Coridea (United States)

Inappropriate control of blood volume redistribution may be a mechanism responsible for exercise intolerance in heart failure with preserved ejection fraction (HFpEF). We propose to address this underlying pathophysiology with selective blockade of sympathetic signalling to the splanchnic circulation by surgical ablation of the right greater splanchnic nerve (GSN). In a single-arm, prospective, two-centre trial, 10 patients with HFpEF (50% male, mean age 70 ± 3 years) all with New York Heart Association (NYHA) class III, left ventricular ejection fraction >40%, pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg with supine cycle ergometry, underwent ablation of the right GSN via thoracoscopic surgery. Patients were evaluated at baseline, 1, 3, 6 and 12 months after the procedure. The primary endpoint was a reduction in exercise PCWP at 3months. There were no adverse events related to the blockade of the nerve during 12-month follow-up but three patients had significant peri-procedural adverse events related to the surgical procedure itself. At 3 months post-GSN ablation, patients demonstrated a reduction in 20 W exercise PCWP when compared to baseline [-4.5 mmHg (95% confidence interval, CI -14 to -2); P=0.0059], which carried over to peak exercise [-5 mmHg (95% CI -11 to 0; P=0.016). At 12 months, improvements were seen in NYHA class [3 (3) vs. 2 (1, 2); P=0.0039] and quality of life assessed with the Minnesota Living with Heart Failure Questionnaire [60 (51, 71) vs. 22 (16, 27); P=0.0039]. In this first-in-human study, GSN ablation in HFpEF proved to be feasible, with a suggestion of reduced cardiac filling pressure during exercise, improved quality of life and exercise capacity.

The splanchnic vascular compartment is the major reservoir for intravascular blood volume, and dysregulation of the compartment was implicated in a series of cardiovascular conditions. We explored feasibility and effectiveness of an implantable cuff system on the greater splanchnic nerve (GSN) in healthy canines for short- and long-term neuromodulation to affect the circulation. Five mongrel hounds underwent minimally invasive right-sided unilateral GSN cuff placement. All animals underwent same day GSN stimulation and repeat stimulation at 9-30 days. Stimulation parameter optimization was conducted both acutely and chronically. Parameters ranged from 1-250 Hz, 0.25 mA-35 mA, 0.1-0.5 ms, and 30-s pulse duration. Two animals were survived for 9 days and 3 animals for 30 days. Stimulation of the right GSN increased mean arterial blood pressure by 36.9 mmHg ± 13.4 (p < 0.0001), central venous pressure by 6.9 mmHg ± 1.7 (p < 0.0001), and mean pulmonary arterial pressure by 6.3 mmHg ± 2.0 (p < 0.0001). Peak effects were observed within 30 s, and magnitude of effects was comparable between stimulation cycles (p = 0.4). Stimulation-induced changes in hemodynamics were independent of afferent nerve fibers (pain response) or the adrenal gland. Necropsy showed no evidence of nerve damage on histologic studies up to 30 days after implantation. GSN stimulation via an implanted nerve cuff provided a reproducible and rapid method to increase arterial, central venous, and pulmonary arterial pressures. The neuromodulation cuff was well tolerated and elicited a response up to 30 days after implantation. The clinical application of GSN stimulation as a tool to change central and peripheral cardiovascular hemodynamics needs to be explored.

Sympathetic overactivity plays a crucial pathogenetic role in the maintenance and aggravation of arterial hypertension in patients with end-stage renal disease (ESRD). Renal denervation has been shown to be effective and safe in reducing blood pressure (BP) in patients with treatment-resistant hypertension; however, there are only case reports in hypertensive patients with ESRD and data are lacking about possibility of renal denervation in small renal arteries. A woman with uncontrolled treatment-resistant hypertension on chronic hemodialysis underwent bilateral native kidney, catheter-based renal denervation. Both native renal arteries were <4 mm. After 6 months without any change of antihypertensive medication or hemodialysis parameters, the authors observed a remarkable BP reduction of 38/30 mm Hg (from baseline 172/100 mm Hg to 134/70 mm Hg) as evaluated by 24-hour ambulatory BP monitoring. The authors report that renal denervation seems to be effective in controlling hypertension in patients with ESRD, even in cases of small renal arteries.