Target doses of guideline-directed medical therapeutic agents predicts response to cardiac resynchronization therapy

Tyler J Kingma; Hossam Albeyoumi; Madhumita Kolluri; Avin Sapowadia; Aryan Mehta; Obada Kholoki; Siddhant Passey; Dorothy Wakefield; Saima Husain

doi:10.1007/s00392-025-02708-2

Target doses of guideline-directed medical therapeutic agents predicts response to cardiac resynchronization therapy

Clin Res Cardiol. 2025 Jun 30. doi: 10.1007/s00392-025-02708-2. Online ahead of print.

Authors

Tyler J Kingma¹, Hossam Albeyoumi², Madhumita Kolluri², Avin Sapowadia³, Aryan Mehta², Obada Kholoki², Siddhant Passey², Dorothy Wakefield⁴, Saima Husain⁴

Affiliations

¹ Internal Medicine, University of Connecticut Health, 263 Farmington Avenue, Farmington, CT, 06030-1235, USA. kingma@uchc.edu.
² Internal Medicine, University of Connecticut Health, 263 Farmington Avenue, Farmington, CT, 06030-1235, USA.
³ Frank H. Netter School of Medicine, 370 Bassett Rd, North Haven, CT, USA.
⁴ Cardiology Department, St Francis Hospital of New England, 114 Woodland Street, Hartford, CT, USA.

PMID: 40586900
DOI: 10.1007/s00392-025-02708-2

Abstract

Background: The mainstay of therapy in patients with heart failure with reduced ejection fraction (HFrEF) has long been guideline-directed medical therapy (GDMT). This is further complicated by those who have concomitant ventricular dyssynchrony due to conduction abnormalities requiring implantable cardioverter-defibrillators or cardiac resynchronization therapy (CRT). The aim in our study was to investigate the role of GDMT in predicting response to CRT.

Methods: We performed a retrospective chart review of 181 patients at St. Francis Hospital of Trinity Health of New England and UConn John Dempsey Hospital with HFrEF diagnosis who underwent CRT between 01/01/2014 to 01/01/2024. Specifically, individual medications were evaluated as either meeting the target dose or not of GDMT prior to CRT. Then, the effect of achieving target doses was then compared in patients deemed CRT 'responders' and 'non-responders'.

Results: Patients receiving a higher number of optimally dosed GDMT showed a significant trend (p = 0.0277) toward responding to CRT. There was no significant difference between 1 and 0 therapies (OR 1.487; 95% CI, 0.689-3.209) and between 1 and 2-4 (OR 0.427; 95% CI, 0.123-1.487). However, patients receiving 2-4 optimally dosed GDMT were 3.48 times (95% CI, 1.050-11.529) more likely to be a responder when compared to those on 0 optimally dosed therapies.

Conclusions: There is a statistically significant trend toward responding to CRT when patients are on a higher number of optimally dosed GDMT, especially with > 2 therapies. Based on this data, patients should be optimized with as many optimally dosed medications as tolerated for improved outcomes.

Keywords: CRT; Cardiac resynchronization therapy; GDMT; Heart failure.