Surgical ablation of the right greater splanchnic nerve for the treatment of heart failure with preserved ejection fraction: first-in-human clinical trial.

AIMS: 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). METHODS AND RESULTS: 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 3 months. 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]. CONCLUSION: 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.

High-density epicardial activation mapping to optimize the site for video-thoracoscopic left ventricular lead implant.

BACKGROUND: The left ventricular (LV) lead local electrogram (EGM) delay from the beginning of the QRS complex (QLV) is considered a strong predictor of response to cardiac resynchronization therapy. We have developed a method for fast epicardial QLV mapping during video-thoracoscopic surgery to guide LV lead placement. METHODS: A three-port, video-thoracoscopic approach was used for LV free wall epicardial mapping and lead implantation. A decapolar electrophysiological catheter was introduced through one port and systematically attached to multiple accessible LV sites. The pacing lead was targeted to the site with maximum QLV. The LV free wall activation pattern was analyzed in 16 pre-specified anatomical segments. RESULTS: We implanted LV leads in 13 patients with LBBB or IVCD. The procedural and mapping times were 142 ± 39 minutes and 20 ± 9 minutes, respectively. A total of 15.0 ± 2.2 LV segments were mappable with variable spatial distribution of QLV-optimum. The QLV ratio (QLV/QRSd) at the optimum segment was significantly higher (by 0.17 ± 0.08, p < 0.00001) as compared to an empirical midventricular lateral segment. The LV lead was implanted at the optimum segment in 11 patients (at an adjacent segment in 2 patients) achieving a QLV ratio of 0.82 ± 0.09 (range 0.63-0.93) and 99.5 ± 0.6% match with intraprocedural mapping. CONCLUSION: Video-thoracoscopic LV lead implantation can be effectively and safely guided by epicardial QLV mapping. This strategy was highly successful in targeting the selected LV segment and resulted in significantly higher QLV ratios compared to an empirical midventricular lateral segment.

Tissue reaction to three different types of tissue glues in an experimental aorta dissection model: a quantitative approach.

Tissue glues are used during surgical treatment of acute aorta dissection although some glues release toxic products and thus alter the histological structure of the vessel wall. The aim of our study was to use a porcine experimental model of infrarenal aorta dissection to compare histological changes of the vessel wall 1, 6 and 12 months after application of BioGlue, Gelatin-resorcin-formaldehyde (GRF) glue and Tissucol. For quantification, stereological methods were used. All types of glue caused stenosis, GRF most and Tissucol least severely. With increasing postoperative survival time, stenosis was again reduced. Elastine length density decreased with increasing survival time in Control as well as in all Experimental groups. The immunohistochemical phenotype of vascular smooth muscle cells was similar in Tissucol and Control samples. In GRF samples, actin, desmin and vimentin expression changed most severely. Similarly, number and distribution of vasa vasorum in the aortic wall was altered most severely in GRF samples. They tended to return to normal with increasing postoperative survival time, but at a slow rate in the GRF samples. It can be concluded that GRF causes the most severe histopathological changes within the treated aorta, which could be a reason for late failures of dissection surgery. However, glue handling and adhesive properties have to be taken into account, too, when certain glue is chosen for surgical intervention. Increased inflammation and vascularisation might even stabilise the aortic wall. Long-term experimental studies would be helpful to assess healing processes after initial disorganisation of the aortic wall structure.