Outpatient medication optimization and the impact on left ventricular ejection fraction recovery: an analysis of recently diagnosed heart failure patients followed at a tertiary care centre

The goal of outpatient heart failure (HF) management is to achieve guideline directed medical therapy (GDMT) to improve left ventricular ejection fraction (LVEF) and consequently quality of life and survival. However, there are barriers to achieving target therapies including side effects or patient intolerance. Our aim was to determine whether a higher composite dose of HF medications is associated with LVEF improvement, and whether there is an interaction of LVEF and achieved dose on mortality. We identified patients aged >18 years with a recent diagnosis of HF with reduced ejection fraction (HFrEF; < 40%) or mid-range ejection fraction (HFmEF; 41-49%) seen at the Toronto General Hospital HF Clinic between 2000-2019. Date of optimization was defined as having a stable HF medication regimen for 2 consecutive visits. Target therapy was defined as at least 75% target dose of GDMT, consisting of an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or angiotensin receptor blocker-neprilysin inhibitor (ACEi, ARB, or ARNI), a beta blocker, and a mineralocorticoid receptor antagonist (MRA). A multivariable logistic regression model evaluated the association between target medical therapy and LVEF improvement, defined as an LVEF >40% accompanied by an increase of >10%. A multivariable Cox proportional hazard model analyzed the association between LVEF improvement and its interaction with target therapy achievement with mortality. We identified 850 patients, median age 55 years (Q1 44, Q3 64); 88% HFrEF and 12% with HFmEF. The median time from first visit to optimization was 17 weeks, with 27% reaching 75-100% dose target. At optimization, 314 (37%) patients experienced improvement in LVEF. Higher target medication was not associated with an improvement in LVEF (OR 1.07, 95% CI 0.57-1.98, p=0.84). During a median follow up of 5 years (Q1 3 – Q3 9), 168 patients died. Achieving >75% target medication was not associated with decreased mortality (HR 0.77, 95% CI 0.39-1.51, p=0.44). For those with improved LVEF, however, increasing doses of GDMT >50% target was associated with decreased mortality while in patients without LVEF improvement, target dose was not associated with mortality. Achieving target HF medication doses continues to remain a challenge in outpatient care. Despite barriers, achieving target doses was not associated with improvement in LVEF or mortality. This study suggests that the benefit of GDMT may still be significant irrespective of doses reached. In those with some reversibility of cardiac dysfunction, higher doses were associated with reduced mortality.