Background: The 2023 ESC Heart Failure (HF) Guidelines recommend the rapid up-titration of guideline-directed medical therapy (GDMT) for all patients after HF hospitalisation. Real-world data on the implementation of a rapid up-titration programme (RTP) are scarce. Methods: We aimed to summarise the primary experiences of a six-week RTP in a multicentre observational study of five cardiology centres, evaluating the GDMT applied and the target doses (TDs) achieved during the RTP. The safety of RTP in relation to exceeding the "safety indicators" used in the STRONG-HF trial and any serious adverse events were observed. Changes in the left ventricular ejection fraction (LVEF) after RTP were evaluated. Results: Among the 90 consecutive patients (age: 56 [49-63] years, HFrEF: 96%, NT-proBNP at discharge: 1390 [735-2835] pg/mL; continuous variables are presented as median and interquartile ranges, while categorical variables are shown as absolute numbers and percentages, respectively), a remarkable proportion of patients received GDMT at hospital discharge; however, target doses were rarely achieved (RASi: 100%, TD RASi: 11%; βB: 97%, TD βB: 6%; MRA: 99%, TD MRA: 82%; SGLT2i: 98%, TD SGLT2i: 98%; triple therapy [TT: RASi + βB + MRA]: 96%, TD TT: 2%, quadruple therapy [QT: RASi + βB + MRA]: 94%, TD QT: 2%). After the six-week RTP, 100% of the total cohort (TC) were receiving RASi; 99-99-99% were receiving βB, MRA, and SGLT2i medications; and altogether, 98-98% were on TT and QT. In total, 78-78% of the patients received ≥50% of the TDs of TT and QT, while 51-51% of the TC were on TDs of TT and QT. During the RTP, no serious adverse events were observed. Between two and four months after the RTP, 51% of HFrEF patients evolved to the HFimpEF category. Conclusions: The present multicentre, observational study confirms that RTP is feasible and safe in real-world clinical practice, leading to a remarkably large proportion of patients receiving GDMT by the end of the six-week RTP, resulting in a significant increase in LVEF.

Type 2 diabetes mellitus (T2DM) is a global health crisis, with cardiovascular disease (CVD) accounting for 75% of mortality in this population. Despite advances in managing traditional risk factors, such as low-density lipoprotein cholesterol (LDL) cholesterol reduction (IMPROVE-IT, FOURIER), antithrombotic therapies (PEGASUS, COMPASS), and triglyceride-lowering agents (REDUCE-IT), a substantial residual cardiovascular risk persists, driven in part by chronic low-grade systemic inflammation. Chronic low-grade inflammation is a central driver of cardiovascular-kidney-metabolic (CKM) syndrome in T2DM, perpetuating residual cardiovascular risk despite optimal management of traditional risk factors. This narrative review synthesizes evidence on how inflammation accelerates coronary heart disease (CHD), heart failure (HF), stroke, diabetic kidney disease (DKD), and peripheral artery disease (PAD). We evaluate the anti-inflammatory mechanisms of current therapies such as statins, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists, as well as emerging agents like colchicine and interleukin (IL)-1β/IL-6 inhibitors, emphasizing their differential efficacy across CKM traits. By integrating pathophysiological insights with clinical trial data, we propose biomarker-guided strategies to target inflammation as a modifiable risk factor, offering a roadmap to bridge the gap in diabetes-related cardiovascular care.

Although sodium-glucose cotransporter 2 inhibitors reduce the risk of cardiovascular death or worsening heart failure (HF) in patients with chronic HF, there are limited data on initiation in hospitalized patients with HF. DAPA ACT HF-TIMI 68 (Dapagliflozin and Effect on Cardiovascular Events in Acute Heart Failure - Thrombolysis in Myocardial Infarction 68) is an international, randomized, double-blind trial evaluating the initiation of dapagliflozin (10 mg daily) vs placebo in 2,401 patients hospitalized for acute HF. Patients were enrolled irrespective of left ventricular ejection fraction, type 2 diabetes status, or chronicity of HF (de novo and worsening chronic HF). Randomized participants receive blinded treatment for 2 months. The primary efficacy endpoint is time to first occurrence of cardiovascular death or worsening HF (worsening HF during the index admission, rehospitalization for worsening HF, or urgent HF visit). Key safety endpoints include symptomatic hypotension and worsening kidney function. This is the first cardiovascular outcomes trial designed specifically to evaluate the efficacy and safety of in-hospital initiation of dapagliflozin in patients hospitalized for the management of acute HF. (Dapagliflozin and Effect on Cardiovascular Events in Acute Heart Failure - Thrombolysis in Myocardial Infarction 68 [DAPA ACT HF-TIMI 68]; NCT04363697; EudraCT # 2022-001262-35).

Heart failure (HF), a chronic and progressive disease, is increasing in prevalence worldwide and is associated with increased hospitalizations and death. Despite notable improvements in medical therapy for HF, patients are still at risk of future negative outcomes. Current guidelines recommend four classes of medication for treating patients with HF, deemed guideline-directed medical therapy (GDMT). The use and adherence of these GDMTs serve as a major predictor of outcomes in those with chronic HF; however, implementation of therapy remains poor, despite substantial evidence of benefit. The acute hospitalization for HF and the subsequent vulnerable period serve as important milestones for adequate disease modification, and implementing a strategy for aggressive medical therapy can improve HF outcomes. Current guidelines also recommend that follow-up with multidisciplinary chronic disease management specific to HF be provided to those living with heart failure, which is essential for improving readmissions and mortality. This follow-up, although important by itself, serves as an important avenue for disease modification through medication titration, and implementing such structured follow-up is essential for further population-wide improvements in HF mortality. In this context, the STRONG-HF trial investigators developed an implementation trial providing evidence for the rapid inpatient initiation and subsequent titration of HF GDMT, demonstrating the importance of implementation strategies in the care of HF patients. In this narrative review, we review the evidence base for treating patients with HF, highlight deficits in our current real-world experience, and provide support for trial evidence like STRONG-HF in the global fight to reduce the burden of HF.

