Pacemaker implantation significantly improves quality of life and survival for bradycardia patients. However, long-term right ventricular (RV) pacing is linked to left ventricular (LV) dysfunction and heart failure (HF), especially with other cardiovascular conditions, leading to a worse prognosis. Current HF and pacing guidelines don't recommend a specific medical treatment strategy for this population due to a lack of evidence. This study aimed to determine whether echocardiographic screening for LV dysfunction in pacemaker patients, followed by optimized medical management, improves clinical outcomes. This is crucial because previous trials either excluded pacemaker patients or lacked subgroup analyses, leaving this high-risk population without evidence-based treatment strategies. The OPT-PACE trial addresses this gap by evaluating a care pathway that combines screening with patient-centered education and optimized medical management for patients with impaired LV function.

Existing literature consistently demonstrates a higher risk of LV dysfunction (LVEF <50%) and overt HF among pacemaker patients compared to the general population. The severity of LV dysfunction correlates with RV pacing burden, showing a linear relationship with HF events and cardiovascular death. Impaired LV function is more prevalent in pacemaker patients with underlying ischemic heart disease (IHD) or myocardial fibrosis. Despite the known adverse effects of RV pacing on LV function and the high prevalence of LV dysfunction in pacemaker patients, the medical management of pacemaker-associated HF remains under-investigated. Optimal care for patients with impaired LV function typically involves renin-angiotensin-aldosterone system inhibitors and β-adrenoceptor antagonists, shown to improve LV remodeling and long-term outcomes. Specialized programs for HFrEF management in specialized settings have also demonstrated improved outcomes. However, most phase III trials of medical therapy for HFrEF did not analyze outcomes specifically in the pacemaker subgroup, resulting in a lack of guideline recommendations beyond algorithms to limit RV pacing and the potential benefits of CRT upgrades in symptomatic patients with LV dysfunction and high ventricular pacing needs.

OPT-PACE was a multicenter, randomized, open-label, parallel-group trial conducted in three UK hospitals. 1264 bradycardia pacemaker patients (>1 year post-implant) were screened, with 1201 (717 men, mean age 75) randomized 1:1 to echocardiography screening or usual care. Baseline data included pacemaker interrogation, medical history, blood tests (including NT-proBNP), and quality-of-life assessment (EQ-5D). In the echocardiography screening arm, LV systolic dysfunction (LVSD) was defined as LVEF <50%. Patients with LVSD were managed either by their primary care physician (two centers) or a specialized multidisciplinary HF and devices clinic (one center). All patients were followed for at least 12 months. The primary outcome was the composite of time to first HF hospitalization or death. Secondary outcomes included guideline-directed medical therapy for HF and quality of life. A prespecified, non-randomized exploratory analysis compared outcomes between primary care and specialist clinic management of patients with LVSD. Statistical analyses included Kaplan-Meier curves, log-rank tests, Cox proportional hazards regression, and analysis of covariance (ANCOVA).

A total of 1,201 patients were recruited. In the echocardiography screening arm (n=600), 201 (34%) patients had LVSD (LVEF <50%). Over a median follow-up of 31 months, the primary outcome occurred in 106/600 (18%) patients in the echocardiography screening group and 115/601 (19%) in the usual care group (hazard ratio [HR] = 0.89; 95% CI = 0.69, 1.17). This difference was not statistically significant. Multivariable analysis showed age, overt IHD, and log(NT-proBNP) as independent predictors of the primary outcome. The adjusted HR remained non-significant (HRadjusted = 0.95; 95% CI = 0.72, 1.24). Patients in the echocardiography screening arm received more medical therapy optimization (e.g., diuretic, β-blocker, ACEi initiation/titration) than those in the usual care group. However, there was no significant difference in quality of life between the groups. The prespecified exploratory analysis (non-randomized) suggested that patients with LVSD managed in the specialist clinic had a lower rate of the primary outcome compared to those managed in primary care (12% vs. 24%; HR = 0.67; 95% CI = 0.46, 0.98). This remained significant after adjusting for baseline differences. Sensitivity analysis within subgroups (diabetes, IHD) showed a neutral effect of echocardiography screening alone on the primary outcome.

OPT-PACE demonstrates that routine echocardiographic screening for LVSD in pacemaker patients identifies a substantial proportion (34%) with undiagnosed LV dysfunction. However, screening alone does not improve clinical outcomes. The lack of significant improvement in the primary outcome despite increased medical therapy optimization in the screening arm highlights the complexity of managing this population. The exploratory analysis, though non-randomized, suggests that a structured care pathway involving a multidisciplinary HF and devices clinic may improve outcomes. This is potentially due to enhanced medical therapy optimization (especially β-antagonist titration), patient education, and coordinated care. This finding requires further validation in a randomized controlled trial. The study contributes valuable information beyond simply evaluating screening, by also exploring two distinct post-screening care pathways and their impact on patient outcomes. This contrasts with many previous trials that only assess the effects of screening without considering the downstream consequences of the screening results.

This study shows that one-third of pacemaker patients have impaired LV function. While echocardiographic screening is effective in identifying this, it does not, in itself, lead to improved clinical outcomes. Further research, particularly a randomized trial comparing specialist clinic-led versus primary care-led management of patients with LVSD identified via echocardiography, is needed to determine whether a coordinated, specialized care pathway can improve outcomes for this patient population.

The study's generalizability might be limited by its recruitment from three hospitals in a single UK region. Digital data extraction for follow-up might have led to incomplete hospitalization data. The relatively short follow-up period may have limited the observation of the long-term effects of medical therapy, and the analysis predates the routine use of newer medications for HFrEF (sacubitril-valsartan and SGLT2 inhibitors). Finally, the non-randomized nature of the post-screening care pathway comparison limits the strength of the findings related to specialist clinic management.