Heart failure learning module 1: background, epidemiology and pathophysiology

Released7 May 2020     Expires: 07 May 2022      Programme:

Sponsorship Statement: Vifor Pharma UK has provided an unrestricted educational grant to fund this activity and has not had any input into any aspect of this learning resource.

Background

Table 1 – Typical symptoms and signs of heart failure

Symptoms Signs
Exertional breathlessness Laterally displaced apex beat
Ankle swelling Third heart sound
Orthopnoea (sensation of breathlessness when lying flat) Peripheral pitting oedema (commonly ankles or sacrum in bedbound patients)
Paroxysmal nocturnal dyspnoea Raised jugular venous pulse
Fatigue Bi-basal fine crackles
Reduced exercise tolerance Heart murmur

Heart failure is a clinical syndrome in which patients have typical symptoms and signs due to an abnormality of cardiac structure or function (table 1).1 Its prevalence is high and increasing due to an ageing population, improved survival rates following myocardial infarction, increasing prevalence of risk factors such as diabetes and obesity – and better medical care. Patients with heart failure have a poor quality of life and reduced life expectancy, often more-so than is associated with some cancers. Effective treatment can improve symptoms and outcome but there are wide variations in the management of heart failure across the UK.2

Clinical definition

HeFREF/HeFNEF/HeFMREF

Patients with heart failure are often sub-divided in relation to their left ventricular ejection fraction (LVEF).

  • heart failure with a reduced ejection fraction (HeFREF) is due to impaired systolic, contractile function of the left ventricle – but it is important to realise that impaired systolic function does not happen in isolation. Patients with HeFREF invariably also have abnormal diastolic function
  • some patients have signs and symptoms of heart failure but have a normal ejection fraction on echocardiography (figure 1). Such patients are variously labelled as having HeFNEF, HeFPEF (where the P stands for ‘preserved’) or ‘diastolic heart failure’ (figure 2).
Figure 1 redraw
Figure 1. Apical four chamber diastolic view of two-dimensional echocardiograms and M-mode echocardiograms of the left ventricle recorded in a normal subject (A, C) and a patient with dilated cardiomyopathy (B, D). The left ventricular size is greatly enlarged and its function reduced in the latter (click to enlarge)
Figure 2. Distribution of left ventricular ejection fraction measured within 12 months of the EuroHeart Failure survey among women (n = 2,048; 41% of total enrolled) and men (n = 3,249; 57% of total enrolled) enrolled in the EuroHeart Failure survey. Where more than one ejection fraction measurement was available, the most recent one was used. 51% of men but only 28% of women had a left ventricular ejection fraction <40%
Figure 2. Distribution of left ventricular ejection fraction measured within 12 months of the EuroHeart Failure survey among women (n = 2,048; 41% of total enrolled) and men (n = 3,249; 57% of total enrolled) enrolled in the EuroHeart Failure survey. Where more than one ejection fraction measurement was available, the most recent one was used. 51% of men but only 28% of women had a left ventricular ejection fraction <40% (click to enlarge)

Around half of all patients with heart failure have normal left ventricular systolic function.3,4 When compared to patients with reduced systolic function (HeFREF), those with normal ejection fraction are:5,6

  • more likely to be female
  • older
  • less likely to have coronary artery disease
  • more likely to have hypertension
  • more likely to have valvular heart disease
  • more likely to have atrial fibrillation
  • more likely to have diabetes or chronic obstructive pulmonary disease (COPD)
  • more likely to have muscle wasting (or sarcopaenia)
  • often given different pharmacotherapy
  • likely to have lower mortality rates.3

HeFNEF remains a controversial entity, and many believe that there is a significant risk of inappropriate diagnosis.

For example, the definition of a ‘normal’ left ventricular ejection fraction (LVEF) depends upon the method used to measure it and the population studied. Echocardiography is most widely used, but LVEF by echo is poorly reproducible: a patient said to have normal LVEF by one operator may, on a different day, or with a different operator, be said to have reduced ejection fraction.

Additionally, although much quoted epidemiological studies suggest that patients with HeFNEF have much the same prognosis as those with HeFREF,7 every trial population in whom LVEF has been measured reports a linear relation between increasing LVEF and increasing survival.

An additional concern is that whilst ejection fraction may qualify as being ‘normal’ by being above some arbitrary cut-point, systolic function can still be abnormal when measured using other techniques, such as longitudinal strain.

The label applied can also be provocative. Many prefer the term ‘preserved’ to describe a normal ejection fraction – although left ventricular ejection fraction might be in the normal range, it might have fallen to reach that point, and cannot be known to be preserved.

