Dapagliflozin With or Without Spironolactone for HFpEF

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures

2. HFpEF diagnosis* (irrespective of time since diagnosis)

3. Male or female patients, aged ≥50 years

4. NYHA Class II-IV

5. LVEF > 40%

6. NT-pro BNP ≥220 pg/mL or BNP ≥80 pg/mL if in sinus rhythm (SR)

7. NT-pro BNP ≥660 pg/mL or BNP ≥240 pg/mL if in atrial fibrillation (AF)

8. Echocardiography with at least one of the following criteria:

9. LAVI ≥29 ml/m2 (≥34 ml/m2 if AF)

10. Lateral E/e' ≥9

11. LVMI ≥115 g/m2 If male or ≥95 g/m2 if female

12. LV wall thickness ≥12mm

13. eGFR ≥30 ml/min/1.73m2 (CKD-EPI formula)

14. Blood Potassium ≤5.5 mmol/L

15. Not treated with MRAs and/or SGLT2i within the previous two weeks before inclusionand have no history of diabetic ketoacidosis while in treatment with SGLT2inhibitors

16. Stable/chronic ambulatory patients i.e., patients without need for hospitalizationwithin the last 30 days due to heart failure decompensation episodes

17. If female, she must be a woman of non-childbearing potential. That is, she must be:

18. Surgically sterilized (e.g. underwent hysterectomy, bilateral salpingectomy orbilateral oophorectomy)

19. Clinically diagnosed infertile

20. In a post-menopausal state, defined as no menses for 12 months without analternative medical cause.

21. A female patient of childbearing potential must have a negative serum pregnancy testat Visit 1 (Day 0) and must agree to use consistently and correctly (from 28 daysprior to first study treatment administration until at least 7 days after last studytreatment administration) one of the following highly effective methods ofcontraception:

22. Abstinence of heterosexual intercourse (when this is in line with preferred andusual lifestyle of the subject)

23. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)

24. Combined (estrogen and progestogen containing) hormonal contraceptionassociated with inhibition of ovulation (oral, intravaginal, transdermal)

25. Intrauterine device

26. Intrauterine hormone-releasing system

27. Bilateral tubal occlusion

28. Vasectomized partner, who has received medical assessment of the surgicalsuccess, or clinically diagnosed infertile partner

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to bothInvestigator staff and/or staff at the study site)

2. Participation in another clinical study with an investigational product during thelast month

3. Unwilling to sign the informed consent form (if the patient wants to participate butcannot sign for any reason, then a third-person testimony may sign/complete informedconsent form on patient's behalf)

4. Major surgical procedure, coronary, cerebral or peripheral vascular events or sepsisin the prior 90 days

5. Cancer (life-limiting or less than 2 years in remission)

6. Any previously confirmed autoimmune disease

7. Type 1 Diabetes

8. Ability to walk is, in the investigator's opinion, clearly limited by joint diseaseor other locomotor problems or lung diseases rather than by cardiorespiratoryfitness

9. Previously confirmed cardiac amyloidosis

10. Severe valvulopathy according to the echocardiogram report

11. Patients with a known hypersensitivity or intolerance to spironolactone ordapagliflozin or any of the excipients of the products.

12. Female patients currently pregnant (confirmed by a positive pregnancy test) orintent to become pregnant or breast feeding.