Heart Failure Flashcards
[Frank-]Starling’s law of the heart
https://www.youtube.com/watch?v=l4jxZGlnf0Q
More EDV = More Preload = More SV = More forceful contraction
The contractile function of an isolated strip of cardiac tissue can be
described by the relationship between the velocity of muscle contraction,
the load that is moved by the contracting muscle, and the extent to
which the muscle is stretched before contracting. As with all other types
of muscle, the velocity of contraction of myocardial tissue is reduced by
increasing the load against which the tissue must contract. However,
in the non-failing
heart, pre-stretching
of cardiac muscle improves the
relationship between the force and velocity of contraction (Fig. 30.5).
This phenomenon was described in the intact heart as an increase
of stroke volume (ventricular performance) with an enlargement of
the diastolic volume (preload), and is known as ‘Starling’s law of the
heart’ or the ‘Frank–Starling relationship’. It has been transcribed into
more clinically relevant indices. Thus, stroke work (aortic pressure
× stroke volume) is increased as ventricular end-diastolic
volume is
raised. Alternatively, within certain limits, cardiac output rises as pulmonary
capillary wedge pressure increases. This clinical relationship
is described by the ventricular function curve (see Fig. 30.5), which
also shows the effect of sympathetic stimulation.
Venous return (preload)
Physiology
Pathophysiology
In the intact heart, myocardial failure leads to a reduction of the
volume of blood ejected with each heart beat and an increase in
the volume of blood remaining after systole. This increased diastolic
volume stretches the myocardial fibres and, as Starling’s law
of the heart (see p. 1025) would suggest, myocardial contraction
is restored. However, the failing myocardium results in depression
of the ventricular function curve (cardiac output plotted against the
ventricular diastolic volume) (see Fig. 10.8).
Mild myocardial depression is not associated with a reduction
in cardiac output because it is maintained by an increase in
venous pressure (and hence diastolic volume). However, the proportion
of blood ejected with each heart beat (ejection fraction) is
reduced early in heart failure. Sinus tachycardia also ensures that
any reduction of stroke volume is compensated for by the increase
in heart rate; cardiac output (stroke volume × heart rate) is therefore
maintained.
When there is more severe myocardial dysfunction, cardiac output
can be maintained only by a large increase in venous pressure and/
or marked sinus tachycardia. The increased venous pressure contributes
to the development of dyspnoea, owing to the accumulation
of interstitial and alveolar fluid, and ascites with hepatic enlargement
and dependent oedema from increased systemic venous pressure.
However, the cardiac output at rest may not be much depressed,
but myocardial and haemodynamic reserve is so compromised that
a normal increase in cardiac output cannot be produced by exercise.
In very severe heart failure the cardiac output at rest is depressed,
despite high venous pressures. The inadequate cardiac output is
redistributed to maintain perfusion of vital organs, such as the heart,
brain and kidneys, at the expense of the skin and muscle.
Outflow resistance (afterload)
Physiology
Pathophysiology
Outflow resistance (afterload) (see Fig. 30.5) is the load or resistance
against which the ventricle contracts. It is formed by:
• pulmonary and systemic resistance
• physical characteristics of the vessel walls
• the volume of blood that is ejected.
An increase in afterload decreases the cardiac output, resulting
in a further increase of end-diastolic
volume and dilation of the
ventricle, which further exacerbates the problem of afterload. This
is expressed by Laplace’s law: the tension of the myocardium (T)
is proportional to the intraventricular pressure (P) multiplied by the
radius of the ventricular chamber (R) – that is, T ∝ PR.
Myocardial contractility (inotropic state)
The state of the myocardium also influences performance. The
sympathetic nervous system is activated in heart failure via baroreceptors
as an early compensatory mechanism, which provides inotropic
support and maintains cardiac output. Chronic sympathetic activation, however, has deleterious effects by further increasing
neurohormonal activation and myocyte apoptosis. This is compensated
by a downregulation of β-receptors.
Increased contractility
(positive inotropism) can result from increased sympathetic drive
and this is a normal part of the Frank–Starling relationship (see Fig.
30.5). Conversely, myocardial depressants (e.g. hypoxia) decrease
myocardial contractility (negative inotropism).
