Ventricular tachycardia burden in heart failure with reduced ejection fraction - can we rely on optimized medical therapy

Abstract Introduction Implantation of cardioverter-defibrillator and/or resynchronization (ICD and CRT-D) devices is aimed to prevent sudden cardiac death, fatal complication of heart failure with reduced ejection fraction (HFrEF). Guidelines propose a period of 3 months receiving maximally titrated guideline-directed medical therapy (GDMT) prior to implantation. Ventricular tachycardia (VT) burden in HFrEF has been related to worse outcomes. The effect of GDMT up-titration on VT incidence after device implantation has not yet been fully clarified. Purpose The main goal of this study is to examine the effects of GDMT evidence-based target doses on VT and appropriate device therapy (ADT) incidence in patients with HFrEF implanted with ICD or CRT-D. Methods This registry-based study included patients with HFrEF who were implanted with ICD or CRT-D from January 2021 to November 2023, with at least one follow-up. Titration of GDMT and incidence of VT/ADT were evaluated. We compared VT/ADT incidence in target dose group to incomplete titration group of each drug class. We also compared GDMT titration and VT/ADT incidence in CRT-D to ICD group. The Fisher exact test was used to evaluate the differences between groups. Results Data on 132 patients were collected (mean age 63±26 years, 16% female). Median follow-up time from device implantation was 201 (30-748) days. Target doses were reached for 24.4% beta blockers (BB), 37.8% angiotensin receptor neprilysin inhibitors (ARNI), 73.5% mineralocorticoid receptor antagonists (MRA), 89.5% sodium-glucose contransporter-2 inhibitors (SGLT2I), and 18.8% of complete GDMT. Total VT and ADT incidence was 32.6% and 12.9%, respectively. In target doses vs. incomplete doses groups, VT incidence was 34.4% vs. 32.0% (p=.83) for BB, 28.0% vs. 35.4% (p=.45) for ARNI, 32.0% vs. 34.3% (p=.84) for MRA, 30.1% vs. 50.0% (p=.23) for SGLT2I and 33.3% vs. 32.4% (p=1) for complete GDMT. ADT incidence was 18.8% vs. 11.0% (p=.36) for BB, 12.0% vs. 13.4% (p=1) for ARNI, 12.4% vs. 14.3% (p=.77) for MRA, 11.0% vs. 21.4% (p=.39) for SGLT2i, and 16.7% vs. 12.0% (p=.51) for complete GDMT. In CRT-D vs. ICD group, 31.5% vs. 19,2% (p=.15) BB, 44.4% vs. 33.3% (p=.21) ARNI, 79.6% vs. 69.2% (p=.16) MRA, 98.1% vs. 83.3% (p<0.05) SGLT2I; and 20.4% vs. 16.7% (p=.65) of complete GDMT were maximally titrated. VT incidence was significantly lower in CRT-D group (18.5% vs. 42.3%, p<0.05). ADT was also lower, but without statistical significance (9.3% vs. 15.4%, p=.43). Conclusions Up-titration of any individual drug or complete GDMT to the evidence-based target dose did not directly correlate with a decrease in VT or ADT incidence. Cardiac resynchronization therapy provides more room for target GDMT doses, particularly of BB. We notice only a modest trend in up-titration of GDMT in patients with CRT-D, who had significantly lower incidence of VT.