Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Serial monitoring of reverse left-atrial remodeling after pulmonary vein isolation in patients with atrial fibrillation: A magnetic resonance imaging study

PURPOSE: To prospectively determine the impact of sinus rhythm restoration on left-atrial (LA) volumes and function assessed by cardiac magnetic resonance (CMR) imaging within the first year after pulmonary vein isolation (PVI). METHODS: Forty-one patients (28 men; age: 57±10years) with paroxysmal or non-paroxysmal atrial fibrillation were studied serially using CMR at baseline and at 1-, 3-, 6- and 12-month intervals following PVI. LA diastolic and systolic volumes were determined by cine imaging with full gapless LA coverage applying Simpson's rule. Successful PVI was defined by a persisting sinus rhythm during the 12-month follow-up after a 3-month blanking period; patients with a relapse of atrial fibrillation after the blanking period were censored (4 patients at 6-month follow-up and additional 6 patients at 12-month follow-up). RESULTS: In all patients, LA diastolic and systolic volumes decreased significantly and progressively during the 12-month follow-up (p<0.001 and p=0.001, respectively). At baseline patients with successful PVI demonstrated a significantly smaller LA diastolic volume compared to patients with relapsed atrial fibrillation (p=0.009). During the 3-month blanking period, patients with successful PVI showed a significant decrease of LA diastolic and systolic volumes (p=0.026 and p=0.006, respectively) and a significant increase of LA ejection fraction (p=0.028); patients with subsequent relapse of atrial fibrillation, however, exhibited no significant change of LA diastolic and systolic volumes or LA ejection fraction. CONCLUSION: Restoration of sinus rhythm led to a significant and progressive decrease of left-atrial diastolic and systolic volumes during one year following pulmonary vein isolation

Image-Based View-Angle Independent Cardiorespiratory Motion Gating for X-ray-Guided Interventional Electrophysiology Procedures

Cardiorespiratory phase determination has numerous applications during cardiac imaging. We propose a novel view-angle independent prospective cardiorespiratory motion gating technique for X-ray fluoroscopy images that are used to guide cardiac electrophysiology procedures. The method is based on learning coronary sinus catheter motion using principal component analysis and then applying the derived motion model to unseen images taken at arbitrary projections. We validated our technique on 7 sequential biplane sequences in normal and very low dose scenarios and on 5 rotational sequences in normal dose. For the normal dose images we established average systole, end-inspiration and end-expiration gating success rates of 100 %, 97.4 % and 95.2 %, respectively. For very low dose applications, the method was tested on images with added noise. Average gating success rates were 93.4 %, 90 % and 93.4 % even at the low SNR value of 5–√, representing a dose reduction of more than 10 times. This technique can extract clinically useful motion information whilst minimising exposure to ionising radiation