Changes in medical therapy after cardiac resynchronization in patients with heart failure: insights from the U.S. Veterans Affairs healthcare system

Abstract

Abstract Background Patients with heart failure with reduced ejection fraction (HFrEF) are often not treated with comprehensive guideline directed medical therapy (GDMT) due to hemodynamic and renal limitations. Cardiac resynchronization therapy (CRT) improves hemodynamics in patients with HFrEF and ventricular dyssynchrony. Whether CRT facilitates intensification of GDMT in patients with HFrEF has not been well-studied. Purpose To assess pre-procedure GDMT (B-blocker, ACEI [angiotensin converting enzyme inhibitor]/ARB [angiotensin receptor blocker], ARNI [angiotensin receptor neprilysin inhibitor], MRA [mineralocorticoid receptor antagonist], SGLT2i [sodium-glucose cotransporter-2 inhibitor]) utilization in HFrEF patients who received CRT and to compare changes in GDMT in patients who received CRT with patients who received implantable cardioverter-defibrillator (ICD). Methods Veterans with left ventricular ejection fraction (LVEF) 35% who received CRT or ICD from Feb 22, 2000 – Jul 28, 2022 were identified. Patients with end-stage renal disease were excluded. Changes in GDMT 12-months following device implant were characterized and compared between CRT and ICD recipients. Mixed effects logistic regression models were generated to evaluate associations between receipt of CRT and the composite of therapy initiation, dose increase, or target dose achievement compared with ICD. Models were adjusted for clinical characteristics and pre-implant GDMT utilization. Similar models were developed to evaluate the adjusted associations between CRT and changes in estimated glomerular filtration rate (eGFR) and blood pressure (BP) compared with ICD. Results A total of 2,082 CRT recipients and 7,263 ICD recipients were identified. Pre-procedure heart rate, BP, serum potassium, and eGFR were within normal ranges and similar between groups. Prior to device implant, ACEI/ARB/ARNI were most frequently prescribed (91%), followed by -blockers (88%), MRA (46%), and SGLT2i (33% in post-SGLT2i era). Pre-procedure GDMT was similar between CRT and ICD recipients. At 12 months follow-up, CRT was independently associated with increased odds of therapy initiation, dose increase, or target dose achievement for ACEI/ARB/ARNI, ARNI, B-blockers, and MRA (Figure 1). ICD was associated with a decline in eGFR while CRT was associated with an increase in eGFR (mean [standard deviation]: -0.95 [0.17] vs. +0.6 [0.29]; p<0.01), while no differences were observed in BP or LVEF at 12 months. Conclusions In a large, contemporary cohort of patients with HFrEF, most patients were not prescribed MRA or SGLT2i prior to receiving CRT or ICD despite no apparent renal or blood pressure-related contraindications. CRT is associated with increased odds of the composite of initiation, dose increase, or target dose achievement for ACEI/ARB/ARNI, ARNI, B-blockers, and MRA compared with ICD. GDMT intensification may be mediated by beneficial changes in kidney function in CRT recipients.Figure 1