ENAVOgliflozin Outcome Trial in Patients With Severe Aortic Stenosis After Transcatheter Aortic Valve Replacement

Inclusion Criteria:

1. Patients aged ≥19 with symptomatic aortic stenosis who underwent successfultranscatheter aortic valve replacement (TAVR)* (either native valve or valve invalve with any approved/marketed device).

• A successful TAVI is defined as device success according to the VARC-2(Valve Academic Research Consortium 2) and VARC-3 criteria:

1. correct positioning of a single prosthetic heart valve into the proper anatomicallocation AND

2. intended performance of the prosthetic heart valve (mean aortic valve gradient <20mmHg, peak velocity <3 m/s, no moderate or severe prosthetic valve regurgitation)AND

3. absence of periprocedural complications (any type of stroke, life-threateningbleeding, acute coronary artery obstruction requiring intervention, major vascularcomplication requiring intervention, unresolved acute valve thrombosis, or anyrequirement of a repeat procedure).

4. Heart Failure with Mildly Reduced or Preserved Ejection Fraction

5. Left ventricular ejection fraction (LVEF) ≥40%

6. structural heart disease_Left ventricular hypertrophy (LVH) or Left atrialenlargement A. Left ventricular hypertrophy (LVH) with septal thickness or posterior wallthickness ≥ 1.1 cm or B. Left atrial (LA) enlargement with at least one of the following: LA width (diameter) ≥3.8 cm or LA length ≥ 5.0 cm, or LA area ≥ 20cm2, or LA volume ≥ 55mL orLA volume index ≥ 29mL/m.

7. NT-proBNP ≥ 300 pg/mL (for patients without ongoing atrial fibrillation) orNT-proBNP must be ≥ 600 pg/mL (for patients with ongoing atrial fibrillation).

8. Patients who voluntarily participated in the written agreement

Exclusion Criteria:

1. Acute decompensated Heart Failure (exacerbation of chronic Heart Failure) requiringintravenous diuretics, vasodilators, inotropic agents, or mechanical support, orhemodynamic instability following the transcatheter aortic valve replacementprocedure.

2. Currently receiving therapy with an SGLT2 inhibitor within 4 weeks prior torandomization; discontinuation of current use of SGLT2 inhibitor for the purposes ofstudy enrolment is not permitted.

3. Known allergy, hypersensitivity, or previous intolerance to an SGLT2 inhibitors.

4. HF with reduced ejection fraction (LVEF <40%).

5. Type 1 diabetes mellitus or diabetes ketoacidosis.

6. Chronic cystitis and/or recurrent urinary tract infection (≥2 times within 1 year).

7. Stroke or transient ischemic attack within 12 weeks prior to enrollment.

8. Symptomatic persistent hypotension and/or a systolic blood pressure (SBP) < 95 mm Hgat screening or at randomization.

9. SBP ≥180 mmHg irrespective of treatment or SBP ≥160 mmHg with at least ≥3antihypertensive drugs at screening or randomization.

10. Heart failure due to any of the following causes; known infiltrative cardiomyopathy (e.g. amyloid, sarcoid, lymphoma, endomyocardial fibrosis, haemochromatosis, Fabrydisease), active myocarditis, constrictive pericarditis, cardiac tamponade, knownhypertrophic obstructive cardiomyopathy, arrhythmogenic right ventricularcardiomyopathy/dysplasia (ARVD), or uncorrected primary valvular disease.

11. Severe renal insufficiency (eGFR <30 ml/min/1.73 m2 of body-surface area based onthe Modification of Diet in Renal Disease (MDRD) formula) or end-stage renal diseaseor requiring dialysis at the time of screening.

12. Acute or chronic liver disease with severe impairment of liver function (e.g.,ascites, esophageal varices, coagulopathy) or serum levels of transminases oralkaline phosphatase more than two times the upper limit of normal at screening.

13. Chronic pulmonary disease requiring home oxygen, oral steroid therapy orhospitalization for exacerbation within 12 months, or significant chronic pulmonarydisease in the Investigator's opinion, or primary pulmonary arterial hypertension.

14. Current or suspicious malignancy or history of malignancy within 5 years

15. Uncontrolled anaemia or haemoglobin <9g/dl

16. Uncontrolled hypothyroidism or arrhythmia or tachycardia

17. Current ongoing alcoholic or drug addict

18. Subjects with non-cardiac co-morbidities with life expectancy less than 12 months

19. Planned major high-risk operation after transcatheter aortic valve replacement (TAVR)

20. Women of childbearing age who have not reached a consensus on the use of highlyeffective contraception. Pregnancy or breastfeeding.

21. Participation in other clinical trials, However, where at least one or moreconditions are satisfied, it could be an exception according to an investigator'sdiscretion;

• Participating in the observational study expected no effect on the safetyand/or effectiveness evaluation of this trial.

• Screening failed before any interventional factor is involved.

• Participants who have completed their involvement in clinical trials and havesurpassed a 4-week period since their last administration of theinvestigational drug.

• Participated in academic trials like strategic or medical device comparisonstudies conducted under standard therapy provided that there is no additionalrisk or a specific procedure to a subject and no interference between thistrial and other studies.