Define heart failure.
- A state in which the heart fails to maintain an adequate circulation for the needs of the body despite an adequate filling pressure.
- A pathophysiological state in which an abnormality of cardiac function is responsible for the failure of the heart to pump blood at a rate commensurate with requirements of the metabolising tissues.
- A clinical syndrome caused by an abnormality of the heart and recognised by a characteristic pattern of haemodynamic, renal, neural and hormonal responses.
Outline the aetiology of heart failure.
- Ischaemic Heart Disease (IHD) is the primary cause of Systolic HF
- Dilated Cardiomyopathy:
I. Bugs (Viral/ Bacterial / Mycobacteria)
II. Alcohol / Drugs / Poisoning
- Valvular Heart Disease / Congenital
- Restrictive Cardiomyopathy e.g. amyloidosis
- Hypertrophic Cardiomyopathy
- Pericardial disease
- High-Output Heart Failure
Outline the progression of Heart Failure - Class I.
Class I – No symptomatic limitation of physical activity
Outline the progression of Heart Failure - Class II.
- Slight limitation of physical activity
- Ordinary physical activity results in symptoms
- No symptoms at rest
Outline the progression of Heart Failure - Class III.
- Marked limitation of physical activity
- Less than ordinary physical activity results in symptoms
- No symptoms at rest
Outline the progression of Heart Failure - Class IV
I. Inability to carry out any physical activity without symptoms
II. May have symptoms at rest
III. Discomfort increases with any degree of physical activity
Outline the physiology of the heart.
- Cardiac Output ~ 5 litres/min
- Stroke Volume ~ 75 ml / beat
- LV end systolic volume ~ 75 ml
- LV end diastolic volume ~ 150 ml
- Ejection Fraction 50% plus
- Weight ~ 330 g
What are the factors affecting cardiac output?
- Heart rate
- Venous capacity (LV preload)
- Myocardial contractility
- Arterial and Peripheral impedance (after load)
State Starling's Law of the Heart and describe the graph.
"The force developed in a muscle fibre depends on the degree to which the fibre is stretched."
Outline the pathophysiology of Left Ventricular Systolic Dysfunction.
- Increased LV capacity
- Reduced LV cardiac output
- Thinning of the myocardial wall
I. Fibrosis and necrosis of myocardium
II. Activity of matrix proteinases
- Mitral valve incompetence
- Neuro-hormonal activation
- Cardiac Arrhythmias
Discuss the Structural Heart Changes.
- Loss of muscle
- Uncoordinated or abnormal myocardial contraction
- Changes to the ECM:
I. Increase in collagen (III>I) from 5% to 25%
II. Slippage of Myocardial fibre orientation
- Change of cellular structure and function
I. Myocytolysis and vacuolation of cells
II. Myocyte hypertrophy
III. Sarcoplasmic reticulum dysfunction
IV. Changes to Calcium availability and/or receptor regulation
Outline Ventricular remodeling after acute infarction.
- Initial infarct.
- Expansion of infarct (hours to days)
- Global remodeling (days to months)
Outline Ventricular remodeling in diastolic and systolic heart failure
- Normal Heart
- Hypertrophied heart (diastolic heart failure)
- Dilated heart (systolic heart failure)
Label the following images.
- Fig 5.2: Normal heart.
- Fig 5.3: Concentric Hypertrophy of left ventricular wall
- Fig 5.4: Eccentric hypertrophy of left ventricular wall
- Fig 5.5: Global dilatation
Outline the pathophysiology of Heart Failure with Preserved Ejection Fraction (HFpEF)
- Previously Diastolic Heart Failure or HFnEF
- Almost 50% of heart failure patients
- Key factors:
I. Frequently elderly and female
II. Often history of hypertension / diabetes / obesity
- Normal LV function with concentric remodelling
- Hospitalisation and mortality similar to systolic HF
- Diagnosis is less clear cut
- Little clinical outcome study data to guide therapy
- Reduced LV compliance and impaired myocardial relaxation:
I. Thicker and shorter cardiomyocytes
II. Increased deposition of collagen
- Impaired diastolic LV filling (with increased LA and PA pressures)
- LV filling becomes dependent on high LA pressure
- RV dysfunction can result from high LA and PA pressure
- Triggers neuro-hormonal activation as per systolic heart failure
Outline the clinical syndromes of heart failure.
