Mapping for Acute Transvenous Phrenic Nerve Stimulation Study (MAPS Study).

BACKGROUND: Central sleep apnea syndrome, correlated with the occurrence of heart failure, is characterized by periods of insufficient ventilation during sleep. This acute study in 15 patients aims to map the venous system and determine if diaphragmatic movement can be achieved by phrenic nerve stimulation at various locations within the venous system. METHODS: Subjects underwent a scheduled catheter ablation procedure. During the procedural waiting time, one multielectrode electrophysiology catheter was subsequently placed at the superior and inferior vena cava and the junctions of the left jugular and left brachiocephalic vein and right jugular and right brachiocephalic vein, for phrenic nerve stimulation (1-2 seconds ON/2-3 seconds OFF, 40 Hz, pulse width 210 µs). Diaphragmatic movement was assessed manually and by a breathing mask. During a follow-up assessment between 2 and 4 weeks postprocedure, occurrence of adverse events was assessed. RESULTS: In all patients diaphragmatic movement was induced at one or more locations using a median threshold of at least 2 V and maximally 7.5 V (i.e., e 3.3 mA, 14.2 mA). The lowest median current to obtain diaphragmatic stimulation without discomfort was found for the right brachiocephalic vein (4.7 mA). In 12/15 patients diaphragmatic movement could be induced without any discomfort, but in three patients hiccups occurred. CONCLUSION: Diaphragmatic stimulation from the brachiocephalic and caval veins is feasible. Potential side effects should be eliminated by adapting the stimulation pattern. This information could be used to design a catheter, combining cardiac pacing with enhancing diaphragm movement during a sleep apnea episode.

Carotid baroreceptor stimulation blood pressure response mapped in patients undergoing carotid endarterectomy (C-Map study).

OBJECTIVE: Continuous stimulation of the carotid baroreceptors has been shown to evoke a sustained systolic blood pressure (SBP) reduction in hypertensive subjects. This study conducted a detailed mapping of the SBP and heart rate response to electrical stimulus at different locations in the carotid sinus region in patients undergoing a carotid endarterectomy (CEA). METHODS: The Carotid Sinus Autonomic Response Mapping (C-Map) Study is a multicenter, prospective, non-randomized, acute feasibility study conducted in 10 hypertensive subjects undergoing CEA. Electrode pairs were placed in multiple locations in the region of the carotid sinus for acute stimulation, and the tests were repeated after plaque removal and vessel repair. RESULTS: The configuration that elicited the largest pressure reduction in 8 of 10 patients was with the electrodes arranged longitudinally along the medial (in relation to the bifurcation) wall of the internal carotid artery (ICA) near the bifurcation (11.2±8.1mmHg, p<0.05). There was no difference in average maximum response pre vs. post plaque removal. Spontaneous baroreflex sensitivity increased from 6.0±3.2ms/mmHg pre-CEA to 8.2±5.4ms/mmHg post-CEA (p=0.040). CONCLUSIONS: Endarterectomy surgery did not affect maximal acute stimulation response but improved baroreflex sensitivity acutely. Acute extravascular baroreceptor stimulation (BRS) mapping demonstrated that blood pressure reductions are dependent on electrode location and orientation. In most subjects, the largest SBP reductions were elicited in the region of the medial wall of the ICA. This area can be targeted for future BRS lead design and implant.

Transvenous vagus nerve stimulation does not modulate the innate immune response during experimental human endotoxemia: a randomized controlled study.

INTRODUCTION: Vagus nerve stimulation (VNS) exerts beneficial anti-inflammatory effects in various animal models of inflammation, including collagen-induced arthritis, and is implicated in representing a novel therapy for rheumatoid arthritis. However, evidence of anti-inflammatory effects of VNS in humans is very scarce. Transvenous VNS (tVNS) is a newly developed and less invasive method to stimulate the vagus nerve. In the present study, we determined whether tVNS is a feasible and safe procedure and investigated its putative anti-inflammatory effects during experimental human endotoxemia. METHODS: We performed a randomized double-blind sham-controlled study in healthy male volunteers. A stimulation catheter was inserted in the left internal jugular vein at spinal level C5-C7, adjacent to the vagus nerve. In the tVNS group (n = 10), stimulation was continuously performed for 30 minutes (0-10 V, 1 ms, 20 Hz), starting 10 minutes before intravenous administration of 2 ng kg(-1) Escherichia coli lipopolysaccharide (LPS). Sham-instrumented subjects (n = 10) received no electrical stimulation. RESULTS: No serious adverse events occurred throughout the study. In the tVNS group, stimulation of the vagus nerve was achieved as indicated by laryngeal vibration. Endotoxemia resulted in fever, flu-like symptoms, and hemodynamic changes that were unaffected by tVNS. Furthermore, plasma levels of inflammatory cytokines increased sharply during endotoxemia, but responses were similar between groups. Finally, cytokine production by leukocytes stimulated with LPS ex vivo, as well as neutrophil phagocytosis capacity, were not influenced by tVNS. CONCLUSIONS: tVNS is feasible and safe, but does not modulate the innate immune response in humans in vivo during experimental human endotoxemia. TRIAL REGISTRATION: Clinicaltrials.gov NCT01944228. Registered 12 September 2013.