Use of type 2 sodium-glucose cotransporter inhibitors (SGLT2i) gliflozines have first been applied to treatment of diabetic patients. In this setting, unexpected benefits on concomitant heart failure (HF) were seen in large trials. This clinical benefit was initially traced back to their natriuretic properties and as such they were also included in the therapeutic armamentarium of HF treatment. However, further insight into their mechanism of action has clarified their complex interaction with kidney function which better explains their prompt effectiveness in ameliorating HF outcome in the long-term, independent of left ventricular ejection fraction (LVEF) phenotype and concomitant presence of diabetes and/or chronic renal disease. This mainly results from the ability of SGLT2i to counteract the HF-associated hyperactivity of the sympathetic system and neurohormonal activation by modifying the pattern of renal tubular sodium and glucose reabsorption which results in curbing the overall sodium reabsorption. Their action results in decreased kidney workload and related oxygen consumption thus indirectly reducing sympathetic activity. The complex renal functional changes associated with HF and their modifications during SGLT2i administration will be reviewed.

Background/Objectives: In heart failure (HF) with reduced ejection fraction (HFrEF), the early diagnosis and proper treatment of comorbidities (CMs) are of fundamental relevance. Our aim was to assess the prevalence of CMs among real-world patients requiring hospitalisation for HFrEF and to investigate the effect of CMs on the implementation of guideline-directed medical therapy (GDMT) and on all-cause mortality (ACM). Methods: The data of a consecutive HFrEF patient cohort hospitalised for HF between 2021 and 2024 were analysed retrospectively. Sixteen CMs (6 CV and 10 non-CV) were considered. Patients were divided into three categories: 0-3 vs. 4-6 vs. ≥7 CMs. GDMT at discharge and ACM were compared among CM categories. The predictors of 1-year ACM were also evaluated. Results: From the 388 patients (male: 76%, age: 61 [50-70] years; NT-proBNP: 5286 [2570-9923] pg/mL; ≥2 cardiovascular-kidney-metabolic disease overlap: 46%), a large proportion received GDMT (RASi: 91%; βB: 85%; MRA: 95%; SGLT2i: 59%; triple therapy [TT: RASi+βB+MRA]: 82%; quadruple therapy [QT: TT + SGLT2i]: 54%) at discharge. Multimorbidity was accompanied with a (p < 0.05) lower application ratio of RASi (96% vs. 92% vs. 85%; 0-3 vs. 4-6 vs. ≥7 CMs) and βB therapy (94% vs. 85% vs. 78%), while MRA (99% vs. 94% vs. 94%) and SGTL2i use (61% vs. 59% vs. 57%) did not differ (p > 0.05). Patients with multimorbidity were less likely to be treated with TT (93% vs. 82% vs. 73%, p = 0.001), while no difference was detected in the implementation of QT (56% vs. 54% vs. 50%, p = 0.685). The 1-year ACM of patients with an increased burden of CMs was higher (9% vs. 13% vs. 25%, p = 0.003). The risk of 1-year ACM was favourably affected by the use of TT/QT and less severe left ventricular systolic dysfunction, while having ≥5 CMs had an unfavourable impact on prognosis. Conclusions: According to our real-world analysis, HFrEF patients with an increased burden of CMs can expect a less favourable outcome. However, modern GDMT can even be applied in this patient population, resulting in a significantly improved prognosis. Thus, clinicians should insist on the early, conscious implementation of a prognosis-modifying drug regime in multimorbid HF patients as well.

Cardiac troponins are essential structural proteins found in the contractile apparatus of cardiac myocytes. During myocardial damage, such as in myocardial infarction (MI), these troponins are released into the bloodstream. As a result, they play a central role in the diagnosis of MI, serving as sensitive and specific markers for cardiac injury. Earlier assays that were used for measuring troponin levels were considered as a dichotomous test, categorizing patients as being positive or negative for MI. The recent introduction of high-sensitivity cardiac troponin assays has revolutionized cardiac troponin detection. These assays can detect troponin levels that are 100 times lower than what traditional methods can detect. Hence it is now considered a quantitative measure of cardiac myocyte injury not only in the setting of MI but also in subjects without MI such as heart failure, in whom it can be regarded as a marker for myocardial stress. This review aims to establish the relationship between high-sensitivity cardiac troponin levels and the prognosis of patients suffering from acute heart failure. Additionally, this seeks to identify other applications where the release of troponin from the cardiomyocyte can provide prognostic information. This information can be vital in determining the appropriate treatment options for patients, ultimately improving their quality of life and positively impacting health economics.

Chronic kidney disease (CKD) presents a significant clinical and economic burden to healthcare systems worldwide, which increases considerably with progression towards kidney failure. The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial demonstrated that patients with or without type 2 diabetes who were treated with dapagliflozin experienced slower progression of CKD versus those receiving placebo. Understanding the effect of long-term treatment with dapagliflozin on the timing of kidney failure beyond trial follow-up can assist informed decision-making by healthcare providers and patients. The study objective was therefore to extrapolate the outcome-based clinical benefits of treatment with dapagliflozin in patients with CKD via a time-to-event analysis using trial data.

Patient-level data from the DAPA-CKD trial were used to parameterize a closed cohort-level partitioned survival model that predicted time-to-event for key trial endpoints (kidney failure, all-cause mortality, sustained decline in kidney function and hospitalization for heart failure). Data were pooled with a subpopulation of the Dapagliflozin Effect on Cardiovascular Events - Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial to create a combined CKD population spanning a range of CKD stages; a parallel survival analysis was conducted in this population.

In the DAPA-CKD and pooled CKD populations, treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function and hospitalization for heart failure. Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years [dapagliflozin: 25.2, 95% confidence interval (CI) 19.0-31.5; standard therapy: 18.5, 95% CI 14.7-23.4] in the DAPA-CKD population. A similar result was observed in the pooled CKD population with an estimated delay of 6.3 years (dapagliflozin: 36.0, 95% CI 31.9-38.3; standard therapy: 29.6, 95% CI 25.5-34.7).

Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for patients who would go on to experience them, including those at modest risk of progression.

Safety and early clinical benefit make sodium-glucose cotransporter-2 inhibitor (SGLT2-i) therapy suitable for in-hospital initiation in patients with heart failure and reduced ejection fraction (HFrEF). Despite randomized controlled trials and guideline recommendations, they are underused, and clinical inertia may play a role.

To assess the impact of initiating SGLT-2i at discharge on 90-day prescription rates in patients with HFrEF during hospitalization for acute heart failure (AHF). Secondary: To evaluate the presence of independent factors associated with prescription, and to explore clinical outcomes at 90 days.

