In a patient with ejection fraction 55‑60 %, NT‑proBNP <36 pg/mL, mild left‑ventricular hypertrophy, grade I diastolic dysfunction, iron deficiency treated with elemental iron and vitamin C, and ongoing occult gastrointestinal bleeding, can dapagliflozin (Jardiance) help prevent progression to overt heart‑failure with preserved ejection fraction?

SGLT2 Inhibitors for Prevention of HFpEF Progression

I would not recommend starting Jardiance (empagliflozin) or any SGLT2 inhibitor in this patient at this time, as they do not meet criteria for heart failure treatment and lack evidence supporting preventive use in asymptomatic structural heart disease. Your patient has structural cardiac abnormalities but does not have symptomatic heart failure, and their NT-proBNP is well below the threshold used in clinical trials.

Why SGLT2 Inhibitors Are Not Indicated Here

Lack of Symptomatic Heart Failure

• SGLT2 inhibitors are indicated for symptomatic heart failure (NYHA class II-IV), not for prevention of HF in patients with structural heart disease alone 1.
• The 2025 Canadian guidelines and 2022 AHA/ACC/HFSA guidelines specify that SGLT2 inhibitors should be used in patients with established HF symptoms, not for primary prevention in those with only structural abnormalities 1, 2.
• Your patient has mild LVH and grade I diastolic dysfunction but no documented HF symptoms requiring treatment.

NT-proBNP Below Trial Inclusion Criteria

• All major SGLT2 inhibitor trials in HFpEF required elevated natriuretic peptides as entry criteria 1.
• EMPEROR-Preserved required NT-proBNP ≥300 pg/mL (or ≥600 pg/mL with atrial fibrillation) 1.
• DELIVER trial used identical NT-proBNP thresholds for enrollment 3, 4.
• Your patient's NT-proBNP <36 pg/mL is more than 8-fold below the minimum threshold used in these trials, suggesting absence of significant hemodynamic stress 3.

Evidence Specific to Low NT-proBNP

• Post-hoc analysis from DELIVER demonstrated that dapagliflozin's efficacy was consistent across NT-proBNP quartiles, but all enrolled patients had elevated levels (median 716 ng/L in non-AF patients) 3.
• While relative risk reduction was similar across NT-proBNP levels, absolute benefit was greatest in those with higher baseline NT-proBNP, as they had higher baseline risk 3.
• No trial data exist for SGLT2 inhibitors in patients with normal NT-proBNP levels 3, 4.

What the Evidence Actually Supports

Prevention Indication (Different Context)

• SGLT2 inhibitors ARE recommended for HF prevention, but specifically in patients with type 2 diabetes and chronic kidney disease, not in patients with isolated structural heart disease 1.
• This represents a distinct population with metabolic disease driving HF risk, not structural cardiac abnormalities alone 1.

Treatment of Established HFpEF

• When HFpEF is present (symptomatic + elevated natriuretic peptides), SGLT2 inhibitors reduce HF hospitalizations by 18-21% and improve quality of life 1, 4.
• Dapagliflozin 10 mg daily or empagliflozin 10 mg daily are the evidence-based doses 1.

Address the Iron Deficiency First

Iron Deficiency Is Highly Relevant

• Iron deficiency is independently associated with impaired diastolic function and reduced aerobic capacity in HFpEF patients 5.
• In patients with HFpEF and iron deficiency, iron parameters correlate with both E/e' ratio and peak VO2 5.
• Your patient's ongoing occult GI bleeding and iron deficiency may be contributing more to their cardiac physiology than the mild structural changes 5.

Prioritize Source Control

• Identifying and treating the source of GI bleeding takes precedence over initiating HF medications in this asymptomatic patient 6.
• The capsule endoscopy is appropriate given two positive FOBTs with negative upper/lower endoscopy.
• Continue oral iron supplementation (65 mg elemental iron + vitamin C) while investigating 5.

When to Reconsider SGLT2 Inhibitors

Monitor for HF Development

• Repeat NT-proBNP if symptoms develop (dyspnea, exercise intolerance, edema) 1, 3.
• If NT-proBNP rises to ≥300 pg/mL with symptoms, SGLT2 inhibitor initiation becomes appropriate 1.
• Serial echocardiography to assess for progression of diastolic dysfunction or development of reduced EF 1.

If Diabetes Develops

• Should your patient develop type 2 diabetes, SGLT2 inhibitors would be reasonable for cardiovascular risk reduction, though this is a different indication than HF prevention 1.

Common Pitfalls to Avoid

• Do not extrapolate HFpEF treatment data to asymptomatic structural heart disease – the trials specifically enrolled symptomatic patients with elevated biomarkers 1, 3, 4.
• Do not use NT-proBNP <125 pg/mL to "rule in" HF – this low level argues strongly against clinically significant HF 3.
• Do not overlook reversible causes – iron deficiency and ongoing blood loss may be more impactful than initiating HF medications prematurely 5.