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Objectives The goal of this study was to evaluate the effect of empagliflozin, in addition to optimal medical treatment, on epicardial adipose tissue (EAT), interstitial myocardial fibrosis, and aortic stiffness in nondiabetic patients with heart failure with reduced ejection fraction (HFrEF). Background Several randomized clinical trials have established the benefits of the inhibitors of the sodium-glucose cotransporter-2 receptor (SGLT2-i) in HFrEF, independent of their hypoglycemic effects. The mechanisms of the benefits of SGLT2-i in HFrEF have not been well defined. Methods This study was a secondary analysis of patients enrolled in the EMPA-TROPISM [ATRU-4] (Are the cardiac benefits of Empagliflozin independent of its hypoglycemic activity?) clinical trial. It was a double-blind, placebo-controlled randomized clinical trial investigating the effect of empagliflozin in nondiabetic patients with HFrEF. Patients underwent cardiac magnetic resonance at baseline and after 6 months. Interstitial myocardial fibrosis was calculated by using T1 mapping (extracellular volume). Aortic stiffness was calculated by using pulsed wave velocity, and EAT was measured from the cine sequences. Results Empagliflozin is associated with significant reductions in EAT volume (–5.14 mL; 95% CI: –8.36 to –1.92) compared with placebo (–0.75 mL; 95% CI: –3.57 to 2.06; P Conclusions Empagliflozin significantly improved adiposity, interstitial myocardial fibrosis, aortic stiffness, and inflammatory markers in nondiabetic patients with HFrEF. These results shed new light on the mechanisms of action of the benefits of SGLT2-i. (Are the “Cardiac Benefits” of Empagliflozin Independent of Its Hypoglycemic Activity [ATRU-4] [EMPA-TROPISM]; NCT03485222 )

Epicardial Adipose Tissue (EAT) is drawing increasing attention. As a quantifiable, modifiable, and potentially new cardiovascular therapeutic target, its accurate measurement is particularly relevant. In Cardiac Magnetic Resonance (CMR) different methods can be used to assess EAT burden. We take advantage of CMR-studies of EMPATROPISM trial to assess EAT through three different methods, evaluate the effect of Empagliflozin and look for significant difference in the ability to detect changes in serial measurements. In some settings such as treatment-induced changes or patient follow-up, multi-slice method of EAT evaluation provides higher accuracy to detect significant differences, otherwise unnoticed by single-slice approaches.

Resumen Los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) fueron incialmente desarrollados para el tratamiento de la diabetes por su actividad hipoglucemiante. Sin embargo, a la luz de los estudios clinicos mas recientes, estan revolucionando el abordaje de la enfermedad cardiovascular ( C V) en el paciente diabetico. En el ano 2015, el ensayo clinico EMPA-REG OUTCOME nos demuestra por primera vez que la empagliflozina –un farmaco considerado «antidiabetico»– reduce la mortalidad CV y por cualquier causa, ademas de eventos CV mayores, hospitalizacion por IC y progresion de enfermedad renal. Posteriormente, otros estudios clinicos con agentes del mismo grupo farmacologico, CANVAS, con canagliflozina y DECLARE-TIMI-58 con dapagliflozina, corroboran la exitencia de los beneficios CV asociados a la inhibicion del receptor SGLT2. Los beneficios observados los situan mas alla de simples agentes hipoglucemiantes, con un demostrado efecto cardionefroprotector en la enfermedad aterosclerotica, insuficiencia cardiaca, mortalidad total, mortalidad cardiovascular y progresion de insuficiencia renal. Actualmente ya son una realidad en pacientes diabeticos de alto y muy alto riesgo cardiovascular, mientras su evidencia en el paciente no diabetico es cada vez mayor. Asistimos, por tanto, a un cambio de paradigma y posiblemente al nacimiento de una nueva especialidad, la cardio-endocrinologia, con la implicacion de nuevos tratamientos que deben ser considerados mas que solo farmacos antidiabeticos.