A third heart failure phenotype has been proposed that lies in the ‘grey area’ between HeFREF and HeFNEF: heart failure with mid-range ejection fraction (HeFMREF) with LVEF 40–49%.1

The prevalence of HeFMREF is between 14–18% of patients with heart failure.8–11 Patients with HeFMREF are older and more likely to be female with greater burden of co-morbidities than patients with HeFREF, but with a similar prevalence of ischaemic heart disease (IHD).12 Patients with HeFMREF are thus similar to patients with HeFNEF. However, their prognosis is similar to that of HeFREF and their causes of death are closer to those seen in patients with HeFREF than HeFNEF.13,14

The clinical and laboratory characterstics of patients with HeFMREF are intermediate between HeFNEF and HeFREF.15 It is possible that those with HeFMREF are in transition from HeFNEF to HeFREF or vice versa.16–19 It is not at all clear as yet whether HeFMREF is a useful concept.

Identifying the heart failure phenotype is essential for management

Despite much debate surrounding the value of LVEF as a measure of cardiac function, there is no doubt that it is helpful in defining patients who are likely to respond to specific therapies. Clinical trials have unequivocally demonstrated the benefit of medical and device therapy for patients with heart failure – but only amongst those with reduced ejection fraction, however that is defined. Conversely, there are no interventions proven to improve outcome in patients with HeFNEF.

Table 2. Precipitants and causes of acute heart failure

Events usually leading to rapid deterioration
Rapid arrhythmia or severe bradycardia/conduction disturbance
Acute coronary syndrome
Mechanical complication of acute coronary syndrome (e.g. rupture of interventricular septum, mitral valve chordal rupture, right ventricular infarction)
Acute pulmonary embolism
Hypertensive crisis
Cardiac tamponade
Aortic dissection
Surgery and perioperative problems
Peripartum cardiomyopathy
Events usually leading to less rapid deterioration
Infection (including infective endocarditis)
Exacerbation of COPD/asthma
Anaemia
Kidney dysfunction
Non-adherence to diet/drug therapy
Iatrogenic causes (e.g. prescription of an NSAID or corticosteroid; drug interactions)
Arrhythmias, bradycardia, and conduction disturbances not leading to sudden, severe change in heart rate
Uncontrolled hypertension
Hypothyroidism or hyperthyroidism
Alcohol and drug abuse
Key: AHF = acute heart failure; COPD = chronic obstructive pulmonary disease; NSAID = non-steroidal anti-inflammatory drug
Reproduced with kind permission from Ponikowski1

There is a lack of clarity on how to treat patients with HeFMREF – both National Institute for Health and Care Excellence (NICE) and European Society of Cardiology (ESC) guidelines only recommend treatment with angiotensin converting enzyme (ACE) inhibitors, beta blockers or mineralocorticoid receptor antagonists (MRAs) in patients with an LVEF <40%. However, evidence is emerging that suggests treatment with proven benefit for patients with LVEF <40% may also be beneficial for patients with LVEF 40-49%.20 More work is required.

Acute heart failure versus chronic heart failure

In classifying heart failure syndromes, perhaps the most useful distinction to make is between acute (or decompensated) heart failure and chronic heart failure.

Acute heart failure is the rapid onset, or worsening, of the symptoms and signs of heart failure (table 2). It includes patients with sudden-onset dyspnoea due to acute pulmonary oedema but also those admitted to hospital with fluid retention without breathlessness at rest.

Patients are often thought to lie along a spectrum with acute pulmonary oedema at one end, and gross fluid retention at the other: this may be mistaken; acute pulmonary oedema is a dramatic event precipitated by a discrete pathology such as acute ischaemia or arrhythmia.

An appropriate working definition is that acute heart failure is heart failure that leads to a patient seeking urgent medical attention and often results in hospitalisation whereas chronic heart failure describes the period of stability between any episodes of decompensation.

The pathophysiology of acute heart failure can usually be understood in terms of abnormal haemodynamics, but the pathophysiology of chronic heart failure, especially when treated, is more complex (see later).

Epidemiology

Cardiovascular disease was responsible for one in four deaths in England and Wales during 2018, second only to cancer as the leading cause of death (figure 3).21 Heart failure is the common final end point for most forms of cardiovascular disease; the majority (50–70%) is due to ischaemic heart disease (IHD).3 Recent years have seen a decline in the number of deaths due to IHD and vast improvements in the detection and management of heart failure,22,23,24 resulting in an increase in the number of new cases and the number of patients living with heart failure.25 There are around 920,000 people living with heart failure in the UK – approximately 1.4% of the UK population26 – while many more may be undiagnosed.27

Heart failure module 1 - Figure 3. Causes of death in England and Wales in 2018
Figure 3. Causes of death in England and Wales in 2018
Table 3. UK prevalence of heart failure
Table 3. UK prevalence of heart failure (click to enlarge)

