CVS Session 11: Heart failure Flashcards
Define heart failure
Heart fails to maintain an adequate circulation for the needs of the body, despite an adequate filling pressure. Abnormality of cardiac function is responsible for failure of the heart to pump blood at a rate commensurate with requirements of the metabolising tissues.
Normally, by Starling’s law, the force developed in the myocardium depends on the degree to which the fibres are stretched (or heart is filled). In HF the heart can no longer produce the same amount of force (cardiac output) for a given level of filling
Clinically recognised by a characteristic pattern of haemodynamic, renal, neural and hormonal responses
Heart failure aetiology?
Main cause= IHD
Other causes:
-hypertension
-dilated cardiomyopathy (viral/bacterial, alcohol/drugs/poisoning, pregnancy, idiopathic)
-valvular heart disease/congential (now less common as picked up before heart fails)
-restrictive cardiomyopathy e.g. amyloidosis
-hypertrophic cardiomyopathy
-pericardial disease
-high output heart failure
-arrhythmias
Describe the 4 stages of the NYHA functional classification of heart failure
Class I: no symptomatic limitations on physical activitiy
Class II: slight limitations, ordinary activity causes symptoms, none at rest
Class III: marked limitation, less than ordinary activity causes symptomes, none at rest
Class IV: can’t carry out physical activity without symptoms, may have symptoms at rest, discomfort increases with any degree of activity. 80% mortality at 3 years so palliative care role
Morbidity of heart failure
~0.2% of UK pop. hospitalised annually for HF
Chronic HF accounts for 5% of all adult general medical admissions and is commonest cause of admission in those >65years
State the factors that influence cardiac output
Heart rate
Myocardial contractility
LV preload (venous capacity)
Afterload (aortic and peripheral impedance)
Describe what happens in systolic dysfunction of the heart
Dilated heart
Increased LV capacity so decreased LV cardiac output
Thinning of the myocardial wall: fibrosis and necrosis of myocardium, activity of matrix proteinases
Mitral valve incompetence
Arrythmias
What structural changes does a failing heart undergo?
Loss of muscle
Uncoordinated or abnormal contraction
ECM changes: increase in collagen (more type III than I) and different fibre orientation
Change of cell structure/function: myocytolysis, myocyte hypertrophy (to compensate for those lost), SR dysfunction, Ca2+ availability changes
List the neuro-hormonal components that can be measured or altered in heart failure
Sympathetic nervous system Renin-angiotensin aldosterone system Natriuretic hormones (biomarker to identify severity) Anti-diuretic hormone Endothelin Prostaglandins/nitric oxide Kallkrien system Tissue necrosis factor alpha
i.e. a variety of systems work together!
What is the early compensatory mechanism to improve cardiac output that is regulated by the sympathetic nervous system?
Cardiac contractility increase
Arterial and venous vasoconstriction
Tachycardia
What are the long term pathological effects of higher sympathetic activity, which originally was helpful in increasing cardiac output?
Beta adrenoceptors are down-regulated: increases heart rate so increased O2 demand–>decreased contractility
Vasoconstriction increases wall stress, causing hypertrophy and increased O2 demand (so decreased contractility)
Noradrenaline:
-induces hypertrophy, myocyte apoptosis and necrosis via alpha receptors
-induces up-regulation of RAAS (so more fluid retention, more wall stress, so hypertrophy eventually)
Reduction in heart rate variability: reduced PNS and increased SNS
Describe the role of the renin-angiotensin-aldosterone system in heart failure
Commonly activated in heart failure: reduced renal blood flow + SNS induction of renin from macula densa Elevated angiotensin II: -potent vasoconstrictor -promotes LVH and myocyte dysfunction -promotes aldosterone release -promotes Na+ and H2O retention
What is the role of angiotensin II in organ damage?
Acts on the AT1 receptor:
- atherosclerosis
- vasoconstriction
- vascular hypertrophy
- endothelial dysfunction
- LV hypertrophy
- fibrosis, remodelling and apoptosis
- decreased glomerular filtration rate
- increased proteinuria and aldosterone release–>glomerular sclerosis
These events can lead to stroke, hypertension, MI, heart failure, renal failure, and death
What is the role of natriuretic hormones/peptide?
Induce the discharge of Na+ in urine: balance the effects of the RAAS on the vascular tone and Na+/H2O balance.
Stretch or increase in cardiac chamber volume leads to release: atrial NP, brain NP (ventricle stretch). Cause vasodilation and increased urinary Na+ excretion (decrease reabsorption in collecting duct). Also inhibits renin and aldosterone secretion
What is hypo-natraemia?
H2O in excess of Na+ retention, due to:
- increased water intake (thirst)
- action of ADH on V2 receptors in the collecting duct
Normally will inhibit ADH release
What are the effects of raised anti-diuretic hormone in heart failure?
- Increased H2O retention
2. Tachycardia and reduced systemic resistance –> increased cardiac output
What are the actions of endothelin?
- vasoconstriction, esp. renal. Autocrine activity so activates RAAS
- in patients with HF, more endothelin = poorer prognosis
- similar effects to angiotensin II, but more aggressive
Which prostaglandins are involved in HF and how?
