Study On Single Left Bundle Branch Anti-heart Failure Pacing System Compatible With Vagus Nerve Stimulation

Background:Significant advances have been made in drug and device therapy based on different pathophysiological mechanisms of chronic heart failure（CHF）.The traditional standard biventricular pacing（BVP）improves the symptoms and prognosis of patients with heart failure by correcting electrical-mechanical desynchronisation and reversing ventricular remodeling,but the treatment is expensive and still non-responsive in about 30%of patients;vagus nerve stimulation（VNS）has shown preliminary efficacy in anti-heart failure by balancing autonomic activity and inhibiting inflammation,but VNS alone leads to lower heart rate and slower atrioventricular node conduction,which in turn leads to haemodynamic disturbances and is not widely available.Based on the development of a modified dual-chamber pacemaker with single left ventricular anti-heart failure pacing and the development of a pacing-compatible VNS device,this study is intended to explore the feasibility of a VNS-compatible single left bundle branch anti-heart failure pacing system for the treatment of CHF,with a view to providing a new option for the clinical treatment of chronic heart failure.Objectives:This study explores the algorithm for automatic optimization of the atrioventricular interval（AVI）by single left bundle branch pacing through post-operative clinical follow-up and interval optimization in patients treated with single left bundle branch pacing to achieve cardiac resynchronization,and proposes to explore the feasibility and methodology of a VNS-compatible single left bundle branch anti-heart failure pacing system to provide a basis for future translational research and development.Methods:1.A total of 42 patients with CHF who met the 2016 ESC Heart Failure Guidelines for CRT Class Ia indications were included in this study,including30 men and 12 women with a diagnosis of dilated cardiomyopathy（DCM）in 30 cases and ischaemic cardiomyopathy（ICM）in 12 cases.All patients were successfully implanted with either single left bundle branch pacing（LBBP）or conventional standard biventricular pacing（BVP）according to standard methods with dual or triple-chamber pacing systems with frequency-adaptive atrial delay（RAAVD）.The control group consisted of 24 patients treated with single LBBP（9 with a dual-chamber pacing system and 15 with a three-chamber pacing system）and 18patients treated with standard BVP（14 with CRT-D and 4 with CRT-P）.2.Patients enrolled in the study were informed and had signed an informed consent form for the study.Baseline data such as preoperative electrocardiogram（ECG）,chest radiograph,NYHA cardiac function class,6-minute walk test（6MWT）,NT-pro BNP,medication use,echocardiography-related parameters were collected from all enrolled patients.Patients were followed up clinically at 1,3,6,12 months post-operatively and once a year thereafter.The follow-up included review of baseline indicators,programmed optimization and medication adjustment.The results of the last follow-up visit were used to compare and analyse the differences between groups and subgroups in clinical parameters,improvement in cardiac function,pacemaker program control optimisation parameters and cardiac ultrasound-related parameters,in order to assess the feasibility and efficacy of implanting different pacing systems for the treatment of chronic heart failure.3.The ratio of optimized AVI to right atrial_（n-1）-right atrial_（n）[RA_（n-1）-RA_（n）]interval for single left bundle branch pacing in the study group was defined as the single left bundle branch pacing coefficientε,namely,ε=optimized AVI/[RA_（n-1）-RA_（n）]interval.Interval optimisation was performed and averaged under 12-lead ECG and echocardiography.4.Based on the above study of the efficacy of single left bundle branch pacing for anti-heart failure and the exploration of automatic AVI optimization,we propose a method for implementing a single left bundle branch anti-heart failure pacing system compatible with vagus nerve stimulation and discuss its feasibility and limitations.Results:1.The average follow-up time was 11.88±6.28 months in the study group and 13.28±4.68 months in the control group.As of the last follow-up,compared with 18 patients in the standard BVP group,24 patients in the LBBP group had shorter QRS duration[（120.54±14.61）ms vs（129.94±9.81）ms,P<0.05]and lower left ventricular threshold[（0.65±0.24）V vs（0.99±0.40）V,P<0.01],the difference was statistically significant;postoperative cardiac ultrasound synchronization indexes IVMD[（42.29±14.91）ms vs（46.83±12.26）ms,P>0.05]and Ts-SD₁₂[（114.58±35.42）ms vs（123.83±18.74）ms,P>0.05]in the LBBP group responded a trend of improvement compared with the standard BVP group,but the difference was not statistically significant.There was no significant difference in other postoperative cardiac ultrasound indices EA/RR,LVFS,LVEF,LAD,LVEDD,LVESD,AVVTI,6MWT,NT-pro BNP,NYHA cardiac function classification and left ventricular impedance between the two groups.2.In subgroup analysis,the dual-chamber pacing system was less costly[（4.40±1.45）thousand yuan vs（11.41±1.32）thousand yuan,P<0.001]and had a longer life expectancy[（8.11±0.70）years vs（5.38±0.78）years,P<0.001]compared to the three-chamber pacing system,with a statistically significant difference.3.Programmed data analysis,the mean heart rate of 24 patients in the single left bundle branch pacing group was 75.22±10.56bpm,the mean[RA_（n-1）-RA_（n）]interval was 812.62±115.27ms,the mean optimized AVI was 106.00±14.82ms,and the meanεwas 0.132±0.019.According to which we obtained Algorithm to automatically optimize anti-heart failure pacing AVI based on[RA_（n-1）-RA_（n）]interval:the atrial channel senses heart rate and for every 5 changes in heart rate,the program can automatically calculate the optimal AVI based on the[RA_（n-1）-RA_（n）]interval:AVIε_（n）=[RA_（n-1）-RA_（n）]interval×ε（n≥2,system default value=0.13）;ifεis poor after system implantation,individual optimisation can be performed.4.Establishment of a VNS-compatible single left bundle branch anti-heart failure pacing system:The pacing system consists of a hardware part and a software part.The hardware component consists of:（i）a three-chamber pacemaker pulse generator;（ii）right atrial pacing electrodes;（iii）left bundle branch pacing electrodes;and（iv）VNS electrodes.The software part consists of:（i）an algorithm for optimising the AVI for anti-heart failure pacing based on the right atrial_（n-1）-right atrial_（n）[RA_（n-1）-RA_（n）]interval;and（ii）a program for automatic disconnection of the VNS when the heart rate falls below the pacemaker LLR.It features a three-chamber pacemaker pulse generator connected to three electrodes respectively,a VNS electrode fixed to the vagus nerve trunk,a left ventricular electrode implanted in the left bundle branch region and a right atrial electrode implanted in the right heart ear.Conclusions:The efficacy of single left bundle branch pacing in anti-heart failure is not inferior to that of standard biventricular pacing,and a VNS-compatible single left bundle branch anti-heart failure pacing system can be established based on automatic optimization of AVI over[RA_（n-1）-RA_（n）]intervals.