Chronic Heart Failure
Heart failure is a clinical syndrome in which structural and/or functional cardiac abnormalities lead to inadequate cardiac output to meet the body’s metabolic demands over time.
Updated UKMLA guide to chronic heart failure based on the NICE 2025 guideline: classification, causes, diagnosis, and management.
Background Information
Definition
Heart failure is a clinical syndrome where structural and/or functional cardiac abnormality results in a reduced cardiac output (CO) that does not meet the body’s metabolic demand [Ref]
High-output heart failure: higher than normal COCardiac output but still insufficient to meet the demands of the body
Classification
By Ejection Fraction (EF)
This applies to left-sided heart failure (by measuring the EF of the left ventricles on echocardiography):
| Type | Full form | Definition |
|---|---|---|
| HFrEF | Heart failure with reduced ejection fraction | LVEFLeft ventricular ejection fraction ≤40% |
| HFmEF | Heart failure with mildly reduced ejection fraction | LVEFLeft ventricular ejection fraction 41-49% |
| HFpEF | Heart failure with preserved ejection fraction | LVEFLeft ventricular ejection fraction ≥50% + structural heart problem As per NICE, at least 2 of the following are necessary:
|
The NYHA (New York Heart Association) Classification
The NYHA classification is based on clinical severity of chronic heart failure and guides management:
| NYHA Class | Description |
|---|---|
| I | No limitation of physical activity. Ordinary physical activity does not cause symptoms. |
| II | Comfortable at rest. Ordinary physical activity causes symptoms. |
| III | Comfortable at rest. Less than ordinary physical activity causes symptoms. |
| IV | Unable to carry out any physical activity without symptoms +/- symptoms at rest. |
Aetiology
High-output heart failure occurs due to either increased peripheral metabolic demand or peripheral shunting (blood shunted away from arterial circulation), NOT a problem with the cardiac output
Main causes of high-output heart failure (ATP2 / AA-TT-PP): [Ref]
- Anaemia
- Arteriovenous fistula / malformation
- Thiamine deficiency (wet beri-beri)
- Thyrotoxicosis
- Paget’s disease of bone
- Pregnancy
Low-output heart failure can be sub-classified into left vs right-sided heart failure
Left-Sided Heart Failure
Causes of left-sided heart failure can be classified depending on the ejection fraction (or systolic vs diastolic dysfunction) [Ref]
| Type | Mechanism | Important causes |
|---|---|---|
| HFrEF (systolic dysfunction) | Loss of viable cardiac muscle / damaged cardiac muscle |
|
| Dilated left ventricle (eccentric hypertrophy) |
|
|
| HFmrEF / HFpEF (diastolic dysfunction) | Left ventricular hypertrophy (concentric hypertrophy) |
|
| Increased left ventricular stiffness |
|
Systolic and diastolic heart failure are out-of-date terms, however they can help understand the underlying mechanism and how it correlates with ejection fraction:
- HFrEF (systolic heart failure) occurs when there is impaired left ventricle contraction during systole → reduced ejection fraction and thus stroke volume → reduced cardiac output
- HFmrEF / HFpEF (diastolic heart failure) occurs when there is impaired left ventricle relaxation during diastole, but contraction remains intact → reduced preload → reduced cardiac output
The 3 leading causes of heart failure are:
- Ischaemic heart disease
- Dilated cardiomyopathy
- Chronic hypertension
Right-Sided Heart Failure
Main causes: [Ref]
- Left-sided heart failure (causes pulmonary congestion → right ventricular overload) – most common
- Left-to-right shunting (e.g. VSD)
- Pulmonary hypertension
- Chronic lung disease (e.g. COPD, interstitial lung disease)
- Pulmonary embolism
- Right ventricular infarction
Left-sided HF frequently leads to secondary right-sided heart failure, while other causes often produce isolated right-sided heart failure without left ventricular involvement.
Diagnosis
Clinical features
Clinical features of chronic heart failure can be classified into left- and right-sided.
The main differentiating factors that suggest acute heart failure over chronic heart failure:
- Rapid onset of symptoms (often over hours to days)
- Sudden and severe symptoms
- Results from a trigger (e.g. myocardial infarction, arrhythmia, infection)
- Pulmonary congestion predominant
NB there is significant overlap in symptoms, as there might be chronic heart failure features present in a case of acute-on-chronic heart failure.
Left-Sided Heart Failure
Symptoms from pulmonary congestion: (Increasing in severity as you go down the list)
- Exertional dyspnoea
- Paroxysmal nocturnal dyspnoea
Sudden episodes of dyspnoea that occur at night, awakening the patient, typically after 1-3 hours of lying down.