Although age-and-sex standardised prevalence is stable (1–2%), the crude number of patients living with heart failure has increased by 23% in the last decade. Similarly, whilst age and sex standardised incidence of heart failure has decreased in the last decade, the crude number of new cases has increased by 12%. The incidence rises with age and has increased significantly amongst patients aged 85 and older (table 3), probably a result of increased use of screening and diagnostic tests (module 2). The average age at diagnosis is 77 years but is significantly lower in areas of economic deprivation.25

In England and Wales, general practitioners (GPs) keep a heart failure registry as part of the Quality and Outcomes Framework (QOF). These registers report a prevalence of heart failure of only 0.75%,28 suggesting that not all patients with heart failure in primary care are being recorded, or perhaps that the epidemiology is incorrect.

The burden of heart failure

Heart failure has a profound negative impact on the lives of patients and their carers and is costly to manage.

Acute or decompensated heart failure is the leading cause of admission to hospital for patients aged ≥65 years and causes or complicates 5% of all hospital admissions in the UK.2,29 Hospitalisation rates have increased by 33% in the last five years, three times greater than the increases seen for any other condition.30 Re-admission rates are high: as many as 23% will be re-admitted in the month after discharge (although not always for heart failure).31

Mortality is stubbornly high: around 10% of patients admitted with heart failure will die in hospital. Of those who survive admission, approximately 15% will die during the month following discharge and 32% will die in the year following hospital admission.2

Death rates following diagnosis in the community are 19%, 49% and 71% at one, five and 10 years respectively with little appreciable change in the last decade.32

A recent epidemiological study of 56,658 patients registered at general practices in Scotland found that mortality rates for heart failure were similar to that of colorectal cancer and worse than those for bladder, prostate and breast cancer during the 11 year study period from 2000 to 2011 (figure 4).33

Heart failure module 1 - Figure 4. Heart failure mortality rates versus some cancer mortality rates
Figure 4. Heart failure mortality rates versus some cancer mortality rates (click to expand)

There has been a worrying upward trend in heart failure death rates recently reported in the USA between 2012 and 2017.34 Although comparisons between our state-run health service in the UK and the insurance-based model in the USA are difficult to draw, the increase in hospital admissions with heart failure and the unchanging high death rates during and after admission are concerning.

Admission with heart failure places a huge burden on the patient and health service: it is associated with long hospital stays (~12 days for patients treated on cardiology wards) accounting for 2% of all NHS ‘bed days’. Heart failure accounts for 2% of the entire NHS annual budget (around £625 million per year); 70% is spent on in-patient care and only around 9% is due to drug costs.35

National Heart Failure Audit

NICOR heart failure audit 2019

The National Heart Failure Audit was established in 2007 and produces annual reports (both as a summary and on a hospital-by-hospital basis) on the demographics, investigations, treatment, place of care, level of specialist input, follow up and outcome of all patients admitted with heart failure in England and Wales.

Records are submitted by individual institutions and, since 2016, have been financially incentivised by the Best Practice Tariff for heart failure. The 2017–18 report captured data from around 76% of all hospital admissions coded as being for heart failure by Hospital Episode Statistics (HES) coding in England and Wales. It is an invaluable source of information on the current ‘state-of-play’ for the quality of care given to patients admitted with heart failure.

Findings from the 2017–18 report

Regarding investigations:

  • 86% and 88% of patients received an electrocardiogram (ECG) and echocardiogram (echo) respectively, in order to establish the diagnosis.
    • The audit does not record the availability and use of natriuretic peptide measurements, which is probably now the best tool to rule-out heart failure as a cause of presentation. Details of natriuretic peptides can be found in module 2: diagnosis.
  • Perhaps unsurprisingly, patients on cardiology wards were more likely to have an echo than patients on general medical wards (95% vs. 84%).
  • Patients who had no specialist input were far less likely to have an echo than those who did (69% vs. 92%)
    • There has been an approximately 10% drop in the number of patients on general medical wards undergoing echocardiography in the last four years perhaps reflecting a shortage of echo services in secondary care.
  • Of those who had an echo; 66% had left ventricular systolic dysfunction, 41% had valve disease, 12% had diastolic dysfunction and 7.3% had left ventricular hypertrophy (LVH).
    • These diagnoses are not mutually exclusive.

