Aims: The sympathetic nervous system plays a central role in cardiac growth but its overstimulation is associated with increased mortality in patients with chronic heart failure. Presynaptic α 2- adrenoceptors are es...
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Aims: The sympathetic nervous system plays a central role in cardiac growth but its overstimulation is associated with increased mortality in patients with chronic heart failure. Presynaptic α 2- adrenoceptors are essential feedback regulators to control the release of norepinephrine from sympathetic nerves. In this study we tested whether a deletion polymorphism in the human α 2C- adrenoceptor gene(α 2CDel322- 325) affects progression of heart failure in patients with dilated cardiomyopathy(DCM). Methods and results: We genotyped and phenotyped 345 patients presenting with DCM in the heart transplant unit of the German Heart Institute, starting in 1994. Patients were treated according to guidelines(99% ACEI, 76% β - blockers)and were followed until December 2002 or until a first event [death, heart transplantation, or implantation of a left ventricular assist device(LVAD) for a life- threatening condition] occurred. Mean follow- up time was 249 weeks(4.9 years) in event- free patients and 104 weeks(2 years) in patients with events. During follow- up, 51% of the patients exhibited an event: death(18% ), implantation of LVAD as bridging for transplantation(7% ), or heart transplantation(25% ). By Kaplan- Meier analysis, DCM patients with the deletion variant Del322- 325 in the α 2C- adrenoceptor showed significantly decreased event rates(P=0.0043). Cox regression analysis revealed that the presence of the deletion was associated with reduced death rate(relative risk: 0.129, 95% CI: 0.18- 0.9441, P=0.044) and event rates(relative risk: 0.167, 95% CI: 0.041- 0.685, P=0.012). Conclusion: α 2C- Adrenoceptor deletion may be a novel, strong, and independent predictor of reduced event rates in DCM patients treated according to guidelines.
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