Retrospective analysis of a consecutive prospective single-center cohort. Adult patients hospitalized between January 2021 and September 2022 with a primary diagnosis of AHF and left ventricular ejection fraction (LVEF) <40% were included. The primary outcome was SGLT2-i prescription rate at 90 days, and the exploratory secondary endpoints was the composite of hospitalization or urgent visit for AHF or all-cause mortality at 90 days.

237 patients were included. Mean age was 76±11 years, and mean LVEF was 29±7%. In patients without contraindications, SGLT2 inhibitors (SGLT2-i) were prescribed during hospitalization in 52.3%. At 90 days, the SGLT2-i prescription rate was 94.2% in those with in-hospital initiation and 14.4% in those without. (p<0.001). Independent factor associated with inpatient prescription was lower LVEF, 0.83 (95% CI: 0.77-0.89) for each point. Patients with in-hospital SGLT2-i initiation showed a lower rate of the combined endpoint of all-cause death, HF rehospitalization, or unplanned HF visit at 90 days (44.4% versus 23.9%, p=0.005).

In-hospital initiation of SGLT-2-i was associated with significantly higher prescription rates and lower prevalence in the secondary combined endpoint at 90 days. This study reflects the presence of medical inertia, particularly in patients with higher LVEF, and highlights the hospitalization period as an optimal time to start SGLT2-i.

We explored timing, settings and predictors of angiotensin receptor-neprilysin inhibitor (ARNI) initiation in a large, nationwide cohort of patients with heart failure (HF) with reduced ejection fraction (HFrEF).

Patients with HFrEF (ejection fraction <40%) registered in the Swedish HF Registry in 2017-2021 and naïve to ARNI were evaluated for timing and location of, and their characteristics at ARNI initiation. ARNI use increased from 8.3% in 2017 to 26.7% in 2021. Among 3892 hospitalized patients, 8% initiated ARNI in-hospital or ≤14 days after discharge, 4% between 15 and 90 days, and 88% >90 days after discharge or never initiated. Factors associated with earlier initiation included follow-up in specialized HF care, more severe HF, previous HF treatment use and higher income, whereas older age, higher comorbidity burden and living alone were associated with later/no initiation. Of 16 486 HFrEF patients, 8.1% inpatients and 5.9% outpatients initiated an ARNI at the index date. Factors associated with initiation in outpatients were overall consistent with those linked with an in-hospital/earlier ARNI initiation; 4.9% of 10 209 with HF duration <6 months and 9.1% of 5877 with HF duration ≥6 months initiated ARNI. Predictors of ARNI initiation in HF duration <6 months were inpatient status, lower ejection fraction, hypertension, whereas previous angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use was associated with less likely initiation. Discontinuation at 1 year ranged between 13% and 20% across the above-reported analyses.

In-hospital and early initiation of ARNI are limited in real-world care but still slightly more likely than in outpatients. ARNI were more likely initiated in patients with more severe HF, which might suggest its use as a second-line treatment and only following worsening of clinical status. One-year discontinuation rates were consistent regardless of the timing/setting of ARNI initiation.

Patients recently hospitalized for heart failure (HF) are at a higher risk of adverse clinical outcomes, but they may experience a greater absolute and relative benefit from effective therapies than individuals who are considered more "stable."

The authors examined the effects of dapagliflozin according to the timing of prior HF hospitalization in a patient-level pooled analysis of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure).

A total of 11,007 patients were randomized in DAPA-HF and DELIVER. The primary outcome was the composite of worsening HF or cardiovascular death.

In total, 12.4% were hospitalized for HF within 3 months of randomization, 14.2% between 3 and 12 months, and 16.8% more than 1 year before randomization, whereas 56.5% had not been hospitalized. The risk of the primary endpoint was inversely associated with time from prior HF hospitalization, and patients with a recent HF hospitalization had the highest risk. Compared with placebo, dapagliflozin reduced the risk of the primary outcome across HF hospitalization category (0-3 months, HR: 0.66 [95% CI: 0.55-0.81]; 3-12 months, HR: 0.73 [95% CI: 0.59-0.90]; >1 year, HR: 0.91 [95% CI: 0.74-1.12]; and no prior hospitalization, HR: 0.83 [95% CI: 0.73-0.94]; Pinteraction = 0.09). The number of patients needed to treat with dapagliflozin to prevent 1 event over the median follow-up of 22 months was 13, 20, 23, and 28, respectively. The beneficial effect was consistent across the range of LVEF regardless of HF hospitalization category.

The relative benefits of dapagliflozin were consistent across the range of LVEF regardless of the timing of the most recent HF hospitalization with a greater absolute benefit in patients with recent hospitalization.

Heart failure with preserved ejection fraction (HFpEF) is common in type 2 diabetes mellitus (T2D), leading to high morbidity and mortality. Managing HFpEF in diabetic patients is challenging with limited treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown potential cardiovascular benefits. This meta-analysis compares the effects of GLP1-RA and SGLT2 inhibitors on HFpEF in T2D patients.

We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating GLP1-RA and SGLT2 inhibitors' impact on HFpEF in T2D patients. Databases searched included PubMed, MEDLINE, and Cochrane Library up to July 2024. Primary outcomes were changes in left ventricular ejection fraction (LVEF), myocardial fibrosis (extracellular volume fraction, ECV), and functional capacity (6-minute walk test, 6MWT). Secondary outcomes included HbA1c, body weight, and systolic blood pressure (SBP).  RESULTS: Twelve studies with 3,428 patients (GLP1-RA: 1,654; SGLT2 inhibitors: 1,774) were included. Both GLP1-RA and SGLT2 inhibitors significantly improved LVEF compared to placebo (GLP1-RA: mean difference [MD] 2.8%, 95% confidence interval [CI] 1.5 to 4.1, p < 0.001; SGLT2 inhibitors: MD 3.2%, 95% CI 2.0 to 4.4, p < 0.001). SGLT2 inhibitors significantly reduced myocardial fibrosis (MD -3.5%, 95% CI -4.2 to -2.8, p < 0.001) more than GLP1-RA (MD -2.3%, 95% CI -3.0 to -1.6, p < 0.001). Functional capacity improved significantly with both treatments (GLP1-RA: MD 45 m, 95% CI 30 to 60, p < 0.001; SGLT2 inhibitors: MD 50 m, 95% CI 35 to 65, p < 0.001). Secondary outcomes showed reductions in HbA1c (GLP1-RA: MD -1.1%, 95% CI -1.4 to -0.8, p < 0.001; SGLT2 inhibitors: MD -1.0%, 95% CI -1.3 to -0.7, p < 0.001) and body weight (GLP1-RA: MD -2.5 kg, 95% CI -3.1 to -1.9, p < 0.001; SGLT2 inhibitors: MD -2.0 kg, 95% CI -2.6 to -1.4, p < 0.001). Both treatments significantly lowered SBP (GLP1-RA: MD -5.2 mmHg, 95% CI -6.5 to -3.9, p < 0.001; SGLT2 inhibitors: MD -4.8 mmHg, 95% CI -6.0 to -3.6, p < 0.001).

