Abstract
Purpose
Finerenone, a highly selective non‐steroidal mineralocorticoid receptor antagonist, was approved for the treatment of patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (diabetic kidney disease, DKD). Finerenone reduced the composite endpoint of heart failure events and cardiovascular death in patients with heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). This study aimed to investigate the safety and cardiac effects of finerenone in patients with DKD with or without HFpEF/HFmrEF in a real‐world setting.
Methods
Patients with DKD were prospectively enrolled and were treated with finerenone according to best clinical practice. Clinical, laboratory and echocardiographic assessments were performed before, 4 weeks and 6 months after starting finerenone.
Results
Thirty‐one patients with DKD were included. At baseline, patients had a typical risk profile with arterial hypertension (90.3%) and hyperlipoproteinemia (87.1%). Most patients were treated with a sodium‐glucose cotransporter 2 (SGLT2) inhibitor (93.5%). Treatment with finerenone was safe and well tolerated: after 4 weeks, the glomerular filtration rate decreased slightly from 52 (43–78) mL/min/1.73 m2 to 48.0 (39.0–71.0) mL/min/1.73 m2 (P = 0.002 vs. baseline), but stabilized thereafter. Similarly, the median potassium value increased from 4.2 (3.8–4.5) mmol/L to 4.4 (4.2–4.8) mmol/L (P = 0.017) after 4 weeks, but remained stable thereafter [4.4 (4.1–4.6) mmol/L (P = 0.079)]. Only one patient (3.2%) had an unplanned hospitalization and concomitant hyperkalaemia up to 6.0 mmol/L. HFpEF/HFmrEF was frequently found in patients with DKD (71.0%), although most patients had a rather early stage with only mild symptoms and a median N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) value of 150.8 (54.5–325.7) ng/L. During treatment with finerenone, NT‐proBNP and left ventricular mass index (LVMI) remained stable. In contrast, left atrial volume index (LAVI) decreased from baseline [31.2 (26.8–39.7) mL/m2] to 4 weeks follow‐up [29.7 (20.8–33.6) mL/m2, P = 0.027] and decreased further after 6 months [26.6 (20.8–34.9) mL/m2, P = 0.029]. In the subgroup of patients with HFpEF/HFmrEF, E/e′ decreased from 11.9 (8.7–14.5) at baseline to 9.9 (8.0–12.4) after 6 months (P = 0.043).
Conclusions
In a real‐world setting, treatment with finerenone is safe and well‐tolerated in patients with DKD and may improve functional and structural cardiac parameters. Further investigation is warranted.
Keywords: chronic kidney disease, diabetic kidney disease, heart failure with preserved ejection fraction, HFmrEF, HFpEF, finerenone, mineralocorticoid receptor antagonist
Introduction
Treatment with finerenone, a highly selective non‐steroidal mineralocorticoid receptor antagonist (MRA), lowers the risk of chronic kidney disease (CKD) progression 1 and improves cardiovascular outcomes 1 , 2 in patients with CKD and type 2 diabetes mellitus (diabetic kidney disease, DKD). In patients with heart failure (HF) with reduced ejection fraction (HFrEF), steroidal MRAs reduce mortality and morbidity. 3 , 4 , 5 In contrast, in patients with HF with mildly reduced ejection fraction (HFmrEF) and in patients with HF with preserved ejection fraction (HFpEF), their efficacy is less well established. For example, in the randomized controlled TOPCAT trial, 6 the steroidal MRA spironolactone failed to reduce cardiovascular mortality in the overall cohort of patients with HFmrEF and HFpEF, although regional differences of the TOPCAT results have raised doubts about the validity of the study results. 7 Based on this data, the American guidelines give a IIb recommendation (‘may be considered’) for therapy with a MRA in patients with HFpEF, while the European guidelines give no recommendation. 8 , 9 In the future, the ongoing randomized controlled SPIRIT‐HF trial may clarify the role of spironolactone for the treatment of patients with HFpEF. 10 Just very recently, it was shown that finerenone—as compared with placebo—led to a significantly lower rate of a composite of worsening HF and death from cardiovascular causes in patients with HFpEF or HFmrEF. 11 However, to date, real world data supporting the use of finerenone in patients with HFpEF remain scarce. Importantly, in many cases, HFpEF is associated with a wide spectrum of comorbidities and there is a broad overlap between HFpEF, CKD and type 2 diabetes. 12 , 13 Therefore, the aim of the present study was to investigate the effects of finerenone in patients with CKD, type 2 diabetes and HFpEF/HFmrEF in a real‐world scenario.
