Optimisation of guideline-directed medical therapy following cardiac resynchronization therapy in patients with heart failure

Background The benefits of cardiac resynchronisation therapy (CRT) in heart failure (HF) with reduced ejection fraction are well established. By promoting left ventricular reverse remodelling, CRT improves systolic function, increases cardiac output, and enhances haemodynamic stability, with consequent reductions in mortality and morbidity. Although guidelines recommend CRT after optimization of medical therapy, guideline-directed medical therapy (GDMT) is often under-implemented prior to implantation, frequently due to tolerability limitations. Whether CRT may facilitate subsequent optimisation of GDMT in real-world practice remains poorly explored. Purpose To assess longitudinal changes in GDMT prescription and dose optimisation following CRT implantation in a contemporary real-world HF cohort. Methods This was a single-centre, retrospective observational study including consecutive patients undergoing CRT implantation between 1 September 2021 and 31 December 2024. The inclusion period was defined to follow publication of the 2021 ESC HF guidelines. The rate of GDMT prescription and dose were assessed at implantation and after 12 and 36 months. Results A total of 174 patients were included (mean age 74.2±8.8 years; 81% male). An ischaemic aetiology was present in 59.2%, mean left ventricular ejection fraction (LVEF) was 33.3±8.0%, and 64.4% had a pre-implant QRS duration ≥150 ms. Most patients were in NYHA class II–III (94.8%). At baseline, 43.4% of patients were receiving quadruple GDMT, with only 28.0% at ≥50% of target dose. Prescription rates were high for beta-blockers (BB, 96.0%) and renin–angiotensin system inhibitors (RASi, 94.3%), while mineralocorticoid receptor antagonists (MRA) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) were prescribed in 74.6% and 51.7%, respectively. At 12 months, significant therapy intensification was observed. Quadruple GDMT prescription increased to 63.2% (p<0.001) and the proportion of patients receiving ≥50% of target dose more than doubled, reaching 61.1% (p<0.001). Achievement of ≥50% target dose rose from 53.6% to 86.5% for BB (p<0.001) and from 51.6% to 62.2% for RASi (p=0.041). SGLT2i use increased to 73.0% (p<0.001), while MRA prescription increased to 81.7% (p=0.441). Loop diuretic use decreased from 78.2% to 58.3% (p<0.001). No further significant uptitration occurred between 12 and 36 months. Conclusion In our real-world retrospective study, CRT was associated with substantial optimisation of GDMT, with increases not only in the rate of quadruple therapy prescription but also in the proportion of patients receiving all four pillars at ≥50% of target dose. Haemodynamic improvement after implantation may enhance drug tolerability and facilitate up-titration, highlighting the complementary role of device and pharmacological therapy in heart failure management.