GLP1-RA and SGLT2 inhibitors significantly benefit HFpEF management in T2D patients. SGLT2 inhibitors reduce myocardial fibrosis more effectively, while both improve LVEF, functional capacity, and metabolic parameters. These therapies should be integral to HFpEF management in diabetic patients. Further research is needed on long-term outcomes and potential combined therapy effects.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were initially developed for their glucose-lowering effects and have shown a modest glycaemic benefit in people with type 2 diabetes mellitus (T2DM). In the past decade, a series of large, robust clinical trials of these therapies have demonstrated striking beneficial effects for various care goals, transforming the chronic disease therapeutic landscape. Cardiovascular safety studies in people with T2DM demonstrated that SGLT2 inhibitors reduce cardiovascular death and hospitalization for heart failure. Subsequent trials in participants with heart failure with reduced or preserved left ventricular ejection fraction demonstrated that SGLT2 inhibitors have beneficial effects on heart failure outcomes. In dedicated kidney outcome studies, SGLT2 inhibitors reduced the incidence of kidney failure among participants with or without diabetes. Post hoc analyses have suggested a range of other benefits of these drugs in conditions as diverse as metabolic dysfunction-associated steatotic liver disease, kidney stone prevention and anaemia. SGLT2 inhibitors have a generally favourable adverse effect profile, although patient selection and medication counselling remain important. Concerted efforts are needed to better integrate these agents into routine care and support long-term medication adherence to close the gap between clinical trial outcomes and those achieved in the real world.

Heart failure (HF) is a clinical syndrome associated with substantial morbidity, mortality, and healthcare costs. Dapagliflozin has proven efficacy in reducing the risk of death and hospitalization in HF patients, regardless of left ventricular ejection fraction (LVEF). This paper aimed to project the potential impact of dapagliflozin on healthcare costs related to HF subsequent hospitalizations (HFHs) in Portuguese hospitals.

The total number of HF-related hospitalizations (hHF), HFHs, and the average length of stay for patients with a primary diagnosis of HF from six Portuguese hospitals, between January 2019 and December 2021, were collected and aggregated by hospital classification. Costs associated with HFHs were calculated according to Portuguese legislation and considering conservative, average, and complex approaches. Cost-saving projections were based on extrapolations from hHF risk reductions reported in dapagliflozin clinical trials.

Considering a 26% risk reduction in hHF reported on pooled-analysis of DAPA-HF and DELIVER as the expected reduction in HFHs, the use of dapagliflozin would be associated with cost savings ranging from EUR 1612851.54 up to EUR 6587360.09, when considering all hospitals and the different approaches, between 2019 and 2021. A similar projection is observed based on 24% RRR derived by weighting DAPA-HF and DELIVER sub-analyses and PORTHOS epidemiological data.

In this projection, dapagliflozin use in all eligible hHF patients is associated with a significant reduction in direct costs. Our data support that, in addition to the improvements in HF-related outcomes, dapagliflozin may have a significant economic impact on healthcare costs in Portuguese hospitals.

Extracellular matrix (ECM) stiffness is closely related to the progress of diabetic cardiomyopathy (DCM) and the response of treatment of DCM to anti-diabetic drugs. Dapagliflozin (Dapa) has been proven to have cardio-protective efficacy for diabetes and listed as the first-line drug to treat heart failure. But the regulatory relationship between ECM stiffness and treatment efficacy of Dapa remains elusive.

This work investigated the effect of ECM stiffness on DCM progression and Dapa efficacy using both in vivo DCM rat model and in vitro myocardial cell model with high glucose injury. First, through DCM rat models with various levels of myocardial injury and administration with Dapa treatment for four weeks, the levels of myocardial injury, myocardial oxidative stress, expressions of AT1R (a mechanical signal protein) and the stiffness of myocardial tissues were obtained. Then for mimicking the stiffness of myocardial tissues at early and late stages of DCM, we constructed cell models through culturing H9c2 myocardial cells on the polyacrylamide gels with two stiffness and exposed to a high glucose level and without/with Dapa intervention. The cell viability, reactive oxygen species (ROS) levels and expressions of mechanical signal sensitive proteins were obtained.

The DCM progression is accompanied by the increased myocardial tissue stiffness, which can synergistically exacerbate myocardial cell injury with high glucose. Dapa can improve the ECM stiffness-induced DCM progression and its efficacy on DCM is more pronounced on the soft ECM, which is related to the regulation pathway of AT1R-FAK-NOX2. Besides, Dapa can inhibit the expression of the ECM-induced integrin β1, but without significant impact on piezo 1.

Our study found the regulation and effect of biomechanics in the DCM progression and on the Dapa efficacy on DCM, providing the new insights for the DCM treatment. Additionally, our work showed the better clinical prognosis of DCM under early Dapa intervention.

Heart failure (HF), especially HF with reduced ejection fraction (HFrEF), presents complex challenges, particularly in the aging population where it often coexists with type 2 diabetes mellitus (T2DM).

To analyze the effect of dapagliflozin treatment on cardiac, renal function, and safety in patients with HFrEF combined with T2DM.

Patients with T2DM complicated with HFrEF who underwent treatment in our hospital from February 2018 to March 2023 were retrospectively analyzed as the subjects of this study. The propensity score matching method was used, and a total of 102 eligible samples were scaled. The clinical efficacy of the two groups was evaluated at the end of the treatment, comparing the results of blood glucose, insulin, cardiac function, markers of myocardial injury, renal function indexes, and 6-min walk test (6MWT) before and after the treatment. We compared the occurrence of adverse effects on the treatment process of the two groups of patients. The incidence of adverse outcomes in patients within six months of treatment was counted.

