Empagliflozin Impact on Hemodynamics in Patients With Heart Failure

A 12-week randomized, double-blind, placebo-controlled trial to explore the effects of
once-daily empagliflozin 10mg on hemodynamic parameters (pulmonary artery pressures) in
patients with heart failure (reduced or preserved ejection fraction, ischemic or non-ischemic
etiology) who already have a CardioMEMs device implanted for non-study related clinical
reasons.

Inclusion Criteria:

1. Established diagnosis of heart failure (for at least 16 weeks prior to the screening
visit) with either preserved (LVEF>40%) or reduced systolic function (LVEF≤40%), due
to either ischemic or non-ischemic etiology, documented by an imaging modality
(echocardiography, nuclear imaging, LV angiography, magnetic resonance imaging) within
the past 24 months.

2. No major change in diuretic management for 48 hours prior to screening visit or 48
hours prior to randomization visit (major change defined by doubling of diuretic dose
or addition of another diuretic medication)

3. NYHA class II, III or IV heart failure symptoms at the screening and randomization
visit

4. Presence of previously (≥ 2 weeks prior to screening visit) implanted CardioMEMs
pulmonary artery pressure monitor for a clinical indication unrelated to the study.

5. PA diastolic pressure ≥ 12 mmHg at the time of the screening visit (last measurement
available prior to the screening visit).

6. Ability to provide informed consent prior to initiating screening visit procedures

Exclusion Criteria:

1. Decompensated heart failure (hospitalization for heart failure within the 2 weeks
prior to screening) or between screening and randomization

2. History of type 1 diabetes

3. Major change in diuretic management during 48 hours prior to screening visit or 48
hours prior to randomization visit. (major change defined by doubling of diuretic dose
or addition of another diuretic medications)

4. Significant variability in baseline PA diastolic pressures during screening period.
Defined as changes greater than +/- 6 mmHg from average PA diastolic pressure during
week 1 of the screening phase and average PA diastolic pressure during week 2 of the
screening phase for those patients with an average baseline PA diastolic pressure
during week 1 of the screening phase of <30 mmHg. If the average baseline PA diastolic
pressure during week 1 of the screening phase is ≥30 mmHg, then ≥20% relative change
in average PA diastolic pressure between week 1 and week 2 of the screening phase will
be used to define significant variability.

5. Initiation of hydralazine, long-acting nitrates, beta blockers, ACEI/ARBs or
Valsartan/sacubitril in the prior 4 weeks prior to screening

6. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 at the screening visit

7. Admission for an acute coronary syndrome (ST-elevation MI, non-ST-elevation MI, or
unstable angina), percutaneous coronary intervention, or cardiac surgery within 30
days prior to the screening visit.

8. Implantation of cardiac resynchronization therapy (CRT) device within the previous 90
days.

9. Implantation of the CardioMEMs device within the past 2 weeks.

10. Planned cardiovascular revascularization (percutaneous intervention or surgical) or
major cardiac surgery (coronary artery bypass grafting, valve replacement, ventricular
assist device, cardiac transplantation, or any other surgery requiring thoracotomy),
or planned implantation of CRT device within the 90 days after the screening visit.

11. Participation in any interventional clinical trial (with an investigational drug or
device) that is not an observational registry within the 4 weeks prior to the
screening visit.

12. History of hypersensitivity to empagliflozin

13. For women of child-bearing potential: Current or planned pregnancy or currently
lactating

14. Life expectancy <1 year at the screening visit

15. Patients who are volume depleted based upon physical examination at the time of the
screening or randomization visit

16. PA diastolic pressure < 12 mmHg at the time of the screening visit (average of last
four measurements available prior to the screening visit).

17. Patients currently being treated with any SGLT-2 inhibitor (dapagliflozin,
canagliflozin, empagliflozin) or having received treatment with any SGLT-2 inhibitor
within the 8 weeks prior to the screening visit

18. Average supine systolic BP <90 mmHg at the screening or randomization visit

19. Current documented history of bladder cancer

20. Active Gross Hematuria

21. Heart failure due to restrictive cardiomyopathy, active myocarditis, constrictive
pericarditis, severe stenotic valve disease, and HOCM (hypertrophic obstructive
cardiomyopathy).

22. History of heart transplant.

23. Patients on heart transplant list as 1a and 1b status