- OrthopnoeaDyspnoea that occurs immediately upon lying down
- Dyspnoea at rest
Symptoms from ↓ cardiac output:
- ↓ Exercise tolerance
- Fatigue
Examination findings:
- Bi-basal fine crepitations on auscultation
- Cardiomegaly → displaced apex beat
- Peripheral hypoperfusion → ↑ CRTCapillary refill time(normally <2 s)Capillary refill time, cold extremities, pallor
Right-Sided Heart Failure
Symptoms from systemic congestion and ↑ CVPCentral venous pressure
- Peripheral oedema
- Ascites → abdominal distention
- Hepatic congestion → RUQ pain and jaundice
- GI congestion → nausea, loss of appetite
Examination findings:
- JVP elevation
- Congestive hepatomegaly
- Hepatojugular reflex
Non-Specific Features
- Tachycardia and various arrhythmias
- Gallop rhythms (diastolic murmurs) can give clues towards the underlying cause:
- S3 heart sound
S3 is an early diastolic sound that occurs just after the second heart sound (S2), during the rapid filling phase of ventricular diastole.
It is generated by the sudden deceleration of blood flow into a compliant or volume-overloaded ventricle, resulting in vibration of the ventricular walls. The S3 can be physiologic in children, young adults, and pregnant women, but in adults over 40, it is most often a marker of pathologic states such as heart failure.
– dilated cardiomyopathy, high-output states - S4 heart sound
S4 is a late diastolic sound that occurs just before the first heart sound (S1), coinciding with atrial contraction and active ventricular filling.
It is generated by the vibration of the ventricular myocardium as blood is forcefully ejected from the atria into a stiff or noncompliant ventricle.
– hypertensive heart disease, HOCM / HCM
- S3 heart sound
- Pulsus alternans
Alternating strong and weak pulse from altering cardiac output.
Investigations and Diagnosis
Diagnostic Tests
1st line: NT-pro-BNP
| NT-pro-BNP level | Next step |
|---|---|
| >2000 ng/L | Refer to specialist and TTETrans-thoracic echocardiography within 2 weeks |
| 400-2000 ng/L | Refer to specialist and TTETrans-thoracic echocardiogram within 6 weeks |
| <400 ng/L | Heart failure less likely, consider alternative diagnosis |
Confirmatory test: transthoracic echocardiography (to also exclude valve disease and intracardiac shunts)
Factors that can affect the interpretation of NT-pro-BNP:
- Causes of ↓ NT-pro-BNP
- Medications – ACE inhibitor, ARB, diuretic, MRA, beta blocker
- Obesity
- African / Afro-Caribbean background
- Causes of ↑ NT-pro-BNP (apart from heart failure)
- >70 y/o
- Renal disease
- COPD
- Diabetes
- Cirrhosis
- Pulmonary embolism
Work Up
A standard heart failure workup includes:
- Chest X-ray
- ECG
- Blood tests (FBC, LFT, U&E, TFT, lipid profile, HbA1c)
- Urinalysis
- Peak flow or spirometry
Management
General / Conservative Management
The following applies to all types of heart failure:
- Offer cardiac rehabilitation
- Avoid potassium-containing salt substitutes
- If patient has excess salt and/or fluid consumption → advise reducing intake (but do not routinely advise salt and fluid restriction)
- Annual influenza vaccination + one-off pneumococcal vaccination
Pharmacological Management
Loop diuretics can be used in all types of heart failure to manage congestion and fluid retention (e.g. dyspnoea, limb oedema)
- Choice of loop diuretic: furosemide, bumetanide (40x more potent than furosemide)
- Note that loop diuretics are NOT disease-modifying (prognostic): they do not reduce disease progression, hospitalisations or mortality
- Their main role is to manage symptoms
Use of other medications depends on the type of heart failure (see classification above).
HFrEF
Step 1 (All Patients)
Offer quadruple therapy of disease-modifying drugs
| Drug class | Licensed drugs (BNF) |
|---|---|
| ACE inhibitors | Perindopril, ramipril, captopril, enalapril, lisinopril |
| Beta blocker | Bisoprolol, carvedilol, nebivolol |
| MRAMineralocorticoid receptor antagonist | Spironolactone, eplerenone |
| SGLT-2 inhibitor | Dapagliflozin, empagliflozin |
If there is intolerance to an ACE inhibitor (e.g. dry cough) (other than angioedema):
- 1st line: switch to ARNIAngiotensin receptor-neprilysin inhibitor (sacubitril valsartan)
- 2nd line: consider switching to ARB (valsartan, losartan, candesartan)
If angioedema develops secondary to an ACE inhibitor → consider switching to ARB (significantly lower risk of angioedema compared to ACE inhibitors)
Prescription information:
- The quadruple therapy should be started one by one over a few weeks, instead of all 4 on the same day (to allow identification of drug intolerance and reduce risk of hypotension, renal impairment, hyperkalaemia etc.)
