Identifying patients at risk of pacemaker-related left ventricular systolic dysfunction using left ventricular mechanics

Right ventricular (RV) pacing (RVP) can lead to left ventricular (LV) remodelling and subsequently increased risk of heart failure hospitalisation (HFH) and mortality. Despite RV pacing avoidance programming now becoming commonplace, pacemaker patients remain at risk of pacing-related LV systolic dysfunction (LVSD). Alternative pacing strategies such as conduction system pacing (CSP) either through His Bundle or Left Bundle Branch area pacing (LBBAP) are available therapeutic options, but it remains unclear which patients should be targeted, and when.
Chapter 4 details an observational cohort study included 514 patients who received their first pacemaker (new implant - NI) (2015-2017) and 510 patients who had pacemaker generator replacements (PGR) (2008-2011). Data was prospectively collected including clinical history, medication, echocardiographic and pacing measurements at baseline (6-week post procedure) and follow up (minimum of 12-month post procedure). Logistic regression identified a history of ischemic heart disease (IHD) and a ventricular pacing burden (VPB) over 80% as significant risk factors for LVSD, defined as an ejection fraction (LVEF) <50%. Cox proportional hazards models found that older age, the presence of atrial fibrillation (AF), LVEF <50%, and being at PGR were independent predictors of a composite outcome of time to HFH or all-cause mortality. This study highlights the complexity of managing pacemaker patients, emphasising the potential need for targeted screening and preventive strategies for those who require high VPB due to atrioventricular block (AVB), have a history of IHD, and multiple comorbidities, particularly at the time of first implant, and at pacemaker generator replacement.
Chapter 5 describes a retrospective analysis of 118 patients with AVB who received pacemaker therapy at two tertiary hospitals in Europe. Speckle tracking echocardiography and non-invasive brachial blood pressure measurements were used to calculate myocardial work (MW) measures using EchoPAC (version 206GEHealthcare Vingmed) software. Repeated measures analysis from baseline (pre implant) to mid-term (0-6-week) and long-term (a minimum of 12-month) follow up post implant, demonstrated LVEF significantly and progressively reduce following RV pacing (RVP), leading to LVSD (defined as LVEF <50%) in 33 patients (28%) patients after a median long-term follow up of 454 (IQR:54-857) days. Advanced echocardiographic measures; global work index (GWI), global constructive work (GCW) and global wasted work (GWW) significantly reduced over time, with a statistically significant difference observed between those who preserved LVEF ≥50% at long-term follow-up, and those who did not (LVEF <50%), suggesting that MW measurements may help identify patients at risk of LVSD from RVP and guide the use of alternative pacing strategies such as CSP or cardiac resynchronisation therapy (CRT).
This led to a prospective study enrolling 145 patients with AVB who received pacemaker therapy between July 2022 and August 2024 at a single tertiary hospital in the UK, detailed in chapter 6. Participants were evaluated at four time points: pre-implant, pre-discharge, 6 weeks after implant, and 6 months after implant. Of these, 90 participants were included for a repeated measure analysis from baseline (pre-implant) to acute (0-6 weeks) to mid-term (6 months) post implantation. LVEF remained stable over time with no significant changes in LV volumes. However, advanced echocardiographic measures; global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW) and septal myocardial work index (MWIs) significantly declined throughout follow-up. Multivariate regression analysis demonstrated age and VPB were associated with adverse LV remodelling, defined as a composite outcome of an increase in left ventricular end systolic volume index (LVESVi) ≥15% and a reduction in LVEF ≤10%, whilst a history of IHD and MWIS measures were not statistically associated. These results suggests that although MWIS measures measurably declined over time, perhaps indicating MW measures can detect more subtle changes in LV remodelling, it may not predict adverse remodelling prior to pacemaker implantation.
Finally, a pilot study was conducted to compare mechanical dyssynchrony between two pacing strategies (CSP and RVP) using echocardiographic measures of MW, detailed in chapter 7. Of 145 patients with AVB who received a pacemaker between October 2022 and October 2024, 17 patients received CSP, of which 10 had sufficient available images for analysis. These 10 CSP patients were aged, and sex matched to 10 patients receiving RVP to allow a comparative analysis. Repeated measures (ANOVA) with Bonferroni correction demonstrated GWI, GWW GWE and MWIS measures were significantly different between CSP and RVP groups from baseline to acute (0-6 weeks) and mid-term (6 months) follow-up post implantation. CSP patients demonstrated a better maintenance of regional LV work compared to patients receiving RVP, potentially offering mechanistic insights into the effects of novel pacing strategies on LV mechanics.
In summary, while VPB is a significant factor, it is not the only predictor of LVSD, HFH, and mortality among pacemaker recipients. My studies highlight key characteristics including a history of IHD and comorbidities of those at risk. MW measurements show promise to detect signs of adverse LV remodelling earlier than traditional echocardiographic measures, with CSP demonstrating superior preservation of regional LV function compared to RVP. The observed changes in MW, particularly in the septal region, suggest its potential for guiding pacing strategies and thus improving patient outcomes. However, these findings indicate that, while MW provides valuable insights, further research is necessary to fully validate its clinical utility.