Regarding specialist input and length of stay:

  • 46% of patients are treated on cardiology wards but there is enormous country-wide variation (0-100%); 31% of patients nationally are cared for on general medical wards.
  • 82% of patients are seen by a cardiology specialist (consultant cardiologist – 57%, general medical consultant with specialist interest in cardiology or heart failure specialist nurse – 49%).
  • Median length of stay is higher for patients on cardiology wards or for those who have received specialist input compared to those in general medicine or who have not seen a specialist (9 days vs. 5-6 days).
    • This is possibly a reflection of an increased likelihood of receiving triple-therapy and the time taken to established patients on these medications which, itself, may translate to improved outcomes (see below).

Regarding treatment:

  • The majority of patients with left ventricular systolic dysfunction (LVSD) are discharged on either an ACE inhibitor or angiotensin receptor blocker (ARB) (84%) and a beta blocker (89%). Around half of patients with LVSD are discharged on a mineralocorticoid receptor antagonist (MRA).
  • 92% are discharged taking a loop diuretic.
  • Prescription rates for ACE inhibitors, ARBs, beta blockers and MRAs fall with age, whereas the prescription rate of loop diuretics increases. Overall, prescription rates of all heart failure medications are increasing over time.
  • Patients treated on cardiology wards or under the care of a specialist are approximately twice as likely to be on ‘triple therapy’ (ACE inhibitor or ARB plus beta blocker plus MRA) than those on general medical wards without specialist input (figure 5)
Heart failure module 1 - Figure 5. Trend of treatment of HeFREF by place of care and specialist input 2014–2018
Figure 5. Trend of treatment of HeFREF by place of care and specialist input 2014–2018

Regarding follow-up and outcome

  • The inpatient mortality rate for patients who receive no specialist input is 66% higher than patients who receive specialist input (15.0% vs. 9.0%) and more than double that of patients treated on cardiology wards (7.3%) (figure 6).
    • The beneficial effect of place of care and specialist input as an in-patient persists to one-year post discharge (figure 7).
  • Patients who have cardiology follow-up have a lower mortality rate than those who do not (24% vs. 39%).
  • Post-discharge mortality is highly dependent on treatment: one-year mortality rate for patients receiving ‘triple therapy’ is 19% compared to 48% for patients on no ACE inhibitor, ARB, beta blocker or MRA (figure 8).
Heart failure module 1 - Figure 6. Inhospital mortality 2017–2018
Figure 6. Inhospital mortality 2017–2018
Heart failure module 1 2020 - Figure 7. All-cause mortality following discharge from hospital according to place of care during admission 2017–2018
Figure 7. All-cause mortality following discharge from hospital according to place of care during admission 2017–2018
Heart failure module 1 2020 - Figure 8. Mortality post-discharge associated with prescribing for patients with HeFREF 2017–2018
Figure 8. Mortality post-discharge associated with prescribing for patients with HeFREF 2017– 2018
Figure 9. Cardiovascular post-discharge mortality by additive drug treatment on discharge for left ventricular systolic dysfunction
Figure 9. Cardiovascular post-discharge mortality by additive drug treatment on discharge for left ventricular systolic dysfunction

QOF indicators, quality standards and best practice tariffs

In the UK, various initiatives are in place to attempt to ensure good quality and even standard of care for patients with acute and chronic heart failure in the in-patient or community setting.

QOF indicators

The performance of general practices in managing patients with heart failure is monitored by the Quality and Outcomes Framework (QOF). QOF, under the guidance of NICE, have developed ‘indicators’ for managing patients with heart failure that act as targets that are financially incentivised (table 4).36

Table 4. QOF indicators related to heart failure, their description and number of QOF points allocated

QoF indicator Description Points allocated
HF001 The contractor establishes and maintains a register of patients with heart failure 4
HF002 50–90% of patients with a diagnosis of heart failure (diagnosed on or after 1 April 2006) confirmed by an echocardiogram or by specialist assessment 3 months before or 12 months after entering on to the register 6
HF003 60–100% of patients with a current diagnosis of heart failure due to left ventricular systolic dysfunction treated with an ACE inhibitor or ARB 10
HF004 40–65% of patients with a current diagnosis of heart failure due to left ventricular systolic dysfunction who are currently treated with an ACE inhibitor or ARB and beta blocker 9
Key: ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; QOF = quality and outcomes framework

The most recent set of QoF indicators (2019–20) no longer rewards practices for referring patients to an exercise-based cardiac rehabilitation programme despite recommendations made in both ESC and NICE chronic heart failure guidelines. This is perhaps a reflection of service-underfunding and the so-called ‘postcode lottery’: exercise-based cardiac rehabilitation can improve symptoms and reduces the risk of heart failure hospitalisation in patients with HeFREF,37,38 but access to such programmes is greatly varied nationwide.

Around 0.7% of patients at general practices nationwide are on their practice’s heart failure register, somewhat below the national heart failure prevalence of 1-2%; the missing patients may be cases of undiagnosed or untreated heart failure.27 Improved coding of electronic records using simple automated methods can greatly increase the apparent prevalence of heart failure,27 and may yield financial reward via the QoF framework.

