Intrinsic Atrioventricular Conduction Research Articles

Role of RA-LV pacing in patients with symptomatic left bundle branch block with CRT - a single centre experience

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiac Resynchronisation Therapy(CRT) is considered as the cornerstone of treatment for patients with heart failure and left ventricular conduction delay ( left bundle branch block) who remain symptomatic despite optimal medical therapy. However, it has been well documented that the responder and success rates of this therapy are highly variable. Contemporary response rates from clinical trials as well as real world data demonstrate non-response rates of between 30–50%. Suboptimal AV delay timing is the most prevalent modifiable factor on follow up for improving response rates. AV Fusion pacing describes the delivery of CRT pacing with a programming strategy to preserve intrinsic atrioventricular (AV) conduction and ventricular activation via the right bundle branch. This concept is utilised in the RA- LV pacing strategies, which have been described in literature. However, RA-LV only pacing raises certain practical , moral and ethical concerns as it has never been a part of contemporary guidelines nor a part of large randomised control trial. Purpose The purpose of this study was to study the clinical as well as hemodynamic effects of RA-LV pacing in patients with a conventional CRT device with a programmed subthreshold RV lead. Methods All patients with a convention CRT indication ( CRT-P as well as CRT-D), with acceptable intrinsic AV conduction, non pacing dependent and normal Right Ventricular function were enrolled into the study. A total of 60 consecutive patients between 2016-2021 were enlisted from after the implant and followed up in the Device clinic of the institution. The baseline as well as follow-up LV function, Battery life and QRS duration was recorded and analysed. Results Total of 60 patients were enlisted of which 30 were males and 30 females. There were 16 patients were with Ischemic Cardiomyopathy in this group. The average follow-up period was 3 year from implant. The mean baseline Left Ventricular Ejection Fraction was 29% while the mean follow-up Left Ventricular Ejection Fraction was 46.5%. The mean QRS duration at implant was 155msec and the mean follow-up QRS was 123 msec. The subset analysis of ischemic vs the nonischaemic cardiomyopathy groups revealed that both groups had a similar response rates to improvement of clinical as well as Echocardiographic parameters including LVEF. The mean follow up LVEF in the ischemic and nonischaemic groups were 44.5 & 46.5% respectively. This finding suggests that the advantage of AV fusion pacing is not significantly impacted with underlying aetiology of the Cardiomyopathy. Conclusion RA-LV with RV subthreshold CRT is a reasonable strategy for achieving traditional response rates of CRT in patients with a good intrinsic AV conduction. This modality overcomes a large number of procedural as well as ethical roadblocks in the use of fusion pacing for CRT therapy optimisation.

Marked first-degree AV block may lead to complete AV block development

Abstract Funding Acknowledgements Type of funding sources: None. Background First-degree atrioventricular (AV) block (PR interval >200 ms) is considered a benign condition with rare progression to a higher degree AV block. The site of block is determined with electrophysiological (EP) study and measurement of His-ventricular (HV) interval, with normal values below 55 ms. Prolonged HV interval > 70 ms is predictive of higher-grade AV block development. Marked first-degree AV block with a PR > 300 ms may lead to symptoms such as fatigue, poor exercise tolerance and palpitations. When symptoms are correlated to the conduction delay, permanent pacemaker (PPM) implantation to restore AV synchrony should be considered. In the Framingham heart study, patients with first-degree AV block had a threefold higher risk of PPM implantation. However, there is no data on the HV intervals and the rate of progression of conduction disorder in patients with marked first-degree AV block. Purpose To assess the predictive value of HV interval measurement in patients with marked first-degree AV block for progression to a higher-degree conduction disorder. Methods We prospectively evaluated consecutive patients with symptomatic marked first-degree AV block that underwent a PPM implantation. His electrograms were recorded during the implantation, and HV intervals were measured from the first deflection of the His signal to the earliest onset of ventricular activation on a 12-lead surface ECG. Patients were followed for 6 months with three out-patient visits, during which the PPM was temporarily inhibited to check for intrinsic AV conduction. Results Seventeen patients were evaluated between January 2020 and September 2022. Ten patients (59%) were male, and 7 (41%) were female, with an average age of 61 ± 19 years. All patients had markedly prolonged PR interval (383 ± 47 ms) and narrow QRS complex (100 ± 16 ms). Three patients (17%) had intermittent type 1 second-degree AV block, right bundle branch block was recorded in two (12%) and left anterior fascicular block in four (24%) patients. Except for one patient with a corrected atrial septal defect, there were no echocardiographic signs of structural heart disease with a left ventricular ejection fraction of 61 ± 5%. The HV intervals were on the upper limit of normal values at 54 ± 6ms and no patient had an HV interval above 70 ms. Two patients (12%) developed complete AV block during follow-up: one female, and one male, 28 and 83 years old, respectively, with a PR interval 392 and 363 ms, QRS 104 and 94 ms, and HV 57 and 48 ms. None of the two had any additional conduction blocks at the time of PPM implant. Conclusion In our cohort of patients with symptomatic first-degree AV block (PR>300 ms), two patients (12%) developed complete AV block despite normal HV intervals at the time of implant. Closer monitoring, beyond only EP measurements, of patients with markedly prolonged PR intervals is warranted for the potential progression of conduction disorder.

