Diastolic heart failure, or Heart Failure with Preserved Ejection Fraction (HFpEF), occurs when the heart struggles to relax and fill properly. This condition has historically lacked specific, effective treatments. Recently, SGLT2 inhibitors, initially developed for managing diabetes, have shown remarkable promise in addressing diastolic heart failure. These inhibitors offer a new approach to improving heart function and patient outcomes.
Understanding Diastolic Heart Failure
Diastolic heart failure, also referred to as Heart Failure with Preserved Ejection Fraction (HFpEF), occurs when the heart’s left ventricle becomes stiff and cannot relax adequately between beats. This stiffness prevents the ventricle from filling with enough blood, even though the heart’s squeezing function might appear normal. Unlike systolic heart failure where the heart’s pumping strength is reduced, HFpEF’s core problem lies in its impaired filling phase.
Common factors contributing to the development of HFpEF include high blood pressure, diabetes, and obesity. The risk of developing HFpEF increases with age, and it is observed in approximately 50% of all heart failure cases. This condition significantly affects quality of life and is associated with substantial healthcare burdens.
Introducing SGLT2 Inhibitors
SGLT2 inhibitors are a class of medications originally developed to manage blood sugar levels in individuals with type 2 diabetes. Their mechanism of action involves targeting sodium-glucose cotransporter 2 (SGLT2) proteins in the kidneys. These proteins are responsible for reabsorbing about 90% of the glucose filtered by the kidneys back into the bloodstream.
By inhibiting SGLT2, these medications prevent the kidneys from reabsorbing as much glucose, leading to increased glucose excretion in the urine. This process lowers blood sugar levels and also results in increased urination, as water follows the glucose out of the body. While their primary role was glucose control, unexpected benefits in cardiovascular and kidney health emerged, leading to their approval for heart failure.
How SGLT2 Inhibitors Support the Heart
SGLT2 inhibitors provide benefits in diastolic heart failure through several mechanisms that extend beyond their original glucose-lowering effects. They promote the excretion of sodium and water, which helps to reduce fluid overload. This diuretic-like effect decreases the volume of blood the heart needs to handle, thereby reducing strain on the heart muscle and improving its ability to fill.
These medications also positively influence cardiac metabolism, potentially by inducing a state of nutrient deprivation and increasing the production of ketones, which the heart can use as an efficient energy source. SGLT2 inhibitors have been shown to reduce inflammation and oxidative stress within the heart and blood vessels. This anti-inflammatory action can help prevent further damage and stiffness in the heart muscle.
They also reduce cardiac stiffness and fibrosis, which are hallmarks of diastolic heart failure. They can decrease the accumulation of scar tissue in the heart, improving its relaxation properties and overall function. Clinical trials, such as EMPEROR-Preserved and DELIVER, have consistently demonstrated that SGLT2 inhibitors reduce heart failure hospitalizations and improve cardiovascular outcomes in patients with HFpEF, solidifying their role as a foundational therapy for this condition.
What Patients Should Know
Patients should be aware of potential side effects and discuss them thoroughly with their healthcare provider. Common side effects include increased urination, which can lead to increased thirst or, less commonly, dehydration if fluid intake is insufficient. Genital mycotic infections (yeast infections) and urinary tract infections may also occur due to increased glucose in the urine, especially in women. Maintaining good hygiene can help reduce this risk.
Though rare, more serious side effects like diabetic ketoacidosis can occur, even in individuals without diabetes or with normal blood sugar levels. Patients should be advised to temporarily stop the medication during acute illness, surgery, or prolonged fasting. SGLT2 inhibitors are part of a comprehensive management plan for heart failure, which may include other medications and lifestyle adjustments. A healthcare professional will determine if they are appropriate based on individual health conditions and kidney function.