Stimulation of the intra-cardiac vagal nerves innervating the AV-node to control ventricular rate during AF: specificity, parameter optimization and chronic use up to 3 months.

BACKGROUND: Stimulation of the intra-cardiac vagal nerves innervating the AV-node (AVNS) is a promising approach to slow down ventricular rate (VR) during atrial fibrillation (AF). Our purpose was to demonstrate that effects on R-R-interval during stable AF can be maintained for several months once optimized and that AVNS affects specifically the nerves innervating the AV-node. METHODS: Our study included both an acute and chronic phase. Fifteen goats were implanted with a pacemaker connected to an atrial and ventricular lead and a neurostimulator connected to an atrial lead placed at a certain septal site, to induce an AV prolongation. In the chronic experiments (n = 9), after assessment of optimal AVNS parameters, the effect of continuous AVNS on VR was studied during stable AF for up to 3 months. The mechanism of AVNS was studied using atropine and esmolol. Next, the effects of AVNS during the atrial refractory period on electrophysiological and hemodynamic parameters were investigated acutely (n = 7). RESULTS: The maximal effect was found at a stimulation frequency of 40 Hz, and increased with increasing pulse width (at lower voltages) and increasing voltage. After 0, 1, and 3 months of AVNS during stable AF, AVNS decreased average VR, respectively, 55% (n = 9), 48% (n = 8), and 28% (n = 6). The AVNS effect appeared to be dominantly parasympathetic. AVNS did not influence (1) the sinus node, (2) the refractory period of the atrial, ventricular tissue, and His and (3) hemodynamic parameters. CONCLUSION: AVNS is efficient in reducing ventricular rate for at least 3 months using optimized parameters and specifically affects the parasympathetic nerves innervating the AV-node.

Cardiac resynchronization therapy in patients undergoing open-chest cardiac surgery.

PURPOSE: Few data are available on the effects of cardiac resynchronization therapy (CRT) in candidates for cardiac surgery and affected by severe heart failure (HF). The aim of our analysis is to evaluate the percentage of patients who maintain indication for CRT after surgery and the efficacy of CRT in those patients subsequently implanted. METHODS: We enrolled 124 HF patients with indication both to heart surgery and to CRT. During surgery, an epicardial left ventricular lead was implanted, tunneled to a subclavear pocket, and capped. Afterward, patients were periodically reassessed to confirm indication for CRT. RESULTS: CRT indication was confirmed within 1 month from surgery in 54 patients (group A) and in 33 patients within 6 months (group B). In group A and B, 63% and 71% of patients were considered responders according to an arbitrary five-point increase of left ventricular ejection fraction (LVEF), respectively. The assessment of clinical response at 1 year, based on the definitions proposed by Packer, identified 63% and 80% of responders in group A and B, respectively. CONCLUSIONS: Our data show that a remarkable percentage of patients maintain an indication for CRT after cardiac surgery (76%), while in the remaining 24% the lack of an indication is confirmed by a higher LVEF at last follow-up. In combination with surgery, CRT proved to be an effective therapy in those patients who were subsequently implanted. The suggested method is simple, without significant adjunctive risks, and allows easier CRT implantation with stable thresholds.

Vagal tone augmentation to the atrioventricular node in humans: efficacy and safety of burst endocardial stimulation.

BACKGROUND: Control of atrioventricular (AV) nodal conduction by endocardial stimulation of efferent AV nodal vagal fibers [atrioventricular nodal vagal stimulation (AVNS)] is a promising approach for long-term device-based modulation of ventricular rate during atrial fibrillation (AF). However, few data on the efficacy of AVNS delivered as high-frequency stimulus packages (burst AVNS) in humans are available. OBJECTIVE: The purpose of this study was to determine whether burst AVNS can to modulate AV nodal conduction during AF and whether burst AVNS delivered during sinus rhythm (SR) in the effective atrial refractory period allows safe implantation of a permanent lead in a position suitable for AVNS. METHODS: Twenty patients (10 in SR and 10 in AF) who were candidates for dual-chamber pacemaker implantation for sick sinus syndrome were enrolled in the study. The posteroseptal right atrium was mapped to identify a location at which burst AVNS would achieve AV nodal conduction modulation (lengthening of PR interval in SR and reduction of ventricular rate in AF). Subsequently, a lead was screwed in at that site and burst stimulation (pulse rate 50 Hz, burst duration 180 ms) was delivered at different burst rates, pulse durations, and amplitudes. RESULTS: In all SR patients, PR-interval prolongation was evoked at 90 and 120 bursts/minute with pulse durations < or =1 ms. Specifically, the mean voltages required to obtain PR-interval prolongation and advanced AV block were 4.3 +/- 2.2 V and 5.4 +/- 1.8 V (at 90 bursts/minute and 1 ms), respectively. Similarly, ventricular rate reduction was obtained in all AF patients, starting from 90 bursts/minute and 0.5-ms pulse duration (at 5.4 +/- 1.8 V). Ventricular arrhythmias were never induced during AVNS. CONCLUSION: Endocardial right atrial burst AVNS reduces ventricular rate during AF. Burst AVNS delivered during SR in the effective atrial refractory period allows optimization of lead positioning for AVNS.

