Background: Sudden cardiac death (SCD) from ventricular tachyarrhythmias accounts for approximately 450,000 annual deaths in the United States; many of these cases involve patients with chronic heart failure (HF). Prediction of which HF patients are most susceptible to SCD is difficult, and it is uncertain whether gene polymorphisms associated with HF outcomes are also linked to arrhythmic risk. Methods: We evaluated 485 patients with chronic HF to see whether the angiotensin receptor type 1 (AT1R) 1166A/C or angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms were associated with a higher rate of ventricular arrhythmias requiring implantable cardioverter defibrillator (ICD) therapies over a 5-year period. We assessed the correlation between polymorphisms and antitachycardia pacing (ATP) and/or ICD shocks. Results: Patients with AT1R-1166CC genotype had an increased rate of all events: ATP plus ICD shocks (P =.02). There was no association between ACE I/D genotype and ICD therapies. Furthermore, circulating levels of microRNA-155 (miR-155), a microRNA known to posttranscriptionally regulate AT1R expression, were significantly decreased in the CC compared with the AC and AA genotypes and were associated with ICD events. Conclusion: Our study suggests that the AT1R-1166CC genotype is associated with increased ICD therapies in patients with chronic HF, and the level of circulating miR-155 may be a potential marker for arrhythmic risk. Although these findings are novel, they will need replication and validation in larger cohorts of chronic HF patients.
Bibliographical noteFunding Information:
The Genetic Risk Assessment of Defibrillator Events (GRADE) study is supported by a NHLBI grant through an R01 mechanism (B.L.). This work was also supported by NIH T32HL007745 (R.R.B.); investigator-initiated grant from Medtronic, Inc . (A.M.Z.); NHLBI Program of Excellence in Nanotechnology (HHSN268201000043C to C.D.S.), VA Merit Review Award (I01 BX000704 to C.D.S.), and a NHLBI R01 Award (HL 109559 to C.D.S.).
- Genetic polymorphisms
- angiotensin type 1 receptor
- heart failure
- sudden cardiac death