Abstract 13906: Increased Mortality in Cystic Fibrosis Transmembrane Conductance Receptor Delta F508 Carriers With Heart Failure
Introduction: Cystic fibrosis is the most common autosomal recessive disease in Caucasians, with a newborn prevalence of about one in 2500 and a carrier frequency of one in 25. Despite this high prevalence, there is very limited data regarding the prognosis of Cystic Fibrosis Transmembrane Conductance Receptor (CFTR) delta F508 (ΔF508). Heart failure models in rabbits have shown a loss of the normal epicardial to endocardial gradient of CFTR mRNA expression. This is thought to delay left ventricular repolarization and play an important role in electrical instability of heart failure patients.
Hypothesis: We hypothesized that ΔF508 CFTR heterozygotes will have more cardiac related death as compared to wild type matched controls.
Methods: DNA isolated from patient's blood samples from Iowa Biobank for Cardiovascular Discovery were used for this study (n = 641). CFTR exon 10 was amplified by real time PCR to determine the presence of heterozygotes for ΔF508 CFTR mutations. In addition, we queried demographic, clinical and physiological information from each patient.
Results: Out of 641 patients 14 were carriers for ΔF508 CFTR with a frequency of one in 45. Mortality was significantly higher in the carrier group, 5 patients (36%) vs 72 patients (12%) in the wild type, (p= 0.024). Sudden death accounted for 4 out of the 5 deaths in the carrier group. Both groups had no significant difference in age, NYHA classification, comorbidities, smoking, or use of beta blockers and angiotensin converting enzyme inhibitors.
Conclusion: ΔF508 CFTR heterozygosity is independently associated with rates of sudden deaths in patients with heart failure. This significant increase in mortality might be related to repolarization abnormalities in ΔF508 CFTR carriers, predisposing them to more arrhythmias and sudden death. Sudden death might also explain the unexpected low prevalence of ΔF508 CFTR in our heart failure population.
- © 2011 by American Heart Association, Inc.