Abstract 19030: High Mortality in Cardiomyopathy Patients Heterozygous for the CFTR ΔF508 Cystic Fibrosis Mutation
Introduction: Cystic fibrosis is among the most common inherited disorders, with ∼ 3% of Caucasians being heterozygous for the common CFTR ΔF508 mutation. Cardiomyopathy is a major cause of morbidity and mortality. While a small preliminary study suggested that cardiomyopathy patients heterozygous for the CFTR ΔF508 mutation have poorer outcomes, the finding has not been replicated and it is not known whether the poor outcomes are related to sudden death and/or heart failure progression.
Methods: We screened 1347 Caucasian cardiomyopathy subjects (EF 21%, 82% male, 75% ischemic) with implantable cardioverter defibrillators (ICDs) from the prospective, multicenter, NIH-funded Genetic Risk Assessment of Defibrillator Events (GRADE) study. CFTR ΔF508 alleles were discriminated by real time fluorescence PCR. GRADE subjects were followed for up to 5 years to the primary endpoint of freedom from appropriate ICD shocks and the secondary endpoints of death and death/heart transplant/VAD placement. The results were compared by genotype using Kaplan-Meier analysis and Log Rank testing.
Results: Genotyping revealed 33 CFTR ΔF508 heterozygotes (allele frequency 2.4%). ΔF508 carriers were older (68 vs 64 yrs, p=0.03); more likely to be diabetic (55 vs 34%, p=0.02), to have had an MI (77 vs 57%, p=0.02), and to have a RBBB on ECG (18 vs 7%, p=0.03); and had lower EFs (19 vs 21%, p=0.01). CFTR ΔF508 carriers had markedly higher rates of death (HR>2; p<0.001) and death/VAD/transplant (p=0.004), with no difference in appropriate ICD shocks (Figure).
Conclusion: We have confirmed that carrying one CFTR ΔF508 allele is associated with an increased mortality in cardiomyopathy patients, and that this is likely not due to increased arrhythmic death. These findings may have implications for the treatment of this high risk heart failure subgroup. Future studies are needed to determine whether the increased mortality stems from a cardiac and/or pulmonary etiology.
Author Disclosures: B. London: None. R. Boudreau: None. I. Halder: None. A. Vargas-Estrada: None. A. Comellas: None. F.L. Johnson: None. J. Zabner: None. R.A. Gutmann: None. H.L. Bloom: None. S.C. Dudley: None. P.T. Ellinor: None. A. Shalaby: None. R. Weiss: None.
- © 2015 by American Heart Association, Inc.