SGLT2 Inhibition in Diabetes and Heart Failure

Study Overview
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Brief Summary
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To determine the effects of SGLT2 inhibition with empagliflozin on cardio-respiratory fitness in patients with systolic heart failure.

Detailed Description
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The investigators hypothesize that Sodium-GLucose coTransporters (SGLT)-2 inhibition will improve cardio-respiratory fitness (CRF) in patients with systolic heart failure. Participants treated with SGLT2 inhibitor Empagliflozin as standard of care will undergo assessments described below. The investigators will measure CRF with a validated cardiopulmonary exercise test at baseline and after 4 weeks of treatment received as standard of care, to determine whether SGLT2 inhibition improves cardio-respiratory fitness assessed by changes in peak oxygen consumption (VO2)(mL/kg/min) and minute ventilation (VE)/carbon dioxide production (VCO2) slope, powerful independent clinical predictors of mortality in HF.

Official Title
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SGLT2 Inhibition in Diabetic Patients With Heart Failure With Reduced Ejection Fraction

Conditions
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Diabetes Mellitus, Type 2, Heart Failure, Systolic

Intervention / Treatment
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* Other: Assessment of cardiorespiratory fitness


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed clinical diagnosis of stable HF (NYHA class II-III) on maximally tolerated HF medical regimen including angiotensin-inhibitors, beta-adrenergic blockers, and loop diuretics Reduced left ventricular systolic function (LVEF<50%) documented in the prior 12 months Poorly controlled T2DM (HbA1c levels between 6.5% and 10.0%) 18 years old and older. Exclusion Criteria: Type I diabetes; Type II diabetes with episodes of severe hypoglycemia <50 mg/dl by history, frequent changes in anti-diabetic regimen class in the past 3 months or with a prior episode of diabetic ketoacidosis (any time); Open label treatment with SGLT2 inhibitors (within the past month); Treatment with thiazolidinedione (within the past month), which may induce volume and sodium retention; Chronic Kidney Disease (GFR<45 ml/kg*min); Uncontrolled thyroid dysfunction (TSH<0.4>4.5 mcIU/ml); Pregnancy or of child-bearing potential; Active or recent (within 2 weeks) genital/urinal infection; Concomitant conditions or treatment which would affect completion or interpretation of the study including physical inability to walk or run on a treadmill such as decompensated HF (edema, NYHA class IV), significant ischemic heart disease, angina, arterial hypotension (BP systolic <90 mmHg), orthostatic arterial hypotension, arterial hypertension (resting BP systolic >160 mmHg), atrial fibrillation with rapid ventricular response, severe valvular disease, severe chronic obstructive or restrictive pulmonary disease, moderate- severe anemia (Hgb<10 g/dl); Abnormal BP or heart rate response, angina or ECG changes (ischemia or arrhy- thmias) occurring during baseline cardio-pulmonary exercise testing; Chronic use of oral corticosteroids; Inability to give informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Assessment of cardiorespiratory fitness|Assessment of cardiorespiratory fitness|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SGLT2 inhibition effects on cardiorespiratory fitness (CRF). | To measure the effects of Empagliflozin on cardiorespiratory fitness in patients with type 2 diabetes and heart failure with reduced ejection fraction or systolic heart failure. The effects on CRF are determined by measuring changes in peak VO2 (mL/kg/min) and the VE/VCO2 slope. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SGLT2, type 2 diabetes mellitus, systolic heart failure, heart failure with reduced ejection fraction