Quality standards

NICE has produced ‘quality standards’ for acute and chronic heart failure that define the standard of care that should be provided.

Acute heart failure quality standard:39

  • Adults presenting to hospital with new suspected acute heart failure have a single measurement of natriuretic peptide.
  • Adults admitted to hospital with new suspected acute heart failure and raised natriuretic peptide levels have a transthoracic Doppler 2D echocardiogram within 48 hours of admission.
  • Adults admitted to hospital with acute heart failure have input within 24 hours of admission from a dedicated specialist heart failure team.
  • Adults with acute heart failure due to LVSD are started on, or continue with, beta blocker treatment during their hospital admission.
  • Adults admitted to hospital with acute heart failure and reduced LVEF are offered an ACE inhibitor and an aldosterone antagonist.
  • Adults with acute heart failure have a follow up clinical assessment by a member of the community – or hospital-based specialist heart failure team within two weeks of hospital discharge.

Chronic heart failure quality standard:40

  • Adults with suspected chronic heart failure who have been referred for diagnosis have an echocardiogram and specialist assessment.
  • Adults with suspected chronic heart failure and either a previous myocardial infarction (MI) or very high levels of serum natriuretic peptides, who have been referred for diagnosis, have an echocardiogram and specialist assessment within two weeks.
  • Adults with chronic heart failure due to LVSD are started on low dose ACE inhibitor and beta blocker medications that are gradually increased until the target or optimal tolerated doses are reached.
  • Adults with chronic heart failure have a review within two weeks of any change in the dose or type of their heart failure medication.
  • Adults with stable chronic heart failure have a review of their condition at least every six months.
  • Adults with stable chronic heart failure are offered an exercise-based programme of cardiac rehabilitation.
  • Adults with chronic heart failure referred to a programme of cardiac rehabilitation are offered sessions during and outside working hours, and the choice of undertaking the programme at home, in the community or in a hospital setting.
Problems with the quality standards

The quality standards require significant resources and do not take into account patient variables that may limit their treatment. They represent a very high standard that many centres may struggle to attain.

  • Quality standards for acute heart failure require that:
    • All patients to have specialist input within the first 24 hours of admission
      • Data from the National Heart Failure Audit shows only 82% of patients get any input from heart failure specialists while an inpatient2
    • All patients get a transthoracic echocardiogram within 48 hours of admission
      • Only 88% of patients get an echocardiogram at all during admission
    • All patients are started or continue on beta blocker during admission and that all patients are offered treatment with ACE inhibitor, ARB and MRA
      • Co-morbidities such as renal dysfunction and hypotension are common amongst patients admitted with heart failure and limit the initiation (and, in some cases, require the discontinuation) of heart failure medications. In practice only 89%, 84% and 53% of patients are taking a beta blocker, ACE inhibitor or ARB and MRA respectively
    • All patients have follow-up with either their GP, a cardiologist, or heart failure specialist nurse within two weeks of discharge
      • This must be one of the most unrealistic targets in the modern NHS.
Best practice tariff

In 2010 the Department of Health in the UK introduced ‘Best Practice Tariffs’; financial incentives for hospitals to meet what was defined as ‘best practice’ for a particular condition. Base payments for treating a certain condition were reduced overall but additional money was available for meeting criteria based on national guidance and expert opinion that defined ‘best practice’ for managing that condition.41

The best practice tariff for heart failure is worth a 10% increase in payment for every admission, but it is not paid on a patient by patient basis: either the hospital meets the best practice tariff criteria and gets the 10% increase in payment for every admission – or it does not.

The best practice tariff for heart failure was introduced in 2016 and includes two criteria:42

  • 60% of patients admitted with failure must receive specialist input during admission as recorded in the national heart failure audit
  • 70% of patients coded as having heart failure must be included in the national heart failure audit.

Syndromes and pathophysiology

Over many years, the heart failure syndrome has attracted a number of different terminologies of varying degrees of usefulness. It makes sense, perhaps, to consider the separate heart failure syndromes only where the pathophysiology of them is distinct: the differences highlight important differences in therapeutic approach.

The most useful distinction to make is between acute and chronic heart failure. However, even then, the terms can be confusing. Here, we will take acute heart failure to describe patients with sufficiently severe symptoms and signs that they present acutely seeking medical attention (and are often admitted to hospital); whereas chronic heart failure describes the syndrome patients have once acute heart failure has been medically treated.

