24th April 2024

Heart Failure

Heart failure (HF) is a clinical syndrome caused by structural and/or functional abnormality that produces raised intracardiac pressures and/or inadequate cardiac output. It affects 1-2% of adults in Europe and prevalence increases with age. HF is classified into phenotypes using the left ventricular ejection fraction (LVEF). This is important when it comes to the medical management: 

• LVEF of 40% or less is HF with reduced ejection fraction (HFrEF).
• LVEF 41-49% is HF with mildly reduced ejection fraction (HFmrEF). 
• LVEF >50% with symptoms of HF is HF with preserved ejection fraction (HFpEF). 

There are many causes of HF, including medications such as NSAIDs (through sodium and water retention) and non-dihydropyridine calcium channel blockers (through their negative inotropic effects). The remainder of this section will focus on prescribing in HF as there is a dedicated section on HF.

Management 

Non pharmacological treatment includes reduced dietary salt intake, exercise-based rehabilitation programmes, smoking cessation and moderating alcohol intake. 

ACE inhibitors (ramipril, enalapril), beta blockers (bisoprolol, metoprolol), SGLT-2 inhibitors (dapagliflozin, empagliflozin) and MRA (spironolactone, eplerenone) are indicated in HFrEF as these medications have been shown to reduced morbidity and mortality. 

When starting ACE inhibitors, blood pressure and renal function should be measured at baseline, 1-2 weeks after initiation and after any dose adjustments. A dry cough is reported in 4-35% of patients taking ACE inhibitors and may occur any time after starting treatment. It can be managed by switching to an angiotensin-II receptor antagonist (ARB) such as losartan. Other side effects of ACE inhibitors include first dose hypotension and angioedema.  

In HFrEF with NYHA class II, III or IV symptoms, ACE-i/ARB can be replaced with an angiotensin receptor/neprilysin inhibitor (ARNI) such as sacubitril/valsartan. This should be initiated after a wash-out period where ACE inhibitor or ARB is stopped. 

Other adjunct therapies include loop diuretics (furosemide, bumetanide) and ivabradine in those in sinus rhythm with a heart rate over 75 bpm and an ejection fraction less than 35%. Digoxin may provide symptomatic relief through positive inotropic and negative chronotropic effects but it has no effect on mortality. Medications such as hydralazine in combination with ISDN can be beneficial in people of African-Caribbean descent.

Vericiguat is a novel oral agent used in symptomatic chronic HFrEF. It does not prolong survival but reduces HF related rehospitalisation and the need for outpatient intravenous diuretics. 

Patients may also benefit from an antiplatelet and statin therapy based on their cardiovascular risk assessment and should be offered an annual influenza vaccine. 

Device therapy with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronisation therapy (CRT) may be considered in selected patients who remain symptomatic despite optimal medical management with LVEF ≤35%, LBBB and/or prolonged QRS.

Management in HFmrEF and HFpEF is aimed at managing modifiable cardiovascular risk factors; improving functional status, reducing symptoms and hospitalizations related to HF. This includes the use of diuretics to improve congestion and the use of sequential nephron blockade using thiazide/thiazide like diuretics and MRAs in diuretic resistance. 

Although RCTs involving ACE-i, ARB, MRA and ARNI have not shown mortality benefit in HFmrEF, selected patients may still be prescribed such medications to reduce rehospitalization particularly those with LVEF toward the lower end of the range. 

An SGLT-2 inhibitor is recommended by the European Society of Cardiology, to reduce HF related hospitalisations and cardiovascular death.

Digoxin 

Digoxin is a cardiac glycoside that increases the force of myocardial contraction and reduces conductivity within the atrioventricular node. Contractility is enhanced via inhibition of the myocardial Na-K ATPase pump, which leads to increased intracellular sodium and calcium in the heart.  Stimulation of the parasympathetic nervous system inhibits the AV node, reducing the heart rate. Digoxin is used for rate control in atrial fibrillation or flutter and symptomatic relief (rather than mortality benefit) in heart failure. 

Digoxin monitoring is not routinely indicated unless toxicity is suspected where levels should be taken 8-12 hours post-dose. Note that toxicity can occur with serum digoxin concentrations within the therapeutic range. Features suggestive of digoxin toxicity include confusion, nausea, anorexia, disturbance of colour vision, and cardiac conduction disturbances. Several factors can precipitate toxicity, including hypokalaemia, renal impairment, hypoalbuminemia and concurrent prescribing of medications (amiodarone, antimicrobials, calcium channel blockers, chloroquine, spironolactone). 

References

• NICE. Chronic Heart Failure. Accessed 1 February 2024. From: https://cks.nice.org.uk/topics/heart-failure-chronic/
• BMJ Best Practice. Heart Failure with Reduced Ejection Fraction. Accessed 1 February 2024. From https://bestpractice.bmj.com/topics/en-gb/61/management-approach
• Jasinska-Piadlo A, Campbell P. (2003) ‘Management of patients with heart failure and preserved ejection fraction’. Heart 2023;109:874-883. 
• NICE, Digoxin. Accessed February 1 2024. From: https://cks.nice.org.uk/topics/atrial-fibrillation/prescribing-information/digoxin/