The overall clinical efficacy rate of patients in the study group was significantly higher than that of patients in the control group (P = 0.013). After treatment, the pancreatic beta-cell function index, left ventricular ejection fraction, and glomerular filtration rate of patients in the study group were significantly higher than control group (P < 0.001), while their fasting plasma glucose, 2-h postprandial glucose, glycosylated hemoglobin, insulin resistance index, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, cardiac troponin I, creatine kinase-MB, N-terminal pro b-type natriuretic peptide, serum creatinine, and blood urea nitrogen were significantly lower than those of the control group. After treatment, patients in the study group had a significantly higher 6MWT than those in the control group (P < 0.001). Hypoglycemic reaction (P = 0.647), urinary tract infection (P = 0.558), gastrointestinal adverse effect (P = 0.307), respiratory disturbance (P = 0.558), and angioedema (P = 0.647) were not statistically different. There was no significant difference between the incidence of adverse outcomes between the two groups (P = 0.250).

Dapagliflozin significantly enhances clinical efficacy, cardiac and renal function, and ambulatory capacity in patients with HFrEF and T2DM without an increased risk of adverse effects or outcomes.

Novel therapies for heart failure with reduced ejection fraction (HFrEF) are angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose co-transporter 2 inhibitor (SGLT2i), etc. The purpose of this review is to determine the effects of ARNI and SGLT2i in heart failure (HF), compare the impact of SGLT2i with ARNI, and finally evaluate the current data regarding the combination of these two drugs in HF. Various trials on the respective medications have shown some significant reduction in all-cause mortality and cardiovascular (CV) death. The combination of these drugs has shown more CV benefits than monotherapy. There is emerging data about these two drugs in patients with heart failure with preserved ejection fraction (HFpEF). At present, there are less head-to-head comparison trials of these two drugs. This review provides insights on the current evidence, comparative efficacy, and combination therapy of ARNI and SGLT2i in managing HF, focussing on HFrEF and HFpEF.

In patients with type 2 diabetes mellitus (T2DM), a history of an ischemic event is associated with increased risk for cardiovascular (CV) disease. Whether patients with T2DM and a recent atherothrombotic diagnosis benefit from early intervention with a sodium-glucose co-transporter 2 inhibitor is unknown.

This study is a secondary analysis of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), which compared empagliflozin to placebo in adults with T2DM and atherosclerotic CV disease (ASCVD). Participants were categorized based on the time since their last qualifying ASCVD diagnosis (≤ 1 year vs > 1 year). Qualifying ASCVD diagnoses included ischemic or hemorrhagic stroke, myocardial infarction, coronary artery disease, and peripheral artery disease. The primary outcome was a composite of CV death, nonfatal myocardial infarction, or nonfatal stroke.

A total of 6796 participants (n = 4547 empagliflozin, n = 2249 placebo) were included. Median time since the last qualifying ASCVD diagnosis was 3.8 years (quartile 1-quartile 3: 1.5-7.6), and most qualifying diagnoses occurred > 1 year before randomization (≤ 1 year, n = 1214; > 1 year, n = 5582). Empagliflozin reduced the incidence of the primary outcome irrespective of the time since the last qualifying ASCVD diagnosis (≤ 1 year: hazard ratio 0.82, 95% confidence interval: 0.57-1.16; vs > 1 year: hazard ratio 0.85, 95% confidence interval: 0.72-1.00; P for interaction = 0.84). Results were similar for the composite of CV death or hospitalization for heart failure.

Empagliflozin improved CV outcomes in participants with T2DM, irrespective of the time since the last qualifying ASCVD diagnosis at randomization. Prospective trials are necessary to investigate the use of sodium-glucose co-transporter 2 inhibitors at the time of an acute ASCVD event.

EMPA-REG OUTCOME (Clinicaltrials.gov identifier: NCT01131676).

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have noted benefits in the treatment of type 2 diabetes, cardiovascular disease, heart failure, and chronic kidney disease. Despite these benefits, the adoption of SGLT2i in clinical practice has been slow. Early initiation of SGLT2i during hospitalization has been proposed to address this gap for 2 important reasons: 1) it provides early clinical benefit in multiple disease states; and 2) hospitalization presents an opportunity for medication optimization and patient education, thereby overcoming clinical inertia. Challenges in SGLT2i adoption necessitate innovative strategies for integration into clinical practice. Ongoing trials and novel care delivery models are anticipated to further elucidate effective strategies for SGLT2i implementation and adherence. This review synthesizes the accrued evidence of SGLT2i across various chronic diseases. It emphasizes the rationale for early in-hospital initiation and discusses barriers and potential solutions for widespread implementation of SGLT2i in hospitalized patients.

Underutilization of guideline-directed medical therapy for heart failure with reduced ejection fraction is a major cause of poor outcomes. For many American Indian patients receiving care through the Indian Health Service, access to care, especially cardiology care, is limited, contributing to poor uptake of recommended therapy.

To examine whether a telehealth model in which guideline-directed medical therapy is initiated and titrated over the phone with remote telemonitoring using a home blood pressure cuff improves guideline-directed medical therapy use (eg, drug classes and dosage) in patients with heart failure with reduced ejection fraction in Navajo Nation.

The Heart Failure Optimization at Home to Improve Outcomes (Hózhó) randomized clinical trial was a stepped-wedge, pragmatic comparative effectiveness trial conducted from February to August 2023. Patients 18 years and older with a diagnosis of heart failure with reduced ejection fraction receiving care at 2 Indian Health Service facilities in rural Navajo Nation (defined as having primary care physician with 1 clinical visit and 1 prescription filled in the last 12 months) were enrolled. Patients were randomized to the telehealth care model or usual care in a stepped-wedge fashion, with 5 time points (30-day intervals) until all patients crossed over into the intervention. Data analyses were completed in January 2024.

A phone-based telehealth model in which guideline-directed medical therapy is initiated and titrated at home, using remote telemonitoring with a home blood pressure cuff.

The primary outcome was an increase in the number of guideline-directed classes of drugs filled from the pharmacy at 30 days postrandomization.

Of 103 enrolled American Indian patients, 42 (40.8%) were female, and the median (IQR) age was 65 (53-77) years. The median (IQR) left ventricular ejection fraction was 32% (24%-36%). The primary outcome occurred significantly more in the intervention group (66.2% vs 13.1%), thus increasing uptake of guideline-directed classes of drugs by 53% (odds ratio, 12.99; 95% CI, 6.87-24.53; P < .001). The number of patients needed to receive the telehealth intervention to result in an increase of guideline-directed drug classes was 1.88.