Neurohormonal and sympathetic system activation:
salt and water retention
The increase in venous pressure that occurs when the ventricles fail
leads to retention of salt and water, and their accumulation in the interstitium,
producing many of the physical signs of heart failure. Reduced
cardiac output also leads to diminished renal perfusion, activating the
renin–angiotensin system and enhancing salt and water retention (see
Fig. 36.6), which further increases venous pressure (Fig. 30.54). The
retention of sodium is, in part, compensated by the action of circulating
atrial natriuretic peptides and antidiuretic hormone (see p. 176).
Myocardial remodelling in heart failure
Process…
Hallmarks…
In cardiomyopathy…
Left ventricular remodelling is a process of progressive alteration of
ventricular size, shape and function owing to the influence of mechanical,
neurohormonal and possibly genetic factors in several clinical
conditions, including myocardial infarction, cardiomyopathy, hypertension
and valvular heart disease.
Its hallmarks include hypertrophy,
loss of myocytes and increased interstitial fibrosis.
Remodelling continues
for months after the initial insult, and the eventual change in
the shape of the ventricle becomes responsible for the impairment
of overall function of the heart (Fig. 30.55A).
In cardiomyopathy, the
process of progressive ventricular dilation or hypertrophy takes place
without ischaemic myocardial injury or infarction (Fig. 30.55B).
Abnormal calcium homeostasis
Calcium ion flux within myocytes plays a pivotal role in the regulation
of contractile function. Excitation of the myocyte cell membrane causes the rapid entry of calcium into myocytes from the extracellular
space via calcium channels. This triggers the release of
intracellular calcium from the sarcoplasmic reticulum and initiates
contraction (see Fig. 30.3). Relaxation results from the uptake and
storage of calcium by the sarcoplasmic reticulum (see Fig. 30.9),
controlled by changes in nitric oxide.
In heart failure, there is a prolongation
of the calcium current in association with prolongation of
contraction and relaxation.
Natriuretic peptides (ANP, BNP and CNP)
ANP
Released from…
ANP induces…
ANP levels increased in…
BNP
Secreted by…
BNP levels increased in…
CNP
Limited to…
• Atrial natriuretic peptide (ANP) is released from atrial myocytes
in response to stretch. ANP induces diuresis, natriuresis,
vasodilation and suppression of the renin–angiotensin system.
Levels of circulating ANP are increased in congestive cardiac
failure and correlate with functional class, prognosis and haemodynamic
state.
• B-type natriuretic peptide (BNP) is predominantly secreted by
the ventricles in response to increased myocardial wall stress.
N-terminal (NT)-proBNP is an inactive protein that is cleaved
from proBNP to release BNP. Both BNP and NT-proBNP are increased
in patients with heart failure, and levels correlate with
ventricular wall stress and the severity of heart failure. BNP and NT proBNP are good predictors of cardiovascular events and
mortality, although monitoring levels are not routinely used to
guide heart failure management.
• C-type natriuretic peptide (CNP), which is limited to vascular
endothelium and the central nervous system, has similar effects to those of ANP and BNP.
Endothelial function in heart failure
Plasma concentration of Endothelin (ET) in heart failure
ET’s actions contribute to…
Treatment
The endothelium has a central role in the regulation of vasomotor
tone. In patients with heart failure, endothelium-dependent
vasodilation
in peripheral blood vessels is impaired and may be one
mechanism of exercise limitation. The cause of abnormal endothelial
responsiveness relates to abnormal release of both nitric
oxide and vasoconstrictor substances, such as endothelin (ET).
The activity of nitric oxide, a potent vasodilator, is blunted in heart
failure. ET secretion from a variety of tissues is stimulated by many
factors, including hypoxia, catecholamines and angiotensin II.
The plasma concentration of ET is elevated in patients with heart
failure, and levels correlate with the severity of haemodynamic
disturbance.
ET has many actions that potentially contribute to the pathophysiology
of heart failure: vasoconstriction, sympathetic stimulation,
renin–angiotensin system activation and left ventricular
hypertrophy. Acute intravenous administration of ET antagonists
improves haemodynamic abnormalities in patients with congestive
cardiac failure, and oral ET antagonists are being developed.