Methods
Study design and study follow‐up
This was a prospective, single‐centre, observational study performed in the University Medical Center Göttingen, Germany between February 2022 and September 2024. In patients with type 2 diabetes and CKD with albuminuria [CKD Stages 1–4, A2 or A3 according to the Kidney Disease Improving Global Outcomes (KDIGO) classification 14 ], treatment with finerenone is indicated and was initiated unless contraindicated. Patients had stable guideline‐directed medication for more than 3 months. The main contraindications for finerenone treatment include 1 : concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole and clarithromycin), 2 hyperkalaemia with a serum potassium level >5.0 mmol/L and 3 pre‐existing treatment with or an indication for MRAs such as eplerenone or spironolactone, primarily in patients with HF with reduced ejection fraction (HFrEF). Consecutive patients were prospectively included. Baseline examination including assessment of medical history, clinical and laboratory assessment, electrocardiogram (ECG) and echocardiography were performed before treatment initiation. According to current recommendations, 15 finerenone was initiated at 20 mg in patients with an estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 and at 10 mg in those with an eGFR of 25–59 mL/min/1.73 m2. Finerenone was not initiated in patients with an eGFR below 25 mL/min/1.73 m2. Follow‐up visits were scheduled after 4 weeks and after 6 months (±14 days). As per finerenone's summary of product characteristics, in patients with a starting dose of 10 mg finerenone, the dose was increased to 20 mg when the potassium value was ≤4.8 mmol/L after 4 weeks and maintained at 10 mg in patients with a potassium value above 4.8 mmol/L. The study complies with the principles of the Declaration of Helsinki, and the local ethical committee approved the study protocol (ethical vote number 38/6/21). All patients provided written informed consent.
Laboratory data, echocardiography and definitions
Plasma creatinine, N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) and albuminuria were routinely analysed by standard methods in the central laboratory of the University Medical Centre Göttingen at inclusion and during follow‐up visits. EGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) creatinine equation. Echocardiographic examinations were performed according to local standard operating procedure. According to guideline recommendations of the European Society of Cardiology (ESC), HFpEF was diagnosed in patients with (1) signs and/or symptoms of HF (or treatment with loop diuretics to prevents signs and / or symptoms of HF), (2) a left ventricular (LV) ejection fraction (LVEF) ≥50% and (3) objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of LV diastolic dysfunction/raised LV filling pressures, including raised natriuretic peptides. 16 The objective evidence of cardiac structural abnormalities was a LV mass index (LVMI) ≥95 g/m2 in females or ≥115 g/m2 in males, a relative wall thickness (RWT) >0.42 and/or a left atrial volume index (LAVI) >34 mL/m2. Objective evidence of functional abnormalities was an early filling velocity on transmitral Doppler/early relaxation velocity on tissue Doppler (E/e′) ratio at rest >9 and/or an estimated pulmonary artery systolic pressure > 35 mmHg. Natriuretic peptide levels were considered increased with a NT‐proBNP level > 125 pg/mL in patients with sinus rhythm or >365 pg/mL in patients with atrial fibrillation.
