Dapagliflozin Effects on Cardiac Deformation in Heart Failure and Secondary Clinical Outcome.
Sodium-glucose cotransporter 2 inhibitors were shown to reduce morbidity and mortality in patients with heart failure.
This study aims to assess potential effects of dapagliflozin in nondiabetic patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE).
This randomized, prospective, single-center, open-label trial compared consecutive nondiabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except sodium-glucose cotransporter type 2 inhibitors. Primary endpoint was the presence of a significant modification of left ventricular global longitudinal strain, diastolic function (as peak atrial longitudinal strain) and right ventricular function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints.
Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n = 44) or to continue with OMT (n = 44). All STE values improved in the dapagliflozin group after 6 months, whereas there was a nonsignificant improvement in OMT group. Moreover, when comparing the modification of STE parameters at follow-up in patients with HFrEF and HFmrEF, only the main treatment effect resulted statistically significant in both groups (P < 0.0001), indicating a significant difference between dapagliflozin and OMT.
This study provided randomized data on the beneficial effect of dapagliflozin in nondiabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique, ie, STE. This suggests its usefulness for left ventricular reverse remodeling and better quality of life in patients with HFrEF and HFmrEF. (Effects of Dapagliflozin on cardiac deformation and clinical outcomes in heart failure with reduced and mildly reduced ejection fraction [DAPA ECHO trial]; EudraCT number: 2021-005394-66).
Pastore MC
，Stefanini A
，Mandoli GE
，Piu P
，Diviggiano EE
，Iuliano MA
，Carli L
，Marchese A
，Martini L
，Pecere A
，Cavigli L
，Giacomin E
，Pagliaro A
，Righini FM
，Sorini Dini C
，Soliman Aboumarie H
，Focardi M
，D'Ascenzi F
，Valente S
，Cameli M
... -
《-》
The effects of Dapagliflozin in a real-world population of HFrEF patients with different hemodynamic profiles: worse is better.
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.
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.
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).
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.
Loria F
，Mone P
，Rispoli A
，Di Fonzo R
，Masarone D
，Mancusi C
，Correale M
，Vitullo A
，Granatiero M
，Mazzeo P
，Mercurio V
，Fiore F
，Di Sarro E
，Falco L
，Izzo C
，Campanile A
，Virtuoso N
，Stabile E
，Bonanno S
，Dattilo G
，Tocchetti CG
，Santulli G
，Vecchione C
，Ciccarelli M
，Visco V
... -
《Cardiovascular Diabetology》
Dapagliflozin in Heart Failure: A Comprehensive Meta-analysis on Functional Capacity, Symptoms, and Safety Outcomes.
To evaluate the comparative effects of dapagliflozin versus placebo in patients with heart failure (HF), focusing on functional capacity, symptoms, and safety outcomes.
Despite advancements in heart failure (HF) therapy, HF is still a significant cause of recurrent hospitalization and death worldwide. Dapagliflozin has demonstrated potential in lowering hospitalizations and mortality associated with heart failure; however, its impact on functional capacity, particularly the 6-min walk distance (6MWD), and the comprehensive assessment of safety outcomes in diverse HF populations, including those with preserved or reduced ejection fraction (HFpEF and HFrEF, respectively), requires further investigation.
PubMed, Web of Science, Cochrane Library, and Scopus databases were comprehensively searched to identify randomized controlled trials (RCTs) investigating the efficacy of dapagliflozin in comparison with control interventions for heart failure. The primary outcome was a change in the 6MWD, KCCQ score, and safety measures included hospitalization, all-cause mortality, and adverse events.