The impact of chronotropic incompetence on atrioventricular conduction times in heart failure patients.

Intrinsic atrioventricular (AV) conduction is used to optimize AV intervals with cardiac resynchronization therapy (CRT) in most device algorithms. Atrial pacing and heart rate affect conduction times, but little is known regarding differeces among chronotropic incompetent(CI) and competent(CC) patients to guide programming. RAVE was a multicenter prospective trial of CRT patients. Heart rate was increased with incremental atrial pacing and with submaximal exercise. According to the maximal heart rate achieved during exercise, patients were classified as either CI or CC. For CI patients, an additional symptom-limited exercise with rate-adaptive pacing activated was performed. Intracardiac intervals were measured from the implantable lead electrograms in multiple postures. There were 12 subjects with CI and 24 with CC. With atrial pacing, AV interval immediately increased and gradually increased with incremental atrial pacing in all patients. However, the changes in the atrial to right ventricular (ARV) and atrial to left ventricular (ALV) intervals with increasing atrial pacing rates were about threefold greater in CI patients compared to CC patients (24.3 ± 28.9 vs. 7.2 ± 5.5ms/10bpm for ARV and 22.7 ± 25.6 vs. 7.1 ± 5.7ms/10bpm for ALV in the standing position, p < 0.05). In CI pacing with rate-adaptive pacing during exercise, AV interval changes with paced heart rate were variable. The AV response to overdrive atrial pacing at rest may provide a simple means of identifying chronotropic competence in CRT patients. For patients with CI, who often require rate-adaptive atrial pacing, rate-adaptive AV algorithms should be adjusted individually.

Differences in Electrical Delay Between the Mid-septum and Apex with the Right Ventricular Lead: Novel Implications for Pacemaker Sensing.

Ventricular sensing relies on the analysis of a local intracardiac electrogram in reference to the QRS on the surface electrocardiogram. If both signals do not coincide in time, there is a delay in sensing intrinsic ventricular activity. We evaluated possible differences in the electrical delay between the mid-septum and apex as determined by the right ventricular (RV) lead position using a pacing system analyzer (PSA) during conventional pacemaker implantation. Patients without significant heart disease and intrinsic atrioventricular conduction underwent their first Medtronic (Minneapolis, MN, USA) or Abbott (Chicago, IL, USA) dual-chamber pacemaker implantation with the RV lead first positioned at the apex and then subsequently at the mid-septum. Real-time ventricular sensing data were obtained through PSA to determine the electrical delay Q-VS value as the time difference between the QRS and the released RV-sensed event marker "VS." Among 212 patients, 139 had narrow QRS and 73 had complete right bundle branch block (RBBB). Overall, both narrow QRS and RBBB patients exhibited shorter Q-VS lengths at the mid-septum compared to the apex (50.4 ± 24.2 ms and 66.7 ± 32.3 ms vs. 63.9 ± 27.6 ms and 71.7 ± 32.2 ms; P < .0001 and P < .001, respectively). The Q-VS in patients with Abbott devices was significantly shorter compared to that in patients with Medtronic devices at both the mid-septum and the apex in both patient groups (P < .0001). In conclusion, RV lead positioning at the mid-septum is associated with a shorter electrical delay compared to positioning at the apex in both narrow QRS and RBBB patients.

Abstract 10530: Incidence and Electrocardiographic Predictors of Atrioventricular Conduction Recovery After Permanent Pacemaker Implantation in Transcatheter Aortic Valve Replacement

Background: High grade atrioventricular (AV) block (HGAVB) after transcatheter aortic valve replacement (TAVR) requiring permanent pacemaker implantation (PPM) is a well-established complication, but recovery of intrinsic AV conduction is not well studied. We assessed the incidence and electrocardiography (ECG) predictors of AV conduction recovery after PPM implantation post-TAVR. Methods: In this multicenter, retrospective study, consecutive patients undergoing TAVR between January 2015 to February 2019 were identified. All patients requiring PPM for HGAVB within 30 days after TAVR were included. Follow up ECGs, PPM checks, and clinic notes were reviewed to determine AV conduction recovery, defined as no need for ventricular pacing. Results: There were 533 TAVR patients, 443 with balloon expandable valves (BEV) and 90 with self-expanding valves (SEV). 5.1% of patients (n=27) required PPM for HGAVB, including 4.5% (n=20) from BEV group and 7.8% (n=7) from SEV group. Right bundle branch block (RBBB) was the most common baseline ECG finding (n=19). Mean time to PPM implant was 3.3±4.5 days. 11 patients received leadless and 16 received conventional pacemakers. At 6 months, 65% (n=13) of BEV group and none of SEV group had AV conduction recovery. BEV patients without AV conduction recovery had significantly longer baseline PR intervals compared to those with recovery (248±85 msec vs 169±22 msec; 95% CI 12.5-147.2; p=0.024). There were no significant differences in baseline QRS duration or presence of RBBB between those with and without AV conduction recovery. Conclusion: AV conduction recovery is more frequent after PPM implantation in TAVR patients receiving BEV (65%) compared to SEV (0%). Normal baseline PR intervals at baseline is associated with higher rate of AV conduction recovery among BEV patients. Temporary pacing with leadless pacemakers may be an alternative to conventional pacemakers in BEV patients without baseline first degree AV block.

