SGLT2 Inhibition in Diabetes and Heart Failure
SGLT2 Inhibition in Diabetes and Heart Failure
To determine the effects of SGLT2 inhibition with empagliflozin on cardio-respiratory fitness
 in patients with systolic heart failure.
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.
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.