Abstract Background Cystic fibrosis (CF) is an autosomal recessive disease affecting multiple organs, however the extent of cardiac involvement in CF is yet to be determined. The remarkable therapeutic advancements with new highly effective CF transmembrane conductance regulator (CFTR) modulator treatment and subsequent increase in life expectancy substantiates further research. Purpose We aimed to explore the prevalence of abnormalities and potential subclinical alterations in cardiac structure and function in adults with CF compared to matched controls and investigate potential cardiovascular risk factors in people with CF (pwCF). Methods In this cross-sectional study, 104 adult pwCF in Denmark underwent clinical and echocardiographic examination. All participants were matched 1:1 with controls from the general population on age and sex. Uni- and multivariable linear regression models with adjustment for heart rate, FEV1, smoking status, hypertension and CF-related diabetes (CFRD) were used to test for differences in echocardiographic parameters between cases and controls. Abnormal cardiac function was defined as left ventricular ejection fraction (LVEF) <50%, left ventricular (LV) global longitudinal strain (GLS) < 16% or presence of diastolic dysfunction. Uni- and multivariable logistic regression models adjusted for age, sex, homozygous genotype, FEV1/FVC, BMI, smoking status, CFRD, pancreatic insufficiency, hypertension, and ischemic heart disease were performed to assess associations between potential risk factors and cardiac dysfunction in CF. Forest plots were constructed to visually represent the findings. Results Of 104 pwCF, 44% were female, mean age was 34 years, 93% received CFTR modulator treatment, and 91% had mutations with only minimal CFTR function (mutation class I-III). The prevalence of abnormal cardiac function in pwCF was 44% versus 22% in controls. Compared to controls, pwCF were found to have smaller LV dimensions, worse LV diastolic function, and more impaired right ventricle (RV) as well as LV systolic function (Table). After multivariable adjustment, LV diastolic function as well as LV and RV systolic function remained impaired in pwCF as compared to controls. Male sex and decreasing FEV1/FVC ratio remained independently associated with abnormal cardiac function in pwCF (male sex: OR 3.94 (1.56; 9.95), p=0.004 and FEV1/FVC ratio: OR 2.05 per 0.1 unit decrease (1.21; 3.52), p=0.008, respectively) (Figure). Conclusion Both left- and right-sided cardiac alterations were found in pwCF. After adjustments for potential risk factors, both RV and LV systolic measures remained altered in pwCF, compared to controls. Male sex and decreasing pulmonary function evaluated by FEV1/FVC-ratio were identified as factors associated with abnormal cardiac function in pwCF.Figure
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