Effects of Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with Chronic Kidney Disease: the DECODE-CKD Trial

Background SGLT2 inhibitors, originally developed as glucose-lowering agents for treatment of type 2 diabetes, have been shown to have cardio- and kidney-protective effects among CKD patients with and without diabetes. However, the mechanisms remain largely unknown. Methods Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with Chronic Kidney Disease (DECODE-CKD) is an investigator-initiated, prospective, single-center, randomized, placebo-controlled trial evaluating the effects of 6 months of treatment with 10 mg of dapagliflozin compared with placebo on cardiac structure and function in 222 adults with CKD. Results The primary objective was to assess whether dapagliflozin improves left ventricular mass index. Secondary and exploratory end points include changes in cardiac and kidney markers, quality of life, depressive symptoms, and cognitive function. Conclusions This is the first study to address the effects of SGLT2 inhibitors on cardiac structure and function in patients with CKD. The results will provide valuable insights into the mechanisms underlying the cardiopro- tective benefits of SGLT2 inhibitors in patients with CKD. Clinical Trial registry name and registration number NCT0535926

Myocardial Work in Patients Hospitalized With COVID‐19:Relation to Biomarkers, COVID‐19 Severity, and All‐Cause Mortality

BACKGROUND: COVID‐19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID‐19. We hypothesized that GWI was associated with disease severity and all‐cause death in patients with COVID‐19. METHODS AND RESULTS: In a multicenter study of patients admitted with COVID‐19 (n=305), 249 underwent pressure‐strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide]), disease severity (oxygen requirement and CRP [C‐reactive protein]), and all‐cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P=0.018). A curvilinear association to NT‐proBNP was observed, with increasing NT‐proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100–mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow‐up (median, 58 days). In multivariable Cox regression, GWI was associated with all‐cause death (hazard ratio, 1.08 [95% CI, 1.01–1.15], per 100–mm Hg% decrease), but did not increase C‐statistics when added to clinical parameters. CONCLUSIONS: In patients admitted with COVID‐19, our findings indicate that NT‐proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all‐cause death, but did not provide prognostic information beyond readily available clinical parameters. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035