Heart failure is the inability of the heart to pump blood adequately around the body leading to reduced tissue oxygenation and fluid congestion. It can be secondary to reduced contraction (systolic heart failure), reduced relaxation (restrictive, heart failure with preserved ejection fraction HFPEF or diastolic heart failure), high output states or compression (constriction/tamponade). Heart failure can be due to dysfunction of the left ventricle, right ventricle or both.

More than 20 million people worldwide suffer from heart failure, and it affects 511,000 (2.1%) Australians per year with 67,000 new cases and 158,000 hospital admissions per year. 1 year heart failure readmission rates are high at 32%. Heart failure costs Australians $3.1 billion annually (Chen et al 2017).

Symptoms of heart failure are proportional to the degree of congestion and reduced perfusion caused by the lack of forward blood flow through the heart. Symptoms often vary depending on whether the left, right or both ventricles are affected.

Left ventricular systolic failure results in fluid overload in the lungs and tissues producing breathlessness and swollen ankles. Low heart output causes reduced tissue blood flow and low blood pressure with symptoms of fatigue, dizziness, confusion and cold extremities.

Right ventricular failure results in congestion of the veins. Patients often complain of breathlessness due to pleural effusions, headache worse on lying flat (Tricuspid valve regurgitation) and symptoms of liver congestion such as bloating, abdominal fullness and right upper abdominal pain. Cardiac weight loss is more often associated with right heart failure due to liver congestion and anorexia due to the substitution of muscle and fat by retained fluid.

The physiology and the anatomy of the right ventricle is completely different from the left ventricle and the symptoms of right and left ventricular failure are different also. The treatment of both should be different too, but all too often they are treated the same, with the same medications, which can often make patients feel worse.

Diastolic heart failure or heart failure with preserved ejection fraction (HFPEF) results in congestion and often presents with breathlessness or swollen ankles similar to systolic heart failure.

Constrictive cardiomyopathy results in signs of right ventricular failure.

There are many different causes of systolic heart failure and it often occurs with multiple co-morbidities. When it is due to heart muscle weakness it is called "cardiomyopathy".

In the Western world, the commonest cause is coronary artery disease (heart attacks) in over 50% of cases. Other common causes are high blood pressure, infective (predominantly viral), heart valve abnormalities, arrhythmias, toxic/drug related (eg chemotherapy, alcohol, cocaine), endocrine (thyroid and diabetes), genetic, infiltrative and connective tissue diseases. When no other cause can be found it is termed “idiopathic”. However, over time as new family members present, idiopathic may be found to be genetic.

The causes of left and right ventricular failure are similar, but there are some conditions predominantly affecting the right ventricle. These include chronic thrombo-embolic disease (blood clots in lung blood vessels), arrhythmogenic right ventricular dysplasia, pulmonary hypertension, left to right cardiac shunts and congenital heart disease.

Restrictive cardiomyopathies are often genetic (hypertrophic cardiomyopathy) or due to infiltration disorders such as cardiac amyloid, sarcoid, haemochromatosis or Fabry’s disease.

Diastolic heart failure or HFPEF can be secondary to stiff scar tissue as a result of myocardial infarction (heat attack) but is more commonly a disease of ageing, particularly hypertensive, diabetic, females.

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Diagnosis starts with a thorough history, particularly assessing risk of coronary artery disease, arrhythmias, genetics, autoimmune disease, infections, endocrine or toxic drug exposure.

Examination helps in establishing whether it is predominantly left sided, right sided or both as well as other possible aetiologies such as valvular, hypertensive or pulmonary hypertension.

Investigations will depend on the clinical scenario. A good starting point is blood tests including kidney and liver biochemistry, full blood count, glucose, thyroid function, Vitamin B12, folate and iron studies. Brain Natriuretic Peptide (BNP or N-Terminal Pro BNP) is a good screening test for heart failure, but is only covered by Medicare for investigation of heart failure in the Emergency department (cost approx. $70). It is useful as a rule out test for heart failure as it has a high negative predictive value.

An ECG, Chest X-ray and transthoracic echocardiogram are easily accessible tests that form the first line of investigation. Up to 20% patients have poor echocardiographic images and may require the use of trans-oesophageal echocardiography, contrast agents or other imaging techniques to elucidate the severity and cause of heart failure.

Coronary angiography either by CT or gold standard invasive technique helps to assess for aberrant coronary anatomy or blocked heart arteries. A left heart study assesses left ventricular function, valvular abnormalities and diastolic dysfunction.

A right heart catheter is often performed to assess fluid status, cardiac function, pulmonary pressures and presence of significant left to right shunts. A fluid challenge may be given to test for diastolic heart failure. If constrictive heart failure is suspected then a simultaneous left and right heart catheter is indicated.

A cardiac biopsy may be performed in cases of suspected myocardial infiltration (sarcoid, amyloid, and haemochromatosis), storage disorders (Fabry’s disease), giant cell myocarditis or eosinophillic myocarditis ^(3-7).

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Treatment depends on the cause and whether the heart failure is acute or chronic, systolic or diastolic and which ventricle is affected; often all conditions co-exist ^(3-7).

Treatment - Systolic Left Ventricular Failure (SLVF)

When assessing patients with heart failure it is useful to ask “are they warm or cold, wet or dry?”

