Genetic polymorphism, medical therapy and sequential cardiac function in patients with heart failure

Background: Functional variants of angiotensin-converting enzyme (ACE) gene may be associated with response to therapy in patients with heart failure (HF). Objective: To test the hypothesis of differences in sequential echocardiographic evaluations of left ventricular ejection fraction in patients with HF on medical therapy, including ACE inhibitors in relation to insertion (I) / deletion (D) polymorphism of the ACE gene. Methods: We studied 168 patients (mean age 43.3 +/- 10.1 years), 128 (76.2%) men, with HF and sequential echocardiograms. The I/D polymorphism was determined by polymerase chain reaction. Left ventricular ejection fraction (LVEF) was analyzed comparatively to genotypes. More than 90% of patients were on ACE inhibitors. Results: There was a significantly greater increase in mean LVEF in patients with the D allele compared to patients with the II genotype (p = 0.07) after a mean follow-up of 38.9 months. The D allele was associated with an increase of 8.8% in mean LVEF over the same period. Furthermore, there was a tendency toward a allele copy number effect on the increase of mean LVEF over time: a 3.5% difference in LVEF variation between patients with the II and the ID genotypes (p = 0.03) and a 5% difference between patients with the II and DD genotypes (p = 0.02). Conclusion: ACE gene deletion polymorphism may be operative in response to medical treatment that included ACE inhibitors in patients with HE Further controlled Studies may contribute to better understanding of genetic influences on response to therapy.