Heart failure (HF) is a condition in which the heart does not contract ("pump") or relax well, leading to insufficient perfusion of vital organs. Ankle swelling, fatigue, and breathlessness are some of the features of this syndrome. There are different causes for HF (eg., infarct and hypertension) and two distinct types: HFrEF - HF with reduced ejection fraction - where the heart does not "pump" properly, and HFpEF - HF with preserved ejection fraction - the heart "pumps" but does not relax well. Treatment for HFrEF is better established than for HFpEF. In HFpEF, only mineralocorticoid receptors antagonists (MRAs) have been shown to reduce hospitalizations, circulating markers of cardiac dysfunction and fibrosis, and blood pressure. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a therapeutic class that reduces morbidity and mortality in patients with high cardiovascular risk and diabetes and in patients with HFrEF with and without diabetes. Trials are underway to test whether SGLT2i may also be useful for the treatment of HFpEF. This work aims to compare the effects of SGLT2i alone and in combination in an MRA in patients with 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:

   1. LAVI ≥29 ml/m2 (≥34 ml/m2 if AF)
   2. Lateral E/e' ≥9
   3. LVMI ≥115 g/m2 If male or ≥95 g/m2 if female
   4. LV wall thickness ≥12mm

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

10. Blood Potassium ≤5.5 mmol/L

11. Not treated with MRAs and/or SGLT2i within the previous two weeks before inclusion and have no history of diabetic ketoacidosis while in treatment with SGLT2 inhibitors

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

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

    1. Surgically sterilized (e.g. underwent hysterectomy, bilateral salpingectomy or bilateral oophorectomy)
    2. Clinically diagnosed infertile
    3. In a post-menopausal state, defined as no menses for 12 months without an alternative medical cause.

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

    1. Abstinence of heterosexual intercourse (when this is in line with preferred and usual lifestyle of the subject)
    2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
    3. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
    4. Intrauterine device
    5. Intrauterine hormone-releasing system
    6. Bilateral tubal occlusion
    7. Vasectomized partner, who has received medical assessment of the surgical success, or clinically diagnosed infertile partner

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
2. Participation in another clinical study with an investigational product during the last month
3. Unwilling to sign the informed consent form (if the patient wants to participate but cannot sign for any reason, then a third-person testimony may sign/complete informed consent form on patient's behalf)
4. Major surgical procedure, coronary, cerebral or peripheral vascular events or sepsis in 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 disease or other locomotor problems or lung diseases rather than by cardiorespiratory fitness
9. Previously confirmed cardiac amyloidosis
10. Severe valvulopathy according to the echocardiogram report
11. Patients with a known hypersensitivity or intolerance to spironolactone or dapagliflozin or any of the excipients of the products.
12. Female patients currently pregnant (confirmed by a positive pregnancy test) or intent to become pregnant or breast feeding.