Atrioventricular (AV) node vagal stimulation by transvenous permanent lead implantation to modulate AV node function: safety and feasibility in humans.

BACKGROUND: Atrioventricular (AV) node vagal stimulation (AVNVS) has recently emerged as a novel approach to controlling AV dromotropic function. Animal studies have demonstrated that selective epicardial AVNVS is effective in controlling ventricular rate (VR) acutely and in the long term. Endocardial AVNVS has been shown to significantly reduce VR acutely during atrial fibrillation (AF) in humans. However, no data are available on its long-term reproducibility. OBJECTIVES: The purpose of this study was to demonstrate that the posteroseptal right atrium is a suitable site for permanent pacing and allows AVNVS in humans both acutely and during follow-up. METHODS: In 12 candidates for implantable cardioverter-defibrillator with a history of AF, the atrial lead was implanted in the posteroseptal right atrium, where advanced AV block was achieved during temporary high-frequency stimulation (HFS). On implantation and 3-month follow-up examination, HFS was delivered through the permanent lead to demonstrate the possibility to gradually slow the VR until complete AV block. RESULTS: On implantation, VR during AF was gradually slowed until complete AV block, which was elicited at 4.3 V (0.2 ms, 50 Hz). After 3 months, this effect remained reproducible. No significant change in pacing thresholds was observed after 3 months. We observed one dislodgment and one microdislodgement of atrial leads. CONCLUSIONS: Our study demonstrates, for the first time in humans, that selective placement of the atrial lead yields electrical characteristics suitable for permanent pacing and enables VR to be significantly reduced under HFS. These results, which were reproducible during follow-up, provide data for the development of device-based control of VR during AF.

Post-operative atrial fibrillation management by selective epicardial vagal fat pad stimulation.

PURPOSE: Post-operative atrial fibrillation (POAF) is a common complication after cardiac surgery and often leads to poorly tolerated fast ventricular rates. Negative dromotropic drugs are not always effective and may not be well tolerated in heart failure patients. Aim of this study is to verify if high-frequency stimulation of the right inferior fat pad (RIFPS) allows an effective decrease in ventricular rate (VR) during POAF. METHODS: We enrolled 32 consecutive patients submitted to bypass; during surgery, a temporary heart wire was implanted in a site where RIFPS evoked a functional AV block. During POAF, RIFPS was delivered from the heart wire to decrease VR. RESULTS: Intra-operative RIFPS evoked complete AV block in 29 patients (91%). Fourteen patients (44%) developed POAF (mean VR 127 +/- 12 bpm). In these patients, RIFPS achieved a 25% reduction of VR and complete AV block with 6.0 +/- 1.9 and 7.5 +/- 1.8 V (duration 0.2 ms, frequency 50 Hz), respectively. CONCLUSION: Epicardial RIFPS represents an effective and feasible technique to decrease VR during POAF.

Endocardial transcatheter stimulation of the AV nodal fat pad: stabilization of rapid ventricular rate response during atrial fibrillation in left ventricular failure.

INTRODUCTION: Recent acute studies demonstrated that atrioventricular (AV) node vagal stimulation during atrial fibrillation (AF) decreases the mean ventricular rate, thus improving hemodynamics. METHODS AND RESULTS: We report a case of a woman with acute heart failure (HF), chronic AF with untreatable ventricular rapid response, in severe hypotensive state due to a cardiogenic shock. The patient underwent left ventricular (LV) pacemaker implantation and received 50 Hz AV node stimulation, delivered through a posteroseptal atrial lead, thus allowing a 100% pacing. Hemodynamics improvements allowed carvedilol titration; the rate was below 85 bpm after 4 days, then the atrial lead was removed. CONCLUSIONS: This novel strategy may allow controlling the rapid AV response in patients undergoing pacemaker implantation.

Management of syncope: clinical and economic impact of a Syncope Unit.

AIMS: Aim of this observational study is to evaluate the clinical performance of a Syncope Unit, in order to assess whether the implemented organization really improves syncope management. METHODS AND RESULTS: The study enrolled patients with unexplained syncope who were consecutively referred to our Syncope Unit, either as outpatients or during hospitalization, in a 2-month period. The design of this observational study consists in three phases: a retrospective analysis of their clinical management in the 9 months prior to the first attendance at the Syncope Unit (phase one), their subsequent clinical management in the Syncope Unit (phase two) and a 9-month follow-up (phase three). The retrospective analysis of phase one showed that 25% of patients had already been hospitalized without diagnosis. After Syncope Unit evaluation, diagnosis was obtained in 82% of patients, with 15% of patients indicated to pacing. In the follow-up, 23% of patients experienced a syncopal recurrence. Our analysis indicated an 85% reduction of hospital costs in the follow-up period. CONCLUSION: The clinical and economic analysis of the three phases of our study demonstrates that a Syncope Unit allows an improved management of patients with syncope.