Inadvertent QRS prolongation by an optimization device-based algorithm in patients with cardiac resynchronization therapy.

Device-based algorithms offer the potential for automated optimization of cardiac resynchronization therapy (CRT), but the process for accepting them into clinical use is currently still ad-hoc, rather than based on pre-clinical and clinical testing of specific features of validity. We investigated how the QuickOpt-guided VV delay (VVD) programming performs against the clinical and engineering heuristic of QRS complex shortening by CRT. A prospective, 2-center study enrolled 37 consecutive patients with CRT. QRS complex duration (QRSd) was assessed during intrinsic atrioventricular conduction, synchronous biventricular pacing, and biventricular pacing with QuickOpt-proposed VVD. The measurements were done manually by electronic calipers in signal-averaged and magnified 12-lead QRS complexes. Native QRSd was 174 ± 22 ms. Biventricular pacing with empiric AVD and synchronous VVD resulted in QRSd 156 ± 20 ms, a significant narrowing from the baseline QRSd by 17 ± 27 ms, P = 0.0003. In 36 of 37 patients, the QuickOpt algorithm recommended left ventricular preexcitation with VVD of 42 ± 18 ms (median 40 ms; interquartile range 30-55 ms, P <0.00001). QRSd in biventricular pacing with QuickOpt-based VVD was significantly longer compared with synchronous biventricular pacing (168 ± 25 ms vs. 156 ± 20 ms; difference 12 ± 11ms; P <0.00001). This prolongation correlated with the absolute VVD value (R = 0.66, P <0.00001). QuickOpt algorithm systematically favours a left-preexcitation VVD which translates into a significant prolongation of the QRSd compared to synchronous biventricular pacing. There is no reason to believe that a manipulation that systematically widens QRSd should be considered to optimize physiology. Device-based CRT optimization algorithms should undergo systematic mechanistic pre-clinical evaluation in various scenarios before they are tested in large clinical studies.

Right ventricular lead sensing latency in pacemaker therapy.

BackgroundPacemaker implantation involves intraoperative testing of ventricular sensing using a device called a pacing system analyzer (PSA). The value obtained is expected to correspond to those taken by the pacemaker after its implantation. This study determined the latency period for sensing intracardiac electrogram (EGM) by the right ventricular (RV) lead.MethodsPatients without significant heart disease and underlying intrinsic atrioventricular (AV) conduction underwent Medtronic or Abbott dual‐chamber pacemaker implantation with the RV lead positioned on the mid‐septum. Real‐time sensing data were obtained through PSA and after pacemaker implantation to evaluate latency as the time interval Q‐VS between the onset of QRS on surface electrocardiogram and the sensed EGM by the RV lead.ResultsOf 157 patients, 105 had narrow QRS (<120 ms) and 52 had wide QRS of complete right bundle branch block (RBBB). Both narrow‐QRS and RBBB patients had longer sensing latency through PSA (50.9 ± 24.2 and 67.8 ± 32.9 ms, respectively) than through pacemaker (18.2 ± 12.8 and 31.2 ± 14.8 ms, respectively, both p < 0.001). RBBB patients had longer sensing latency compared with narrow QRS patients, either through PSA or through pacemaker (p < 0.001). The sensing latency of Medtronic recipients was longer than those of Abbott in narrow‐QRS (p < 0.05), but not in RBBB.ConclusionWe demonstrated longer RV lead sensing latency (1) through PSA than through pacemaker, (2) in RBBB than in narrow‐QRS, and (3) in Medtronic pacemakers compared with Abbott pacemakers. Knowledge of sensing latency helps the optimization of the AV delay.

Impact of synchronized left ventricular pacing rate on risk for ventricular tachyarrhythmias after cardiac resynchronization therapy in patients with heart failure.

The adaptive cardiac resynchronization therapy (aCRT) algorithm automatically produces synchronized left ventricular pacing (sLVP) with intrinsic atrioventricular conduction to improve clinical outcomes. However, relationship between sLVP percentage and risk for ventricular tachyarrhythmia (VT/VF) remains unclear. This study aimed to evaluate the clinical impact of sLVP rate on VT/VF occurrence. In total, 1,419 device interrogation data from 42 consecutive patients who underwent new aCRT device implantation were retrospectively analyzed. The primary endpoint was the first time VT/VF episode after aCRT device implantation. During a median follow-up of 34months, 15 patients had VT/VF episodes. Patients were divided into a high sLVP (the average sLVP percentage of ≥ 51.5%, n = 27) or low sLVP group (< 51.5%, n = 15). The high sLVP group had a significantly lower VT/VF incidence (22% vs. 60%; p = 0.014) and an independent predictor for VT/VF occurrence on multivariate analysis (hazard ratio 0.21; p = 0.007). LV ejection fraction improvements after 6months (12.3 ± 8.7% vs. 2.8 ± 10.3%; p = 0.004) and 12months (13.8 ± 9.3% vs. 6.2 ± 11.1%; p = 0.030) were significantly greater in the high sLVP group than in the low sLVP group. Age, PR interval, and left atrial diameter were significantly associated with the sLVP rate after aCRT. Patients with high sLVP percentage after aCRT had lower long-term risk of VT/VF incidence with a favorable response to CRT. A synchronized pacing algorithm using intrinsic conduction may prevent malignant arrhythmias, as well as recover cardiac functions.