- Both ACE inhibitors and beta blockers should be titrated up to the maximum tolerated dose (usually increased every 2-4 weeks)
Step 2
Symptomatic despite step 1 quadruple therapy: switch ACE inhibitor to ARNIAngiotensin receptor-neprilysin inhibitor (e.g. sacubitril valsartan)
ACE inhibitors/ARBs should be discontinued for at least 36 hours before starting an ARNI. [Ref]
This washout period is necessary as concomitant use significantly increases the risk of bradykinin-mediated angioedema (higher risk with ACEi to ARNI vs ARB to ARNI).
Step 3 (Specialist Treatment)
| Drug | Indications |
|---|---|
| Ivabradine | Recommended if ALL the following are met:
|
| Hydralazine + nitrate |
|
| Digoxin |
|
All recommended drugs are prognostic (i.e. reduce mortality in HFrEF), except for loop diuretics and digoxin.
Rate-limiting calcium channel blockers (verapamil and diltiazem) should be avoided in HFrEF.
Iron status in HFrEF
NICE recommends assessing iron status, and for anaemia in patients with HFrEF
- Measure: haemoglobin, serum ferritin, transferrin saturation
Consider IV iron therapy if there is anaemia (specifically defined by Hb <150 g/L) PLUS iron deficiency (specifically defined by serum ferritin <100 ng/mL OR transferrin saturation <20%)
- Evidence shows that this improves exercise tolerance and quality of life, with some trials demonstrating reduction in hospitalisation for heart failure
- NB other causes of anaemia should be excluded
- As per ESC guidelines, oral iron is NOT recommended due to poor absorption in heart failure (gut oedema, inflammation), and oral iron failed to improve peak VO2 and exercise capacity in the IRONOUT HF trial [Ref]
Iron deficiency in heart failure can be absolute (depleted total body iron) or functional (adequate stores but impaired mobilisation), and both forms contribute to anaemia and worsen symptoms, exercise capacity, and prognosis.
The pathophysiology is multifactorial and distinct from other causes of anaemia, with iron deficiency often present even in the absence of anaemia. [Ref]
HFmrEF
Consider the same quadruple therapy in HFrEF:
- ACE inhibitors (e.g. perindopril, enalapril, ramipril) (alternative: ARBAngiotensin receptor blocker)
- Beta blocker (e.g. bisoprolol, carvedilol, metoprolol)
- MRAMineralocorticoid receptor antagonist (e.g. spironolactone, eplerenone)
- SGLT2 inhibitor (e.g. dapagliflozin, empagliflozin)
The latest NICE heart failure guideline now recommends that patients with HFmrEF can receive the same prognostic drugs as those with HFrEF. This is a change from previous guidelines, where HFmrEF was managed similarly to HFpEF and did not receive the full suite of disease-modifying (prognostic) therapies.
HFpEF
Consider dual therapy:
- SGLT-2 inhibitor (dapagliflozin or empagliflozin)
- MRAMineralocorticoid receptor antagonist (e.g. spironolactone, eplerenone)
The latest evidence suggests that both SGLT-2 inhibitors and MRAMineralocorticoid receptor antagonist are disease-modifying (prognostic) therapies in HFpEF.
Other drugs have NO prognostic benefits.
Interventional Management
Devices
CRT CRT: cardiac resynchronisation therapy CRT is a specialised pacemaker system allowing biventricular pacing
- NYHA class II-IV despite optimal medical therapy, and
- LVEFLeft ventricular ejection fraction ≤35%, and
- Evidence of ventricular dyssynchrony (wide QRS ≥120 ms with LBBB)
ICDImplantable cardioverter defibrillator main indications:
- Primary prevention: LVEF ≤35%
- Secondary prevention: sustained VT / VF
If the indications for both CRT and ICD are met, a CRT-D is typically implanted.
Disclaimer: only the key indications, and exam-relevant points are mentioned above. These do not reflect the exact guideline recommendations.
Other Interventions
- Coronary revascularisation – do not routinely offer in HFrEF and concurrent coronary artery disease
- Cardiac transplantation – consider in severe refractory symptoms or refractory cardiogenic shock
- LVADLeft ventricular assist devices – to be used as a short-term intervention (typically as a bridge to transplant or recovery)
Heart Failure Pharmacology
ACE Inhibitor / ARNI / ARB / MRA
Blood tests to monitor:
- Renal function (eGFR and serum creatinine), and
- Electrolytes (esp. potassium levels)
Measure the above blood tests in:
- Before starting (baseline)
- 1-2 weeks after starting treatment
- 1-2 weeks after dose changes
- Every 3-6 months once the maximum tolerated dose has been established
- Any time renal function may be compromised
Beta Blockers
ECG (checking for rate, rhythm and conduction abnormalities) should be performed before starting a beta blocker
Do not offer a beta blocker to:
- High degree heart block (2nd / 3rd degree) without a pacemaker
- Heart rate <50 bpm
References
NICE guideline Chronic heart failure in adults: diagnosis and management