Antidiuretic hormone (vasopressin)
Raised in…
High ADH concentration precpitates…
Antidiuretic hormone (ADH) is raised in severe chronic heart failure,
particularly in patients on diuretic treatment. A high ADH concentration
precipitates hyponatraemia, which is an ominous prognostic
indicator.
Heart failure with reduced ejection fraction (HFREF)
Commonly caused by…
Heart failure with reduced ejection fraction (HFREF) (ejection
fraction <40%) is commonly caused by ischaemic heart disease
but can also occur with valvular heart disease and hypertension.
It is only in this group of patients that heart failure therapies have
been demonstrated to have benefit with reduced morbidity and
mortality.
Heart failure with preserved left ventricular ejection fraction
Ejection fraction…
Echocardiography
Diastolic heart failure…
Left Ventricular Ejection Fraction (LVEF) 40-50%…
(HFPEF)
Heart failure with preserved left ventricular ejection fraction (HFPEF) is a syndrome consisting of symptoms and signs of heart failure with an ejection fraction of >50%. There is increased stiffness in the ventricular wall and decreased left ventricular compliance, leading to impairment of diastolic ventricular filling and hence decreased cardiac output.
Echocardiography may demonstrate an increase in left ventricular wall thickness, increased left atrial size and abnormal left ventricular relaxation with normal or near-normal left ventricular volume.
Diastolic heart failure is more common in elderly hypertensive patients but may occur with primary cardiomyopathies (hypertrophic, restrictive, infiltrative).
Those patients in the grey zone with an LVEF of 40–50% have recently been classified as having heart failure with mid-range ejection fraction (HFmrEF).
Right ventricular systolic dysfunction (RVSD)
May occur secondary to…
May also occur with…
Right ventricular systolic dysfunction (RVSD) may be secondary to chronic left-sided heart disease but can occur with primary and secondary pulmonary hypertension, right ventricular infarction, arrhythmogenic right ventricular cardiomyopathy and adult congenital heart disease.
Clinical features of heart failure
Symptoms
Signs
Symptoms
• Exertional dyspnoea
• Orthopnoea
• Paroxysmal nocturnal dyspnoea
• Fatigue
Signs
• Tachycardia
• Elevated jugular venous pressure
• Cardiomegaly
• Third and fourth heart sounds
• Bi-basal crackles
• Pleural effusion
• Peripheral ankle oedema
• Ascites
• Tender hepatomegaly
New York Heart Association (NYHA) classification
of heart failure
The NYHA classification of heart failure (Box 30.23) can be used
to describe the symptoms of heart failure and limitation of exercise
capacity, and is useful for assessing response to therapy.
Class & Features
Class I
No limitation. Normal physical exercise does
not cause fatigue, dyspnoea or palpitations
Class II
Mild limitation. Comfortable at rest but normal
physical activity produces fatigue, dyspnoea
or palpitations
Class III
Marked limitation. Comfortable at rest but
gentle physical activity produces marked
symptoms of heart failure
Class IV
Symptoms of heart failure occur at rest and are
exacerbated by any physical activity
Diagnosis of heart failure
Should be based on…
Diagnosis of HF-REF & HF-PEF requires conditions to be satisfied…
The diagnosis of heart failure should be based on a detailed history,
clinical findings, natriuretic peptide levels and objective evidence
of cardiac dysfunction using measures of left ventricular structure
and function (usually echocardiography). The underlying cause of
heart failure should be established in all patients (Box 30.24 and
Fig. 30.56).
Box 30.24 Diagnosis of heart failure (European Society of
Cardiology guidelines)
- *Diagnosis of HF-REF requires three conditions to be satisfied**
1. Symptoms typical of heart failure
2. Signs typical of heart failure
3. Reduced LV ejection fraction
Diagnosis of HF-PEF requires four conditions to be satisfied
1. Symptoms typical of heart failure
2. Signs typical of heart failure
3. Normal or only mildly reduced LV ejection fraction and LV not dilated
4. Relevant structural heart disease (LV hypertrophy/left atrial enlargement)
and/or diastolic dysfunction
HF-REF = heart failure and a reduced ejection fraction; HF-PEF = heart failure with ‘preserved’ ejection fraction; LV = left ventricular.
