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Antegrade Conduction Rescues Right Ventricular Pacing-Induced Cardiomyopathy in Complete Heart Block.

ABSTRACT: BACKGROUND:Right ventricular (RV) pacing-induced cardiomyopathy (PICM) occurs in ?30% of patients with RV leads. This study evaluated the long-term effects of restoring antegrade conduction with a biological pacemaker in a porcine model of RV PICM. OBJECTIVES:The goal of this study was to determine if antegrade biological pacing can attenuate RV PICM. METHODS:In pigs with complete atrioventricular (AV) block, transcription factor T-box 18 (TBX18) was injected into the His bundle region in either of 2 experimental protocols: protocol A sought to prevent PICM, and protocol B sought to reverse PICM. In protocol A, we injected adenoviral vectors expressing TBX18 (or the reporter construct green fluorescent protein) after AV node ablation, and observed the animals for 8 weeks. In protocol B, PICM was established by using AV node ablation and 4 weeks of electronic RV pacing, at which point TBX18 was injected into the His bundle region. RESULTS:In protocol A, TBX18 biological pacing led to superior chronotropic support (62.4 ± 3 beats/min vs. 50.4 ± 0.4 beats/min; p = 0.01), lower backup pacemaker utilization (45 ± 2.6% vs. 94.6 ± 1.4%; p = 0.001), and greater ejection fraction (58.5 ± 1.3% vs. 46.7 ± 2%; p = 0.001). In protocol B, full-blown RV PICM was evident 4 weeks after complete AV block in both groups; subsequent intervention led to higher mean heart rate (56 ± 2 beats/min vs. 50.1 ± 0.4 beats/min; p = 0.05), less backup pacemaker utilization (53 ± 8.2% vs. 95 ± 1.6%; p = 0.003), and a greater ejection fraction (61.7 ± 1.3% vs. 49 ± 1.6%; p = 0.0003) in TBX18-injected animals versus control animals. CONCLUSIONS:In a preclinical model, pacemaker-induced cardiomyopathy can be prevented, and reversed, by restoring antegrade conduction with TBX18 biological pacing.

SUBMITTER: Dawkins JF

PROVIDER: S-EPMC6726386 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Antegrade Conduction Rescues Right Ventricular Pacing-Induced Cardiomyopathy in Complete Heart Block.

Dawkins James F JF Hu Yu-Feng YF Valle Jackelyn J Sanchez Lizbeth L Zheng Yong Y Marbán Eduardo E Cingolani Eugenio E

Journal of the American College of Cardiology 20190401 13

<h4>Background</h4>Right ventricular (RV) pacing-induced cardiomyopathy (PICM) occurs in ∼30% of patients with RV leads. This study evaluated the long-term effects of restoring antegrade conduction with a biological pacemaker in a porcine model of RV PICM.<h4>Objectives</h4>The goal of this study was to determine if antegrade biological pacing can attenuate RV PICM.<h4>Methods</h4>In pigs with complete atrioventricular (AV) block, transcription factor T-box 18 (TBX18) was injected into the His b ...[more]

PMID: 30947921

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Project description:Guidelines recommend patients undergoing a first pacemaker implant who have even mild left ventricular (LV) impairment should receive biventricular or conduction system pacing (CSP). There is no corresponding recommendation for patients who already have a pacemaker. We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies assessing device upgrades. The primary outcome was the echocardiographic change in LV ejection fraction (LVEF). Six RCTs (randomizing 161 patients) and 47 observational studies (2644 patients) assessing the efficacy of upgrade to biventricular pacing were eligible for analysis. Eight observational studies recruiting 217 patients of CSP upgrade were also eligible. Fourteen additional studies contributed data on complications (25 412 patients). Randomized controlled trials of biventricular pacing upgrade showed LVEF improvement of +8.4% from 35.5% and observational studies: +8.4% from 25.7%. Observational studies of left bundle branch area pacing upgrade showed +11.1% improvement from 39.0% and observational studies of His bundle pacing upgrade showed +12.7% improvement from 36.0%. New York Heart Association class decreased by -0.4, -0.8, -1.0, and -1.2, respectively. Randomized controlled trials of biventricular upgrade found improvement in Minnesota Heart Failure Score (-6.9 points) and peak oxygen uptake (+1.1 mL/kg/min). This was also seen in observational studies of biventricular upgrades (-19.67 points and +2.63 mL/kg/min, respectively). In studies of the biventricular upgrade, complication rates averaged 2% for pneumothorax, 1.4% for tamponade, and 3.7% for infection over 24 months of mean follow-up. Lead-related complications occurred in 3.3% of biventricular upgrades and 1.8% of CSP upgrades. Randomized controlled trials show significant physiological and symptomatic benefits of upgrading pacemakers to biventricular pacing. Observational studies show similar effects between biventricular pacing upgrade and CSP upgrade.

