Protocol-driven approach to guideline-directed medical therapy optimization for heart failure: A real-world application to recovery

Abstract

The objective of our study was to evaluate the real-world effects of an aggressive, personalized protocol for guideline-directed medical therapy (GDMT) titration in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We conducted a two-center retrospective cohort study. Patients with HFrEF who presented to a HF clinic from January 2020 to December 2022 were placed on a GDMT protocol. 180 patients were included in the study. Mean GDMT score significantly increased from 4.7 to 5.9 (p < 0.001) between initial and final visits. Mean left ventricular ejection fraction (LVEF) significantly increased from 28 % to 33 % (+5 %, p < 0.001). 27 (15.7 %) of the 172 patients with complete New York Heart Association (NYHA) classification data had improvement by at least 1 class, while 2 (1.2 %) patients had worsening NYHA classification. 140 (77.8 %) patients had no unplanned hospitalizations between visits. 21 (11.7 %) patients had an unplanned hospitalization for acute HF during the study period with a mean time from first clinic visit to hospitalization of 183 days (range: 13-821 days). 2 (1.1 %) patients were hospitalized due to GDMT-associated adverse drug events (i.e. hypotension, hyperkalemia). 7 (3.9 %) patients died during the study period, which was lower than the predicted 1-year death rate for our cohort (12.3 %) using the MAGGIC score. In conclusion, an aggressive, personalized protocol for GDMT titration in patients with HFrEF led to significant improvements in LVEF, NYHA classification, hospitalization, and mortality in a real-world setting. This protocol may help serve as a road map to lessen the gap between clinical knowledge and practice surrounding optimization of GDMT and move HFrEF patients toward a path to recovery.

Keywords: Guideline-directed medical therapy; Heart failure; Protocol; Reduced ejection fraction; Titration.

Fig. 1

Medication prescription rates by GDMT class (n = 180). Bar graph showing the percent of patients on a medication class at initial visit compared to final visit. Abbreviations: ACEI angiotensin converting enzyme inhibitor; ARB angiotensin receptor blocker; ARNI angiotensin receptor-neprilysin inhibitor; BB beta blocker; GDMT guideline-directed medical therapy; H-ISDN hydralazine and isosorbide dinitrate; MRA mineralocorticoid receptor antagonist; SGLT2I sodium-glucose cotransporter-2 inhibitor.

Fig. 2

Target dose achievement by GDMT class (n = 180). Bar graph showing the percent of patients on the target dose of a medication by GDMT class at initial visit compared to final visit. Abbreviations as in Fig. 1.

Fig. 3

Improvements in clinical parameters following GDMT. Violin plots showing the distribution of data for heart rate, NYHA classification, and LVEF at initial visit compared to final visit. The width of each curve corresponds to the frequency of data points in that region. The middle dashed line represents the median. The upper and lower dotted lines represent the first and third quartiles. Abbreviations: BPM beats per minute; LVEF left ventricular ejection fraction; NYHA New York Heart Association.

Fig. 4

Hospitalization and mortality rates. Dot plots of 100 dots showing an approximation of the percent of patients (180 patients total) who were hospitalized and died during the study period. Abbreviation: AVF arteriovenous fistula; HF heart failure.

Fig. 5

GDMT effect on blood pressure and LVEF over time. Line graph showing a conceptual depiction of the effect of GDMT on blood pressure and LVEF over time. Up-titration of GDMT may transiently lower blood pressure but should also gradually improve LVEF. As LVEF improves, cardiac output increases, and blood pressure increases, allowing for cyclical up-titration of GDMT. Abbreviations as in Fig. 1, Fig. 3.