Dr Byung-Su Yoo
Cardiologist/ Professor, Division of Cardiology, Wonju College of Medicine, Yonsei University, Korea

Clinical Cases from Korea: NT-proBNP for Differential diagnosis of patients with dyspnoea


70-year old man

Key signs and symptoms

Fever, Cough, Sputum, and Diarrhea for 3 days
Chest discomfort or shortness of breath (-)
Edema (-)
Pneumonia without Cardiomegaly

Medical history

COVID-19 positive (3 days ago)
Hypertension (+)

Clinical examination

Dyspnea on exertion/Paroxysmal nocturnal dyspnea (-/-) (PND)
Rapid Heart Beat without murmur
Crackles in both lung fields

Laboratory test results

Test Value Reference Range
PO2, Blood 65.6 mmHg 83.0~108.0 mmHg
PCO2, Blood 31.3 mmHg 32.0~45.0 mmHg
Hb (hemoglobin) 11.7 g/dL 13.5~17.0 g/dL
Cr (creatinine) 0.76 mg/dL 0.20~1.30 mg/dL
CK-MB 3.58% < 5.0%
hs Troponin I 80 ng/L 0.00~45.43 ng/L
NT-proBNP 200 pg/mL < 125 pg/mL
D-Dimer 278 ng/mL 0~325 ng/mL


Chest PA shows pneumonic consolidation
on both lower lung fields


ECG is normal sinus rhythm without other abnormality

Dr Yoo Clinical Case - 1

What should be done next considering the COVID-19 infection status?

Author’s opinion

  • In the ICON study NT-proBNP was a valuable tool for the diagnosis of acute heart failure with the age-independent “rule-out” cut-off of 300pg/mL which had very high sensitivity and the age-stratified triple “rule-in” cut-points of 450 pg/mL (< 50 years) 900 pg/mL (50-75 years) and 1800 pg/mL (>75 years) demonstrating a high sensitivity and specificity. 1

  • This case demonstrated NT-proBNP is useful to rule out the diagnosis of heart failure in the acute setting when the diagnosis is inconclusive based on the clinical information.

  • NT-proBNP at 125 pg/mL is a cut off value for patients suspicious of heart failure in the non-acute setting, the age stratified cut off values should be used in acute setting.2

  • Patients with COVID-19 often demonstrate significant elevation of NT-proBNP. The significance of this finding is uncertain and should not necessarily trigger an evaluation or treatment for heart failure unless there is clear clinical evidence for the diagnosis (such as clinical signs and symptoms).3

  1. Januzzi, et al, Eur H Jour 2006; 27:330
  2. Mueller C, et al, Eur J Heart Fail. 2019 Jun; 21(6):715-731
  3. Troponin and BNP use in COVID-19, ACC Cardiology Magazine, March 18, 2020 https://www.acc.org/latest-in-cardiology/articles/2020/03/18/15/25/troponin-and-bnp-use-in-covid19

38-year old woman

Key signs and symptoms

Exertional dyspnea for 2 weeks
Sudden dyspnea developed 1 day ago

Medical History

Major depression without medication
Bed–ridden lifestyle

Clinical examination

BP 132/87 mmHg
RR 23/min

Laboratory test results

Test Value Reference Range
PO2, Blood 54.1 mmHg 83.0~108.0
PCO2, Blood 23.0 mmHg 32.0~45.0
Hb (hemoglobin) 14.6 g/dl 13.5~17.0
Cr (creatinine) 0.81 mg/dl 0.20~1.30
CK-MB 0.58 ng/ml < 5.0
Troponin I 2.50 pg/ml 0.00~45.43
NT-proBNP 389 pg/mL < 125
D-Dimer > 17600 ng/ml 0~325


Chest AP shows left pleural effusion


ECG shows sinus tachycardia

Pulmonary CT

Pulmonary CT shows thrombotic
occlusion in both pulmonary trunks


Echocardiography shows enlarged RV and movable thrombus in RA  
Dr Yoo Clinical Case - 2

What is the diagnosis of this case?

Author’s opinion

  • Acute Heart Failure (AHF) is one of the common causes for NT-proBNP elevation.

  • For patients suspected of AHF, when NT-proBNP levels are within the normal range it makes the diagnosis highly unlikely. (thresholds: NT-proBNP < 300pg/mL)11

  • The elevated levels of NPs do not automatically confirm the diagnosis of AHF, as they may also be associated with a wide variety of cardiac and non-cardiac causes.1 In addition, we think about acute conditions associated with elevated NP levels other than CHF are as follows: renal failure, pulmonary disease and pulmonary embolism, older age, liver cirrhosis, and sepsis.1

  • In acute setting with suspected heart failure, we have to consider causes of AHF (CHAMP: acute coronary syndrome, hypertensive emergency, arrhythmia, acute mechanical causes, pulmonary thromboembolism).2

  • Plasma NT-proBNP is elevated in the majority of cases of pulmonary embolism resulting in right ventricular overload.

  • Plasma NT-proBNP levels reflect the degree of right ventricular overload and may help to predict short-term outcomes.

  • Acute pulmonary embolism should be considered in the differential diagnosis of patients with dyspnea and abnormal levels of natriuretic peptide.

  1. Januzzi et al, Eur H Jour 2006; 27:330
  2. Ponikowski P et al 2016 Eur J Heart Fail 2016; 18:891–975

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