Renal Denervation in Patients With Heart Failure and Severe Left Ventricular Dysfunction.
Renal Denervation in Patients With Heart Failure and Severe Left Ventricular Dysfunction.
It is a randomized prospective controlled study evaluating the effect of transcatheter renal
 denervation on the clinical status of patients with chronic heart failure and its safety
 procedures. The working hypothesis of the study is that by performing transcatheter renal
 denervation in patients with chronic heart failure and severe left ventricular systolic
 dysfunction there will a resultant reduction in the renal sympathetic activation which in
 turn will reduce the number of hospitalizations and deaths from heart failure.
Chronic heart failure in the European countries occurs in 2-3% of the population with a
 significant increase in the higher age groups (1). Improved treatment of acute conditions
 (especially myocardial infarction) has resulted in more patients entering into the category
 of chronic heart failure. Chronic heart failure has a poor prognosis. Diagnosis and treatment
 are challenging both medically and economically. Half of the patients with systolic heart
 failure die within 4 years and more than 50% of patients with severe heart failure (NYHA
 functional class of IV) die within one year (1). The current treatments for heart failure are
 not only aimed at influencing the symptoms, but also preventing the progression of heart
 failure to reduce mortality.

 Heart failure leads to the activation of compensatory mechanisms designed to restore adequate
 cardiac output. These mechanisms are initially beneficial, but their long-term activation
 leads to further progression of the pathological process and deterioration of cardiac
 function. One of the basic pathophysiological processes in heart failure is excessive
 activation of the sympathetic nervous system. This causes increased levels of circulating
 catecholamines which is proportional to the severity of the disease that is patients with the
 highest levels of norepinephrine have the worst prognosis. Beta-blocker therapy which is
 designed to inhibit activity of sympathetic nervous system causes milder symptoms of heart
 failure in patients by modifying disturbed hemodynamics and ultimately the clinical status.
 In recent years, the therapeutic efficacy of beta-blockers in chronic heart failure has been
 verified in a number of controlled clinical trials (2-5). These studies have confirmed that
 long-term treatment with beta-blocker therapy alleviates the symptoms of heart failure,
 improves the clinical condition of the patients and reduces mortality like ACE inhibitors.

 High activity of renal sympathetic nerves in patients with chronic heart failure is an early
 predictor of increased mortality (6). The main pathophysiological basis of this finding is
 probably excessive sodium retention due to direct activation of sympathetic fibers
 innervating renal tubules (7). Recent experimental work on animals have shown that surgical
 renal denervation inhibits an increase in renal vascular resistance, prevents a decrease in
 renal blood flow (8), and also prevents changes in expression of angiotensin receptors in the
 kidney (8).

 Surgical sympathectomy began to be used for the treatment of severe and malignant
 hypertension more than 50 years ago. But this was a rather complicated procedure, which was
 accompanied by a number of adverse effects (orthostatic hypotension and tachycardia,
 shortness of breath, bowel and sexual disorders]. Moreover it required a long hospitalization
 of 2-4 weeks and then required a recovery period of 1-2 months. However this intervention led
 to a rapid decrease in pressure and a higher survival rate after surgery in a large
 observational study(9).

 In recent years a method has been developed in which destruction of renal sympathetic nerves
 that are present in the adventitia of renal arterial walls is done by catheterization (10).
 This procedure uses a catheter with a radiofrequency ablator at its tip (Symplicity, Ardian /
 Medtronic, USA), which is introduced through the femoral artery and then progressively
 introduced into the renal arteries. A randomized study has demonstrated that this procedure
 has a high degree of safety for the patients and a high rate of efficacy as well. In patients
 with resistant hypertension treated with transcatheter renal denervation there was a
 significant drop in blood pressure of 33/11 mmHg (p < 0.0001) that occurred after 6 months
 compared to a control group receiving unmodified pharmacological treatment (11).
Inclusion Criteria:

 -  Patients over 18 years of age with chronic heart failure, ischemic and non-ischemic
 etiology.

 -  NYHA (New York Heart Association) class II-IV.

 -  LVEF (Left Ventricular Ejection Fraction) ≤ 35%.

 -  Patients treated with maximum tolerated doses of standard pharmacotherapy for heart
 failure, who were stable for at least four weeks without acute decompensated heart
 failure.

 -  Prior to enrollment, patients must give informed consent.

 Exclusion Criteria:

 -  Patients with history of acute coronary syndrome or stroke within the last 6 months.

 -  Significant valvular defects and/or planned cardiac surgery.

 -  Systolic blood pressure <110 mmHg.

 -  Advanced renal insufficiency (estimated GFR (Glomerular Filtration Rate) according to
 MDRD <30 ml/min/1.73 square meters).

 -  Unsuitable anatomy of renal arteries (presence of significant renal stenosis, renal
 artery narrower than 4 mm).

 -  Patients who underwent renal angioplasty or stent placement into the renal artery in
 the past.

 -  Severe coagulation disorders.

 -  Pregnancy or lactation.

 -  Refusal of the patient.

 -  Other diseases limiting prognosis of the patient to less than 2 years.

 -  Other reasons which in the opinion of the attending physician would preclude the
 individual from participating in the study.