- Left Sided Heart Failure
- Right Sided Heart Failure
- Biventricular (congestive) cardiac failure
- LVSD (‘pump failure’)
- HFpEF (‘failure of LV relaxation’)
Identify the signs and symptoms of Left Heart Failure
II. Exertional dyspnoea
IV. Paroxysmal nocturnal dyspnoea (PND)
- In mild left sided heart failure, there may be few clinical signs, but as the heart failure progresses you may see:
II. Cardiomegaly (displaced apex beat, may be sustained)
III. 3rd or 4th heart sound (‘Gallop rhythm’)
IV. Functional murmur of mitral regurgitation
V. Basal pulmonary crackles (fluid in the lungs)
VI. Peripheral oedema
Outline the aetiology of Right Heart Failure.
- Chronic lung disease
- Pulmonary embolism / pulmonary hypertension
- Pulmonary/tricuspid valvular disease
- Left-to-right shunts (ASD/VSD)
- Isolated right ventricular cardiomyopathy
- The most frequent cause is secondary to left heart failure = Congested or Biventricular Heart Failure
What are the signs and symptoms of Right Heart Failure?
Relate to distension and fluid accumulation in areas drained by the systemic veins:
- Fatigue, dyspnoea, anorexia, nausea
- ↑ JVP
- Tender, smooth hepatic enlargement
- Dependent pitting oedema
- Pleural effusion
Describe the features of neuro-hormonal activation.
- Sympathetic Nervous System
- Renin-Angiotensin-Aldosterone System
- Natriuretic Hormones
- Anti-Diuretic Hormone
- Prostaglandins / Nitric Oxide
- Kallikrien System
- Tissue Necrosis Factor – α
Outline the involvement of the Sympathetic Nervous System in heart failure.
- Baroreceptor-mediated response
- Early compensatory mechanism to improve CO:
I. Cardiac contractility
II. Arterial and venous vasoconstriction
- However long-term deleterious effects:
- β-adrenergic receptors are down-regulated / uncoupled
- Induces cardiac hypertrophy / myocyte apoptosis and necrosis via α-receptors
- Induce up-regulation of the RAAS
- Reduction in heart rate variability (reduced paraSNS and increased SNS)
When is RAAS commonly activated in Heart Failure?
- Reduced renal blood flow
- SNS induction of renin from macula densa
Outline the effects of elevated Angiotensin II.
Elevated Angiotensin II:
- Potent vasoconstrictor
- Promotes LVH and myocyte dysfunction
- Promotes aldosterone release
- Promotes Na+ /H2O retention
- Stimulates thirst by central action?
Explain how Angiotensin II plays a key role in organ damage.
- Brain: Atherosclerosis -> Stroke
- Vessels: Vasoconstriction, Vascular hypertrophy, Endothelial dysfunction -> Hypertension
- Heart: LV hypertrophy, Fibrosis, Remodeling, Apoptosis -> Heart failure (MI)
- Kidney: Decreased GFR, Increased Proteinuria, Increased Aldosterone release Glomerular sclerosis -> Renal failure
All can progress to death.
Outline the Renin-Angiotensin-Aldosterone System
Outline the effect of Natriuretic Hormones.
- Atrial: stretch (A&V):
I. Predominate renal action – constricts afferent and vasodilates efferent arterioles
II. Decreases Na+ reabsorption in the collecting duct
III, Inhibits secretion of renin and aldosterone
IV. Systemic arterial and venous vasodilatation
- Brain: stretch (V) – similar effects
- C-Type: CNS and endothelium – limited effects
- These peptides balance the effects of the RAAS on the vascular tone and Na+ /H2O balance
- Role as sensitive marker for HF (low false negative)
Outline the effect of ADH (Vasopressin)
- Hyponatraemia results from H2O in excess of Na+ retention and can be due to:
I. Increased H2O intake (thirst)
II. Action of ADH on V2 receptors in the collecting duct
- Normally hyponatraemia / hypoosmolality inhibits ADH release – but ADH is increased in HF:
I. Increased H2O retention
II. Tachycardia and reduced systemic resistance resulting in increased CO
Outline the effect of Endothelin.