Statistical analysis
The data were analysed using the Statistical Package for the Social Sciences (SPSS) Version 29.0.0.0 (IBM Corp., Armonk, NY, USA) and GraphPad Prism Version 9 (GraphPad Software, San Diego, CA, USA). To assess time‐dependent changes, paired Student T‐test or Wilcoxon signed rank test was used, where appropriate. Differences between subgroups were compared by an independent T‐test or Mann–Whitney U test for continuous variables or the Pearson's χ 2 test or Fisher's exact test for categorical values. Results are expressed as mean ± standard deviation (SD), median with interquartile range (IQR) or as a number with percentage for categorical variables. The threshold for statistical significance was chosen to be P < 0.05.
Results
Study population
A total of 31 patients with DKD were treated with finerenone over 6 months of follow‐up. Baseline characteristics of the study patients are reported in detail in Table 1. In brief, patients had a median age of 68.0 (64.0–72.0) years, and most of them were male (74.2%). The most common comorbidities were arterial hypertension in 90.3% and hyperlipoproteinemia in 87.1%. All patients were treated with angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers. Antidiabetic treatment included metformin in 23 patients (74%), GLP‐1 receptor agonists in 12 (39%), sodium‐glucose cotransporter 2 (SGLT2) inhibitor in 29 (94%), insulin in 13 (42%) and DPP‐4 inhibitors in 7 (23%). At baseline, the mean LVEF was 53.0% ± 6.6%, and the mean heart rate was 71.0 ± 10.9 beats per minute. All 31 patients (100%) had clinically diagnosed DKD as the underlying cause of CKD. Given that 29 patients (94%) had concomitant arterial hypertension, a hypertensive nephropathy contributing to kidney damage is likely in the majority of cases. In one patient (3%), diabetic kidney disease coexisted with biopsy‐proven membranous glomerulopathy.
Table 1.
Baseline characteristics of included patients.
| All patients (n = 31) | Patients with HFpEF/HFmrEF (n = 22, 71.0%) | Patients without HF (n = 9, 29.0%) | ||
|---|---|---|---|---|
| Age (years) | 68.0 (64.0–72.0) | 70.0 (65.0–74.3) | 64.0 (61.0–68.5) | 0.038 |
| Sex = female | 8 (25.8%) | 6 (27.3%) | 2 (22.2%) | 1.000 |
| BMI (kg/m2) | 28.7 (26.0–32.4) | 28.9 (25.9–32.7) | 28.7 (26.1–34.0) | 0.862 |
| Comorbidities and cardiovascular risk factors | ||||
| Obesity (BMI ≥ 30 kg/m2) | 12 (38.7%) | 9 (40.9%) | 3 (33.3%) | 1.000 |
| Arterial hypertension | 28 (90.3%) | 22 (100.0%) | 6 (66.7%) | 0.019 |
| Hyperlipoproteinaemia | 27 (87.1.0%) | 20 (90.9%) | 7 (77.8%) | 0.560 |
| Active smoker | 11 (35.5%) | 5 (22.7%) | 6 (66.7%) | 0.038 |
| Coronary artery disease | 11 (36.7%) | 11 (50.0%) | 0 (0.0%) | 0.014 |
| Previous stroke | 7 (22.6%) | 5 (22.7%) | 2 (22.2%) | 1.000 |
| Chronic obstructive pulmonary disease | 5 (16.1%) | 4 (18.2%) | 1 (11.1%) | 1.000 |
| Laboratory and urinary assessment | ||||
| Serum creatinine (mg/dL) | 1.21 (0.91–1.57) | 1.23 (0.97–1.61) | 1.17 (0.74–1.55) | 0.473 |
| eGFR (mL/min/1.73 m2) | 52.0 (43.0–78.0) | 51.5 (41.8–72.0) | 63.0 (45.5–91.0) | `0.421 |
| eGFR < 60 mL/min/1.73 m2 | 18 (58.1%) | 14 (63.6%) | 4 (44.4%) | 0.433 |
| UACR (mg/g) | 190.7 (44.7–413.9) | 141.2 (43.7–473.9) | 284.8 (44.8–561.3) | 0.728 |
| UACR > 30 mg/g creatinine | 28 (90.3%) | 20 (90.9%) | 8 (88.9%) | 1.000 |
| Previous medication | ||||
| SGLT2 inhibitor | 29 (93.5%) | 20 (90.9%) | 9 (100.0%) | 1.000 |
| Beta‐blocker | 21 (67.7%) | 20 (90.9%) | 1 (11.1%) | <0.001 |
| ACE inhibitor/ARB | 31 (100%) | 22 (100.0%) | 9 (100.0%) | 1.000 |
| Diuretics | 19 (61.3%) | 17 (77.3%) | 2 (22.2%) | 0.012 |
| Loop diuretic | 11 (35.5%) | 11 (50.0%) | 0 (0.0%) | 0.012 |
| Statins | 27 (87.1%) | 19 (86.4%) | 8 (88.9%) | 1.000 |
Abbreviations: ARB, angiotensin receptor blocker; BMI, body mass index; eGFR, estimated glomerular filtration rate; UACR, urinary albumin–creatinine ratio.