Assessment of fusion pacing on exercise capacity in patients with cardiac resynchronisation therapy devices

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Local Departmental Research Funding Background Cardiac resynchronisation therapy (CRT) using fusion pacing requires correct timing of left ventricular pacing to right ventricular activation. The SyncAV™ algorithm, achieves this by dynamic reassessment of intrinsic atrio-ventricular (AV) conduction to adjust the paced/sensed AV delay. However, it is unclear whether AV optimisation maintains resynchronisation during exercise, or whether loss of fusion could lead to decreased exercise capacity. Cardio-pulmonary exercise testing (CPET) is the gold standard method for assessing exercise performance and can provide prognostic information in the heart failure population. Purpose We therefore used CPET measures of exercise capacity to compare the SyncAV™ algorithm to conventional pacing with fixed AV delays, in a double blinded, randomised crossover study (NCT03768804). Methods Patients at least 6 months post-CRT implant performed 2 CPET tests at least 1 week apart, with randomisation to either SyncAV™ with fusion pacing or conventional biventricular pacing with a fixed AVD of 120ms. All other programming was optimised to produce the narrowest QRS duration possible at rest in each case. Results Twenty patients (11 male, age 71 [65-77] years, median [interquartile range]) were recruited, with both ischaemic and non-ischaemic aetiology of heart failure. All had clinical and/or echocardiographic response to CRT. Optimised Fixed AVD and SyncAV™programming resulted in similar narrowing of QRS duration (QRSd) from intrinsic rhythm at rest (131 [103-137] vs 134 [110-137] ms for fixed AVD and SyncAV™ groups respectively, p=0.85). Overall, there was no difference in peak oxygen consumption (V̇O2peak) between programming (14.91 [12.61-18.16] vs 15.61 [12.18-19.70] ml/kg/min, p=0.19), or oxygen consumption at anaerobic threshold (VT1) (7.36 [6.93-8.94] vs 7.87 [6.77-9.24] ml/kg/min, p=0.42), or in the time to reach either V̇O2PEAK (p=0.81) or VT1 (p=0.39). The BORG rating of perceived effort was also similar between groups. CPET performance was also analysed comparing whichever programming gave the narrowest QRSd at rest (119 [96-136] vs 134 [119-142] ms, p&amp;lt;0.01). Eight were narrower with fixed AVD, 8 with SyncAV™ and in 4 there was no difference. QRSd during exercise (p=0.03), peak O2 pulse (ml/beat, a surrogate of stroke volume, p=0.03) and cardiac efficiency (watts/ml/kg/min, p=0.04) were significantly improved when programmed to the narrowest QRS duration at rest. Conclusion There is no significant difference in exercise capacity or QRSd between the use of optimised fixed AVD or SyncAV™, lending reassurance to fusion pacing being adequately maintained on exercise. In addition, programming with whichever algorithm gives the narrowest QRSd at rest is associated with a narrower QRSd during exercise, higher peak stroke volume and improved cardiac efficiency. This supports the use of SyncAV™ in the 40% of patients where this gave the narrowest QRSd at rest.

Diagnostic reliability of AV synchrony self-diagnostics in leadless VDD pacemakers

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Leadless pacemakers (PMs) capable of atrio-ventricular (AV) synchronous pacing have been introduced recently. These devices provide mechanical atrial sensing by detection of the atrial contraction via an accelerometer. Atrial tracking may be disturbed by external influences such as body motions and higher heart rates in real life. To track the amount of AV synchronous pacing, the device statistic classifies all sensed and paced QRS complexes according to presumed AV synchrony. The reliability of this self-diagnostics to estimate the true degree of AV synchrony, however, is insufficiently studied. Purpose To investigate the informative value of the device statistics offered by leadless VDD PMs regarding true AV snychrony. Methods We prospectively included all patients who received a leadless VDD PM between 07/2020 and 05/2021 at our center in this observational study. During the regular outpatient follow-ups, device interrogation was performed, which included evaluation of the PM statistics. True AV synchrony (defined as a QRS complex preceded by a p-wave within 300ms) was analyzed repeatedly during follow-up using Holter ECGs. Results We analysed 34 Holter ECGs from 20 outpatients (816 hours of ECG in total). Patients had a median age of 80 years (interquartile range 76-86 years), 55% were females. For Holter ECG sequences that showed high degree or complete AV-Block (&amp;gt;80% ventricular pacing), the percentage of paced beats that were presumed to be AV synchronous by the device statistic (ratio "AM-VP"/total VP) correlated well with AV synchrony as assessed using Holter-ECGs (Kendall’s τ=0.312, p&amp;lt;0.001). AV synchrony in the Holter ECG was different in patients with &amp;lt;66.6% presumed AV synchrony than in patients with &amp;gt;66.6% presumed AV synchrony (p&amp;lt;0.001, figure). For Holter ECG sequences with mostly preserved intrinsic AV conduction (&amp;lt;20% ventricular pacing), the ratio "AM-VP"/total VP was not predictive for true AV synchrony (Kendall’s τ=0.07, p=n.s.). In this situation, however, "VS only" (Kendall’s τ=0.110, p=0.005) correlated with true AV synchrony (due to AV conduction mode switch) and "VP only" showed an inverse correlation with AV synchrony (Kendall’s τ=-0.215, p&amp;lt;0.001). Conclusion Leadless PMs provide device statistics that show a correlation with true AV synchrony. The clinical setting as well as the device programming (e.g. AV conduction mode switch) significantly influence the predictive value of the different parameters of the device’s statistics.

