Cardiac Structure and Function in Patients with Cystic Fibrosis

Background:

Previous studies using standard echocardiography have shown contradictory results regarding left ventricle (LV) structure and function in patients with CF. By the use of strain rate analyses, few studies have identified LV systolic abnormalities even in the setting of preserved conventional echocardiographic measures of LV systolic function such as left ventricular ejection fraction (LVEF) and fractional shortening. The expression of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in myocytes of different mammalian species including mice and humans has been known for many years. Two studies showed that CFTR is involved in regulation of cardiomyocyte contraction in mice and another study demonstrated that loss of CFTR function in mice led to LV remodeling and increased aortic stiffness. The presence of CFTR in the myocardium has prompted debate regarding a possible intrinsic cardiac impairment due to loss of CFTR. A recent study found an association between severity of genotype in patients with CF and cardiac impairment. Several studies of pediatric CF patients with none or mild respiratory manifestations have also demonstrated early signs of cardiovascular impairments, such as arterial stiffness, increased pulmonary artery pressure (PAP) and abnormalities of right ventricular (RV) structure and function.

Primary hypothesis: CF is independently associated with higher prevalence of asymptomatic cardiac dysfunction and abnormal cardiac structure determined by conventional and advanced echocardiographic deformation measures (cross sectional study).

Secondary hypotheses: 1) CF is associated with elevated levels of specific cardiac biomarkers (cross sectional study). 2) CF is associated with higher pulmonary artery systolic pressure and higher prevalence of pulmonary hypertension determined by echocardiography (cross sectional study). 3) Asymptomatic cardiac dysfunction and abnormal cardiac structure assessed by conventional and advanced echocardiographic deformation measurements are early markers identifying CF patients in high risk of cardiac disease (prospective study).

Objective: