Personalised reprogramming to prevent progressive pacemaker-related left ventricular dysfunction: A phase II randomised, controlled clinical trial

Background Pacemakers are widely utilised to treat bradycardia, but right ventricular (RV) pacing is associated with heightened risk of left ventricular (LV) systolic dysfunction and heart failure. We aimed to compare personalised pacemaker reprogramming to avoid RV pacing with usual care on echocardiographic and patient-orientated outcomes. Methods A prospective phase II randomised, double-blind, parallel-group trial in 100 patients with a pacemaker implanted for indications other than third degree heart block for ≥2 years. Personalised pacemaker reprogramming was guided by a published protocol. Primary outcome was change in LV ejection fraction on echocardiography after 6 months. Secondary outcomes included LV remodeling, quality of life, and battery longevity. Results Clinical and pacemaker variables were similar between groups. The mean age (SD) of participants was 76 (+/-9) years and 71% were male. Nine patients withdrew due to concurrent illness, leaving 91 patients in the intention-to-treat analysis. At 6 months, personalised programming compared to usual care, reduced RV pacing (-6.5±1.8% versus -0.21±1.7%; p<0.01), improved LV function (LV ejection fraction +3.09% [95% confidence interval (CI) 0.48 to 5.70%; p = 0.02]) and LV dimensions (LV end systolic volume indexed to body surface area -2.99mL/m2 [95% CI -5.69 to -0.29; p = 0.03]). Intervention also preserved battery longevity by approximately 5 months (+0.38 years [95% CI 0.14 to 0.62; p<0.01)) with no evidence of an effect on quality of life (+0.19, [95% CI -0.25 to 0.62; p = 0.402]). Conclusions Personalised programming in patients with pacemakers for bradycardia can improve LV function and size, extend battery longevity, and is safe and acceptable to patients. Trial registration ClinicalTrials.gov identifier: NCT03627585.

Understanding Pacemaker-Induced Cardiomyopathy Incidence and Predictors in Patients with Right Ventricular Pacing: A Systematic Review

This study aimed to figure out the incidence and predictors of pacemaker-induced cardiomyopathy (PICM) in patients with right ventricular (RV) pacing. We systematically searched in PubMed on March 18, 2020, for English language abstract and full-article journals, using the following criteria: pacemaker induced cardiomyopathy AND right ventricular AND pacemaker AND patients AND human NOT implantable cardioverter defibrillator NOT ICD NOT animal. Four studies were included in this review after filtering 35 studies through year of publication and abstract selection. The average PICM incidence from 1,365 patients included from the four studies was 10.7 to 13.7%. One study stated that preimplantation left ventricular ejection fraction (LVEF) was the predictor for the development of PICM. Three studies mentioned that RV pacing burden was the predictor for the development of PICM. However, the percentage differ in three studies: ≥20, >40, and 60%. In addition, one of the studies also included interventricular dyssynchrony as another predictor. The incidence of PICM in patients with RV pacing ranged from 10.7 to 13.7%. Preimplantation LVEF, interventricular dyssynchrony, and burden of RV pacing are reported as the predictors for the development of PICM in patients with RV pacing.

Pacemaker Induced Cardiomyopathy: An Overview of Current Literature

: Pacemaker induced cardiomyopathy (PICM) is commonly defined as a reduction in left ventricular (LV) function in the setting of right ventricular (RV) pacing. This condition may be associated with the onset of clinical heart failure in those affected. Recent studies have focused on potential methods of identifying patients at risk of this condition, in addition to hypothesizing the most efficacious ways to manage these patients. Newer pacing options, such as His bundle pacing, may avoid the onset of PICM entirely.

