Association between dyspnea, chest pain, nt-probnp and cardiac impairment in people with cystic fibrosis
Authors: Flarup Dons M , Steen Duus L , Faber Thudium R , Dam Nielsen S , Olsen M F , Qvist T , Lassen M C H , Skaarup K G , Johansen N D , Bluhme T M S , Katzenstein T L , Pressler T , Faurholt-Jepsen D , Biering-Soerensen T 
Published: October 2024

Abstract

Background
Cystic fibrosis (CF) is an autosomal recessive disease affecting multiple organs. Emerging evidence indicates an elevated risk of cardiovascular complications in people with CF (pwCF), with some studies implicating CF-related cardiomyopathy as an underlying mechanism. Whether screening for cardiac symptoms and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels may aid in identifying cardiac impairment in pwCF remains unknown.

Purpose
To assess prevalence of dyspnea and chest pain in pwCF and investigate whether symptoms and NT-pro-BNP are predictive of cardiac impairment.

Methods
We interviewed 104 adult pwCF and 104 age- and sex-matched controls from the general population about symptoms of dyspnea and chest pain. All participants were examined with transthoracic echocardiography and NT-proBNP. Cardiac impairment was defined as left ventricular (LV) ejection fraction (LVEF) &lt;50%, LV global longitudinal strain (GLS) &lt; 16% or presence of diastolic dysfunction.

Results
Chest pain was more frequent in pwCF than in controls: (29% vs. 1%, p&lt;0.001), although primarily characterized as atypical and non-exertional chest pain (27%). PwCF also suffered more from dyspnea than controls (89% vs. 18%, p&lt;0.001) (Figure 1) and more pwCF had abnormal cardiac function compared to controls (44% versus 22%, p&lt;0.001).
Median NT-proBNP in pwCF was 50.0 pg/ml (40.7; 100.8) and increasing NT-proBNP level was associated with decreasing FEV1 (L) (estimate: -0.008, p&lt;0.001). NT-proBNP level was not associated with neither dyspnea nor chest pain (p=0.60 and p=0.15, respectively). PwCF with dyspnea did not differ from those without on clinical or echocardiographic parameters. However, pwCF with chest pain had lower absolute GLS compared to pwCF without (17.4% vs.18.5%, p=0.026). Neither dyspnea nor chest pain was more frequent in pwCF with cardiac impairment versus normal cardiac function (54% vs. 39%, p=0.17 and 29% vs. 28%, p=0.91, respectively). Decreasing absolute GLS was associated with increased odds of chest pain (OR 1.25, 95% CI 1.02; 1.53, p=0.030) (Figure 2). Neither dyspnea or chest pain alone, nor in combination with NT-proBNP were able to predict abnormal cardiac function. While dyspnea and chest pain combined showed a slight improvement in sensitivity and positive predictive value for diagnosing cardiac impairment, the combination of symptoms and increased NT-proBNP did not enhance diagnostic accuracy.

Conclusions
In this cross-sectional study, dyspnea and atypical, non-exertional chest pain were common symptoms in adult pwCF. While abnormal cardiac function was prevalent in pwCF, neither symptoms, NT-proBNP nor a combination of these were associated with increased odds of cardiac impairment. Dyspnea and chest pain, though prevalent, are multifactorial in pwCF and do not seem to serve as sensitive markers of cardiac impairment, even when combined with NT-proBNP level.