Echocardiographic screening for heart failure and optimization of the care pathway for individuals with pacemakers: a randomized controlled trial

People with standard pacemakers implanted for bradycardia are at elevated risk of LV systolic dysfunction and heart failure, partly due to adverse effects of long-term right ventricular pacing. Despite this risk, individuals with pacemakers have been underrepresented or not analyzed as a subgroup in major HFrEF therapy trials, and current HF and pacing guidelines do not recommend a specific medical treatment strategy for this population. The study tested the hypothesis that implementing echocardiography screening to detect LV dysfunction in pacemaker patients, coupled with subsequent management pathways, would improve clinical outcomes compared with usual care without screening.

Prior observational and mechanistic studies show that chronic right ventricular pacing can impair left ventricular function and is associated with higher rates of HF events and mortality; LV dysfunction correlates with RV pacing burden and is more frequent in those with ischemic heart disease or myocardial fibrosis. Although guideline-directed medical therapy (e.g., RAAS inhibitors, beta-blockers, MRAs) improves outcomes in HFrEF generally, trials have not reported outcomes specifically for patients with standard pacemakers. Guidelines mention limiting unnecessary RV pacing and consider CRT upgrade in selected patients but provide no clear medical management pathway for pacemaker-associated LV dysfunction. Screening with natriuretic peptides in pacemaker populations has shown modest specificity for LVSD; echocardiographic screening of the general asymptomatic population has low yield and no proven outcome benefit, but the higher prevalence of LV impairment among pacemaker patients provides a rationale for targeted echo screening.

Design: OPT-PACE was a multicenter, randomized, open-label, parallel-group trial conducted at three UK hospitals. Participants were randomized 1:1 to echocardiographic screening versus usual care. A prespecified, nonrandomized exploratory analysis compared outcomes among screen-positive patients managed in primary care vs a specialist multidisciplinary HF and devices clinic (available at one site). Ethical approval: South Yorkshire Research Ethics Committee (12/YH/0487); informed consent obtained. Participants: Adults with a pacemaker implanted for bradycardia ≥12 months, attending routine follow-up, not previously known to have LV dysfunction. Exclusions: known HFrEF, ICD or CRT devices, age <18, pregnancy, current HF clinic care or awaiting transplant, anticipated life expectancy <1 year, significant cognitive impairment. Baseline procedures: Pacemaker interrogation; medical history; blood tests (full blood count, renal function, NT-proBNP); quality of life (EQ-5D). Quality-of-life follow-ups were mailed. Intervention: Echocardiography arm underwent LVEF assessment by Simpson’s biplane per ESC criteria. Those with LVEF ≥50% continued standard follow-up. Those with LVEF <50% followed center-level pathways: (a) primary-care–led management (two centers), or (b) referral to a specialized multidisciplinary HF and device service (one center) for coordinated patient-centered care, education, and initiation/titration of HF medical therapy led by HF nurses and cardiac physiologists. Usual care arm received standard pacemaker follow-up; all centers programmed to avoid unnecessary RV pacing where appropriate. Outcomes: Primary outcome was time to first heart failure hospitalization (HFH) or all-cause death comparing randomized groups. Secondary outcomes were provision of guideline-directed medical therapy (GDMT) for HFrEF at 12 months and quality of life (EQ-5D) at 12 months. Prespecified exploratory analysis compared outcomes by follow-up pathway in screen-positive patients (specialist clinic vs primary care). Follow-up and data sources: Minimum 12 months follow-up for all; median 31 months (IQR 30–40). Outcomes and therapies assessed via hospital and primary care digital records, including national datasets. Statistical analysis: Intention-to-treat Kaplan–Meier with log-rank testing for the primary outcome. Sample size powered to detect reduction from 15% to 9% events (HR ~0.58), requiring 146 events in ≥1,070 participants; target recruitment increased to 1,200. Multivariable Cox regression adjusted for baseline predictors (age, IHD, atrial rhythm, log NT-proBNP, ventricular pacing burden, sex, diabetes). ANCOVA assessed EQ-5D VAS change adjusted for baseline. Chi-square assessed attainment of medical therapy. Exploratory comparisons were nonrandomized and adjusted for baseline imbalances where specified.

