This study was stopped after the publication of the Symplicity HTN-3 trial even before patient inclusion.

The protocol (including the renal denervation device) were revised and a new trial conducted ( NCT04947670).

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.

Inclusion Criteria:

• New York Heart Association Class II-III symptoms of chronic heart failure
• Systolic left ventricular dysfunction as assessed by echocardiogram with left ventricular ejection fraction in a range of 10%- 40%.
• GFR >30 mL/min/1.73m2
• Brain natriuretic Peptide (BNP) >100 pg/ml or N terminal (NT)-Pro-BNP >400 pg/ml.
• Optimal medical therapy according to current guidelines for CHF management. Treatment for HF must be stable (including drug and dose) for at least 4 weeks prior to procedure, with the exception of diuretics, where stability is required for at least 2 weeks.
• others

Exclusion Criteria:

• Renal arterial anatomy that is ineligible for treatment
• CHF caused by pericarditis or by acute myocarditis or by endocrine diseases.
• Myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within three 12 weeks of the screening visit.
• Office systolic BP at screening less than 90 mmHg
• Primary pulmonary hypertension.
• Clinically significant cardiac structural valvular disease, unless corrected by a properly functional prosthetic valve
• Major surgery, including bariatric surgery, in the previous 12 weeks before baseline.
• Contrast media administration in the previous 30 days before baseline.
• Known hypersensitivity to material of the Symplicity Catheter.
• Inpatient hospitalization for decompensated HF in the previous 60 days before baseline.
• others