E2 and I2
Stimulated by NA and RAAS
Vasodilation of afferent renal arterioles to attenuate the effects of NA/RAAS
Role of nitric oxide in HF?
Normally a potent vasodilator produced by endothelial cells
In HF, nitric oxide synthase may be blunted in HF causing loss of vasodilatation balance
Role of bradykinin in HF?
Promotes natriuresis and vasodilatation, and stimulates prostaglandin production
What is the significance of raised alpha-TNF in HF?
Depresses myocardial function
What factors contribute to increased peripheral resistance in HF?
SNS
RAAS
Reduced NO
Increased endothelin
Changes in skeletal muscle in HF?
Reduced skeletal muscle blood flow–>cachexia affecting all muscles
In limbs reduces motility and in diaphragm inhibits breathing
This contributes to fatigue and exercise intolerance
Renal effects of severe HF?
Renal blood flow falls: reduced GFR therefore rise in serum urea and creatinine
Can be worsened by treatment inhibiting the actions of angiotensin II
How is GFR maintained in early HF?
Haemodynamic changes at the glomerulus
How does heart failure cause anaemia?
Chronic inflammatory disease
Expanded plasma volume
Drug therapy: ACEi (can damage bone marrow), aspirin
Iron malabsorption (e.g. due to oedematous gut wall)
Chronic renal failure
In which patients is diastolic dysfunction more common?
Elderly
Female
History of hypertension, diabetes, obesity
What is the state of the left ventricle in diastolic dysfunction?
Concentric left ventricular hypertrophy
but
normal LV function
Pathophysiology of diastolic dysfunction?
Hypertrophied heart
Reduced LV compliance
Impaired myocardial relaxation
Impaired diastolic LV filling, with increased LA and PA pressures: unable to compensate by increased LV EDP (Starling)
therefore
LOW CARDIAC OUTPUT, which triggers neuro-hormonal activation as per systolic heart failure
Describe the clinical syndromes that heart failure is often divided into (n.b. it is rare for any part of the heart to fail in isolation)
Right sided HF
Left sided HF
Biventricular (congestive) HF
Systolic HF (pump failure) Diastolic HF (relaxation failure)
Symptoms of left HF?
Fatigue
Exertational dyspnoea
Orthopnoea (sob lying flat)
Paroxysmal nocturnal dyspnoea (depression of resp. centre during sleep plus lying flat)
Mild cases of left sided HF may not have clinical signs. What are the signs as the HF progresses?
Tachycardia and cardiomegaly (displaced apex beat) : due to compensatory SNS mechanisms
“Gallop rhythm”-S3 or S4 heart sound
Functional murmur of mitral regurgitation (due to dilation of LVH)
Basal pulmonary crackles
Peripheral oedema
Aetiology of right heart failure?
Most frequent: secondary to left heart failure
Others: Chronic lung disease Pulmonary embolism Pulmonary hypertension Pulmonary or tricuspid valve disease Left to right shunts (ASD, VSD) Isolated right ventricular cardiomyopathy
Symptoms and signs of right HF? Due to distention and fluid accumulation in areas drained by the systemic veins
Symptoms: fatigue, dyspnoea, anorexia, nausea
Signs: raised JVP, tender hepatic enlargement, pitting oedema, ascites, pleural effusion
Lifestyle modifications to treat HF?
Reduce salt, alcohol and blood pressure
Increase aerobic exercise
Pharmacological management of HF?
Diuretics ACEi or ARB (angiotensin II receptor blockers for patients who can't take ACE inhibitors) Vasodilators-hydralazine/nitrate Beta blocker Spironolactone (diuretic) Cardiac glycosides e.g. digoxin Antiarrhythmics
Acute setting: inotropes, phosphodiesterase inhibitors
What cardiac surgeries can be tried to treat HF?
Heart transplant (v small numbers) Mechanical assist devices Implantable pacemakers Implantable defibrillators For underlying cause: valve surgery, revascularisation
What is activated in HF to try to maintain cardiac output, and what are the effects of this?
RAAS
Sympathetic nervous system
These make the already-struggling heart work harder, and angiotensin II has additional damaging effects on the heart and other organs
Why does HF stimulate renin release from the kidney?
HF causes a drop in blood pressure
What is renin?
An enzyme which catalyses conversion of angiotensinogen to angiotensin I
What is angiotensin converting enzyme and how can its inhibition be used in HF management?
Converts angiotensin I to angiotensin II
ACE inhibitors prevent production of angiotensin II and thus aldosterone release. They have an indirect vasodilatory and diuretic effect (both beneficial in treatment)
What is aldosterone?
Released from adrenal cortex upon stimulation by angiotensin II
Causes salt and water retention in the kidneys, which increases blood volume
Why are diuretics a useful HF treatment?
They reduce blood volume and thus oedema
Why does peripheral oedema occur in right sided HF?
Right side of heart doesn’t pump effectively
Venous pressure is raised
Capillary hydrostatic pressure is raised, favouring movement of water out of the capillaries
Why does pulmonary oedema occur in left sided HF?
Left side of heart doesn’t pump effectively
Left atrial pressure increases and thus pressure of vessels in pulmonary system is increased
These vessels have a low resistance so there is also an increased pulmonary artery pressure
