Impact of Guideline-Directed Medical Therapy on Left Ventricular Function in Heart Failure Patients with Conventional Right Ventricular Pacing

Background/Objectives: Heart failure (HF) in patients with conventional right ventricular pacing with significant pacing percentages is still a subject of concern, and management of HF in this population has historically been difficult; however, novel HF pillar medications, such as SGLT2 inhibitors (SGLT2i) and angiotensin receptor/neprilysin inhibitors (ARNi), have fundamentally transformed contemporary pharmacological HF management. The aim of this study was to assess left ventricular (LV) function after current guideline-directed medical therapy (GDMT) in patients with chronic right ventricular (RV) pacing and HF. Methods: Patients with a lifetime ventricular pacing percentage > 20% (Vp > 20%) and HF diagnosed according to ESC guideline criteria were included. Device interrogation and transthoracic echocardiography (TTE), including assessment of left ventricular ejection fraction (LVEF) and mitral annular plane systolic excursion (MAPSE), were performed at GDMT initiation and during subsequent follow-up. Changes in LVEF and MAPSE were assessed overall and according to baseline HF phenotype. Multivariable linear regression analyses were performed to identify independent predictors of changes in LVEF and MAPSE. Results: Among 550 conventionally paced patients screened for HF, 127 (23.1%) met the inclusion criteria and underwent GDMT initiation. Mean age was 68.2 ± 12.1 years, and mean follow-up duration was 10.2 ± 6.3 months. Baseline LVEF and MAPSE were 48.7 ± 6.3% and 12.0 ± 2.4 mm, respectively. All patients received SGLT2i therapy, while 24 (18.9%) received ARNi. Overall, LVEF increased by 1.94 ± 2.47% and MAPSE by 0.84 ± 0.96 mm (both p < 0.001). Patients with HFrEF (n = 25) showed an increase in LVEF of 5.84 ± 2.53% and MAPSE of 1.72 ± 1.21 mm. In patients with HFmrEF, LVEF increased by 2.50 ± 1.54% and MAPSE by 0.83 ± 0.92 mm, whereas in HFpEF, LVEF increased by 0.67 ± 0.78% and MAPSE by 0.58 ± 0.71 mm. NYHA functional class improved by at least one class in 100 patients (78.7%). In multivariable analysis, ARNi use was independently associated with greater improvement in LVEF and MAPSE, while lower baseline LV function was associated with greater subsequent improvement. Conclusions: In patients with HF and chronic RV pacing, GDMT was associated with modest but statistically significant improvements in LV systolic function, assessed by LVEF and MAPSE, across the HF spectrum. The greatest improvements were observed in patients with HFrEF. However, given the observational design, absence of a control group, and universal use of SGLT2i, these findings do not establish a causal treatment effect or demonstrate superiority of any specific GDMT combination. Prospective controlled studies are warranted to determine the clinical significance of these changes and the independent contribution of individual therapies.