and to prolong quality of life.
targeting the RAAS
ACEIs and AT1R antagonists reduce arterial and venous vasoconstriction, through direct activity of angiotensin-II in causing vasoconstriction as well as by reducing salt retention - decrease blood volume. also inhibits aldosterone production - prevents the fibrosis and stiffening of the heart. these effects prevent cardiac remodelling.
AT1R antagonists (e.g., losartan/valsartan) don’t lead to the bradykinin mediated cough seen in ACEIs. ACE metabolises bradykinin, thus ACEIs increase [bradykinin], which sensitises nerves in the airway.
Diuretics
prevent water retention. e.g., thiazides (bendroflumethiazide) which is used in mild failure and the elderly - acts at the distal convoluting tubule.
loop diuretics (furosemide) act at the loop of Henle. especially treat pulmonary oedema.
Aldosterone receptor antagonist
spironolactone. reverses left ventricular hypertrophy.
B-AR antagonists
they reduce disease progression, symptoms and mortality. used in stable or moderate failure. they reduce sympathetic stimulation, HR and O2 consumption. they have anti arrhythmic activity, which reduces sudden death.
What is atrial fibrillation and treatments
a common consequence of CHF. it is impaired rhythm of contraction of the atria. can lead to thrombi formation.
Prophylaxis, warfarin or aspirin to treat/prevent
digoxin is a positive inotrope that inhibits Na+/K+ ATPase.
Na+ can accumulate in myocytes, promoting Ca2+ influx - thus increased contractility. Impairs atrioventricular conduction. it controls the ventricular rate and reduces the rate at which the contraction passes from the atria to the ventricles. it is not commonly used due to toxicity.
SGLT2 inhibitors
e.g., dapagliflozin, canagliflozin
they inhibit glucose reabsorption in the kidneys through the sodium-glucose cotransporter 2.
exert cadio and renal protection. they decrease the BP without effect on HR. by prevention of renal damage they decrease sympathetic signalling. decreased mortality rates in patient with HF
Soluble guanylate cyclase stimulator
vericiguat
stimulates GC in absence of NO
Guanylate cyclase activates cGMP which activates PKG which then causes dilatation of smooth muscle
leads to increased renal blood flow and renal function. promotes diuresis.
also increases coronary blood flow and reduces workload on the heart via vasodilatation
Selective cardiac myosin inhibitors
omecamtiv mecarbil
It reduces the rate of release of phosphate. this thus reduces ATP binding to myosin, maintaining myosin bound to actin. this increases the force of contraction of cardiac muscle
Neprilysin inhibitors
sacubitril
neprilysin inhibitor. neprilysin is a peptidase that metabolises and deactivates natriuretic peptides such as ANP, BNP, and CNP. its inhibition leads to vasodilatation, decreased cardiac hypertrophy and increased natriuresis - increased Na+ excretion leading to reduced blood volume.
neprilysin also metabolises angiotensin-II, thus it should be taken in combination with an AT1R antagonist such as valsartan - increases effectiveness
myeloperoxidase and drugs targeting it
MPO is produced by neutrophils in inflammation. it catalyses the formation of hypochlorous acid - targets pathogens, but can also lead to the oxidation of NO. this would impair endothelium-dependent vasodilatation
MPO has a role in atherosclerosis, playing a role in vascular injury needed for the formation of atherosclerotic plaques. it causes microvascular inflammation. MPO activity has been found to be increased in heart failure.
AZD4831 is a MPO inhibitor in phase 2 clinical trials. it reduces inflammation and fibrosis, as well as improves the microvascular function in animal models of heart failure.
