Heart Failure Diagnosis: NT-proBNP, ECG, Echo and Staging

Heart failure is diagnosed with a natriuretic peptide test, a 12-lead ECG and an echocardiogram, in that order of priority. If the BNP or NT-proBNP level and the ECG are both normal, acute heart failure is very unlikely and an echocardiogram is not needed to exclude it. If either is abnormal, a transthoracic echocardiogram confirms the diagnosis and classifies the heart failure by ejection fraction.

Dr. Rajpal Singh R L, Director Cardiology, Fortis Hospitals, Bannerghatta Road, Bangalore, India, built his teaching on detection around the ESC (European Society of Cardiology) 2021 guidelines and the 2023 focused update. His central point for physicians was that heart failure can be found earlier than most doctors find it, with tests that are widely available, and that the earlier it is found, the more there is to gain. This article covers the diagnostic algorithm, the role of natriuretic peptides, classification by ejection fraction, the four stages of heart failure, the investigations that establish the cause, and the prevention that keeps at-risk patients from progressing. The complete guide to heart failure detection and management gives the overall pathway, and the four pillars article covers treatment.

How heart failure is diagnosed: the ESC algorithm

Heart failure is diagnosed in four steps: clinical assessment, an ECG, a natriuretic peptide level and, if either test is abnormal, an echocardiogram. For a patient with shortness of breath, the guideline algorithm Dr. Singh presented runs as follows:

1. Clinical assessment: history, symptoms and risk profile, followed by physical examination.
2. A 12-lead ECG.
3. A natriuretic peptide level: BNP (B-type natriuretic peptide) or NT-proBNP (its N-terminal fragment). Both are useful; use whichever is easily available.
4. A transthoracic echocardiogram if the natriuretic peptide is raised or the ECG is abnormal.

A chest X-ray and routine biochemistry support the assessment. If the natriuretic peptide is normal and the ECG is normal, acute heart failure has been more or less ruled out as the cause of the symptoms, and the clinician should look elsewhere. If either is abnormal, the echocardiogram is the next step, and once heart failure is confirmed the clinician classifies it and looks for its cause and any precipitating factors.

Dr. Singh recognised that echocardiography may not be easily available in every practice. He encouraged physicians with an interest in cardiology to learn it, noting that a focused course of two to three weeks is enough to learn what to look for on an echo and to start diagnosing these patients locally.

Why NT-proBNP comes before the echo

NT-proBNP and BNP come first because a normal result, together with a normal ECG, makes acute heart failure unlikely without an echocardiogram. Natriuretic peptides are released by the heart muscle in response to stretch or stress. When the ventricle is under strain, from left ventricular failure or congestive cardiac failure, levels rise. A normal level therefore means there is no significant myocardial stress, which makes a cardiac cause for breathlessness unlikely. Levels can also be raised by other conditions, including kidney dysfunction, atrial fibrillation and older age, so a raised result has to be read in context.

That is what makes the test so useful at the front door. In established ESC thresholds for the acute setting, an NT-proBNP below 300 pg/mL or a BNP below 100 pg/mL makes acute heart failure unlikely. In the non-acute, outpatient setting the rule-out thresholds are lower: an NT-proBNP below 125 pg/mL or a BNP below 35 pg/mL makes chronic heart failure unlikely. Each assay has its own reference values, so results should always be read against the test actually used. A raised level means the patient needs further assessment and treatment.

The guidelines recommend natriuretic peptides in several roles, and for diagnosis and exclusion the recommendation is class I:

• Diagnosis and exclusion in patients presenting with breathlessness. Dr. Singh pointed out a benefit that is easy to overlook: a normal result also takes the worry of heart failure off the patient's mind.
• Risk stratification in established heart failure. A baseline level, repeated at each admission, identifies patients at higher risk: those with persistently raised levels face a higher risk of worsening heart failure and cardiac death.
• Monitoring during admission. Comparing the level at admission and at discharge shows whether treatment is working.
• Screening patients at risk before symptoms appear, and deciding which recently hospitalised patients need closer follow-up.

In Dr. Singh's heart failure clinic, NT-proBNP is measured at every visit, alongside creatinine and haemoglobin. A falling level confirms the patient is settling; a spike prompts the question of whether fluid is reaccumulating and what can be done about it.

Cardiac or respiratory breathlessness?

The same logic separates heart failure from lung disease. In a breathless patient with a normal BNP and a normal ECG, the chance that heart failure is the cause of the acute deterioration is very small, and the cause is likely to be non-cardiac, for example respiratory. A raised level points towards the heart and justifies the echocardiogram.

HFrEF, HFmrEF and HFpEF: classifying heart failure by ejection fraction

Heart failure is classified by ejection fraction into three groups: reduced (40% or less), mildly reduced (41 to 49%) and preserved (50% or more). Dr. Singh was firm that the terms "systolic dysfunction" and "diastolic dysfunction" are old jargon. Current guidelines classify heart failure by the left ventricular ejection fraction (EF), the percentage of blood the left ventricle pumps out with each beat:

Patients once described as having "diastolic heart failure" now fall under HFpEF; diastolic dysfunction on an echo without the clinical syndrome is not heart failure. The category matters because the strongest drug and device evidence applies to HFrEF.

The four stages of heart failure

The four stages of heart failure run from A (at risk) and B (structural disease without symptoms) to C (symptomatic) and D (advanced). The staging system describes heart failure as a progression, and Dr. Singh used it to define the role of the physician: catch patients as early as possible and stop them moving to the next stage.