Late unexpected complete fracture of a right ventricular lead still capturing the myocardium

A 72-year-old man presented for routine dual chamber pacemaker interrogation 13 years following insertion for sick sinus syndrome. Increased noise, impedance and threshold of the right ventricular (RV) lead were identified. RV capture was maintained with an overall RV pacing burden of 47%. A routine generator replacement was scheduled alongside RV lead replacement. Fluoroscopy at the start of the procedure revealed an unexpected striking fracture of the RV pacing lead with complete separation of the proximal and distal portions within the RV. The patient was asymptomatic and described no predisposing factors. He underwent implantation of a new ventricular lead and generator and has remained well. This case demonstrates clear RV lead fracture as a late complication of pacemaker implantation despite maintained capture. This emphasises the need for a chest X-ray when a change in device parameters is noted at device interrogation even in the absence of symptoms.

The Short Term Influence of RV Pacing Burden on Numerous Echocardiographic and Spiroergometric Parameter In Patients With Preserved LVEF - The Mechanism of The Worsened Clinical Outcome Due To High RV Pacing Burden Remains Unclear.

Background: The cause of worsened clinical outcome due to high RV pacing burden remains unclear.Objective: To investigate the impact of RV pacing on several echocardiographic and spiroergometric parameter Methods: In 60 pacemaker patients with preserved LVEF serial echocardiographies and spiroergometries were performed over a time course of 12 months. Additionally in 50 patients retrospective echocardiographic analyses of the LV- and RV function were carried out up to 24 months after pacemaker implantation.Results: The patients were divided into two groups: The high RV pacing burden group (hRVP: ≥ 40%) and the low RV pacing group (lRVP <40%) according to the definitions in previous randomized MOST and DAVID trials. After a period of 12 month pacemaker therapy there could not revealed any changes LVEDD, LVESD, LVEF, E/A-ratio; E/E’-ratio and TAPSE independently of the RV pacing burden. Additionally, after 24 month long term follow-up there were no changes in LVEF and TAPSE in both groups. Accordingly to these echo data no relevant changes of peak exercise capacity, ventilatory anaerobic threshold and maximal oxygen consumption could be revealed independently of the RV pacing. Conclusions: In pacemaker patients with preserved LVEF the burden of RV pacing has no adverse influence, neither to several echocardiographic parameters nor to the clinical exercise capacity after a follow-up of 12 to 24 month. Therefore, the mechanism of the worsened clinical outcome due to high RV pacing burden in patients without a relevant structural heart disease remains unclear.

Site-Specific Ventricular Tachycardia Inducibility

Introduction Programmed electrical stimulation is an essential part of VT ablation procedures but VT is not always inducible, usually for reasons that are not clear. We sought to review pacing site-specific failure of programmed electrical stimulation (PES) to induce scar-related ventricular tachycardia (VT). Methods A series of patients in whom aggressive programmed stimulation from traditional RV pacing sites failed to induce VT, but VT was easily inducible from a non-traditional site are reviewed. Computer simulations in a simple 2-dimensional model of reentry were performed. Results Six patients who had no inducible sustained VT from the RV apex/outflow tract with at least 3 extrastimuli, but relatively easily induced VT from the LV, basal RV, epicardium, or atrium are described. In 5 of these patients, the site that induced VT was closer to the likely reentry circuit region based on mapping and ablation. Computer simulations illustrated that the spatial relation between the pacing site and the entrance and exits of a reentry isthmus can determine the ease of initiation of reentry by determining the time available for recovery of excitability at the initial region of block. Conclusions The site of PES has a marked effect on inducibility of VT in some patients such that PES from the RV apex and outflow regions will fail to expose clinically relevant VTs. The frequency with which this occurs is not certain. Stimulation from alternative sites is a reasonable consideration in selected patients.

Conduction disturbances after TAVR: rates of pacemaker implantation, burden of ventricular pacing and prognostic significance

