SGLT2 Inhibition in Diabetes and 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.