Project description:Objectives to backgroundTo compare electromechanical ventricular synchrony when pacing from different sites, including right ventricular apex pacing (RVAP), right ventricular septum pacing (RVSP), His bundle pacing (HBP), left bundle branch pacing (LBBP), and RVSP during unipolar pacing from the ring electrode of LBBP lead (RVSPring ) in each patient and evaluate the correlations between electrophysiological characteristics and ventricular synchrony.MethodsTwenty patients with complete atrioventricular block indicated for dual-chamber pacemaker implantation were included in the study. Unipolar pacing at different sites, including RVAP, RVSP, HBP, LBBP, and RVSPring , was successively performed in each patient. The pacing characteristics and echocardiogram parameters were collected and compared among intrinsic rhythm and pacing at different sites.ResultsSimilar to HBP (114.84 ± 18.67 ms), narrower paced QRSd was found in LBBP (116.15 ± 11.60 ms) as compared to RVSPring (135.11 ± 13.68 ms), RVSP (141.65 ± 14.26 ms), and RVAP (160.15 ± 19.35 ms) (p < .001). LBBP showed comparable pacing parameters to RVAP or RVSP and was significantly better than HBP, with maintained cardiac function. TS-12-SD was significantly improved in LBBP (41.80 ± 20.97 ms) than RVAP (69.70 ± 32.42 ms, p = .003) and RVSP (63.30.56 ± 32.53 ms, p = .018) but similar to HBP (51.50 ± 25.67 ms, p = .283) or RVSPring (57.80 ± 25.65 ms, p = .198). Among these pacing strategies, negative values of interventricular mechanical delay (IVMD) were only identified in LBBP (-19.25 ± 18.43 ms), significantly different from RVAP (35.00 ± 30.72 ms), RVSP (22.85 ± 22.05 ms), HBP (5.20 ± 18.64 ms), and RVSPring (16.00 ± 26.76 ms (all p < .05). Using Pearson's analysis, Sti-LVAT was positively correlated with QRS duration, IVMD, TS-12-SD, LVEDV, and LVESV, while a negative relationship could be observed for left ventricular ejection fraction.ConclusionsHis-Purkinje conduction system pacing (HPCSP) achieved better electrical and mechanical synchrony than conventional RV pacing. For interventricular synchrony, only LBBP initiated earlier LV activation than RV, in accordance with the right bundle branch block (RBBB) pattern of paced QRS during LBBP. Sti-LVAT might be a good parameter correlating with LV systolic function and mechanical synchrony.