Right ventricular lead sensing latency in pacemaker therapy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Pacemaker’s ventricular sensing function relies on the analysis of the intracardiac electrogram (EGM) including the timing of the intrinsic detection. The phenomenon of ventricular sensing latency refers to the gap of time by which the intrinsic signal gets delayed to be detected compared with the surface electrogram (ECG). A pacing system analyzer (PSA) unit is needed to record the EGM during pacemaker operation, which is expected to correspond to those taken following implantation. Purpose We sought to determine the latency period for sensing EGM by the right ventricular (RV) lead, either through the PSA or through the implanted pacemaker on the same patient. Methods Patients without significant heart disease and intrinsic atrioventricular conduction underwent conventional dual-chamber Medtronic or Abbott pacemaker implantation with the RV lead positioned on mid-septum. Real time sensing data was obtained through PSA and after pacemaker implantation. The RV lead sensing latency was defined as the time interval Q-VS measured from the beginning of QRS on ECG to the released ventricular sensed (VS) event marker on either device. Results Of 157 patients, 105 had narrow QRS (&amp;lt;120 ms) and 52 had wide QRS (≥120 ms) of right bundle branch block (RBBB). Both narrow QRS and RBBB patients had longer sensing latency through PSA (50.9 ± 24.2 ms and 67.8 ± 32.9 ms, respectively) than through pacemaker (18.2 ± 12.8 ms and 31.2 ± 14.8 ms, respectively, both p&amp;lt;0.001). RBBB patients had longer sensing latency compared with narrow QRS patients, either through PSA or through pacemaker (p&amp;lt;0.001). The sensing latency of Medtronic recipients was longer than those of Abbott in narrow QRS, but not in RBBB (p=0.03 and p=0.08, respectively). Conclusion We demonstrated longer RV lead sensing latency (1) through PSA than through the implanted pacemaker, (2) in RBBB than in narrow QRS, (3) in Medtronic pacemakers compared with Abbott pacemakers. Knowledge of the RV lead sensing latency helps optimization of atrioventricular delay and reduces unnecessary ventricular pacing.

AV timing in pacemaker patients with first-degree AV block: which is preferable, intrinsic AV conduction or pacing?

Some patients with pacemakers present with first-degree atrioventricular (AV) block. To avoid right ventricular (RV) pacing, preserving intrinsic AV conduction as much as possible is recommended. However, there is no clear cutoff AV interval to determine whether intrinsic AV conduction should be preserved or RV pacing should be delivered. This study aimed to compare a pacing mode-preserving, intrinsic AV conduction with the DDD mode delivering RV pacing in terms of echocardiographic parameters in patients with first-degree AV block and to investigate whether RV pacing induces heart failure (HF). Stroke volume (SV) was measured to determine the optimal AV delay with the intrinsic AV conduction rhythm and the DDD pacing delivering RV pacing. Echocardiographic evaluation was performed for 6-month follow-up period. Seventeen patients were studied. At baseline, mean intrinsic PQ interval was 250 ± 40 ms. SV was greater with RV pacing with optimal AV delay of 160 ms than with intrinsic AV conduction rhythm in all patients. Therefore, pacemakers were set to the DDD to deliver RV pacing. During follow-up, seven patients developed HF. Mean baseline E/E′ ratio in patients who developed HF (HF group) during RV pacing was higher than in patients without HF (non = HF group; 17.9 ± 8 versus 11.5 ± 2, P = 0.018) Even within HF group patients without a high baseline E/E′ ratio, it increased with RV pacing (22.2 ± 6 versus 11.6 ± 2; P < 0.001). In patients with pacemaker and first-degree AV block, RV pacing with the optimal AV delay of 160 ms increased SV. However, the risk of HF may be increased with RV pacing if the E/Eʹ ratio is > 15 during intrinsic AV conduction or RV pacing. RV pacing should be avoided in patients with high E/Eʹ ratio under intrinsic AV conduction or RV pacing.

Dynamic optimization of CRT pacing using a novel algorithm improves survival in a real-world cohort of patients

