Patients on the sodium-glucose-cotransporter-2 inhibitor (SGLT2i) had a 2.40-mmHg reduction in pulmonary capillary wedge pressure (PCWP) during exercise, regardless of whether or not a patient had type-2 diabetes mellitus (DM), Dr. Massar Omar of Odense University Hospital in Denmark and colleagues found.
"This clinically meaningful result is despite a stable, well-treated, less symptomatic (NYHA II in 83%) and euvolemic HFrEF population. Whether reduction in filling pressure would be greater in a sicker heart-failure population is speculative," Dr. Omar told Reuters Health by email.
Patients with HFrEF have low cardiac output and increased left ventricular (LV) filling pressure, he and his colleagues note in the Journal of the American College of Cardiology. Several studies suggest that SGLT2 is of benefit to HF and HFrEF patients, they add, but their mechanism of action is not clear.
To investigate their hypothesis that these medications would improve the ratio of PCWP to cardiac index (CI, cardiac output divided by body surface area) during exercise, the researchers randomly assigned 70 HFrEF patients to empagliflozin 10 mg a day or placebo. Patients' mean LV ejection fraction was 26%, and 17% had diabetes.
Right-heart catheterization at rest and during exercise showed no change in peak PCWP/CI ratio from baseline to 12 weeks. PCWP was reduced at the full range of exercise loads, but CI was not. Results were similar for patients with and without diabetes.
"Mechanistic studies help provide clinicians and patients alike with an understanding of why each therapy should be used. In stable HFrEF patients, exercise mechanistic hemodynamics provides additional insight into the exertional performance pathway of a given drug," Dr. Omar said.
A secondary analysis found "a rightward shift in the end-diastolic pressure-volume relationship, revealing a decrease in left ventricular chamber stiffness," he added.
Dr. James L. Januzzi Jr. of Massachusetts General Hospital (MGH) and Harvard Medical School in Boston, who co-authored a linked editorial, told Reuters Heath by email, "I tell my patients in the MGH Heart Center that these drugs have a benefit that is hard to explain, yet we still use them because those benefits are unmistakable: they improve quality of life, they reduce biomarker levels, and they are linked to reduction in risk for hospitalization or death."
As he and his coauthor, Dr. Nasrien E. Ibrahim of MGH, point out, he added, "there are far more review articles on 'possible mechanisms of benefit' from SGLT2 inhibitors than actual studies exploring the mechanisms. This must change. The study in this issue of the JACC is a step in the right direction."
"Though the results were modest, they add some to the discussion about short-term treatment with SGLT2 inhibitors and how they may exert the very early benefits that are seen with the drug," he said.
SOURCE: https://bit.ly/33CNM8a and https://bit.ly/37n2gKg Journal of the American College of Cardiology, online November 30, 2020.
By Anne Harding
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