- Secreted by vascular endothelial cells
- Potent system and renal vasoconstrictor acting via autocrine (local) activity thus activating RAAS
- Evidence of increased levels in some patients with HF
- Correlates with indices of severity (poor prognostic sign)
Outline the effect of other chemicals:
- Prostaglandin E2 and I2
- Nitric Oxide
- Tumour Necrosis Factor (α-TNF)
- Prostaglandin E2 and I2:
I. Stimulated by NA and RAAS
II. Act as vasodilators on afferent renal arterioles to attenuate effects of NA / RAAS
III. NSAID Rx blocks de novo PG synthesis
- Nitric Oxide
I. Usually potent vasodilator produced by endothelial cells via NO synthase
II. NO synthase may be blunted in HF
III. Loss of vasodilatation balance
I. Promotes natriuresis and vasodilatation
II. Stimulates production of PGs
- Tumour Necrosis Factor (α-TNF)
I. Increased in HF
II. Depresses myocardial function
III. Stimulates NO synthase??
IV. Role in cachexia?
What is Oedema?
- Oedema is the excessive volume of fluid within the tissues:
- Heart failure is one cause
- Changes to capillary dynamics leads to oedema
- Don’t forget about the RAAS
Explain what is meant by:
Net Filtration Pressure = Hydrostatic Pressure – Osmotic Pressure
Explain the role of the vascular endothelium in heart failure.
- Increase in peripheral arterial resistance:
III. Reduced NO
IV. Increased endothelin
- Alterations in vascular tone exacerbate the clinical deterioration
- Leads to skeletal muscle changes, renal effects, anaemia
Outline the skeletal muscle changes associated with changes in the vascular endothelium.
- Reduced skeletal muscle blood flow
- Reduction in skeletal muscle mass (cachexia) – Affects all muscle including:
II. Respiratory eg diaphragm
- Abnormalities of structure and function
- Contribute to fatigue and exercise intolerance
Outline the renal effects associated with changes in the vascular endothelium.
- GFR is maintained in early HF by haemodynamic changes at the glomerulus
- Increased Na+ /H2O retention due to neurohormonal activation
- However, in severe HF, renal blood flow falls leading to reduced GFR and a subsequent rise in serum urea and creatinine.
- This can be exacerbated by treatment inhibiting the actions of Angiotensin II
Outline the anaemia associated with changes in the vascular endothelium.
- Contributes to symptoms
- Common and easily treated
- Multi-factorial aetiology:
I. Chronic inflammatory disease
II. Expanded plasma volume
III. Drug therapy (ACEi / Aspirin)
IV. Iron malabsorption
V. Chronic renal failure
Outline the manifestations of a diseased myocardium.
Diseased myocardium – Ischaemic Heart Disease:
- Myocardial scar
- Myocardial stunning/hibernation
- Epicardial coronary artery disease
- Abnormal coronary microcirculation
- Endothelial dysfunction
Outline abnormal loading conditions.
- Valve and myocardium structural defects
I. Acquired – Mitral, aortic, tricuspid and pulmonary valve diseases
II. Congenital – atrial and ventricular septum defects and others
- Toxic damage
I. Recreational substance abuse – alcohol, cocaine, amphetamine, anabolic steroids
II. Heavy metals – copper, iron, lead, cobalt
III. Medications – cytostatic drugs, antidepressant drugs, NSAID’s, anaesthetics
Outline, briefly, the clinical signs and symptoms of chronic heart failure.
- Clinical signs
I. Pulmonary congestion
II. Venous congestion
III. Dependent oedema
Outline the Vicious Cycle of Heart Failure
Outline how the overactivation of the RAAS and SNS is detrimental in HFrEF and underpins the basis of therapy