Coronary sinus electrode does not reduce atrial defibrillation thresholds.

BACKGROUND: Atrial defibrillation can be achieved with a conventional dual-coil, active pectoral implantable cardioverter-defibrillator (ICD) lead system. Shocking vectors that incorporate an additional electrode in the CS have been used, but it is unclear if they improve atrial DFTs. OBJECTIVE: The objective of this prospective, randomized study was to determine if a coronary sinus (CS) electrode reduces atrial defibrillation thresholds (DFTs). METHODS: This was a prospective study of 36 patients undergoing initial ICD implant for standard indications. A defibrillation lead with superior vena cava (SVC) and right ventricular (RV) shocking coils was implanted in the RV. An active can emulator (Can) was placed in a pre-pectoral pocket. A lead with a 4 cm long shocking coil was placed in the CS. Atrial DFTs were determined in the following 3 shocking configurations in each patient, with the order of testing randomized: RV --> SVC + Can (Ventricular Triad), distal CS --> SVC + Can (Distal Atrial Triad), and proximal CS --> SVC + Can (Proximal Atrial Triad). RESULTS: The Proximal and Distal Atrial Triad configurations were both associated with significant reductions in peak current (p < 0.01), but this effect was offset by significant increases in shock impedance (p < 0.01), resulting in no net change in the peak voltage or DFT energy in comparison to the Ventricular Triad configuration (Ventricular Triad: 4.9 +/- 6.6 J, Proximal Atrial Triad: 3.3 +/- 4.1J, Distal Atrial Triad: 4.4 +/- 6.7 J, p > 0.2). CONCLUSION: Shocking vectors that incorporate a CS coil do not significantly improve atrial defibrillation efficacy. Since the Ventricular Triad shocking pathway provides reliable atrial and ventricular defibrillation, this configuration should be preferred for combined atrial and ventricular ICDs.

Improved extraction of ePTFE and medical adhesive modified defibrillation leads from the coronary sinus and great cardiac vein.

BACKGROUND: Permanent leads with shocking coils for defibrillation therapy are sometimes implanted in the coronary sinus (CS) and great cardiac vein (GCV). These shocking coils, as documented by pathologic examination of animal investigations, often become tightly encapsulated by fibrosis and can be very difficult to remove. METHODS: One of three configurations of the Guidant model 7109 Perimeter coronary sinus shocking lead was implanted into the distal portion of the GCV of 24 sheep for up to 14 months. Group 1 had unmodified coils (control), group 2 had coils backfilled with medical adhesive (MA), and Group 3 had coils coated with expanded polytetrafluoroethylene (ePTFE). Eighteen leads, three from each group at 6 and 14 months were transvenously extracted from the left jugular vein. The remaining six animals were not subject to extraction. All animals were euthanized for pathological and microscopic examination. RESULTS: All six of the control, three of the MA, and one of the ePTFE leads required the use of an electrosurgical dissection sheath (EDS) for extraction. Five control, two MA, and none of the ePTFE leads had significant fibrotic attachments to the shocking coils. Significant trauma was observed at necropsy for those leads requiring the use of the EDS for extraction. CONCLUSIONS: Tissue ingrowth is a major impediment to the removal of defibrillation leads implanted in the CS and GCV of sheep. Reduction of tissue ingrowth by coating the shocking coils with ePTFE or by backfilling with MA facilitates transvenous lead removal with reduced tissue trauma.

Mapping the coronary sinus and great cardiac vein.

The purpose of this study was to develop a better understanding of the pacing and sensing characteristics of electrodes placed in the proximal cardiac veins. A detailed mapping of the coronary sinus (CS) and great cardiac vein (GCV) was done on 25 patients with normal sinus rhythm using a deflectable electrophysiological catheter. Intrinsic bipolar electrograms and atrial and ventricular pacing voltage thresholds were measured. For measurement purposes, the GCV and the CS were each subdivided into distal (D), middle (M), and proximal (P) regions, for a total of six test locations. Within the CS and GCV, the average atrial pacing threshold was always lower (P < 0.05) than the ventricle with an average ventricular to atrial ratio > 5, except for the GCV-D. The average atrial threshold in the CS and GCV ranged from 0.2- to 1.0-V higher than in the atrial appendage. Diaphragmatic pacing was observed in three patients. Atrial signal amplitude was greatest in the CS-M, CS-D, and GCV-P and smaller in the CS-P, GCV-M, and GCV-D. Electrode spacing did not significantly affect P wave amplitude, while narrower electrode spacing attenuated R wave amplitude. The average P:R ratio was highest with 5-mm-spaced electrodes compared to wider spaced pairs. The P:R ratio in the CS was higher (P < 0.05) than in all positions of the GVC. It is possible to pace the atrium independent of the ventricle at reasonably low thresholds and to detect atrial depolarization without undue cross-talk or noise using closely spaced bipolar electrode pairs. The areas of the proximal, middle, and distal CS produced the best combination of pacing and sensing parameters.