Abstract Background The AdaptivCRT (aCRT) algorithm continuously adjusts cardiac resynchronization therapy (CRT) according to intrinsic atrioventricular (AV) conduction status, providing synchronized left-ventricular pacing in patients (pts) with a normal PR interval and adaptive biventricular (BiV) pacing in pts with a prolonged PR interval. Prior secondary analyses of prospective trials demonstrated a reduction in mortality and atrial fibrillation incidence with aCRT. Objective To compare mortality in a large real-world population of pts with and without aCRT using electronic health record (EHR) data. Methods An Optum® de-identified EHR dataset and Medtronic CareLink device data were linked to identify pts (age&amp;gt;18 years) with a CRT implanted between 2014–2018 who survived ≥35 days post implant and with a documented baseline left ventricular ejection fraction (LVEF). Pts were grouped with aCRT set to either Adaptive BiV+LV (aCRT group) or standard CRT (control group). Two pt subgroups were identified: (i) pts with left bundle branch block (LBBB) and no AV block, (ii) pts with either no LBBB or with AV block. Kaplan-Meier curves and log-rank were used to estimate and compare survival between treatment and control groups in both the full cohort and subgroups. Multivariate Cox regression was used to estimate the aCRT treatment effect while controlling for baseline characteristics. Results Among 8624 patients implanted with a CRT device with EHR data available for a median of 23.5 months post implant [IQR: 12.6, 37.3], 3994 patients had the aCRT feature activated. Pts in the aCRT group were younger (median 69 [IQR:60, 76] vs 73 [IQR: 65, 79] years), more frequently female (35% vs 26%), and more frequently had LBBB (72% vs 51%); p's&amp;lt;0.001. Median QRS duration was 150ms (IQR: 133, 164) for the aCRT group and 152ms (IQR: 134, 172) for the control group (p&amp;lt;0.001). Median LVEF was 22% (IQR: 18, 30) for the aCRT group and 25% (IQR: 20, 30) for the control group (p&amp;lt;0.001). Through 60 months post implant, the overall mortality rate was 23.6% (95% CI: 20.7%-26.3%) for the aCRT group and 37.6% for the control group (95% CI: 34.9%-40.1%), p&amp;lt;0.001. Subgroup analysis demonstrated a significant reduction in mortality with aCRT in both pts with LBBB without AV block (Figure, left panel) and pts without LBBB and with AV block (Figure, right panel). After accounting for baseline differences, the reduction in mortality remained significant in the LBBB/no AV block group (HR: 0.54, 95% CI: 0.39–0.76, p&amp;lt;0.001) and trended toward significance in the no LBBB/with AV block group (HR: 0.89, 95% CI: 0.79–1.01; p=0.08). Conclusion In a large, real-world population of pts implanted with CRT devices, the AdaptivCRT algorithm was associated with significantly reduced mortality, with a greater reduction observed among pts with LBBB and without AV block. These results are being tested prospectively in the ongoing AdaptResponse multi-national, randomized clinical trial. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Medtronic, Inc. Cumulative probability of death by group

Fusion Pacing with Biventricular, Left Ventricular-only and Multipoint Pacing in Cardiac Resynchronisation Therapy: Latest Evidence and Strategies for Use.

Despite advances in the field of cardiac resynchronisation therapy (CRT), response rates and durability of therapy remain relatively static. Optimising device timing intervals may be the most common modifiable factor influencing CRT efficacy after implantation. This review addresses the concept of fusion pacing as a method for improving patient outcomes with CRT. Fusion pacing describes the delivery of CRT pacing with a programming strategy to preserve intrinsic atrioventricular (AV) conduction and ventricular activation via the right bundle branch. Several methods have been assessed to achieve fusion pacing. QRS complex duration (QRSd) shortening with CRT is associated with improved clinical response. Dynamic algorithm-based optimisation targeting narrowest QRSd in patients with intact AV conduction has shown promise in people with heart failure with left bundle branch block. Individualised dynamic programming achieving fusion may achieve the greatest magnitude of electrical synchrony, measured by QRSd narrowing.

Assessment of the SyncAV fusion pacing algorithm on exercise capacity in patients with cardiac resynchronisation therapy device

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation (BHF) and Local Departmental Research Funding Background Fusion pacing as part of cardiac resynchronization therapy (CRT) requires correct timing of left ventricular pacing to right ventricular activation. The SyncAV algorithm, available in Quadra Allure and Assura CRT devices, is designed to allow optimal fusion pacing by dynamic reassessment of intrinsic atrio-ventricular (AV) conduction to adjust the paced/sensed AV delay. However, it is unclear whether AV optimisation continues to maintain resynchronisation during exercise, or whether potential loss of fusion pacing with changes in intrinsic AV conduction could lead to decreased exercise capacity. Cardio-pulmonary exercise testing (CPET) is the gold standard method for assessing exercise performance. Purpose To assess exercise capacity using the SyncAV algorithm for fusion pacing, compared with conventional biventricular pacing with fixed AV delays (AVD) for CRT. Methods Patients at least 6 months post-CRT implant were recruited in a prospective single-centre randomized single-blind crossover study. Patients performed 2 CPET tests at least 1 week apart, with randomization to either SyncAV with fusion pacing or conventional biventricular pacing with a fixed AVD of 120ms. All other programming was optimised to produce the narrowest QRS duration possible at rest in each case. Results Nine patients (5 male, age 70 ± 10 years, mean ± standard deviation) were recruited, with both ischaemic and non-ischaemic aetiology of heart failure. All had clinical or echocardiographic response to CRT. There was no difference in peak oxygen consumption (V̇O2max) between programming (1.47 ± 0.57 vs 1.50 ± 0.65 l/min for fixed AVD and SyncAV groups respectively, p = 0.59), or oxygen consumption at anaerobic threshold (VT1) (0.72 ± 0.20 vs 0.74 ± 0.25 l/min, p = 0.57). There was no difference in oxygen pulse (V̇O2/heart rate - a surrogate of stroke volume) at peak (12.3 ± 3.8 vs 13 ± 5.0 ml/beat , p = 0.28) or VT1 (8.4 ± 2.2 vs 8.7 ± 2.1 ml/beat, p = 0.67) and also no change in time to V̇O2max (1400 ± 491 vs 1367 ± 543 seconds, p = 0.38) or VT1 (518 ± 211 vs 534 ± 200 seconds, p = 0.75). Average heart rate at the median stage of exercise showed no difference between programming (96 ± 18 vs 93 ± 15 bpm respectively, p = 0.32). There was no difference in BORG Rating of Perceived Exertion (BORG-RPE) score at either peak exercise (median 19 [interquartile range (IQR) 2] vs 17 [IQR 2], p = 0.23) or at the median stage of exercise (median 13 [IQR 1] vs 13 [IQR 2], p = 0.30). Conclusion Fusion pacing using the SyncAV algorithm does not appear to improve exercise capacity compared to optimised conventional biventricular pacing with fixed AVD.

