Determining the cause of breathlessness – how blood testing can help

Dyspnea (alternative names: breathlessness and shortness of breath) is a common reason for individuals to seek medical help either in primary care or the hospital emergency room.

The possible causes are legion, so that assessment of the patient complaining of breathlessness is a common and often difficult diagnostic challenge. As this recently published review article makes clear, laboratory testing has a role in meeting this clinical challenge.

The main focus of this paper is three blood tests with proven value in the assessment of acute dyspnea: brain natriuretic peptide (BNP), cardiac troponins, and D-dimer.

By way of introduction to this main focus, the authors briefly discuss dyspnea in general terms, revealing for example, that dyspnea is defined as the ”subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity”. 

They make the point that dyspnea is a normal response to intense physical exertion but is pathological if it occurs in the context of minimal or absent exertion. It is, apparently, the chief complaint for approximately 4 million emergency room visits in the US, which amounts to 3.5 % of all such visits.

The focus on BNP in this article is an acknowledgement that this test, along with related N-terminal-proBNP (NT-proBNP) test, is currently the gold standard blood test for diagnosis/exclusion of heart failure, a common condition – especially among the elderly – whose chief presenting symptom is dyspnea. 

The authors discuss the physiological (hormonal) function of BNP as well as its cardiac origin and the mechanism of normal release of BNP from ventricular cardiac cells to blood in response to ventricular wall distension. They explain the distinction between BNP (active hormone) and NT-proBNP (inactive pro-hormone peptide) and the renal and non-renal routes for elimination of both. 

There follows extended discussion of the evidence base for, and the detail of, application of BNP/NT-proBNP measurement for excluding/including a diagnosis of heart failure among patients with dyspnea. The second main focus of the article, cardiac troponins I and T (cTnT and cTnI), is an acknowledgement that dyspnea can be the sole presenting symptom of myocardial infarction. 

This section includes a full discussion of the established role of cardiac troponin measurement for exclusion/inclusion of a diagnosis of myocardial infarction. The application of high-sensitive cTnT and cTnI assays, allowing speedier MI diagnosis is highlighted. 

The final part of this section is devoted to discussion of some other cardiac and non-cardiac causes of increased cardiac troponins that are commonly associated with dyspnea (e.g. heart failure, pulmonary embolus, and acute exacerbation of chronic obstructive pulmonary disease (COPD)).

The third main focus of the article, the D-dimer test, is an acknowledgement that dyspnea is the most common presenting feature of pulmonary embolus (PE). The authors discuss the way in which the D-dimer test is used to exclude a diagnosis of PE. 

This includes a pretesting clinical assessment that determines the probability of PE. As the authors explain only those with low probability of PE are generally submitted for D-dimer testing; a normal result under these circumstances reliably excludes a diagnosis of PE. 

Apart from BNP/NT-proBNP, cardiac troponins and D-dimer, the authors also briefly discuss the value of blood gas analysis in the assessment of the dyspneic patient, and three novel biomarkers that have potential, but as yet unproven value, in elucidating the cause of dyspnea.