Funding Acknowledgements Type of funding sources: None. BACKGROUND The occurrence of conduction disturbances remains frequent after TAVR. However, the effect of PM on mortality is controversial and many patients may recover spontaneous AV conduction during follow-up. PURPOSE To evaluate the incidence of PM implantation after TAVR, PM dependency and burden of ventricular pacing during follow-up and their influence on mortality. METHODS AND RESULTS We performed a retrospective analysis of all consecutive 293 patients who underwent TAVR from 2015 to 2019 at our hospital, regional hub for this procedure. Patients were classified into 3 groups: patients without PM (no-PM), patients with a PM implanted prior to TAVR (pre-PM) and patients requiring a PM following TAVR (post-PM) and their clinical and procedural characteristics are listed in Table 1. The rate of PM implantation after TAVR was 20,8%, at a median of 3.6 days after the procedure. The most common indication was complete AV block. A VVIR pacemaker was implanted in 28 patients, a DDD/DDDR PM in 27 patients and 2 patients received a CRT device. Among post-PPM patients, only 16% were PM-dependent at 2-month and 1-year follow-up. All of them received a PM for complete AV block (AVB). At 1-year follow-up, RV pacing burden was 60% among AVB patients and 23% in patients with a PM implanted for other reasons. PM implantation after TAVR was not associated with a mortality difference at 30-day, 1-year and long-term follow-up. Pre-PPM patients showed a higher mortality rate at long-term follow-up although not statistically significant. CONCLUSIONS Our data suggest that a single chamber device should be preferred in patients implanted for reasons other than complete AVB; in patients with AVB, the use of dual chamber device with an algorithm to minimize RV pacing should be the most suitable choice. Overall (293)No PPM (216)Pre-PPM (19)Post-PPM (57)p-valueAge, median(IQR)82(80-86)82(80-86)82(79-87)82(80-86)0,53Female, n(%)160(55)129(59)6(32)25(44)0,40NYHA III-IV, n(%)191(65)147(68)15(79)29(51)0,06Logistic Euroscore, mean (IQR)7,53(3,5-8,3)7(3,5-8)9,83(3,6-12)6(3,5-7,4)0,51Right bundle-branch block, n(%)21(7)13(6)na8(14)0,04AVA, mean ± SD0,69 ± 0,190,7 ± 0,190,7 ± 0,160,66 ± 0,180,23Self-expandable valve, n(%)181(62)123(57)12(63)46(81)0,001Balloon-expandable valve, n(%)102(35)86(40)7(37)8(14)0,0003Implant depth, mean ± SD6,87 ± 2,96,32 ± 2,65,71 ± 39,12 ± 30,0001Abstract Figure. Kaplan-Meier survival curve

The pitfalls of unipolar voltage mapping of the right ventricle

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): The department of cardiology from Leiden University Medical Center receives unrestricted grants from Edwards Lifesciences, Biotronik, Medtronik, Boston Scientific and BioSense Webster. MS was supported by the Research Fellowship of the European Society of Cardiology 2017/2018. Background The current golden standard to accurately delineate scar potentially related to ventricular tachycardia relies on electroanatomical voltage mapping. Endocardial unipolar voltage (UV) mapping is increasingly used to detect intramural or subepicardial non-ischemic scars. 3D mapping systems determine and display the largest peak-to-peak amplitude of the electrogram within the window-of interest usually set from the QRS onset, but cannot not identify far-field electrograms or artifacts. Purpose To evaluate the influence of manual adjustment of the window-of-interest on the amplitude of endocardial and epicardial right ventricular (RV) unipolar electrograms. Methods Patients who underwent ablation of a RV scar-related VT with combined endo- and epicardial RV mapping were included. Endo- and epicardial points were reviewed with special interest towards the unipolar signal. In case a far-field, ST-segment elevation/depression or artifact was present, the window-of-interest was adjusted and the corresponding unipolar amplitude was collected. Results Thirty-three patients were included (age 50 ± 14years and 79% male). The underlying aetiology was definite arrhythmogenic right ventricular cardiomyopathy (ARVC; n = 17), athlete’s right ventricular outflow tract scar in (n = 9), cardiac sarcoidosis in (n = 3), scar of unknown origin (n = 2), borderline ARVC (n = 1) or myocarditis (n = 1). In total, 4225 endocardial points and 1960 epicardial points were re-analyzed. In 2987 (71%) endocardial points and 689 (65%) epicardial points the window-of-interest needed to be adjusted. Reason for this adjustment was ‘inclusion of far-field’ in 1380 (33%) endocardial- and 700 (36%) epicardial points; ‘inclusion of ST-segment elevation/depression’ in 1246 (29%) endocardial- and 316 (16%) epicardial points; RV-pacing artefact in 266 (6%) endocardial- and 116 (6%) epicardial points; and miscellaneous (e.g. unstable baseline or ablation point with artifact) in 95 (2%) endocardial- and 139 (7%) epicardial points (Figure). The median difference between the ‘automatically generated’ UV and the ‘adjusted’ UV was 0.81mV (IQR: 0.40-1.39) for the endocardial points and 0.54mV (IQR: 0.27-0.98) for the epicardial points. In 320 (8%) endocardial points the UV was changed from &gt;5.5mV to &lt;5.5mV, in 412 (10%) points from &gt;4.4 to &lt;4.4mV and in 396 (9%) points from &gt;3.8mV to &lt;3.8mV. Conclusion In the majority of endocardial and epicardial points the window-of-interest for unipolar voltage mapping needs to be adjusted to exclude far-field signal or ST-segment elevation/depression contributing to the automatically determined amplitude. Unadjusted unipolar voltage mapping underestimates low UV regions. RV-pacing generates a large unipolar far-field signal, which can obscure the local unipolar near-field signal. Accordingly, RV UV mapping during RV pacing should be used with caution. Abstract Figure. The pitfalls of UV mapping of the RV