Acute heart failure

Most patients (~80%) with heart failure are initially diagnosed during a hospitalisation.43 Acute heart failure is a problem of fluid distribution. Broadly, patients divide into those with acute pulmonary oedema, where there is fluid in the airspaces in the lung, and those with peripheral oedema, where the problem is fluid retention.

Pulmonary oedema

Pulmonary oedema is an acute medical emergency. Patients present with severe breathlessness, which is usually of abrupt onset. The experience for the patient is terrifying: she has to sit upright, is barely able to speak and often fears that she will die.

Table 5. Common precipitants of acute pulmonary oedema
Table 5. Common precipitants of acute pulmonary oedema

The breathlessness is often accompanied by wheeze and cough productive of pink frothy sputum. There is usually an acute precipitant that has triggered the episode of illness (table 5).

On examination there is massive sympathetic nervous system activation, and the patient is thus usually pale and clammy, with a tachycardia and often hypertension. There is usually a gallop rhythm and widespread crackles and wheezes through the lung fields.

Pathophysiology

Pulmonary oedema is best understood in haemodynamic terms. Fluid is held in the pulmonary capillaries by the balance between the hydrostatic pressure in the capillary tending to push fluid out and the colloid osmotic pressure (largely generated by plasma proteins) tending to hold fluid in the vascular space. There is a net (small) constant transudation of fluid from the pulmonary capillaries which is removed by the lymphatics.

Left ventricular work (and cardiac output) is determined by left ventricular filling pressure (that is, end-diastolic pressure). This is the Frank-Starling relation (figures 10 and 11): as filling pressure rises, so does cardiac output. In the acutely failing left ventricle, the relation is shifted downward and to the left so that to maintain any given cardiac output, a higher filling pressure is required.

Heart failure module 1 2020 - Figure 10. Starling’s law of the heart. In the normal heart (blue), ventricular work increases as a function of preload. The horizontal lines show the ventricular work required at rest, then for mild and finally severe exertion. With increasing severity of heart failure (brown lines), a greater preload is needed for a given level of activity. Note the ‘descending limb’ of the Starling curve for patients with severe heart failure: the implication is that a reduction in preload might (paradoxically) increase ventricular work
Figure 10. Starling’s law of the heart. In the normal heart (blue), ventricular work increases as a function of preload. The horizontal lines show the ventricular work required at rest, then for mild and finally severe exertion. With increasing severity of heart failure (brown lines), a greater preload is needed for a given level of activity. Note the ‘descending limb’ of the Starling curve for patients with severe heart failure: the implication is that a reduction in preload might (paradoxically) increase ventricular work (click to enlarge)
Figure 11. Dr Ernest Starling who, along with Otto Frank, developed the Frank–Starling law of the heart
Figure 11. Dr Ernest Starling who, along with Otto Frank, developed the Frank–Starling law of the heart (click to enlarge)

As the filling pressure is the same as the pulmonary venous pressure, the rise results in an increase in the rate of transudation from pulmonary capillaries into the lung tissues, and the rate eventually exceeds the rate at which fluid can be removed by the lymphatics. At this point, fluid accumulates in the interstitium of the lung and then the alveoli (figure 12).

Heart failure module 1 - Figure 12. Diagram showing the physiology of how fluid accumulates in the interstitium of the lung. A illustrates the normal physiology, while B depicts increased venous pressure
Figure 12. Diagram showing the physiology of how fluid accumulates in the interstitium of the lung. A illustrates the normal physiology, while B depicts increased venous pressure

A point often ignored is that the increase in filling pressure requires an input of energy: this can only come from the right ventricle. In acute pulmonary oedema, there must be a temporary imbalance between the output of the two ventricles: the relative excess output from the right results in the increase in left ventricular diastolic pressure and represents the fluid accumulating in the lungs.

Peripheral oedema

More common than pulmonary oedema as a cause of hospitalisation is fluid retention (table 6). In contrast with patients with pulmonary oedema (who may have a low circulating volume due to accumulation of fluid in the lungs), patients with peripheral oedema have an absolute excess of body fluid and an increased circulating volume. The fluid tends to accumulate gradually over many days or weeks; it takes around 5L of excess fluid before peripheral oedema appears.

Table 6. Comparison between patients with acute pulmonary oedema and those with peripheral oedema
Table 6. Comparison between patients with acute pulmonary oedema and those with peripheral oedema

The order of deposition of oedema is dictated by gravity, so for most patients it starts in the ankles and works upward – and may involve the abdominal, and even thoracic, wall. Patients are usually not breathless at rest, although are unable to do much exercise.

On examination the patient may have a tachycardia with a low volume pulse and a low blood pressure. Around 25% will be in atrial fibrillation. The jugular venous pressure is invariably raised, but may be so high that the top of the column of blood cannot be seen even with the patient sitting upright. Pitting oedema usually starts in the feet and ankles, but be wary of the bed-bound patient in whom sacral oedema may be prominent.