Detrimental Immediate- and Medium-Term Clinical Effects of Right Ventricular Pacing in Patients With Myocardial Fibrosis.

Long-term right ventricular (RV) pacing leads to heart failure or a decline in left ventricular (LV) function in up to a fifth of patients. We aimed to establish whether patients with focal fibrosis detected on late gadolinium enhancement cardiovascular magnetic resonance (CMR) have deterioration in LV function after RV pacing. We recruited 84 patients with LV ejection fraction ≥40% into 2 observational CMR studies. Patients (n=34) with a dual-chamber device and preserved atrioventricular conduction underwent CMR in 2 asynchronous pacing modes (atrial asynchronous and dual-chamber asynchronous) to compare intrinsic atrioventricular conduction with forced RV pacing. Patients (n=50) with high-grade atrioventricular block underwent CMR before and 6 months after pacemaker implantation to investigate the medium-term effects of RV pacing. The key findings were (1) initiation of RV pacing in patients with fibrosis, compared with those without, was associated with greater immediate changes in both LV end-systolic volume index (5.3±3.5 versus 2.1±2.4 mL/m2; P<0.01) and LV ejection fraction (-5.7±3.4% versus -3.2±2.6%; P=0.02); (2) medium-term RV pacing in patients with fibrosis, compared with those without, was associated with greater changes in LV end-systolic volume index (8.0±10.4 versus -0.6±7.3 mL/m2; P=0.008) and LV ejection fraction (-12.3±7.9% versus -6.7±6.2%; P=0.012); (3) patients with fibrosis did not experience an improvement in quality of life, biomarkers, or functional class after pacemaker implantation; (4) after 6 months of RV pacing, 10 of 50 (20%) patients developed LV ejection fraction <35% and were eligible for upgrade to cardiac resynchronization according to current guidelines. All 10 patients had fibrosis on their preimplant baseline scan and were identified by >1.1 g of fibrosis with 90% sensitivity and 70% specificity. Fibrosis detected on CMR is associated with immediate- and medium-term deterioration in LV function following RV pacing and could be used to identify those at risk of heart failure before pacemaker implantation.

Resynchronizing Right and Left Ventricles With Right Bundle Branch Block intheCongenitalHeart Disease Population.

This study describes a single center experience with the use of cardiac resynchronization therapy (CRT) in a difficult patient population, including single systemic right ventricles (RVs), subpulmonary RVs, and left ventricles (LVs) with right bundle branch block (RBBB). CRT remains challenging in the congenital heart disease population. Consecutive patients undergoing resynchronization of single RVs, subpulmonary RVs, or LVs in the setting of RBBB were identified between 2016 and 2019. Patients who had CRT performed for complete heart block or had <3months of follow-up were excluded. Patients underwent pre-procedural advanced imaging by echocardiogram, computed tomography, or cardiac magnetic resonance to assess ventricular function and synchrony; intraoperative mapping was performed to identify optimal lead placement. All patients undergoing resynchronization presented with at least moderate systolic ventricular dysfunction in the setting of intrinsic atrioventricular nodal conduction and RBBB. Seven patients were identified. Two patients underwent CRT of a single RV, 3 with subpulmonary RVs and 2 with systemic LVs. The median age at CRT was 5 years (range 0.6 to 48 years). The median follow-up was 9months (range 3 to 18months). The median baseline QRS duration was 180ms (range 115 to 260ms). Post-CRT, the QRS duration decreased by a median of 34% (range 19% to 38%). All patients had improvement in their systolic ventricular function. Targeted resynchronization in systemic and subpulmonary RVs can be used to improve ventricular function and heart failure in the congenital heart disease population. Similar techniques can be applied to successfully treat patients with LV dysfunction and RBBB and improve their long-term outcomes.