In this heart failure trial in Navajo Nation, a telephone-based strategy of remote initiation and titration for outpatients with heart failure with reduced ejection fraction led to improved rates of guideline-directed medical therapy at 30 days compared with usual care. This low-cost strategy could be expanded to other rural settings where access to care is limited.

ClinicalTrials.gov Identifier: NCT05792085.

The use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as a new class of drug in treating type 2 diabetes has expanded beyond its original framework. Positive results have been achieved in reducing symptoms in patients with cardiovascular disease (CVD). The aim of this article is to present an in-depth review of the basic principles of this class of medications and how it has brought benefits to patients affected particularly by heart failure.

Following a thorough PubMed search, this review includes 62 studies published between 2015 and 2023. Keywords searched included 'sodium-glucose cotransporter 2 inhibitors', 'cardiovascular disease', 'heart failure', 'chronic kidney disease', and 'type 2 diabetes'. The most recent and comprehensive data were used.

Positive results have been achieved in reducing symptoms in patients with CVD. SGLT2 inhibitors have also been shown to be useful in other contexts such as nonalcoholic fatty liver disease (NAFLD) by reducing liver fat accumulation, kidney benefits by improving body weight and vascular endothelium, improving eGFR, and reducing progression to end stage kidney disease (ESKD). SGLT2 inhibitors are also effective in reducing the need for heart failure hospitalizations and the risk of serious cardiac adverse events, including cardiovascular and all-cause mortality, in patients with reduced or preserved left ventricular (LV) ejection fraction and in acute or decompensated settings.

SGLT2 inhibitors have evolved into metabolic drugs because of their multisystem action and are indicated for the treatment of all spectrums of heart failure, type 2 diabetes, and chronic kidney disease.

Guideline-directed medical therapy (GDMT) remains underutilized in patients with heart failure with reduced ejection fraction, leading to morbidity and mortality.

The Medly Titrate (Use of Telemonitoring to Facilitate Heart Failure Mediation Titration) study was an open-label, randomized controlled trial to determine whether remote medication titration for patients with heart failure with reduced ejection fraction was more effective than usual care (UC).

In this study, 108 patients were randomized to remote GDMT titration through the Medly heart failure program (n = 56) vs UC (n = 52). The primary outcome was the proportion of patients completing GDMT titration at 6 months. Secondary outcomes included the number of clinic visits and time required to achieve titration, patient health outcomes, and health care utilization, including urgent clinic/emergency department visits and hospitalization.

At 6 months, GDMT titration was completed in 82.1% (95% CI: 71.2%-90.8%) of patients in the intervention arm vs 53.8% in UC (95% CI: 41.1%-67.7%; P = 0.001). Remote titration required fewer in-person (1.62 ± 1.09 vs 2.42 ± 1.65; P = 0.004) and virtual clinic visits (0.50 ± 1.08 vs 1.29 ± 1.86; P = 0.009) to complete titration. Median time to optimization was shorter with remote titration (3.42 months [Q1-Q3: 2.99-4.04 months] vs 5.47 months [Q1-Q3: 4.14-7.33 months]; P < 0.001). The number of urgent clinic/emergency department visits (incidence rate ratio of remote vs control groups: 0.90 [95% CI: 0.53-1.56]; P = 0.70) were similar between groups, with a reduction in all-cause hospitalization with remote titration (incidence rate ratio: 0.55 [95% CI: 0.31-0.97]; P = 0.042).

Remote titration of GDMT in heart failure with reduced ejection fraction was effective, safe, feasible, and increased the proportion of patients achieving target doses, in a shorter period of time with no excess adverse events compared with UC. (Use of Telemonitoring to Facilitate Heart Failure Mediation Titration [Medly Titrate]; NCT04205513).

Approximately half of patients with heart failure and a reduced ejection fraction (HeFREF) are discharged from hospital on triple therapy [angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs), beta-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs)]. We investigated what proportion of patients are on optimal doses prior to discharge and how many might be eligible for initiation of sacubitril-valsartan or sodium-glucose co-transporter-2 inhibitors (SGLT2Is).

Between 2012 and 2017, 1277 patients admitted with suspected heart failure were enrolled at a single hospital serving a local community around Kingston upon Hull, UK. Eligibility for sacubitril-valsartan or SGLT2I was based on entry criteria for the PIONEER-HF, DAPA-HF, and EMPEROR-Reduced trials. Four hundred fifty-five patients had HeFREF with complete data on renal function, heart rate, and systolic blood pressure (SBP) prior to discharge. Eighty-three per cent of patients were taking an ACE-I or ARB, 85% a BB, and 63% an MRA at discharge. More than 60% of patients were eligible for sacubitril-valsartan and >70% for SGLT2I. Among those not already receiving a prescription, 37%, 28%, and 49% were eligible to start ACE-I or ARB, BB, and MRA, respectively. Low SBP (≤105 mmHg) was the most frequent explanation for failure to initiate or up-titrate therapy.

Most patients admitted for heart failure are eligible for initiation of life-prolonging medications prior to discharge. A hospital admission may be a common missed opportunity to improve treatment for patients with HeFREF.

Sodium-glucose-cotransporter 2 (SGLT-2) inhibitors are widely used for diabetes management especially because their effects go beyond glucose control. More recently, their indications and usage have expanded to heart failure (HF) and renal dysfunction therapy in patients both with and without diabetes. Beneficial effects, especially for HF readmission, accrue very early in their treatment trajectory, and this has promoted their use in the hospital setting. Data on their safety and efficacy for inpatient use are accumulating but have lagged behind the outpatient data for their use. The objective of this counterpoint piece is to highlight areas of benefit for starting or continuing SGLT-2 inhibitors in the inpatient setting.

Discussion after literature review of available studies with a focus on HF outcomes and SGLT-2 inhibitor use.

The benefits of starting or continuing an SGLT-2 inhibitor in the inpatient setting are well documented, mainly in HF. Similar data are not available for glucose or renal outcomes alone. Starting in the hospital allows the ability to titrate medications with similar effects, such as diabetes and HF agents, as well as reducing treatment inertia to obtain and start new medications after patients are discharged home. It is important to choose patients appropriately and hold these drugs when patients are without nutrition or on low-carbohydrate diets which can lead to diabetic ketoacidosis.