Safety of finerenone treatment in a real‐world setting
All patients completed 6 months of follow‐up. Finerenone was started at a dose of 10 mg/day in 27 of 31 patients (87.1%) and at 20 mg/day in the remaining 4 patients (12.9%). After 4 weeks, finerenone was up‐titrated in most patients (24 of 27 patients (88.9%) with a starting dose of 10 mg). At 6 months follow‐up, 22 of 31 patients (71.0%) were still receiving full dose. The remaining 9 patients (29%) received 10 mg/day. Treatment was stopped in none of the patients. The mean and the median dose of finerenone at 6 months was 17.1 (±4.6) and 20.0 (10.0–20.0) milligram (mg) per day, respectively.
Median systolic blood pressure (SBP) was 136 (128–155), 137 (130–150) and 133 (120–149) mmHg at baseline and at the follow‐up visits after 4 weeks and 6 months, respectively (P not significant; Figure 1). At baseline and at 4 weeks of follow‐up, none of the patients had an SBP below 100 mmHg; after 6 months, in 2 patients (7.4%) SBP was below 100 mmHg.
Figure 1.
Systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR) and potassium level during treatment with finerenone.
The median eGFR at baseline was 52 (43–78) mL/min/1.73 m2 and decreased to 48.0 (39.0–71.0) mL/min/1.73 m2 after 4 weeks (P = 0.002 vs. baseline). At the 6 months follow‐up, median eGFR stabilized at 51.5 (40.3–84.3) mL/min/1.73 m2 (P = 0.776 vs. 4 weeks of treatment and P = 0.299 vs. baseline; Figure 1).
The median potassium value at baseline was 4.2 (3.8–4.5) mmol/L with a maximum of 4.7 mmol/L. At the follow‐up visit after 4 weeks, the median potassium value increased to 4.4 (4.2–4.8) mmol/L (P = 0.017 compared with baseline); 4 patients had potassium ≥ 5.0 mmol/L and none of the patients had a potassium > 5.5 mmol/L. At 6 months follow‐up, the median potassium value remained stable [4.4 (4.1–4.6) mmol/L (P = 0.079) compared with the value at the 4 weeks follow‐up; Figure 1]. Importantly, during the time of follow‐up, only one patient (3.2%) had an unplanned hospitalization due to hyperkalaemia (maximum of 6.0 mmol/L). This was due to acute kidney injury Stage 1 caused by dehydration following a gastrointestinal infection with diarrhoea. This patient was treated with an oral potassium binder thereafter and, after a short break, finerenone treatment was continued at a dose of 10 mg/day.
HF with preserved LV ejection fraction (HFpEF) in patients with diabetes mellitus and CKD
Table 2 gives an overview of clinical, laboratory and echocardiographic parameters of HFpEF/HFmrEF and diagnostic algorithms. Signs and symptoms of HF were frequently found in patients with DKD: 20 patients (64.5%) had dyspnoea on exertion, 8 patients (25.8%) presented with peripheral oedema and 10 patients (32.3%) reported nocturia with ≥2 urinations per night. Twenty‐one patients (67.7%) had at least one sign or symptom of HF at presentation. Furthermore, 11 patients (35.5%) were pretreated with oral loop diuretics. Twenty‐two (71.0%) patients had either signs or symptoms of HF and/or a pretreatment with loop diuretics to prevent signs or symptoms of HF. Regarding the HF phenotype, no patients had a prior history of hospitalization for HF or a prior diagnosis of HF with reduced ejection fraction (HFrEF) at baseline, making HF with improved EF unlikely in this cohort.
