Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3772_Библиотеки_им_академика_М_И_Перельмана

The normal reex loop of afferent and efferent signals con­necting the kidney to the CNS can be perturbed, creating pathologic feedback in the setting of intentional modica­tion, injury or systemic disease. Endovascular electrical stimulation of renal arteries has been shown to prompt changes in BP, although the effects are mixed, with various studies showing elevation in BP [50–57], no effect on BP [58], and a decrease in BP [59] (this phenomenon is described further below). These disparate effects may be related to the fact that response to afferent renal nerve stimulation appears to depend on the location of stimulation. It has been further suggested that functional afferent nerve bers may have a characteristic distribution, with the proximal segment of the renal artery containing primarily sympatho-stimulatory bers [53] while the distal segment near the renal hilum con­tains primarily sympatho-inhibitory bers [18].

Before oral antihypertensive drugs were an option, surgical thoracolumbar splanchectomy was often attempted for treat­ment of patients with HTN [121, 122]. An early large obser­vational study of patients undergoing nonselective surgical splanchectomy versus those treated with medical therapy

USA) to perform several independent ablations using a uni­polar RF system [133, 134]. Subsequently, the Symplicity HTN-3 trial, which had a neutral outcome, used an updated catheter design, and operators were instructed to start in the distal portion of the renal artery and rotate the catheter in a helical pattern as they pulled back to the proximal portion of the artery to create “point-by-point” ablation [135]. This technique introduced new variables including operator dependence and differences in catheter curve and tissue con­tact pressure, which affected the number of patients who had adequate ablation [136]. However, the data remained mixed: while a recent randomized trial comparing distal versus stan­dard (trunk) RDN in 51 patients found distal ablation to be more efcacious for lowering BP [137], these ndings were not reproduced in another randomized study of 47 patients comparing full-length versus proximal ablation [138]. Most recently, the SPYRAL ON-MED and SPYRAL OFF-MED (SPYRAL Pivotal) were randomized, sham-controlled trials which excluded patients with isolated systolic HTN as well as patients with resistant HTN used a modied multi­electrode catheter with a further revised ablation technique focusing on distal ablation [139, 140]. These trials were both positive, with patients in SPYRAL ON-MED averaging sys­tolic BP reductions of 6.8 and 7.4mmHg, for ofce and 24-h BP monitoring, respectively, versus the sham control; the BP reductions in SPYRAL OFF-MED were slightly more mod­est (6.5 and 3.9mmHg, respectively) but still signicant.

Assessing the success of RDN requires careful differen-

RDN trials have investigated both ambulatory and ofce BP.While RDN signicantly reduces both ambulatory and ofce BP, ofce BP reductions are generally more dramatic [118, 188]. For instance, the landmark Symplicity HTN-2 trial showed a reduction in ofce BP of 32/12mm Hg but a reduction of only 11/7mm Hg in ambulatory 24-h BP [188]. The relatively smaller change in ABPM may be explained the selection criteria for both the Symplicity HTN-1 and -2 trials did not exclude white coat HTN, thus inherently bias­ing the results towards lower effects of RDN on ABPM compared to ofce BP.Similarly, the more recent SPYRAL HTN-OFF MED Pivotal trial, part of the rst series of RDN trials to include a sham control arm, enrolled patients with HTN not on medications (i.e., the trial excluded patients with resistant HTN) and demonstrated larger decreases in ofce systolic BP (−6.6mmHg compared to control) than for ABPM (−4.0mmHg compared to control) [140]. Just as BP at trial entry predicts whether RDN will be successful, ABPM at entry is a major predictor of response to therapy. This relationship is also seen in drug treatment trials [200]. Reductions in ofce BP have been observed for periods of at least 2 years [174]. In addition to changes in mean arterial pressure, RDN also reduces 24-h BP variability [201]. The clinical relevance of the standard deviation of systolic BP has been demonstrated by Parati et al. who studied 109 hypertensive patients and showed that higher BP variability led to more end organ damage independent of the mean sys­tolic BP [202]. Moreover, there is evidence that visit-to-visit or day-to-day BP variability is similarly a negative prognos­tic indicator for cardiovascular mortality, stroke, and overall mortality [203–205]. Taken together, ofce BP and ABPM as well as characteristics such as BP variability and the pat­tern or time-dependence of BP reduction are all well suited to serve as surrogate outcomes for successful RDN.In addi­tion, risk factors such as the presence of endothelial dys­function, which is clearly linked to increase risk of cardiovascular disease, could be used as accessory surrogate markers [206]. While control of HTN is the current gold standard in the assessment of technical success in RDN, hard clinical outcomes including mortality may be impacted even in the absence of BP changes, indicating that addi­tional clinical surrogates should be considered in future clinical trials of RDN.

Decreased exercise capacity as well as excessive increases in systolic BP and heart rate during exercise are associated with increased cardiovascular morbidity and mortality [222, 223]. Conversely, increases in exercise tolerance are associated with improved outcomes. RDN has been shown to improve exercise capacity with attenuations of systolic BP at peak exercise of about 21 mmHg without compromising chrono­tropic competence [179]. To date, there is only one study directly studying the HF population in this regard: in the REACH pilot study, 7 patients with HF with reduced ejec-

Elevated resting heart rate is considered a risk factor for arte­rial HTN [233], CAD [234], and HF [235]; it is also a well­established surrogate outcome associated with cardiovascular mortality [236, 237]. Pharmacological suppression of heart rate with ivabradine decreased a composite outcome of car­diovascular death and hospitalization in a HF population [238]. In a sub-population of patients with a resting heart rate of over 75 beats per minute, ivabradine reduced cardiovascu­lar and all-cause mortality [239]. These data suggest that heart rate may be a potential surrogate outcome for RDN.RDN trials have repeatedly demonstrated a reduction in heart rate [175, 240]; the effect was more pronounced with higher heart rate at baseline. Theoretical intraprocedural out­come candidates, such as changes in heart rate and heart rate variability, are made less attractive due to the requirements for analgesia and anxiolytics during the procedure which lower heart rate and blunt variability. Unfortunately, while reducing heart rate may be associated with long term benets of therapeutic RDN, heart rate has little value in guiding patient selection or intraprocedural therapy.