In most patients, the heart is dilated and there is a loud third and often fourth heart sound. Some degree of pulmonary venous hypertension is almost invariable, and patients usually have basal crackles in both lung fields.

Pathophysiology

Peripheral oedema develops in much the same was as pulmonary oedema. The increased circulating volume causes in an increase in hydrostatic pressure (with gravity ensuring that the hydrostatic pressure is highest in the feet). The capacity of the lymphatics to drain away the transudate is exceeded, and oedema fluid starts to form.

What is less certain is why there is salt and water retention in the first place. It may be related to the primary need for the body to maintain blood pressure: if, as a consequence of the failing heart, blood pressure falls, the resultant neurohormonal activation (involving renin-angiotensin-aldosterone system [RAAS], antidiuretic hormone and sympathetic system activation) causes salt and water retention in the kidneys. Additionally, reduced renal perfusion is another stimulus to renin production.

This cannot be the whole explanation as in some patients oedema develops despite normal blood pressure; and in others, there is fluid retention despite aggressive treatment with neurohormonal antagonists.

Chronic heart failure

Although some patients with fluid retention are thought of as having chronic heart failure, particularly if they do not actually need to be hospitalised, the term is best reserved for patients with treated acute heart failure.

Successful treatment of acute heart failure results in patients entering a chronic disease state: they usually have some degree of exercise limitation, but where it is well treated, do not have congestion and oedema.

Chronic heart failure is iatrogenic in the sense that before modern therapies were available, acute heart failure had a very bleak prognosis. Diuretics and treatment with neurohormonal antagonists allows chronic heart failure to develop.

The cardinal symptom of chronic heart failure is exercise limitation. Patients complain of breathlessness or fatigue on exertion, with the dominant symptom varying with the kind of exercise performed. The origin of symptoms is not clear and is likely to be a result of abnormal haemodynamics, neurohormonal activation and skeletal muscle changes.

Pathophysiology

Haemodynamics: In most patients with chronic heart failure, remodelling causes progressive dilation of the left ventricle. Stroke volume is maintained by an increase in left ventricular wall tension by the law of Laplace.

Cardiac output is usually normal at rest and during submaximal exercise, but may not be able to rise normally during more strenuous activity. However, there is little relation between haemodynamic variables, particularly when measured at rest, and exercise capacity.

Neurohormonal activation: The insight that many neurohormonal systems are activated in chronic heart failure has been the key to the success of modern medical therapy for heart failure:

The renin-angiotensin-aldosterone system (RAAS) (figure 13) is activated by reduced renal perfusion. With worsening NYHA class symptoms, so the concentrations of angiotensin and aldosterone rise. Of note, the introduction of diuretic therapy results in further RAAS activation. The consequences are, inter alia, vasoconstriction, salt and water retention, increased vascular fibrosis and a positive interaction with…

Figure 13. The renin angiotensin aldosterone system
Figure 13. The renin angiotensin aldosterone system (click to enlarge)

The sympathetic nervous system (figure 14). With worsening heart failure, so sympathetic nervous system activation and concentrations of circulating noradrenaline increase. The consequences for the heart include tachycardia, myocardial fibrosis and apoptosis, increased risk of arrhythmia and peripheral vasoconstriction (figure 15).

Figure 14. Overactivity of sympathetic nervous system
Figure 14. Overactivity of sympathetic nervous system (click to enlarge)
Figure 15. The ‘vicious cycle’ of untreated heart failure
Figure 15. The ‘vicious cycle’ of chronic heart failure pathophysiology (click to enlarge)

Natriuretic peptide concentrations rise as a homeostatic response to dilation of the cardiac chambers. Antidiuretic hormone (arginine vasopressin) is also increased, further enhancing water retention. Other hormone systems are activated, although their clinical relevance is not always clear. The potent vasoconstrictor, endothelin, is raised, and more intriguingly, there is activation of components of the immune system, with increases in tumour necrosis factor and c-reactive protein, for example.

Skeletal muscle changes: these can be very prominent in some patients resulting in cachexia, but almost all patients have some degree of loss of lean muscle bulk. The skeletal muscle changes correlate closely with impaired exercise capacity, and appear to be implicated, at least in part, as the cause of sympathetic nervous system activation.

Peripheral changes: these include the down-regulation of baroreceptors (making them unlikely to be the source of sympathetic nervous system activation) and enhancement of chemoreceptors. The ergoreflexes, a neurally mediated reflex arising from exercising muscle in proportion to work done, is enhanced.

