6th March 2024

Heart Failure

Heart failure

Pathophysiology

Heart failure (HF) is a syndrome which occurs when cardiac output is unable to meet the perfusion needs of the body. Damage or overload to the heart muscle plays a part in the pathogenesis. The normal response to increased ventricular volumes is to increase the force of contraction. This increases the cardiac output (CO) and is known as the Frank-Starling law. In a person with HF, this mechanism fails, leading to tissue hypoperfusion and chronic activation of the renin-angiotensin-aldosterone-system (RAAS). Over time, this leads to fluid retention and left ventricular dilation. The prognosis of HF is poor and approximately 50% of patients are dead within 5 years. 

Clinical manifestations 

Recognising that each ventricle supplies different parts of the circulation, signs and symptoms can be divided into left and right sided. The left ventricle (LV) supplies systemic circulation and failure results in congestion into the lungs, producing predominantly respiratory symptoms: frothy cough, dyspnoea, tachypnoea and crackles auscultated at lung bases. Dyspnoea may be worse when lying flat (orthopnoea) or wake the person up in the night (paroxysmal nocturnal dyspnoea). Fatigue and reduced exercise tolerance occur as a result of insufficient oxygen supply. LV volume overload eventually results in hypertrophy and lateral displacement of the apex beat.  

In right sided HF venous congestion will manifest with peripheral oedema, ascites, hepatosplenomegaly and jugular venous pressure (JVP) distension, all of which contribute to progressive dyspnoea. Increased right ventricle (RV) pressure may be demonstrated by a parasternal heave due to the increased strength of contraction. 

Congestion may impact the synthetic function of the liver, resulting in hypoalbuminemia and decreasing the oncotic pressure. This leads to oedema as fluid is retained within tissues and not reabsorbed into the capillaries. 

A combination of venous congestion, chronic RAAS activation due to renal hypoperfusion and hypoalbuminemia contribute to water retention and fluid build-up in tissues. The resulting peripheral oedema is dependent, affecting the feet and ankles of people who are mobile and the sacrum of people who are sitting or lying down.  

Early manifestations are present on exertion leaving the patient relatively symptom free at rest. As the condition progresses, affected people will have both right and left sided symptoms in congestive cardiac failure (CCF). Advanced HF results when people experience severe symptoms interfering with daily life despite maximum (medical plus cardiac resynchronisation) therapy.  

Symptom severity can be categorised using the New York Heart Association (NYHA) functional classification (Table 1).

Table 1: New York Heart Association (NYHA) Functional Classification

Diagnostics

Diagnosis of HF requires signs and symptoms with objective evidence of cardiac dysfunction, usually through an echocardiogram. A 12 lead ECG may show atrial fibrillation, Q waves, widened QRS or left ventricular hypertrophy (LVH). 

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels above 125 pg/mL or BNP > 35pg/mL warrants echocardiography to confirm HF and HF phenotype based on LV ejection fraction (LVEF):

LVEF <40% is defined as HF with reduced ejection fraction (HFrEF). 

LVEF 41-49% is defined as HF with mildly reduced ejection fraction (HFmrEF) 

LVEF > 50% is defined as HF with preserved ejection fraction (HFpEF). 

Blood tests, including urea and electrolytes, full blood count, liver function tests, HbA1C, fasting lipids, iron studies and thyroid function tests, can help to differentiate HF from other conditions. A chest x-ray is recommended to exclude other diagnoses, such as pulmonary disease, and may show findings supporting HF, such as cardiomegaly or upper lobe diversion. 

Management

RAAS and the sympathetic nervous system are modulated with angiotensin-converting enzyme inhibitors (ACE-I) or an angiotensin-neprilysin inhibitors (ARNI), beta blockers and mineralocorticoid receptor antagonists (MRA). These have shown to improve survival, reduce hospitalisation due to worsening HF and reduce symptoms in patients with HFrEF. 

Sodium-glucose co-transporter 2 (SGLT2) inhibitors dapagliflozin and empagliflozin are recommended for all patients with HFrEF already receiving ACE-I/ARNI, beta blocker and MRA, regardless of whether or not they have diabetes. Fluid retention is managed with diuretics and recommended in congested patients with HFpEF to alleviate symptoms.

In patients who are symptomatic despite ACE-I/ARNI, beta blocker and MRA, Ivabradine an inhibitor of the cardiac pacemaker current (If) should be considered if LVEF <35% and the patient is in sinus rhythm with a resting heart rate > 70 beats per minute.

Cardiac resynchronisation therapy (CRT) is recommended for symptomatic HF patients on maximal pharmacotherapy who are in sinus rhythm with a QRS duration of > 150ms with LBBB and LVEF < 35%. 

Vericiguat, an oral soluble guanylate cyclase stimulator, has been shown to reduce the risk of cardiovascular mortality and hospitalisations due to HF and may be considered in addition to standard therapy for HFrEF. 

References

• National Institute for Health and Care Excellence (UK). Heart failure – chronic. How should I assess a person with suspected chronic heart failure? Last revised August 2021. Available at https://cks.nice.org.uk/topics/heart-failure-chronic/diagnosis/how-to-assess/
• UpToDate. Clinical Manifestations and Diagnosis of Advanced Heart Failure. Last updated 7th April 2020. Available at https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-advanced-heart-failure?source=history_widget
• European Society of Cardiology. 2021 ESC Guidelines for The Diagnosis and Treatment of Acute and Chronic Heart Failure. 27th August 2021. Available at https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Acute-and-Chronic-Heart-Failure