- Enrollment and allocation: 1,201 participants randomized (600 echocardiography screening; 601 usual care). Baseline characteristics balanced; mean age 75±12 years; 60% male; comorbidities included type 2 diabetes 21%, prior MI 18%. - Screening yield: Among 600 screened, mean LVEF 50%±10%; LVSD (LVEF <50%) detected in 201/600 (34%). One participant had non-diagnostic images. - Primary outcome: Over median 31 months (IQR 30–40), the composite of first HF hospitalization or death occurred in 106/600 (18%) with echocardiography vs 115/601 (19%) with usual care; HR 0.89 (95% CI 0.69–1.17), not significant. Adjusted treatment effect: HR 0.95 (95% CI 0.72–1.24), consistent with no benefit. - Predictors of outcome: In adjusted analyses, older age HR 1.07 per year (95% CI 1.05–1.09), ischemic heart disease HR 1.52 (95% CI 1.15–2.02), and higher log NT-proBNP HR 1.69 (95% CI 1.46–1.96) were associated with higher risk. - Secondary outcomes (12 months): Among those with complete therapy data (468 screening; 435 usual care), the screening arm had more therapy optimization episodes (diuretic 118 vs 79; beta-blocker 247 vs 211; ACEi initiation/titration 255 vs 214). CRT upgrades were infrequent (7/600 [1.2%] screening vs 4/601 [0.6%] usual care). Quality of life (EQ-5D) was similar at baseline and showed no meaningful difference at 12 months; ANCOVA mean VAS difference 0.85 (95% CI −1.38 to 3.08). - Exploratory analysis (nonrandomized): Among LVSD patients in the screening arm, management via the specialist HF and device clinic had a lower primary event rate than primary-care–led management (12% vs 24%); HR 0.67 (95% CI 0.46–0.98). After adjustment for baseline differences (atrial rhythm, systolic BP, resting heart rate, AF burden, ventricular pacing proportion, LVEF), HR 0.62 (95% CI 0.40–0.97). No difference between usual care and screening with primary-care management (HR 1.01; 95% CI 0.72–1.40; adjusted HR 0.88; 95% CI 0.61–1.27). In LVSD subgroup, specialist pathway was associated with higher odds of beta-blocker titration/initiation (OR 2.92; 95% CI 1.43–5.99) and MRA use (OR 2.95; 95% CI 1.01–8.61) at 12 months; ACEi changes not significantly different (OR 1.64; 95% CI 0.86–3.14).

The trial addressed whether adding echocardiographic screening for LV dysfunction to routine pacemaker follow-up improves patient outcomes. Screening identified LVSD in about one-third of patients, confirming a high burden of previously unrecognized dysfunction in this population. However, screening alone did not reduce the composite of HF hospitalization or death compared with usual care, indicating that identification without an integrated treatment pathway is insufficient to change outcomes. A prespecified, nonrandomized exploratory analysis suggests that when screening is coupled with a coordinated specialist HF and device clinic focused on education and proactive initiation/titration of GDMT, outcomes may improve versus primary-care–led management. These findings highlight that the benefit may reside in the comprehensive multidisciplinary care pathway following detection of LVSD rather than screening per se. The results are hypothesis-generating for care models integrating device and HF management in pacemaker patients with LV dysfunction.

In a large, pragmatic RCT of pacemaker recipients, routine echocardiographic screening frequently detected LVSD (~34%) but did not, by itself, improve the risk of HF hospitalization or death. Exploratory evidence indicates that a specialist multidisciplinary HF and devices clinic pathway for screen-positive patients may confer better outcomes than primary-care–led management, potentially through greater optimization of GDMT. Future research should validate these findings in randomized comparisons of care pathways, assess longer-term outcomes, and evaluate the impact of contemporary HFrEF therapies (e.g., ARNI, SGLT2 inhibitors) integrated into specialist care models. Development and testing of targeted screening strategies to identify highest-risk pacemaker patients for echocardiography may also be beneficial.

- Single-region study across three UK hospitals, potentially limiting generalizability. - Open-label design; allocation to post-screening care pathway was nonrandomized and site-dependent, introducing potential confounding in exploratory comparisons. - Hospitalization data extracted from local systems may miss admissions to other hospitals, though such occurrences were considered unlikely; national mortality data were comprehensive. - Study not designed to determine etiology of LV dysfunction (e.g., pacing-induced vs other causes). - Clinical benefits of medical therapy may accrue slowly, especially in less symptomatic patients; longer follow-up might reveal differences. - Trial largely conducted before widespread use of sacubitril–valsartan and SGLT2 inhibitors in HFrEF, possibly underestimating benefits achievable with modern therapy. - One participant had non-diagnostic echocardiography; some secondary outcome data (QoL, medication) were incomplete at 12 months.