Which sodium‑glucose co‑transporter‑2 (SGLT‑2) inhibitor is appropriate for a patient with concentric left ventricular hypertrophy, preserved left ventricular ejection fraction (~63%), grade I diastolic dysfunction, mildly reduced right ventricular systolic function, normal pulmonary artery pressure, and normal inferior vena cava compressibility?

SGLT2 Inhibitor Selection for Heart Failure with Preserved Ejection Fraction and Left Ventricular Hypertrophy

Either empagliflozin or dapagliflozin is appropriate for this patient with concentric left ventricular hypertrophy, preserved ejection fraction (63%), and grade I diastolic dysfunction, as both are guideline-recommended SGLT2 inhibitors with Class 2a evidence for HFpEF (LVEF >40%). 1

Guideline-Directed Recommendations

The 2022 AHA/ACC/HFSA guidelines and 2023 ACC Expert Consensus provide Class 2a recommendations for SGLT2 inhibitors in patients with symptomatic heart failure and LVEF >40%, based on landmark trials EMPEROR-Preserved (empagliflozin) and DELIVER (dapagliflozin). 1

Evidence Supporting Either Agent:

• Empagliflozin reduced the composite endpoint of cardiovascular death or HF hospitalization by 21% (driven primarily by 29% reduction in HF hospitalization) in EMPEROR-Preserved, which enrolled 5,988 patients with LVEF >40%. 1

• Dapagliflozin demonstrated similar benefits in the DELIVER trial with 6,263 patients with LVEF >40%, showing consistent reductions in HF hospitalizations and cardiovascular events. 1

• Both agents showed benefit regardless of diabetes status (45-49% of trial participants had type 2 diabetes). 1

Specific Relevance to This Patient's Presentation

Left Ventricular Hypertrophy Benefits:

Empagliflozin specifically demonstrates direct effects on left ventricular hypertrophy regression through multiple mechanisms in preclinical models, including:

• Significant reduction in LVH and myocardial fibrosis 2
• Enhanced metabolic efficiency with improved ATP synthesis and reduced energy cost of contraction 2
• Normalization of intracellular sodium levels and improved coupling of glycolysis with glucose oxidation 2
• Down-regulation of mTOR signaling pathway, which is implicated in pathological cardiac hypertrophy 2

Diastolic Dysfunction Benefits:

Both agents improve diastolic function, but empagliflozin has been specifically shown to:

• Enhance autophagy via the AMPK/mTORC1 pathway, which directly ameliorates diastolic dysfunction 3
• Improve left ventricular diastolic function and contractile reserve in HFpEF models 3
• Reduce cardiac hypertrophy and fibrosis, the structural substrates of diastolic dysfunction 3

Right Ventricular Function Considerations:

While this patient has mildly reduced RV systolic function, SGLT2 inhibitors have demonstrated:

• Reduction in total HF hospitalizations and slowing of eGFR decline, which indirectly benefits RV function by reducing volume overload 1
• Improvements in functional capacity (6-minute walk test increased by 25-30 meters) and quality of life (KCCQ scores improved by 5-10 points) 4

Practical Implementation

Starting Either Agent:

• Empagliflozin: 10 mg once daily (can increase to 25 mg if tolerated) 1
• Dapagliflozin: 10 mg once daily 1

Key Monitoring Parameters:

• Volume status (both agents have diuretic effects; may need to adjust loop diuretic doses) 1
• Blood pressure (monitor for symptomatic hypotension, which occurred in ~7% vs 5% with placebo) 4
• Renal function (SGLT2 inhibitors slow eGFR decline long-term but may cause initial small decreases) 1
• Genital mycotic infections (occurred in ~2.5% vs 0.5% with placebo) 4

Critical Timing Consideration:

Initiate SGLT2 inhibitor therapy early and maintain continuous treatment, as benefits appear rapidly but decline quickly after discontinuation. 5 The EMPULSE trial demonstrated benefits when initiated during or soon after acute decompensation, supporting early initiation in stable outpatients. 5

Clinical Pitfalls to Avoid

• Do not delay initiation waiting for "optimization" of other therapies—SGLT2 inhibitors can be started alongside other guideline-directed medical therapy 1
• Do not discontinue during periods of clinical stability, as benefits may decline rapidly after withdrawal 5
• Do not withhold based on age alone (though adoption has been lower in older patients despite similar efficacy) 6
• Do not restrict to patients with diabetes only—benefits are consistent regardless of glycemic status 1

Additional Cardiovascular Benefits

Beyond HF outcomes, SGLT2 inhibitors in this patient may provide:

• Reduction in ventricular arrhythmias (RR 0.38) and ventricular tachycardia (RR 0.60) 7
• Decreased cardiovascular mortality (RR 0.39 in ICD patients) 7
• Improved metabolic efficiency and reduced myocardial fibrosis specific to hypertrophic phenotypes 2