Stage A: at risk

Stage A patients have no symptoms and no structural heart disease, but carry a high-risk profile. Dr. Singh's list:

• obesity
• hypertension
• diabetes
• a family history of premature vascular disease or of cardiomyopathy
• a previous myocardial infarction or unstable angina
• exposure to cardiotoxic chemotherapy
• smoking and heavy alcohol intake

For these patients he recommends an ECG, an echocardiogram and an NT-proBNP. If all three are normal, the patient has not developed heart failure, but that is not the end of it: he asks them to return once a year for the same checks. Heart failure is dramatic in some patients, but in most it is insidious, particularly in people with diabetes or obesity, smokers and heavy drinkers, who often do not notice it until it hits them.

Stage B: pre-heart failure

Stage B patients have structural heart disease with few or no symptoms. Rheumatic mitral stenosis or mitral regurgitation is a typical example: filling pressures are raised before symptoms appear. A raised natriuretic peptide in such a patient shows that heart failure is developing even without symptoms, and picking it up and treating it at this point makes a large difference.

Stage C: symptomatic heart failure

Stage C covers patients with current or past symptoms, presenting either acutely or with chronic symptoms. This is the group in which the four pillars of drug therapy are started.

Stage D: advanced heart failure

Some patients miss every earlier opportunity and present late, with orthopnoea (breathlessness lying flat), paroxysmal nocturnal dyspnoea (waking at night breathless) and repeated hospital admissions. These patients need specialist assessment for the options described in the article on referral for ICD, CRT, LVAD or transplant.

Tests to find the cause of heart failure

Once heart failure is suspected or confirmed, the cause has to be found, because some causes are reversible. Dr. Singh asks whether anaemia, alcohol-related toxicity, renal failure or thyroid disease (hypothyroidism or hyperthyroidism) is contributing, alone or in combination. His baseline panel for most patients:

• full blood count
• renal function
• liver function tests
• thyroid function tests
• 12-lead ECG
• echocardiogram

When coronary disease or a rarer cause is suspected

Patients with an abnormal ECG and a history of exertional angina should be evaluated early for coronary artery disease, with an invasive coronary angiogram, a myocardial perfusion scan, a CT coronary angiogram or a cardiac MRI. Dr. Singh's advice is to involve a cardiologist once the baseline tests are done, to decide which of these is needed.

A family history of premature vascular disease or heart failure raises the possibility of an inherited cardiomyopathy, such as hypertrophic cardiomyopathy. Where there is a family history of sudden cardiac death, or a non-ischaemic cardiomyopathy in a young patient, genetic counselling and testing should be considered. Genetic testing for cardiomyopathies is now widely available, and first-degree relatives of a patient with cardiomyopathy should be screened early.

Dr. Singh illustrated why a thorough work-up matters with a case from his own practice. A man first had a pacemaker for apparent sinus node disease about ten years earlier, when his echocardiogram was normal. Over the following years he developed heart failure; an angiogram showed a circumflex artery narrowing, which was stented. When he returned with ventricular tachycardia, a repeat angiogram showed a patent stent and no new coronary disease, yet his left ventricle was globally impaired. A cardiac MRI showed absent perfusion in a territory whose artery had no narrowing, and an FDG PET-CT then pointed to cardiac sarcoidosis. The lesson, in his words, is that these surprises happen, and in younger patients the full evaluation is worth doing.

Heart failure follow-up: ECG and NT-proBNP every six to twelve months

For stable heart failure patients, Dr. Singh asks physicians to repeat two tests every six months to a year: an ECG and an NT-proBNP. Together they show how the patient is doing electrically and haemodynamically.

• NT-proBNP rises with silent worsening of heart failure, before the patient notices symptoms.
• The ECG changes as myocardial fibrosis progresses. A patient with a normal QRS complex may develop a broadening QRS and then a right or left bundle branch block. Optimal treatment slows this progression, but does not always stop it.

The ECG matters because it drives the device decisions: a low ejection fraction with a broad QRS identifies patients at high risk of sudden cardiac death who may benefit from a defibrillator or resynchronisation therapy.

Preventing heart failure in patients at risk

Prevention is where Dr. Singh sees the greatest leverage for the general physician, because once heart failure is established it is much harder to treat.

Risk factors first. Overweight, hypertension, diabetes, heavy alcohol intake and smoking should be addressed early. Left untreated, they lead in time to a dilated or, more often, an ischaemic cardiomyopathy.

Hypertension. In a hypertensive patient with an ejection fraction below 40%, the first antihypertensive should be an ACE inhibitor or an angiotensin receptor blocker, which improves asymptomatic left ventricular dysfunction and reduces mortality. In hypertensive patients with heart failure and a reduced ejection fraction, it should be combined with a beta blocker and a mineralocorticoid receptor antagonist, which treats the blood pressure and the heart failure together. Dr. Singh expects the evidence for ARNIs as first-line therapy to strengthen in future guideline updates.

Diabetes. SGLT2 inhibitors should be used early. Metformin used to be the universal first drug; in people with diabetes and established cardiovascular disease, heart failure or chronic kidney disease, guidelines now recommend an SGLT2 inhibitor regardless of metformin use or glucose level.

Established cardiovascular disease. Lipids, glucose and blood pressure should be controlled, with antiplatelet therapy and statins where indicated. Statins have no proven benefit for heart failure itself, but there is no evidence that they worsen it, so most of Dr. Singh's patients remain on one.

Cancer treatment. Growing numbers of patients receive cardiotoxic cancer drugs. Dr. Singh advises a multidisciplinary approach involving the oncologist and a cardiologist with a specific interest in cardio-oncology, rather than any cardiologist.

Monitoring. Patients identified as at risk need lifestyle education and change, and periodic natriuretic peptide testing to catch the first sign of progression.

Physicians who want to compare perspectives can read Dr. Biswarup Purkayastha's guide to heart failure and coronary artery disease in African patients, and Dr. Singh's answers to doctors' questions on BNP during the session are in the Live Discussion. Related material is in the cardiology specialty hub.