I. Research Objectives This study is a prospective, open-label, single-arm cardiac imaging trial. It focuses on patients with diabetic kidney disease (DKD) and heart failure with a left ventricular ejection fraction (LVEF) ≥ 40%. The objective is to quantitatively evaluate the changes in myocardial fat infiltration, myocardial fibrosis (Extracellular Volume fraction, ECV), global left ventricular longitudinal systolic strain (GLS), and other myocardial remodeling indices using advanced imaging techniques-Cardiac Magnetic Resonance (CMR) and MR Spectroscopy (MRS)-following 6 months of Finerenone treatment.
II. Research Background Mineralocorticoid receptor (MR) activation is considered a key factor in the pathophysiological mechanism of heart failure. MR activation triggers downstream intracellular signaling, leading to sodium and water retention, systemic hypertension, endothelial dysfunction, as well as pathological fibrosis, hypertrophy, and inflammatory responses in both the heart and kidneys. Conventional mineralocorticoid receptor antagonists (MRAs), such as Spironolactone and Eplerenone, have been proven to improve survival rates and clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF, LVEF \< 40%). However, the efficacy and role of MRAs in non-systolic heart failure, particularly heart failure with preserved ejection fraction (HFpEF), remain controversial.
Post-hoc analysis of the TOPCAT trial indicated that Spironolactone could reduce the risk of heart failure hospitalization and cardiovascular death in HFpEF patients, but it was accompanied by side effects such as hyperkalemia and worsening renal function. Finerenone is a next-generation non-steroidal MRA with higher MR selectivity and a balanced tissue distribution between the heart and kidneys. Clinical studies have shown that compared to Spironolactone, Finerenone carries a lower risk of inducing hyperkalemia and renal function impairment in patients with chronic kidney disease (CKD). Finerenone has been approved by the U.S. FDA and Taiwan TFDA for use in patients with type 2 diabetes and chronic kidney disease to delay the progression of renal failure and reduce cardiovascular risks. The FINEARTS-HF multinational, multicenter, phase 3 clinical trial published in 2024 was the first to evaluate Finerenone in heart failure patients with LVEF \> 40% (including both mildly reduced and preserved ejection fraction). The results showed that Finerenone significantly reduced the risk of worsening heart failure events and cardiovascular death; however, the underlying pathophysiological mechanisms are not yet fully elucidated, necessitating further research. The study drug, Finerenone (trade name: Kerendia®, Taiwan FDA No. 028326), is approved and marketed in Europe, the United States, and Taiwan, with a dosage of once-daily oral administration. Kerendia® is currently indicated for the treatment of chronic kidney disease associated with type 2 diabetes, effectively slowing the decline in glomerular filtration rate (eGFR) and reducing the risks of cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure.
Myocardial remodeling, especially left ventricular remodeling, refers to the structural and functional changes triggered by myocardial injury and hemodynamic alterations during the progression of heart failure. Improvements in left ventricular remodeling are closely linked to patient prognosis. In clinical practice, conventional echocardiography is commonly used to assess indices such as left ventricular internal diameter, ejection fraction, and diastolic function (e.g., E/e' ratio). However, its sensitivity is often insufficient to detect early myocardial functional changes in patients with heart failure with mildly reduced or preserved ejection fraction. This study utilizes advanced imaging techniques-Cardiac Magnetic Resonance (CMR) and MR Spectroscopy (MRS)-to further quantitatively assess the degree of myocardial fat infiltration and myocardial fibrosis. Therefore, this study aims to explore the effects of Finerenone treatment on myocardial fat infiltration, myocardial fibrosis, GLS, and other myocardial remodeling indicators in DKD patients with heart failure and LVEF ≥ 40%, while further analyzing the correlation between these changes and clinical prognosis.
III. Research Design and Process This is a domestic multicenter, prospective, open-label, single-arm cardiac imaging study. The study focuses on DKD patients with heart failure and LVEF ≥ 40%. It compares and quantitatively evaluates the degree of myocardial fat infiltration and myocardial fibrosis utilizing Cardiac Magnetic Resonance (CMR) and MR Spectroscopy (MRS) after 6 months of Finerenone treatment.
