Mutations Linked to Severe CF Seen to Affect Health of Heart’s Left Ventricle in Study

Alice Melão, MSc avatar

by Alice Melão, MSc |

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cardiac health and CF

Mutations in the CFTR gene that associate with severe disease can also lead to cardiac problems — specifically, the development of subclinical left ventricular dysfunction — in cystic fibrosis patients, a study suggests.

The study, “Subclinical Left Ventricular Dysfunction is Influenced by Genotype Severity in Patients with Cystic Fibrosis,” was published in the journal Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine.

More than 2,000 genetic variants of the CFTR gene have been identified, of which 276 are known to cause cystic fibrosis (CF). Some of these mutations are known to cause a complete loss of the CFTR protein, while others only lower CFTR protein production, sometimes to levels resulting in a milder disease presentation and longer survival rates.

The impact of CFTR mutations in the lungs, pancreas, liver, and sweat ducts has been widely explored and characterized. But, as muscle cells (myocytes) also have CFTR protein, cardiac health can also be affected by CFTR mutations.

To explore the existence of a possible CF-related heart disease (cardiomyopathy), researchers at Monash University, in Australia, reviewed the clinical records of 100 CF patients. All attended the Cystic Fibrosis Service at Alfred Health between 2000 and 2015, and had at least one identified CF-causing CFTR mutation.

A total of 79 patients were carriers of two copies of CFTR mutations known to cause severe disease (classification groups 1-3), and 21 had one copy of the mutated gene associated with milder CF presentation.

Cardiac function was evaluated by transthoracic echocardiogram, a non-invasive method that allows assessment of the dimensions of the heart’s chambers, cardiac muscle thickness, and pumping efficiency.

The researchers failed to find any differences regarding right ventricular systolic pressure and lung function — determined by forced expiratory volume in 1 second (FEV1) — between patients with milder or more severe CF.

However, patients with CFTR mutations associated with severe disease had significantly lower fractional shortening (a measure of the chamber contractibility) and slightly lower ejection fraction (a measure of the blood ejection potential) in the left ventricle. They also had lesser area and volume of the left atria of the heart.

These findings demonstrate for the first time that functional classification of CF-related CFTR mutations are associated with cardiac impairment, “while severity of lung disease was unrelated,” the researchers wrote.

Additional studies are required to recognize the impact of CFTR-mediated cardiac dysfunction, as well as to explore if disease-modifying therapies can improve heart health in CF patients.

“Patients with severe CF genotype [CFTR mutational status] and cardiac dysfunction should be identified to evaluate cardiac response to gene-modifying treatments prior to consideration for lung transplantation,” the researchers also suggest.