Project description:A significant number of right bundle branch block (RBBB) patients receive cardiac resynchronization therapy (CRT), despite lack of evidence for benefit in this patient group. His bundle (HBP) and left bundle pacing (LBP) are novel CRT delivery methods, but their effect on RBBB remains understudied. We aim to compare pacing-induced electrical synchrony during conventional CRT, HBP, and LBP in RBBB patients with different conduction disturbances, and to investigate whether alternative ways of delivering LBP improve response to pacing. We simulated ventricular activation on twenty-four four-chamber heart geometries each including a His-Purkinje system with proximal right bundle branch block (RBBB). We simulated RBBB combined with left anterior and posterior fascicular blocks (LAFB and LPFB). Additionally, RBBB was simulated in the presence of slow conduction velocity (CV) in the myocardium, left ventricular (LV) or right ventricular (RV) His-Purkinje system, and whole His-Purkinje system. Electrical synchrony was measured by the shortest interval to activate 90% of the ventricles (BIVAT-90). Compared to baseline, HBP significantly improved activation times for RBBB alone (BIVAT-90: 66.9 ± 5.5 ms vs. 42.6 ± 3.8 ms, p < 0.01), with LAFB (69.5 ± 5.0 ms vs. 58.1 ± 6.2 ms, p < 0.01), with LPFB (81.8 ± 6.6 ms vs. 62.9 ± 6.2 ms, p < 0.01), with slow myocardial CV (119.4 ± 11.4 ms vs. 97.2 ± 10.0 ms, p < 0.01) or slow CV in the whole His-Purkinje system (102.3 ± 7.0 ms vs. 75.5 ± 5.2 ms, p < 0.01). LBP was only effective in RBBB cases if combined with anodal capture of the RV septum myocardium (BIVAT-90: 66.9 ± 5.5 ms vs. 48.2 ± 5.2 ms, p < 0.01). CRT significantly reduced activation times in RBBB in the presence of severely slow RV His-Purkinje CV (95.1 ± 7.9 ms vs. 84.3 ± 9.3 ms, p < 0.01) and LPFB (81.8 ± 6.6 ms vs. CRT: 72.9 ± 8.6 ms, p < 0.01). Both CRT and HBP were ineffective with severely slow CV in the LV His-Purkinje system. HBP is effective in RBBB patients with otherwise healthy myocardium and Purkinje system, while CRT and LBP are ineffective. Response to LBP improves when LBP is combined with RV septum anodal capture. CRT is better than HBP only in patients with severely slow CV in the RV His-Purkinje system, while CV slowing of the whole His-Purkinje system and the myocardium favor HBP over CRT.

Project description:Background: Left bundle branch area pacing (LBBAP) is a novel pacing modality with stable pacing parameters and a narrow-paced QRS duration. We compared heart failure (HF) hospitalization events and echocardiographic measures between LBBAP and right ventricular pacing (RVP) in patients with atrioventricular block (AVB). Methods and Results: This multicenter observational study prospectively recruited consecutive AVB patients requiring ventricular pacing in five centers if they received LBBAP or RVP and had left ventricular ejection fraction (LVEF) >50%. Data on electrocardiogram, pacing parameters, echocardiographic measurements, device complications, and clinical outcomes were collected at baseline and during follow-up. The primary outcome was first episode hospitalization for HF or upgrade to biventricular pacing. LBBAP was successful in 235 of 246 patients (95.5%), while 120 patients received RVP. During a mean of 11.4 ± 2.7 months of follow-up, the ventricular pacing burden was comparable (83.9 ± 35.1 vs. 85.7 ± 30.0%), while the mean LVEF differed significantly (62.6 ± 4.6 vs. 57.8 ± 11.4%) between the LBBAP and RVP groups. Patients with LBBAP had significantly lower occurrences of HF hospitalization and upgrading to biventricular pacing than patients with RVP (2.6 vs. 10.8%, P <0.001), and differences in primary outcome between LBBAP and RVP were mainly observed in patients with ventricular pacing >40% or with baseline LVEF <60%. The primary outcome was independently associated with LBBAP (adjusted HR 0.14, 95% CI: 0.04-0.55), previous myocardial infarction (adjusted HR 6.82, 95% CI: 1.23-37.5), and baseline LVEF (adjusted HR 0.91, 95% CI: 0.86-0.96). Conclusion: Permanent LBBAP might reduce the risk of HF hospitalization or upgrade to biventricular pacing compared with RVP in AVB patients requiring a high burden of ventricular pacing. Clinical Trial Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03851315; URL: http://www.chictr.org.cn; Unique Identifier: ChiCTR2100043296.

Dataset Information

Antegrade Conduction Rescues Right Ventricular Pacing-Induced Cardiomyopathy in Complete Heart Block.

Publications

Antegrade Conduction Rescues Right Ventricular Pacing-Induced Cardiomyopathy in Complete Heart Block.

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