The effects of Dapagliflozin in a real-world population of HFrEF patients with different hemodynamic profiles: worse is better

Abstract

Background: Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) represent a deep revolution of the therapeutic approach to heart failure (HF), preventing its insurgence but also improving the management of the disease and slowing its natural progression. To date, few studies have explored the effectiveness of SGLT2i and, in particular, Dapagliflozin in a real-world population. Therefore, in this observational prospective study, we evaluated Dapagliflozin's effectiveness in a real-world HF population categorized in the different hemodynamic profiles.

Methods: From January 2022 to June 2023, we enrolled 240 patients with chronic HF and reduced ejection fraction (HFrEF) on optimal medical therapy, according to 2021 ESC guidelines, that added treatment with Dapagliflozin from the HF Clinics of 6 Italian University Hospitals. Clinical, biochemical, and echocardiographic parameters were collected before and after 6 months of Dapagliflozin introduction. Moreover, the HFrEF population was classified according to hemodynamic profiles (A: SV ≥ 35 ml/m²; E/e' < 15; B: SV ≥ 35 ml/m²; E/e' ≥ 15; C: SV < 35 ml/m²; E/e' < 15; D: SV < 35 ml/m²; E/e' ≥ 15). Then, we compared the Dapagliflozin population with two retrospective HF cohorts, hereinafter referred to as Guide Line 2012 (GL 2012) group and Guide Line 2016 (GL 2016) group, in accordance with the HF ESC guidelines in force at the time of patients enrolment. Precisely, we evaluated the changes to baseline in clinical, functional, biochemical, and echocardiographic parameters and compared them to the GL 2012 and GL 2016 groups.

Results: Dapagliflozin population (67.18 ± 11.11 years) showed a significant improvement in the echocardiographic and functional parameters (left ventricular ejection fraction [LVEF], LV end-diastolic volume [LVEDV], LVEDV index, stroke volume index [SVi], left atrium volume index [LAVi], filling pressure [E/e' ratio], tricuspid annular plane systolic excursion [TAPSE], tricuspid annular S' velocity [RVs'], fractional area change [FAC], inferior vena cava [IVC diameter], pulmonary artery systolic pressure [sPAP], NYHA class, and quality of life) compared to baseline. In particular, TAPSE and right ventricle diameter (RVD1) ameliorate in congestive profiles (B and D); accordingly, the furosemide dose significantly decreased in these profiles. Comparing the three populations, the analysis of echocardiographic parameters (baseline vs follow-up) highlighted a significant decrease of sPAP in the Dapagliflozin population (p < 0.05), while no changes were recorded in the GL 2012 and GL 2016 population. Moreover, at the baseline evaluation, the GL 2012 and 2016 groups needed a higher significant dose of furosemide compared to Dapagliflozin group. Finally, Dapagliflozin patients had significantly fewer rehospitalizations (1.25%) compared with the other two groups (GL 2012 18.89%, p 0.0097; GL 2016 15.32%, p 0.0497).

Conclusions: We demonstrate that Dapagliflozin is rapidly effective in an HFrEF real-world population; furthermore, the more significant effect is recorded in HFrEF patients with a congestive profile (B and D), supporting the introduction of Dapagliflozin in patients with a congestive profile and a worse prognosis. In conclusion, our data suggest evaluating the patient's hemodynamic state beyond LVEF in HFrEF.

Keywords: Cardiac function; Dapagliflozin; Heart failure with reduced ejection fraction; Hemodynamic profile; SGLT2 inhibitors.

Fig. 1

Changes from baseline to 6 months follow-up of clinical, biochemical, echocardiographic and pharmacological parameters of Dapagliflozin population. The graphs show that a significant improvement was observed in LVEF (A), LVEDV (B), E/e′ ratio (C), FAC (D), RVs’ (E), sPAP (F), and quality of life (G). In contrast, there were no significant changes in dose of furosemide (H) and glomerular filtration (I). LVEF, Left ventricular ejection fraction; LVEDV, Left ventricle end-diastolic volume; E, Early-wave transmitral diastolic velocity; e′, Early-diastolic velocity at tissue Doppler imaging; FAC, Fractional area change; RVs’, Tricuspid annular S′ velocity; sPAP, Pulmonary artery systolic pressure

Fig. 2

Baseline hemodynamic profile of Dapagliflozin population: profile A (normal flow, normal pressure); profile B (normal flow, high pressure); profile C (low flow, normal pressure); profile D (low flow, high pressure)

Fig. 3

Changes from baseline to 6 months follow-up of echocardiographic parameters of the four hemodynamic profiles. A LVEF significantly improved in all profiles. B E/e′ significantly improved in all profile. C LVEDV significantly improved only in profile A. D LVESV significantly improved only in profile A and B. E RVs’ significantly improved in congestive profiles (B and D). F TAPSE significantly improved in congestive profiles (B and D). G FAC significantly improved in profile A, B and D. LVEF, Left ventricular ejection fraction; E, Early-wave transmitral diastolic velocity; e′, Early-diastolic velocity at tissue Doppler imaging; LVEDV, Left ventricle end-diastolic volume; LVESV, Left ventricle end-systolic volume; RVs’, Tricuspid annular S′ velocity; TAPSE, Tricuspid annulus plane systolic excursion; FAC, Fractional area change

Fig. 4

Changes from baseline to 6 months follow-up of quality of life (A), dose of furosemide (B) and glomerular filtrate (C)

Fig. 5

Changes from baseline to 6 months follow-up of NYHA class according to the four hemodynamic profiles. The Sankey diagrams show that patients of all four hemodynamic profiles significantly improved in the NYHA class. NYHA, New York Heart Association

Fig. 6

Comparison of GL 2012, GL 2016 and Dapagliflozin population in terms of glomerular filtrate (A), dose of loop diuretic (B), sPAP (C) and HF rehospitalizations (D). GL, Guideline; HF, Heart Failure; sPAP, Pulmonary artery systolic pressure; #, p (baseline vs. follow up) > 0.05