Right ventricular function and the risk of pulmonary exacerbations in people with cystic fibrosis – a prospective cohort study

Background

Despite therapeutic advances with cystic fibrosis transmembrane conductance regulators (CFTRs), people with cystic fibrosis (pwCF) exhibit cardiac changes, including altered right ventricular (RV) function. RV free wall longitudinal strain (RVFWLS) is a sensitive marker of RV function, but whether it’s associated with risk of pulmonary exacerbations (PEx) in pwCF remains unclear. We aimed to explore the association between RVFWLS and the risk of PEx in pwCF.

Methods

Clinically stable pwCF 18 years of age were prospectively included from a CF outpatient clinic and underwent clinical and echocardiographic assessment. Clinical characteristics associated with reduced RVFWLS were examined with logistic regression. The endpoint was PEx requiring hospitalization and/or intravenous antibiotics. PEx were analyzed as count data. IIncidence rates per 100 PY were estimated using negative binomial regression and reported as IRR.). RVFWLS was modelled using restricted cubic splines. A p-value <0.05 was considered statistically significant. All strain values are reported as absolute values.

Results

A total of 104 pwCF were included (44.2% female, mean age 33.5 years); 96.2% received CFTR modulators and 39.4% had CF-related diabetes. Mean left ventricular ejection fraction (LVEF) was 54.0% and mean RVFWLS was 24.3%.

During a median follow up of 3.02 years (), 20 pwCF (19%) experienced PEx, of which 12 pwCF experienced one PEx, 6 experienced two, and 2 experienced three PEx, corresponding to a mean PEx rate of 7.18 PEx/100 PY. Those with PEx had worse pulmonary function and lower RVFWLS (mean RVFWLS 24.4%), vs. 21.0% (), p=0.019) (Table 1). Lower forced expiratory volume in 1 second (FEV1) was associated with higher odds of having RVFWLS below the mean (OR 1.05 per 0.1L decrease in FEV1, 95% CI 1.01-1.09, p=0.021).

Restricted cubic spline analysis confirmed that lower RVFWLS was associated with a higher risk of PEx (IRR 1.15 per 1% reduction in RVFWLS, 95% CI 1.02-1.29, p=0.019) (Figure 1). After multivariable adjustment for age, sex, CFTR, and PEx rate in the 12 months prior to baseline, RVFWS remained associated with PEx (IRR 1.11 per 1% reduction in RVFWLS, 95% CI 1.01-1.22, p=0.037). However, further adjustment for FEV1 attenuated the association between RVFWLS and PEx (IRR 1.04 per 1% reduction in RVFWLS, 95% CI 0.93-1.16, p=0.53).

Conclusion

In pwCF, worse pulmonary function was associated with altered RVFWLS, and lower RVFWLS was associated with an increased risk of PEx independent of age, sex, CFTR, and prior PEx rate. However, this association was attenuated after adjustment for FEV1. These findings suggest that RV dysfunction may reflect pulmonary disease severity and could have potential clinical relevance for risk stratification and management in pwCF.The association between RWFWLS and PExBaseline characteristics - PEx at follow-up