SGLT2 Inhibitors for Heart Failure with Secondary Mitral Regurgitation
Yes, SGLT2 inhibitors are appropriate and should be initiated for heart failure caused by mitral regurgitation, as they are recommended as foundational therapy for all patients with heart failure and reduced ejection fraction (HFrEF), regardless of the underlying etiology. 1
Guideline-Directed Medical Therapy Takes Priority Over Etiology
The current evidence-based approach to HFrEF management does not differentiate treatment based on whether mitral regurgitation is the causative factor. SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) should be initiated early as first-line therapy in all HFrEF patients, including those with secondary mitral regurgitation. 1
Key Supporting Evidence:
The European Society of Cardiology recommends SGLT2 inhibitors as foundational therapy for HFrEF, to be started concurrently with mineralocorticoid receptor antagonists (MRAs), followed by beta-blockers and renin-angiotensin system inhibitors. 1
SGLT2 inhibitors are specifically recommended to lower the risk of heart failure hospitalization in patients with diabetes, and this benefit extends to non-diabetic patients with HFrEF. 2
The benefits of SGLT2 inhibitors are incremental and consistent regardless of background medical therapy, demonstrating efficacy even when added to optimal guideline-directed medical therapy. 2
Integration with Mitral Regurgitation Management
When managing heart failure caused by mitral regurgitation, the treatment algorithm should include:
Medical Optimization First:
Standard heart failure management with SGLT2 inhibitors, ACE inhibitors/ARBs (or sacubitril/valsartan), beta-blockers, and MRAs should be administered as optimal medical therapy before considering interventional approaches for the mitral regurgitation. 2
Cardiac resynchronization therapy (CRT) should be performed for heart failure if indicated, as part of comprehensive guideline-directed medical therapy. 2
SGLT2 Inhibitors in the Context of Secondary MR:
For patients with secondary mitral regurgitation and HFrEF, SGLT2 inhibitors are explicitly included in the guideline-directed medical therapy that should be optimized before considering transcatheter edge-to-edge repair (TEER) or other interventional procedures. 2
The COAPT trial criteria for mitral intervention specifically require assessment after optimization of guideline-directed medical therapy, which now includes SGLT2 inhibitors. 2
Practical Implementation
Timing of Initiation:
SGLT2 inhibitors can and should be initiated during hospitalization for acute decompensated heart failure, as in-hospital initiation is consistent with regulatory labels and clinical practice guidelines. 2
Early initiation leads to clinically meaningful reductions in clinical events that reach statistical significance within days to weeks, with benefits accruing rapidly. 3
Safety Profile Favoring Early Use:
SGLT2 inhibitors have minimal effects on blood pressure, making them particularly well-suited for initiation during heart failure hospitalization. 2, 3
There is no excess risk of acute kidney injury; rather, SGLT2 inhibitors exert renal protective effects and reduce the risk of hyperkalemia, which actually facilitates tolerance of other neurohormonal therapies. 3
Clinical trial data demonstrate a strong safety and tolerability profile with minimal glycemia-related adverse events. 3
Contraindications to Monitor:
Do not start SGLT2 inhibitors if eGFR is <30 mL/min/1.73m² (though some agents may be continued if already established). 2
Avoid in pregnancy or breastfeeding. 2
Clinical Outcomes
SGLT2 inhibitors significantly reduce cardiovascular and all-cause mortality irrespective of diabetes status, and reduce heart failure hospitalization in patients with HFrEF. 4
The mortality benefit and reduction in heart failure events occur independent of the underlying cause of cardiomyopathy, including secondary mitral regurgitation. 4, 3
Common Pitfalls to Avoid
Do not defer SGLT2 inhibitor initiation to the outpatient setting. Deferring in-hospital initiation exposes patients to excess risk of early post-discharge clinical worsening and death, with the real possibility that the medication will never be prescribed due to clinical inertia. 2
Do not wait for complete optimization of other heart failure medications before starting SGLT2 inhibitors. The efficacy of SGLT2 inhibitors is independent of background therapy and they can be initiated early, even simultaneously with other foundational therapies. 2, 1
Do not withhold SGLT2 inhibitors based on the presence of mitral regurgitation. The etiology of heart failure does not change the indication for SGLT2 inhibitor therapy in HFrEF. 2