Patients who are warm and dry are the most stable and may allow for up titration of heart failure therapy or reduction of 'water tablets" (diuretics).  Patients who are wet require fluid removal (diuresis) and patients who are cold either require reduction of medications or intravenous drugs that make the heart contract stronger (inotropes). Cold and wet patients are often the sickest, frequently requiring hospital admission.

Lifestyle modification and withdrawal of exacerbating factors or treatment of the underlying causes are essential. Patients should weigh themselves daily in the morning after urinating (1kg=1Litre), have a low salt diet (2g/day) and monitor their fluid input (<2litres/day average or 1.5L/day if wet).

Revascularization with coronary stents or bypass surgery and valve replacements often have a marked beneficial effect.

Diuretics or water tablets (frusemide, bumetanide, hydrochlorothiazide, indapamide, spironolactone, eplerenone) are used for symptom relief in patients who are congested or wet.

Angiotensin converting enzyme inhibitors (ACEi) have been shown to improve survival by 30% in SLVF. These should be commenced at low dose and up titrated frequently (2-4 weekly) to maximum tolerated dose as per dosing guidelines.

Angiotensin 2 receptor blockers (A2RB) should only be used instead of ACEi if patients are allergic or intolerant due to cough. Currently only candesartan, valsartan and losartan have evidence in SLVF. The evidence for adding an A2RB to ACEi is currently conflicting and adding candesartan should only be used when other options are exhausted. Hydralazine (300mg) and oral nitrates (180mg) can be substituted for patient who are intolerant of ACEi/ A2RB, but they are not as beneficial in reducing mortality.

Entresto is a new combination drug (Valsartan and Sacubitril) with improved mortality and morbidity benefits compared to ACEi/A2RB alone but may lower blood pressure more than ACEi/A2RB.

Heart failure β-blockers have been shown to improve survival by a further 30% when added to ACEi/A2RB. β-blockers should only be commenced or up titrated when patients are dry and they can often feel unwell for 2-4 weeks after up titration. More cardio-selective β-blockers (bisoprolol, nebivolol) should be used in patients with low blood pressure, asthma, fatigue and male impotence. β-blockers may also be used for control of arrhythmias such as atrial fibrillation or ventricular tachycardia.

Aldosterone antagonists (spironolactone, eplerenone) also reduce mortality when added to ACEi and beta-blocker therapy for symptomatic patients.

A diabetic medication called SGLT-2 inhibitors (empagliflozin/dapagliflozin) are now part of the 4 Pillars of heart Failure Therapy and used in addition to the above.

Ivabradine is a heart slowing agent and is indicated as an “add on” therapy for SLVF patients in normal rhythm who have a contraindication to, or are on maximum tolerated dose of, beta-blockers with resting heart rate > 70/min.

Fish oils 3000mg daily (850mg/day DHA/EPA) have been shown to reduce mortality by 2% over 4 years. There is no evidence for Krill or Calamari oil.

Routine use of aspirin or warfarin has not been shown to improve outcomes in SLVF unless indicated for other comorbidities. Warfarin can be considered in severely dilated and impaired SLVF or if a blood clot is present within the Left ventricle.

Both cardiac resynchronization therapy (CRT) and prophylactic implantable cardioverter-defibrillator (ICD) devices have been shown to reduce mortality in SLVF.

Iron (carboxymaltose) infusions have been shown to improve morbidity but not mortality in SLVF patients with functional iron deficiency, even without anaemia.

For end-stage SLVF, mechanical support with devices such as a left ventricular assist device (LVAD) or heart transplantation may be required. The average survival post heart transplantation in Australasia is 12-14 years.

Treatment - Diastolic Heart Failure/ Restrictive Cardiomyopathy/ Constrictive Cardiomyopathy

Currently the only treatments of benefit in diastolic heart failure are SGLT-2 inhibitors (empagliflozin/dapagliflozin) and spironolactone. Good fluid balance, low salt intake, blood pressure control and maintenance of normal rhythm are paramount. There is no evidence for the use of ACEI, A2RB, β-blockers, Entresto, nitrates, hydralazine or sildenafil. However, exercise and weight loss are also beneficial.

In constrictive cardiomyopathy, diuretics may improve symptoms but the only definitive treatment is pericardiectomy.

Treatment – Systolic Right Ventricular failure (SRVF)

There is no evidence for the use of ACEI, A2RB or β-blockers in isolated SRVF. The only treatments are diuretics with aldosterone antagonists, digoxin, pulmonary vasodilators and inotropes.

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Prior to the discovery of ACEi, A2RB, β-blockers, Entresto, SGLT-2 inhibitors and devices, the mortality at 1 year from heart failure was approximately 50%; the same as for lung cancer. That figure has now reduced to around 10% per annum but is higher in patients presenting with severe symptoms.

Outcome for SLVF can roughly be classified into 3 even groups: a) full recovery, b) partial recovery or c) no recovery or deterioration. Recovery can often take up to 2 years but most occurs within the first 3-6 months. Ischaemic cardiomyopathy patients may have less recovery due to scar tissue.

Regarding medication cessation, patients should be advised to continue therapy with ACEi/A2RB and β-blockers lifelong once recovery occurs as a recent study showed significant re-deterioration within 6 weeks of cessation.

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Entresto™

Entresto™ (Valsartan / Sacubitril) is a new combination of an angiotensin II receptor blocker and a novel neprilysin inhibitor, sometimes called an ARNI. When compared to enalopril in the PARADIGM-HF study there was a 16% relative risk reduction in all cause death.

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