Investigations in heart failure
• Blood tests
Full blood count, serum creatinine and electrolytes, liver biochemistry, cardiac enzymes (eg troponin) in acute heart failure, BNP or NT-proBNP, and thyroid function should be measured.
• Chest X-ray
Look for cardiomegaly, pulmonary congestion with upper lobe diversion, fluid in fissures, Kerley B lines and pulmonary oedema.
• ECG
Identify ischaemia, ventricular hypertrophy or arrhythmia.
• Echocardiography
Assess cardiac chamber dimension, systolic and diastolic function, regional wall motion abnormalities, valvular disease and cardiomyopathies.
• Stress echocardiography
Assess viability in dysfunctional myocardium – dobutamine identifies contractile reserve in stunned or hibernating myocardium.
**• Nuclear cardiology** Radionucleotide angiography (RNA) can quantify ventricular ejection fraction; SPECT or PET can demonstrate myocardial ischaemia and viability in dysfunctional myocardium.
• Cardiac MRI (CMR)
Assess cardiac structure and function and viability in dysfunctional myocardium with the use of dobutamine for contractile reserve or with gadolinium for delayed enhancement (‘infarct imaging’).
• Cardiac catheterization
This technique is employed for the diagnosis of ischaemic heart failure (and suitability for revascularization) and for measurement of pulmonary artery pressure, left atrial (wedge) pressure, left ventricular end-diastolic pressure.
• Cardiac biopsy
This is used for diagnosis of cardiomyopathies, such as amyloid (see p. 1357), and for follow-up of transplanted patients to assess rejection.
• Cardiopulmonary exercise testing
Peak oxygen consumption (VO2) is predictive of hospital admission and death in heart failure. A 6-minute exercise walk is an alternative.
• Ambulatory 24-hour ECG monitoring (Holter)
This is used in patients with suspected arrhythmia, and may be employed in those with severe heart failure or inherited cardiomyopathy to determine whether a defibrillator is appropriate (non-sustained ventricular tachycardia).
Management of heart failure
Measures to prevent heart failure…
Management is aimed at relief of symptoms, prevention and control
of disease leading to cardiac dysfunction and heart failure, retarding
of disease progression, and improvement in quality and length of life.
Measures to prevent heart failure include cessation of smoking,
alcohol and illicit drugs, effective treatment of hypertension, diabetes
and hypercholesterolaemia, and pharmacological therapy following
myocardial infarction.
The management of heart failure requires any factor aggravating
the failure to be identified and treated. Similarly, the cause of heart
failure must be elucidated and, where possible, corrected. Community
nursing programmes to help with drug compliance and detect
early deterioration may prevent acute hospitalization.
Drug management
Stages of heart failure and their treatment options
Box 30.25 lists the drugs used in heart failure. (Spread throughout the other flashcards)
Fig. 30.57 shows the
stages of heart failure and the treatment options.
Drug management - Inotropic and vasopressor agents
Intravenous inotropes and vasopressor agents (see Box 30.29) are used in patients with acute heart failure and severe haemodynamic compromise. Although they produce haemodynamic improvements, they have not been shown to improve long-term mortality when compared with placebo.
Non-pharmacological treatment - Cardiac resynchronization therapy or implantable cardioverter–defibrillator
What is Cardiac resynchronization therapy (CRT)?
Effect therapy in addition to optimal medical treatment in patients with…
Resynchronization may… (Effects)
Which NYHA class(es) benefit the most from CRT?
Patients with end-stage heart failure (NYHA IV) on ICD
Cardiac resynchronization therapy (CRT) entails simultaneous pacing of both ventricles (biventricular pacing) using a lead placed in the right ventricle and another in the coronary sinus to pace the left ventricle (Fig. 30.58).
It is an effective therapy in addition to optimal medical treatment
in patients with significant left ventricular impairment and a prolonged QRS interval (left bundle branch block).
Resynchronization may reverse the process of ventricular remodelling, reduce functional mitral regurgitation and improve left ventricular function.