In the right setting, using an SGLT-2 inhibitor in the hospital can affect multiple aspects of a patient's treatment trajectory and should be a consideration.

Use of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) reduces hospitalization in heart failure (HF) patients across the spectrum of ejection fraction, but no study has comprehensively explored their impact on quality of life (QoL) with respect to different subgroup populations. We aimed to explore the QoL impact of SGLT2i use in HF patients across the spectrum of ejection fraction and over time.

We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) covering the period from 2019 to February 2022. We included placebo-controlled randomized controlled trials (RCTs) enrolling HF patients that evaluated QoL as an outcome. Two reviewers independently assessed studies for eligibility, extracted data, and assessed risk of bias (RoB), using the Cochrane RoB2 tool, and certainty of evidence, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Primary and secondary outcomes were the mean difference in QoL, and clinically important improvement in QoL, as defined in the original study, respectively. We conducted subgroup analyses based on ejection fraction category, SGLT2i agent, and timing of QoL measurement.

From 1477 identified reports, we included 14 RCTs (n = 23,361). The mean age was 68 years, and 34% were female. All included RCTs reported QoL using the Kansas City Cardiomyopathy Questionnaire (KCCQ). SGLT2i use improved KCCQ-overall summary score, compared with placebo (mean difference 2.0, 95% confidence interval 1.6-2.5; high certainty). More patients receiving an SGLT2i achieved a clinically important QoL improvement (risk ratio 1.14, 95% confidence interval 1.02-1.28; moderate certainty). Similar improvements were observed in the KCCQ clinical summary and total symptom subscores, and across all subgroups and timeframes.

Use of an SGLT2i consistently provides a clinically important improvement in QoL among patients with HF, regardless of ejection fraction, with noticeable improvements seen as early as week 2.

Treatment for heart failure has experienced a major revolution in recent years, and current evidence shows that a combination of four medications (angiotensin receptor-neprilysin inhibitors + β-blockers + mineralocorticoid receptor antagonists + sodium.glucose cotransporter 2 inhibitors) offer the greatest benefit to our patients with significant reductions in cardiovascular mortality, heart failure hospitalisations and all-cause mortality. Unfortunately, despite their proven benefits, the implementation of these therapies is still low. Clinical inertia, and unfounded fear of using these drugs might contribute to this. Recently, evidence from randomised clinical trials has shown that intensive implementation of these therapies in patients with heart failure is safe and effective. In this review, we attempt to tackle some of these misconceptions/fears regarding medical therapy for heart failure and discuss the available evidence showing the best strategies for implementation of these therapies.

Soluble ST2 (sST2) is the expression of a pathogenic process related to adverse remodeling that ultimately leads to increased mortality in heart failure (HF). Risk score models provide a comprehensive approach for mortality prediction, beyond the use of biomarkers alone. The objective was to determine the additional value of sST2 and two well-validated contemporary risk scores, BCN-Bio-HF and MAGGIC-HF, in predicting mortality and readmission in the acute setting. This prospective study included 129 patients (mean age 75 ± 9 years; 52% males) after an urgent HF visit. Baseline sST2 levels were measured and the two risk scores were calculated. The primary endpoint was all-cause mortality, and the secondary endpoint was HF readmissions. The follow-up period was 3.6 ± 1.9 years. Patients who died (46%) had higher sST2 concentrations (80.5 vs. 42.7 ng/ml; p < 0.001). The BCN-Bio-HF calculator with sST2 demonstrated the best discriminative ability for mortality prediction (area under the ROC curve: 0.792; p < 0.001). In multivariate analysis for each risk score, the MAGGIC-HF score retained its predictive value only in the model without sST2 (3-year risk: HR = 1.036; 95% CI 1.019-1.054; p < 0.001). However, the BCN-Bio-HF score maintained its prognostic value with sST2 (HR = 1.032; 95%CI 1.020-1.044; p < 0.001), as well as without sST2 (HR = 1.035; 95% CI 1.021-1.049; p < 0.001). sST2 was not associated with readmission, and only the BCN-Bio-HF risk of HF hospitalization showed independent predictive value (OR = 1.040; 95% CI 1.005-1.076; p = 0.023). For predicting long-term mortality in HF in the emergency department, the BCN-Bio-HF calculator with sST2 demonstrated superior discrimination and allows estimation of the risk of HF hospitalizations.

Cardiovascular outcomes trials of sodium-glucose co-transporter-2 (SGLT2) inhibitors have demonstrated consistent signals of benefit in terms of both prevention and treatment of heart failure (HF), in patients with and without type 2 diabetes (T2D). In response to growing evidence of the benefits of SGLT2 inhibitors, including increased survival, reduced hospitalizations and improved patient-reported symptoms, functional status, and quality of life, the treatment landscape for HF has evolved. Importantly, these agents have also demonstrated safety and tolerability in individuals with HF across the spectrum of left ventricular ejection fraction, with improvements in clinical and patient-reported outcomes occurring as early as days to weeks after treatment initiation. For patients with heart failure with reduced ejection fraction (HFrEF), SGLT2 inhibitors are now increasingly recognized as foundational disease-modifying therapy. An updated joint guideline from the American College of Cardiology and American Heart Association now recommends including SGLT2 inhibitors for patients with HF across the spectrum of ejection fraction, irrespective of the presence of diabetes, and regardless of background therapy (Class 1 recommendation for HFrEF, Class 2a recommendation for HF with mildly reduced ejection fraction [HFmrEF] and HF with preserved ejection fraction [HFpEF]). The European Society of Cardiology also include a Class I recommendation to use SGLT2 inhibitors for patients with HFrEF to reduce the risk of hospitalization for HF and CV death, irrespective of T2D status. This chapter reviews published clinical trial data about the efficacy and safety of SGLT2 inhibitors among patients with HFrEF, HFpEF, and patients hospitalized for HF.

Patients who experience hospitalizations due to heart failure (HF) face a significant risk of readmission and mortality. Our objective was to evaluate whether the risk of hospitalization and mortality following discharge from HF hospitalization differed based on adherence to the outpatient follow-up (FU) protocol comprising an appointment with a general practitioner (GP) within 15 days, a cardiologist within 2 months or both (termed combined FU).