Complications

Arrhythmias are common complications of heart failure, especially atrial fibrillation (AF) (figure 16) which can increase the risk of stroke and thromboembolism or ventricular arrhythmias.1

Figure 16. ECG showing atrial fibrillation (click to enlarge)
Figure 16. ECG showing atrial fibrillation (click to enlarge)

Atrial fibrillation

If patients with heart failure develop AF (figure 16) either permanent or paroxysmal, should be assessed for potentially reversible causes and stroke risk. Unless there is a very strong contra-indication, patients with heart failure and AF should be anticoagulated.

Potential reversible causes of AF in heart failure

  • hyperthyroidism
  • electrolyte disorders
  • uncontrolled hypertension
  • mitral valve disease.

Potential precipitating factors of AF in heart failure

  • recent surgery
  • chest infection or exacerbation of COPD/asthma
  • acute myocardial ischaemia
  • alcohol binge.

Ventricular arrhythmias

Episodes of asymptomatic, non-sustained ventricular tachycardia are common. “Complex ventricular arrhythmias”, include frequent premature ventricular complexes and non-sustained ventricular tachycardia are associated with a poor outcome.1

Co-morbidities

Patients with heart failure have a wide range of co-morbidities in part related to age. Some co-morbidities may cause heart failure in the first place, for example, cancer after treatment with chemotherapy. Others are risk factors for developing heart failure, such as obesity or hypertension (see below). Polypharmacy is a common consequence and can be very challenging.

Co-morbidities of heart failure include:

• Anxiety and depression

Common in patients with heart failure with around one in three patients reporting symptoms of low mood and one in five patients meeting diagnostic criteria for a depressive illness. Depression in patients with heart failure is associated with a worse clinical status, poor prognosis, poor adherence to treatment and social isolation.44

• Anaemia

Chronic heart failure and anaemia frequently co-exist – up to 40% of patients with CHF are anaemic (Hb <13g/dL in men and <12 g/dL in women).45 The cause of anaemia in patients with CHF is multifactorial;46 a combination of disease severity, co-morbidities (such as renal dysfunction), poor diet, haematinic deficiencies, and side-effects of treatment. Anaemia should be considered the end point of iron depletion, which in itself, may be detrimental. Anaemia in a patient with CHF is associated with more severe symptoms, and poorer prognosis.47,48

• Diabetes

Diabetes affects approximately one third patients with heart failure and is associated with poorer prognosis and reduced functional status.49 Hyperglycaemia is associated with endothelial dysfunction, myocardial fibrosis and increased activation of the sympathetic nervous system and renin-angiotensin-aldosterone system.50

• Chronic kidney disease (CKD)

Very common amongst patients with chronic heart failure: ~50% of patients with CHF have an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2.51 Both CKD and worsening renal function during treatment are associated with a poor prognosis.52 Patients with CHF and CKD have worse symptoms, higher levels of circulating RAAS hormones and natriuretic peptides, are more likely to take a diuretic but are less likely to be treated with ACE inhibitors, ARB, beta blockers or MRA.53,54

• COPD

Another common co-morbidity affecting around 10% of patients but may have negligible impact on prognosis.55 Rates of COPD are much higher in patients with HeFNEF, prompting concerns about misdiagnosis of a patient with exertional dyspnoea. There’s a danger that a diagnosis of COPD in patients with HeFREF will lead to under-prescription of beta blocker.

• Hyperuricaemia and gout

Common; diuretics play a role either causing or aggravating gout.56

• Hypertension

More common in patients with HeFNEF. The incidence of heart failure is reduced by antihypertensive therapy with the exception of alpha-adrenoreceptor blockers.57

• Obesity

Obesity is risk factor for heart failure, independent of lifestyle factors that may contribute to, or are associated with, being obese such as physical inactivity, diabetes and hypertension.58 There is potential for misdiagnosis in an obese patient with exertional dyspnoea and ankle swelling. In some patients, obesity may have a negative effect on the quality of the echocardiogram.

• Sleep disturbances

Disturbed sleep is a common complaint of patients with heart failure and sleep-disordered breathing affects up to one-third.5 Obstructive sleep apnoea is associated with intermittent hypoxaemia, hypercapnia, sympathetic activation, pulmonary and systemic hypertension and atrial fibrillation.

Conclusion

Heart failure has a profound impact on quality of life, prognosis and survival of those affected. Its incidence and prevalence rise with age, and are rising in the population due to better healthcare and therapeutic advances. A large proportion of the health care budget is spent in heart failure hospitalisations.

The pathophysiology of heart failure remains key to understanding how to diagnose and manage the different types of heart failure accordingly.

In following modules, we will explore investigations, diagnosis algorithm and pharmacological and non-pharmacological options for the management of heart failure.

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