Tricuspid and mitral valve regurgitation in a chronic canine model implanted with a novel leadless pacemaker

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Boston Scientific and Abbott Background One of the presumed advantages of leadless pacemaker (LP) therapy is that tricuspid regurgitation (TR) occurrence and severity would be less than with conventional pacemakers due to the absence of leads. However, TR and mitral regurgitation (MR) may also worsen due to chronic right ventricular (RV) pacing per se. Purpose To determine whether a novel LP is associated with increased TR and MR severity in a chronic canine model and to evaluate predictors of TR and MR worsening. Methods Healthy canine subjects were implanted with a novel LP programmed at a lower rate of 80/min. TR and MR were assessed by transthoracic echocardiography (TTE) prior to implant, at 90 days and at 18 months after implant. Further were assessed percentage of pacing, presence of pacing during TTE, and wall motion abnormalities (WMA) observed during TTE, indicating ventriculo-ventricular dyssynchronous pacing. Paired t-tests were performed to compare TR and MR severity before and after implant. Univariable and multivariable generalized estimating equation (GEE) models were used to evaluate factors predictive of increased TR and MR severity. Paired t-tests were used to evaluate whether the increase of TR and MR differed between subgroups where pacing or WMA were observed or not. Results An LP was implanted in 73 subjects. TR and MR severity at 90 days (n = 55) were significantly increased from baseline (p = 0.02 and 0.001, confidence intervals [CIs] 0.05-0.64 and 0.20-0.75, respectively); at 18 months (n = 37) TR severity remained significantly increased but MR did not (p = 0.01 and 0.62, CI [0.09, 0.69] and [-0.15, 0.25], respectively). Multivariable GEE (figure) showed that WMA and absence of TR at baseline are significant predictors for increased TR, while WMA and a shorter RV long axis are significant predictors for increased MR. Subgroup analysis demonstrated that TR and MR at day 90 were only significantly increased in subjects with observed pacing or WMA (n = 29; p = 0.0014 and p &lt; 0.0001 respectively), but not in subjects without observed pacing or WMA (n = 26; p = 0.56 and 0.16, respectively). At 18 months, the same observation was found for TR but not MR (pacing or WMA [n = 15], p &lt; 0.0001 and p = 0.33 respectively: no pacing or WMA [n = 26], p = 0.23 and 1, respectively). Conclusion In absence of pacing, the novel EMPOWER LP was not associated with increased TR and MR severity in a canine model. When pacing was observed TR and MR did increase. Increased MR severity did not persist at 18 months. Abstract Figure 1

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

Background: 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. Methods: 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. Results: 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/m 2 ; 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/m 2 ; 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. Conclusions: 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.