In an adult patient with hypertrophic obstructive cardiomyopathy who also has type 2 diabetes or heart‑failure, are sodium‑glucose cotransporter‑2 inhibitors contraindicated?

SGLT2 Inhibitors Are NOT Contraindicated in Hypertrophic Obstructive Cardiomyopathy

SGLT2 inhibitors should be used in patients with hypertrophic obstructive cardiomyopathy (HOCM) who have type 2 diabetes or heart failure, as they improve diastolic function, functional capacity, and heart failure outcomes without causing harm. There is no contraindication to their use in this population.

Evidence Supporting SGLT2i Use in HOCM

Direct Evidence in HOCM Patients

• A prospective study specifically evaluated SGLT2 inhibitors in patients with nonobstructive hypertrophic cardiomyopathy (nHCM) and type 2 diabetes, demonstrating that 70.8% of patients achieved significant improvements in diastolic function (E/e' improved from 16.3 to 13.3) and functional capacity (6-minute walk distance increased from 295 to 343 meters) after 6 months of therapy 1.

• The same study showed improvements in all diastolic parameters including E/A ratio (2.8 to 2.4), left atrial volume (45.6 to 40.8 ml/m²), and NT-proBNP levels (481.4 to 440.9 pg/ml), with only one patient discontinuing due to a urinary tract infection 1.

• Importantly, SGLT2 inhibitors did not cause adverse changes in left ventricular mass or function in these HOCM patients 1.

Guideline-Based Indications

For patients with HOCM who have type 2 diabetes:

• The 2019 ESC guidelines recommend empagliflozin, canagliflozin, or dapagliflozin in patients with T2DM and cardiovascular disease or at very high/high cardiovascular risk to reduce cardiovascular events 2.

• The 2023 ACC/AHA guidelines provide a Class 1 recommendation for SGLT2 inhibitors in patients with chronic coronary disease and type 2 diabetes to reduce major adverse cardiovascular events 2.

For patients with HOCM who have heart failure:

• The 2023 ACC/AHA guidelines recommend SGLT2 inhibitors (Class 1) for patients with heart failure regardless of ejection fraction (both HFrEF and HFpEF) to reduce cardiovascular death and heart failure hospitalization 2.

• The 2024 ESC quality indicators mandate that SGLT2 inhibitors be prescribed to all patients with heart failure across the entire LVEF spectrum in the absence of contraindications 2.

• The 2023 ADA Standards of Care state that in adults with type 2 diabetes who have heart failure with either reduced or preserved ejection fraction, an SGLT2 inhibitor is recommended for glycemic management and prevention of heart failure hospitalizations 2.

Mechanisms of Benefit in HOCM

• SGLT2 inhibitors improve diastolic dysfunction through multiple mechanisms including reduction of oxidative stress, improvement in nitric oxide production, reduction in cardiac inflammatory cytokine signaling, inhibition of calcium overload, and improvement in cardiac energy metabolism through ketone body production 3.

• These agents prevent and reverse adverse cardiac remodeling by reducing apoptosis, improving autophagy, and optimizing myocardial oxygen supply and demand 4.

• The benefits are particularly relevant for HOCM patients who characteristically have diastolic dysfunction and left ventricular hypertrophy 1.

Clinical Implementation Algorithm

Step 1: Identify eligible patients

• Any patient with HOCM who has type 2 diabetes (regardless of heart failure status) 2
• Any patient with HOCM who has heart failure symptoms (regardless of diabetes status) 2

Step 2: Exclude true contraindications

• eGFR <20 mL/min/1.73 m² (though continuation may be acceptable if already established at eGFR 20-30) 2
• History of diabetic ketoacidosis or type 1 diabetes
• Active urinary tract infections or recurrent genital infections

Step 3: Initiate therapy

• Start empagliflozin 10 mg daily or dapagliflozin 10 mg daily 2
• No dose titration required for cardiovascular benefits 5
• Can be initiated during or immediately after heart failure hospitalization 6

Step 4: Monitor response

• Assess functional capacity (NYHA class, 6-minute walk distance) at 3-6 months 1
• Monitor renal function every 3 months initially 7
• Continue therapy indefinitely as benefits decline rapidly after discontinuation 6

Common Pitfalls to Avoid

• Do not confuse SGLT2 inhibitors with thiazolidinediones (TZDs): TZDs are absolutely contraindicated in heart failure due to fluid retention, but SGLT2 inhibitors have the opposite effect and are recommended 8.

• Do not withhold SGLT2 inhibitors based on ejection fraction: These agents benefit patients across the entire LVEF spectrum, including those with preserved ejection fraction typical of HOCM 2, 6.

• Do not delay initiation: Early administration, even during acute decompensation, is beneficial and should not be postponed 6.

• Do not discontinue without strong reason: Persistence of treatment is critical as benefits may decline rapidly after withdrawal 6.