862Syncav with multipoint pacing improves acute left ventricular hemodynamics

Abstract Funding Acknowledgements Abbott Introduction SyncAV has been shown to improve electrical synchronization by automatically adjusting atrioventricular delay (AVD) according to the intrinsic atrioventricular conduction time. Additional incremental electrical synchronization may be gained by the addition of second left ventricular (LV) pulse with MultiPoint Pacing (MPP). While the electrical synchronization benefits of SyncAV have been previously explored, there has been no assessment of the acute hemodynamic impact of SyncAV with or without MPP. Objective Evaluate the acute LV hemodynamic impact of SyncAV with and without MPP. Methods Heart failure patients with LBBB and QRS duration (QRSd) &amp;gt; 140 ms undergoing CRT-P/D implant with a quadripolar LV lead were enrolled in this prospective study. A guidewire or catheter with pressure transducer was placed in the LV chamber and the maximum pressure change (dP/dtmax) was recorded during the following pacing modes: intrinsic conduction, conventional biventricular pacing with SyncAV (BiV + SyncAV), and MPP with SyncAV (MPP + SyncAV). Twelve-lead surface ECG was used to determine the patient-tailored SyncAV offset that minimized QRSd. Results Twenty-seven patients (67% male, 44% ischemic, 30 ± 7% ejection fraction) completed the acute recordings. Relative to the intrinsic QRSd of 163 ms, BiV + SyncAV reduced QRSd by 21.5% to 124 ms (p &amp;lt; 0.001 vs. intrinsic) and MPP + SyncAV reduced QRSd by 26.6% to 120 ms (p &amp;lt; 0.05 vs. BiV + SyncAV). Beyond electrical synchronization, SyncAV significantly improved acute hemodynamics. Relative to the intrinsic dP/dtmax of 842 mmHg/s, BiV + SyncAV elevated dP/dtmax by 6.3% to 900 mmHg/s (p &amp;lt; 0.001 vs. intrinsic) and MPP + SyncAV elevated dP/dtmax by 8.8% to 926 mmHg/s (p &amp;lt; 0.005 vs. BiV + SyncAV). Despite both QRSd and dP/dtmax improvement with SyncAV and MPP, correlation between electrical and hemodynamic measurements was poor (R2 = 0.0 for BiV + SyncAV, R2 = 0.1 for MPP + SyncAV). Conclusion SyncAV may significantly improve acute LV hemodynamics in addition to electrical synchrony in LBBB patients. Further incremental improvement was achieved by combining SyncAV with MPP. Abstract Figure.

Real-world behavior of CRT pacing using the AdaptivCRT algorithm on patient outcomes: Effect on mortality and atrial fibrillation incidence.

BackgroundThe AdaptivCRT (aCRT) algorithm continuously adjusts cardiac resynchronization therapy (CRT) according to intrinsic atrioventricular conduction, providing synchronized left ventricular pacing in patients with normal PR interval and adaptive BiV pacing in patients with prolonged PR interval. Previous analyses demonstrated an association between aCRT and clinical benefit. We evaluated the incidence of patient mortality and atrial fibrillation (AF) with aCRT compared with standard CRT in a real‐world population.Methods and ResultsPatients enrolled in the Medtronic Personalized CRT Registry and implanted with a CRT from 2013‐2018 were divided into aCRT ON or standard CRT groups based upon device‐stored data. A Frailty survival model was used to evaluate the potential survival benefit of aCRT, accounting for patient heterogeneity and center variability. Daily AF burden and first device‐detected AF episodes of various durations were recorded by the device during follow‐up.A total of 1814 CRT patients with no reported long‐standing AF history at implant were included. Mean follow‐up time was 26.1 ± 16.5 months and 1162 patients (64.1%) had aCRT ON. Patient survival probability at 36 months was 88.3% for aCRT ON and 83.7% for standard CRT (covariate‐adjusted hazard ratio [HR] = 0.71, 95% CI: 0.53‐0.96, P = .028). Mean AF burden during follow‐up was consistently lower in aCRT ON patients compared with standard CRT. At 36 months, the probability of AF was lower in patients with aCRT ON, regardless of which AF definition threshold was applied (6 minutes‐30 days, all P < .001).ConclusionUse of the AdaptivCRT algorithm was associated with improved patient survival and lower incidence of AF in a real‐world, prospective, nonrandomized registry.

Optimization of Chronic Cardiac Resynchronization Therapy Using Fusion Pacing Algorithm Improves Echocardiographic Response

BackgroundWhether reprogramming of cardiac resynchronization therapy (CRT) to increase electrical synchrony translates into echocardiographic improvement remains unclear. SyncAV is an algorithm that allows fusion of intrinsic conduction with biventricular pacing. We aimed to assess whether reprogramming chronically implanted CRT devices with SyncAV is associated with improved echocardiographic parameters. MethodsPatients at a quaternary center with previously implanted CRT devices with a programmable SyncAV algorithm underwent routine electrocardiography-based SyncAV optimization during regular device clinic visits. This analysis included only patients who could be programmed to the SyncAV algorithm (i.e., in sinus rhythm with intrinsic atrioventricular conduction). Echocardiography was performed before and 6 months after CRT optimization. ResultsOf 64 consecutive, potentially eligible patients who underwent assessment, 34 who were able to undergo SyncAV programming were included. Their mean age was 74 ± 9 years, 41% were female, and 59% had ischemic cardiomyopathy. The mean time from CRT implant to SyncAV optimization was 17.8 ± 8.5 months. At 6-month follow-up, SyncAV optimization was associated with a significant increase in left ventricular ejection fraction (LVEF) (mean LVEF 36.5% ± 13.3% vs 30.9% ± 13.3%; P < 0.001) and a reduction in left ventricular end-systolic volume (LVESV) (mean LVESV 110.5 ± 57.5 mL vs 89.6 ± 52.4 mL; P < 0.001) compared with baseline existing CRT programming. ConclusionCRT reprogramming to maximize biventricular fusion pacing significantly increased LVEF and reduced LVESV in patients with chronic CRT devices. Further studies are needed to assess if a continuous fusion pacing algorithm improves long-term clinical outcomes and to identify which patients are most likely to derive benefit.