In our meta-analysis of ten studies involving 12,695 patients with heart failure, dapagliflozin showed significantly improved Kansas City Cardiomyopathy Questionnaire (KCCQ) scores [risk ratio (RR) of 2.75, 95% confidence interval (CI) (1.95-3.569), p < 0.00001] and no significant differences in 6-min walk distance [6MWD; RR of 3.59, 95% CI (- 1.44 to 8.63), p = 0.16]. Dapagliflozin demonstrated a notable reduction in hospitalization for heart failure [RR of 0.76, 95% CI (0.68-0.84), p < 0.00001], significant overall reduction on the effect of any cause mortality [RR of 0.90, 95% CI (0.83-0.99), p = 0.03). There was, however, no significant effect on adverse events [RR of 0.96, 95% CI (0.98-1.03), p = 0.39).
Our meta-analysis of ten trials concluded that dapagliflozin significantly improved KCCQ scores in both HFrEF and HFpEF. The improvement in 6MWD was not statistically significant but trended toward dapagliflozin. Dapagliflozin also showed a mortality benefit in patients with reduced ejection fraction; however, in patients with preserved ejection fraction, the result was not statistically significant. There was also a statistically significant reduction in heart failure hospitalizations across all classes.
Addo B
，Agyeman W
，Ibrahim S
，Berchie P
... -
《-》
Effect of optimisation to contemporary HFrEF medical therapy with sacubitril/valsartan (Entresto) and dapaglifloziN on left Ventricular reverse remodelling as demonstrated by cardiac magnetic resonance (CMR) Imaging: the ENVI study.
Heart failure with reduced ejection fraction (HFrEF) guidelines recommend 'four pillars' of medical therapy and device therapy if left ventricular ejection fraction (LVEF) remains ≤35% after 3 months optimum medical therapy.We conducted the first study to examine the effects of optimisation to contemporary medical therapy on cardiac reverse remodelling, as demonstrated by cardiac magnetic resonance imaging (CMR).We hypothesised a proportion of patients would undergo beneficial remodelling and LVEF improvement above the threshold for complex device prescription after 6 months.
HFrEF patients with symptomatic LVEF≤35% despite ACE inhibitor/beta blocker/mineralocorticoid receptor antagonist therapy, and qualified for sacubitril/valsartan switchover were recruited to this single centre prospective study.CMR was performed at baseline and at follow-up. Clinical, volumetric and outcome data were collected and compared.
Between June 2021 and August 2022, 49 patients were recruited. The majority (80%) were male, mean age 63±14 years. 35 (71%) had non-ischaemic cardiomyopathy. 2 (4%) patients died and 47 were followed up for a median of 7.4 months. There were no heart failure hospitalisations.Significant reductions were seen in median indexed left atrial volume: 54 mL/m2 (41-72) to 39 mL/m2 (30-60) (p<0.001); indexed left ventricular end-diastolic volume: 109 mL/m2 (74-125) to 76 mL/m2 (58-102) (p<0.001); indexed left ventricular end-systolic volume: 74mL/m2 (50-92) to 43 mL/m2 (27-58) (p<0.001) and mean indexed left ventricular mass: 72±13 g/m2 to 62±13 g/m2 (p<0.001).Median LVEF increased by 12 points from 31% to 43% (p<0.001). 29 (59%) patients improved to LVEF>35%. 13 (27%) patients improved to LVEF≥50%.Median N-terminal pro B type natriuretic peptide (NTproBNP) reduced from 883 ng/L (293-2043) to 429 ng/L (171-1421) (p<0.001).
Optimisation to contemporary HFrEF medical therapy results in beneficial cardiac reverse remodelling and significant improvements in LVEF and NTproBNP at 6 months as demonstrated by CMR. 59% of our cohort no longer met complex device indications. Guidelines suggest re-assessment of LVEF at 3 months, but our data suggests a longer period is required.
NCT05348226.
Zheng A
，Adam R
，Peebles C
，Harden S
，Shambrook J
，Abbas A
，Vedwan K
，Adam G
，Haydock P
，Cowburn P
，Young C
，Long J
，Walkden M
，Smith S
，Greenwood E
，Olden P
，Flett A
... -
《Open Heart》
ResearchGate
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