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(2) Measurement of NPs are recommended, if available. A plasma concentration of B-type natriuretic peptide (BNP) <35 pg/mL, N-terminal pro-B-type natriuretic peptide (NT-proBNP) <125 pg/ mL, or mid-regional pro-atrial natriuretic peptide (MR-proANP) <40 pmol/L68 make a diagnosis of HF unlikely. These will be discussed in more detail in section 4.2.69,70 (3) Basic investigations such as serum urea and electrolytes, creatinine, full blood count, liver and thyroid function tests are recommended to differentiate HF from other conditions, to provide prognostic information, and to guide potential therapy. (4) Echocardiography is recommended as the key investigation for the assessment of cardiac function. As well as the determination of the LVEF, echocardiography also provides information on other parameters such as chamber size, eccentric or concentric LVH, regional wall motion abnormalities (that may suggest underlying CAD, Takotsubo syndrome, or myocarditis), RV function, pulmonary hypertension, valvular function, and markers of diastolic function.16,71 (5) A chest X-ray is recommended to investigate other potential causes of breathlessness (e.g. pulmonary disease). It may also provide supportive evidence of HF (e.g. pulmonary congestion or cardiomegaly).

4.2 Natriuretic peptides

Plasma concentrations of NPs are recommended as initial diagnostic tests in patients with symptoms suggestive of HF to rule out the diagnosis. Elevated concentrations support a diagnosis of HF, are useful for prognostication,72 and may guide further cardiac investigation.73 However, it should be noted that there are many causes of an elevated NP—both CV and non-CV—that might reduce their diagnostic accuracy (Table 7). These causes include AF, increasing age, and acute or chronic kidney disease.74 Conversely, NP concentrations may be disproportionately low in obese patients.75 4.2.1 Use in the non-acute setting The diagnostic value of NPs, in addition to signs and symptoms and other diagnostic tests, such as an ECG, has been assessed in several studies in the primary care setting.68,7680 The aim of these studies was to either exclude or establish a diagnosis of HF. The Task Force considered studies of adequate quality that included NP cut-off points in their diagnostic algorithms, below which the probability of having HF was extremely low. The upper limits of normal in the non-acute setting are 35 pg/mL for BNP, and 125 pg/mL for NT-proBNP. In these studies, the negative predictive values of NP concentrations below these thresholds range from 0.94 to 0.98.7678 Fewer data are available for MR-proANP in CHF than in AHF. A concentration of <40 pmol/L can be used to rule out HF.68

4.3 Investigations to determine the

underlying aetiology of chronic heart failure Recommended tests to determine the underlying aetiology of CHF are summarized in Table 5.

Recommended diagnostic tests in all patients with suspected chronic heart failure

Recommendations Classa Levelb BNP/NT-proBNPc I B 12-lead ECG I C Transthoracic echocardiography I C Chest radiography (X-ray) I C Routine blood tests for comorbidities, including full blood count, urea and electrolytes, thyroid function, fasting glucose and HbA1c, lipids, iron status (TSAT and ferritin) I C

BNP = B-type natriuretic peptide; ECG = electrocardiogram; HbA1c = glycated haemoglobin; NT-proBNP = N-terminal pro-B-type natriuretic peptide; TSAT = transferrin saturation. aClass of recommendation. bLevel of evidence. cReferences are listed in section 4.2 for this item. Table 6 Symptoms and signs typical of heart failure

Symptoms Signs Typical More specific Breathlessness Orthopnoea Paroxysmal nocturnal dyspnoea Reduced exercise tolerance Fatigue, tiredness, increased time to recover after exercise Ankle swelling Elevated jugular venous pressure

Hepatojugular reflux Third heart sound (gallop rhythm) Laterally displaced apical impulse

Less typical Less specific Nocturnal cough Wheezing Bloated feeling Loss of appetite Confusion (especially in the elderly) Depression Palpitation Dizziness Syncope Bendopneaa Weight gain (>2 kg/week)

Weight loss (in advanced HF) Tissue wasting (cachexia) Cardiac murmur Peripheral oedema (ankle,

sacral, scrotal) Pulmonary crepitations Pleural effusion Tachycardia Irregular pulse Tachypnoea Cheyne-Stokes respiration Hepatomegaly Ascites Cold extremities Oliguria Narrow pulse pressure

HF = heart failure. aThis symptom of advanced HF corresponds to shortness of breath when leaning forward.67

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