The CARE-HF and COMPANION trials reported symptomatic benefit and a reduction in heart failure events and mortality following CRT implantation in patients with heart failure in NYHA classes III and IV. Similar findings have been noted in more recent trials in patients with mild heart failure or no symptoms.
Most patients with heart failure who receive CRT also meet the
criteria for use of an ICD and should receive a combined device
(CRT-D).
Patients with end-stage heart failure (NYHA IV) or other co morbidities that may significantly reduce lifespan are generally not candidates for an ICD.
Non-pharmacological treatment - Cardiac transplantation
Treatment of choice for…
Heart allografts do not function normally, as…
Stiff heart syndrome
Transplantation of an inapproriately small donor heart…
What is the major cause of long-term graft failure and it is due to what?
Cardiac transplantation has become the treatment of choice for younger
patients with severe intractable heart failure, whose life expectancy is
less than 6 months.
With careful recipient selection the expected 1-year
survival for patients following transplantation is over 90%, and 75% at
5 years. Irrespective of survival, quality of life is dramatically improved
for the majority. The availability of heart transplantation is limited.
Heart allografts do not function normally, as cardiac denervation
results in a high resting heart rate, loss of diurnal blood pressure
variation and impaired renin–angiotensin–aldosterone regulation.
Some patients develop a ‘stiff heart’ syndrome, caused by rejection, denervation and ischaemic injury during organ harvest and implantation.
Transplantation of an inappropriately small donor heart can
also result in elevated right and left heart pressure.
The complications of heart transplantation are summarized in Box
30.26. Many (infection, malignancy, hypertension and hyperlipidaemia)
are related to immunosuppression.
Allograft coronary atherosclerosis is the major cause of long-term graft failure and is present in 30–50% of patients at 5 years. It is due to a ‘vascular’ rejection process in conjunction with hypertension and hyperlipidaemia.
There are specific contraindications to cardiac transplantation
(Box 30.27); notably, high pulmonary vascular resistance and active
malignancy are absolute contraindications.
Management of Acute heart failure (AHF)
Goals of treatment
Patients with AHF need regular measurements of…
Which medication do all patients with AHF require?
Initial therapy includes…
If intravenous nitrates are required…
Which drugs can be added in patients who do not respond to initial therapy?
Patients with profound hypotension may require…
The goals of treatment in a patient with AHF include:
• immediate relief of symptoms and stabilization of haemodynamics
(short-term benefits)
- reduction in length of hospital stay and hospital re-admissions
- reduction in mortality from heart failure.
Patients with AHF should be managed in a high-dependency
area with regular measurement of temperature, heart rate, blood
pressure and cardiac monitoring.
All require prophylactic anticoagulation
with low-molecular-weight heparin.
Individuals with haemodynamic compromise may need arterial
lines for invasive blood pressure monitoring and arterial gas
sampling, central venous cannulation (intravenous medication,
inotropic support, monitoring of central venous pressure) and
pulmonary artery catheterisation (calculation of cardiac output/
index, peripheral vasoconstriction and pulmonary wedge
pressure).
Initial therapy (Fig. 30.59 and Box 30.29) includes **oxygen and diuretics (e.g. i.v. furosemide 50 mg).**
If intravenous nitrates (e.g.
glyceryl trinitrate infusion 10–200 μg/min) are required (e.g. concomitant
myocardial ischaemia, severe hypertension), careful monitoring of the blood pressure is mandatory.
Inotropic support (see p. 222) with **dobutamine, phosphodiesterase inhibitors or levosimendan** can be added in patients who do not respond to initial therapy.
Nesiritide (recombinant human B-type natriuretic peptide)
can also be used in AHF as a bolus injection followed by an infusion.
Patients with profound hypotension may require inotropes
and vasopressors to improve haemodynamic status and alleviate
symptoms but these have not been shown to improve mortality.
Non-invasive
continuous positive airway pressure/positive pressure
ventilation (CPAP/NIPPV; see p. 229) has been shown to provide
earlier improvement in dyspnoea and respiratory distress than standard
oxygen via mask; mortality is, however, unaffected.
Box 30.29 Pharmacological therapy in acute heart failure
