Renal Denervation in Patients With Chronic Heart Failure

Cardio-Renal Syndrome, Chronic Heart Failure

Chronic Heart Failure, Cardio-Renal Syndrome, Renal Denervation, Symplicity, Sympathetic activation

The purpose of the trial is to investigate the safety and effectiveness of renal denervation for the treatment of chronic heart failure (CHF).

Heart failure is a major public health problem. It is associated with high mortality, frequent hospitalization and represents a large cost to the health care system. Therapies to ameliorate the high mortality and morbidity of heart failure have focused on abrogation of activated neurohormonal systems associated with this condition. These systems include the renin-angiotensin-aldosterone system and the sympathetic nervous system. Strategies to ameliorate sympathetic activation have primarily focused on blockade of the beta-adrenoceptors that mediate the adverse effects of activation of this system upon the myocardium. This has been a highly successful strategy with beta-blockers resulting in an approximately 35% reduction in mortality as well as improvements in hospitalization and quality of life and attenuation of disease progression. However, less than full blockade of the effects of the sympathetic nervous system is achieved with the use of conventional doses of beta-blockers. Moreover, a not insignificant fraction of patients are unable to tolerate beta-blockers or are not able to have them up-titrated to target effective doses, in large part because of the systemic nature of these agents, whereas renal denervation allows the selective removal of the kidney's contribution to central sympathetic drive without blunting other compensatory mechanisms. The renin-angiotensin-aldosterone axis has also been found to be a key system involved in heart failure disease progression and it too may be inhibited by renal sympathetic denervation. Therefore, a clear need exists for further strategies to beneficially manipulate the sympathetic activation that is characteristic of the heart failure disease process. Cardiorenal syndrome is a major comorbid condition of patients with advanced chronic heart failure. In the setting of renal hypoperfusion and/or activation of neurohormonal and cytokine systems there is a reduction in glomerulofiltration. Renal function has been found to be a major determine of prognosis in these patients. Strategies to ameliorate cardiorenal syndrome are being actively pursued. There is considerable a priori evidence to suggest that the sympathetic nervous system, in particular renal sympathetic, is a key factor to the progression of cardiorenal syndrome and impaired tubulo-glomerular feedback. In particular renal sympathetics reduce renal perfusion through vascular alpha adrenergic receptor stimulation as well as, indirectly, through stimulation of local release of adenosine causing afferent glomerular arteriole constriction. We hypothesize that by disrupting renal sympathetic afferent and efferent activity these salutary adenosine inhibitory mediated effects will be demonstrated using the renal denervation approach. A number of studies with hypertension patients indicate that the Symplicity Catheter System can safely denervate the kidney without significant periprocedural complications. In a small first-in man pilot study, involving seven normotensive patients with chronic heart failure, six months after renal denervation their 6-min walk distance improved significantly and the patients' self-assessment of well-being also improved. No procedural or post procedural complications following renal denervation in patients in 6 months of intensive follow-up were found. The investigators believe that therapeutic renal denervation using the Symplicity Catheter is a promising therapy for patients with elevated sympathetic activity, as in CHF.

No related papers found yet.

Austria, Germany, Sweden, Switzerland