We studied all adults admitted for a first HF hospitalization from 2016 to 2020 in France's Grand Est region. Association between adherence to outpatient FU and outcomes were assessed with time-dependent survival analysis model. Among 67 476 admitted patients (mean age 80.3 ± 11.3 years, 53% women), 62 156 patients (92.2%) were discharged alive and followed for 723 (317-1276) days. Combined FU within 2 months was used in 21.1% of patients, with lower rates among >85 years, women, and those with higher comorbidity levels (p < 0.0001 for all). Combined FU was associated with a lower 1-year death or rehospitalization (adjusted hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.88-0.94, p < 0.0001) mostly related to lower mortality (adjusted HR 0.65, 95% CI 0.62-0.68, p < 0.0001) whereas HF readmission was higher (adjusted HR 1.19, 95% CI 1.15-1.24, p < 0.0001). When analysing components of combined FU separately, 1-year mortality was more related to cardiologist FU (HR 0.65, 95% CI 0.62-0.67, p < 0.0001), than GP FU (HR 0.87, 95% CI 0.85-0.90, p < 0.0001).

Combined FU is carried out in a minority of patients following HF hospitalization, yet it is linked to a substantial reduction in 1-year mortality, albeit at the expense of an increase in HF hospitalizations.

We aimed to describe the safety and tolerability of initiation of sodium-glucose cotransporter 2 inhibitors (SGLT2i) during hospitalisation with heart failure, and the frequency of, and reasons for, subsequent discontinuation. In total, 934 patients who were not already prescribed a SGLT2i were hospitalised with heart failure, 77 (8%) were initiated on a SGLT2i a median of five (3-8.5) days after admission and two (0.5-5) days prior to discharge. During a median follow-up of 182 (124-250) days, SGLT2i were discontinued for 10 (13%) patients, most frequently due to deteriorating renal function. We observed reductions in body weight (mean difference 2.0 ± 0.48 kg, p<0.001), systolic blood pressure (mean difference 9.5 ± 1.9 kg, p<0.001) and small, non-significant reductions in estimated glomerular filtration rate (eGFR mean difference 2.0 ± 1.5 ml/min/1.73 m2, p=0.19) prior to initiation, with further modest reductions in weight (mean difference 1.2 ± 0.4 kg, p=0.006) but not systolic blood pressure (2.4 ± 1.5 mmHg, p=0.13) or eGFR following initiation of SGLT2i. At discharge the proportion prescribed a beta blocker (44% to 92%), angiotensin-receptor/neprilysin inhibitor (6% to 44%) and mineralocorticoid-receptor antagonist (35% to 85%) had increased. In conclusion, inpatient initiation of SGLT2i was safe and well tolerated in a real-world cohort of patients hospitalised with worsening HF. We observed a 13% frequency of discontinuation or serious side effects.

Heart failure affects more than 6 million people in the United States, and hospitalizations for decompensated heart failure confer a heavy toll in morbidity, mortality, and health care costs. Clinical trials have demonstrated effective interventions; however, hospitalization and mortality rates remain high. Key components of effective hospital care include appropriate diagnostic evaluation, triage and risk stratification, early implementation of guideline-directed medical therapy, adequate diuresis, and appropriate discharge planning.

To describe healthcare resource utilization (HCRU) and costs, in patients with newly diagnosed heart failure (HF) according to ejection fraction (EF) in Spain.

Retrospective cohort study that analyzed anonymized, integrated and computerised medical records in Spain. Patients with ≥ 1 new HF diagnosis between January 2013 and September 2019 were included and followed-up during a 4-year period. Rates per 100 person-years of HCRU and costs were estimated.

Nineteen thousand nine hundred sixty-one patients were included, of whom 43.5%, 26.3%, 5.1% and 25.1% had HF with reduced, preserved, mildly reduced and unknown EF, respectively. From year 1 to 4, HF rates of outpatient visits decreased from 1149.5 (95% CI 1140.8-1159.3) to 765.5 (95% CI 745.9-784.5) and hospitalizations from 61.7 (95% CI 60.9-62.7) to 15.7(14.7-16.7) per 100 person-years. The majority of HF-related healthcare resource costs per patient were due to hospitalizations (year 1-4: 63.3-38.2%), followed by indirect costs (year 1-4: 12.2-29.0%), pharmacy (year 1-4: 11.9-19.9%), and outpatient care (year 1-4: 12.6-12.9%). Mean (SD) per patient HF-related costs decreased from 2509.6 (3518.5) to 1234.6 (1534.1) Euros (50% cost reduction). At baseline, 70.1% were taking beta-blockers, 56.3% renin-angiotensin system inhibitors, 11.8% mineralocorticoid receptor antagonists and 8.9% SGLT2 inhibitors. At 12 months, these numbers were 72.3%, 65.4%, 18.9% and 9.8%, respectively.

Although the economic burden of HF decreased over time since diagnosis, it is still substantial. This reduction could be partially related to a survival bias (sick patients died early), but also to a better HF management. Despite that, there is still much room for improvement.

Recent international guidelines recommend rapid initiation and titration of basic treatments of heart failure but do not explain how to achieve this goal. Despite these recommendations, implementation of treatment in daily practice is poor. This may be partly explained by the profile of the patients (frailty, comorbidities), safety considerations and tolerability issues related to kydney function, low blood pressure or heart rate and hyperkalaemia. In this special article, we intended to help the physician, through an algorithmic approach, to quickly and safely introduce guideline-directed medical therapy in the field of heart failure with ejection fraction under 50%.

Heart failure (HF) is associated with a high morbidity and mortality burden. In light of more recent evidence, SGLT2 inhibitors are currently recommended as first-line therapy in managing patients with HF, regardless of ejection fraction, to reduce HF burden. The DAPA-HF and DELIVER trials, and particularly, the pooled analysis of both studies, have shown that dapagliflozin significantly reduces the risk of cardiovascular death, all-cause death, total HF hospitalizations, and MACE in the whole spectrum of HF, with sustained benefits over time. Recent data have shown that the full implementation of dapagliflozin in clinical practice would translate into a robust reduction in hospitalizations for HF and death in real-life populations. Many pathophysiological mechanisms have been involved in these benefits, particularly the positive effects of dapagliflozin on reversing cardiac (atrial and ventricular) remodeling, reducing cardiac fibrosis and inflammation, and improving endothelial dysfunction. In this manuscript, we reviewed from a practical point of view the role of dapagliflozin in the management of the whole spectrum of patients with HF.