Large clinical trials established the benefits of sodium-glucose cotransporter 2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia.The purpose of this study was to assess the effect of empagliflozin on left ventricular (LV) function and volumes, functional capacity, and quality of life (QoL) in nondiabetic HFrEF patients.In this double-blind, placebo-controlled trial, nondiabetic HFrEF patients (n = 84) were randomized to empagliflozin 10 mg daily or placebo for 6 months. The primary endpoint was change in LV end-diastolic and -systolic volume assessed by cardiac magnetic resonance. Secondary endpoints included changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, 6-min walk test, and quality of life.Empagliflozin was associated with a significant reduction of LV end-diastolic volume (-25.1 ± 26.0 ml vs. -1.5 ± 25.4 ml for empagliflozin vs. placebo, respectively; p 0.001) and LV end-systolic volume (-26.6 ± 20.5 ml vs. -0.5 ± 21.9 ml for empagliflozin vs. placebo; p 0.001). Empagliflozin was associated with reductions in LV mass (-17.8 ± 31.9 g vs. 4.1 ± 13.4 g, for empagliflozin vs. placebo, respectively; p 0.001) and LV sphericity, and improvements in LV ejection fraction (6.0 ± 4.2 vs. -0.1 ± 3.9; p 0.001). Patients who received empagliflozin had significant improvements in peak OEmpagliflozin administration to nondiabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for sodium-glucose cotransporter 2 inhibitors in the treatment of HFrEF patients independently of their glycemic status. (Are the "Cardiac Benefits" of Empagliflozin Independent of Its Hypoglycemic Activity? [ATRU-4] [EMPA-TROPISM]; NCT03485222).

The sodium-glucose co-transporter 2 inhibitors (SGLT2i) were first conceived to treat type 2 diabetes due to their hypoglycaemic effect. However, due to an increasing number of studies, SGLT2i are changing the way we treat, and understand, diabetes, and cardiovascular risk, in general. The EMPA-REG OUTCOME clinical trial, in 2015, showed for the first time that empagliflozine - a glucose lowering agent - lowers the risk of death from cardiovascular causes and death from any cause. Also, this SGLT2i lowered hospital admission for heart failure and delayed renal function worsening. From then on, other clinical trials with SGLT2i such as CANVAS (canagliflozin) and DECLARE-TIMI-58 (dapagliflozin) confirmed these positive effects. With a proven and non-related glucose-lowering effect on heart failure, overall death, cardiovascular death, and renal function, SGLT2i stands out among the rest of anti-diabetic drugs. Since its role in treating patients with heart failure and type 2 diabetes has been undoubtedly established, new studies are paving the way for non-diabetic patients as well. A potential paradigm shift is being witnessed and, probably, the dawn of a new field, cardio-endocrinology, which involves new and far-reaching pharmacological agents.

Epicardial adipose tissue (EAT) plays a role in the development and outcomes of coronary artery disease and atrial fibrillation. However, the role of EAT in heart failure (HF) remains obscure. The aim of this study was to determine whether EAT predicts outcomes in HF patients Cardiac magnetic

The SGTL2 inhibitor empagliflozin (Empa) reduces HF. We have recently demonstrated 1) the mechanism is due to a switch in myocardial metabolism towards ketone bodies (KB) consumption; and 2) KB infusion improves LV systolic function in a porcine HF model. However, there is no information about the

SGLT2 inhibitor empagliflozin (EMPA) reduces CV death by 40% and heart failure by 35%. Of note, there is no decrease in myocardial infarction or stroke. In fact, there is a numerical increase in stroke rate in the EMPA-treated group (a non-significant trend, p=0.12). The reduction in volemia and the

Mechanisms behind heart failure reduction with SGLT2 inhibitor empagliflozin (EMPA) in clinical trials remain unclear. Given that EMPA causes mild, persistent hyperketonemia, we hypothesized that cardiac benefits of EMPA are due to a shift in myocardial fuel metabolism away from glucose oxidation (

Introduction: The mechanism causing heart failure with preserved ejection fraction (HFPEF) is not clear, but interstitial myocardial fibrosis (IMF) has been proposed to have a causal role. T1 mapping is able to quantify IMF non-invasively. The aim of our study was to assess IMF in HFPEF patients

Background: Rheumatic heart disease (RHD) has classically been considered to primarily affect the valves in the chronic phase. Whether mild RHD also affects myocardium and creates interstitial myocardial fibrosis (IMF) in the chronic phase remains undetermined. We therefore analyzed patients with

Background: Cardiac magnetic resonance (CMR) has excellent diagnostic accuracy in patients with suspected acute myocarditis. The role of T1 mapping in myocarditis assessment is evolving Methods: We included consecutive patients with clinical suspicion of acute myocarditis referred to CMR between