Table 2.
Overview of clinical, laboratory and echocardiographic parameters of HFpEF/HFmrEF.
| All patients (n = 31) | |
|---|---|
| Clinical assessment: Signs and symptoms of heart failure (HF) | |
| Dyspnoea at exertion | 20 (64.5%) |
| NYHA II | 17 (54.8%) |
| NYHA III | 3 (9.7%) |
| Peripheral oedema | 8 (25.8%) |
| Nocturia (≥2× per night) | 10 (32.3%) |
| Any sign or symptom of HF | 21 (67.7%) |
| Known heart failure or reduced ejection fraction at baseline | |
| Known HFpEF | 3 (9.7%) |
| Known HFmrEF | 0 (0%) |
| Mean left ventricular ejection fraction (EF) at baseline (n = 30) | 53.0 ± 6.6 |
| Left ventricular ejection fraction (EF) at baseline (n = 30) | |
| EF ≥ 50% | 93.3% |
| EF 40%–49% | 6.7% |
| HFA‐PEFF score | |
| Functional parameters | |
| Septal e′ (cm/s, n = 29) | 5.6 (4.9–6.8) |
| Septal e′ < 7 cm/s | 79.3% |
| Lateral e′ (cm/s, n = 29) | 7.8 (6.4–9.9) |
| Lateral e′ < 10 cm/s | 23 (79.3%) |
| E/e′ (n = 30) | 10.6 (7.8–14.2) |
| E/e′ ≥ 15 | 3 (10.0%) |
| E/e′ 9–14 | 15 (50.0%) |
| TR velocity > 2.8 m/s or PASP > 35 mmHg | 1 (3.3%) |
| Morphological parameters | |
| LAVI (mL/m2) (n = 30) | 31.2 (26.8–39.7) |
| LAVI > 34 mL/m2 | 14 (46.7%) |
| LAVI 29–34 mL/m2 | 7 (23.3%) |
| LVMI (g/m2) (n = 30) | 97.6 (82.7–114.5) |
| LVMI ≥ 122 (female) or ≥149 (male) g/m2 | 0 (0%) |
| LVMI > 95 (female) or >115 (male) g/m2 | 10 (33.3%) |
| RWT (n = 30) | 0.51 (0.40–0.66) |
| RWT > 0.42 | 22 (73.3%) |
| LV wall thickness (n = 30) | |
| Interventricular wall thickness (end‐diastolic) (mm) | 11.9 (10.0–13.0) |
| Posterior wall thickness (end‐diastolic) (mm) | 12 (11.0–14.9) |
| LV wall thickness ≥12 mm | 20 (66.7%) |
| Biomarker | |
| NT‐proBNP | 150.8 (54.5–325.7) |
| NT‐proBNP > 220 pg/mL (SR) or >660 pg/mL (AF) | 10 (32.3%) |
| NT‐proBNP 125–220 pg/mL (SR) or 365–660 pg/mL (AF) | 7 (22.6%) |
| HFA‐PEFF score | |
| Points (n = 30) | |
| Points ≥ 5 (HFpEF confirmed) | 11 (36.7%) |
| Points 2–4 (requires further diagnostic work‐up) | 18 (60.0) |
| Points 0–1 (HFpEF excluded) | 1 (3.3%) |
| HFpEF according to ESC guideline criteria | |
| EF ≥ 50% (n = 30) | 28 (93.3%) |
| Signs and/or symptoms of HF or loop diuretics (to prevent) | 22 (71.0%) |
| Objective evidence, defined as at least one of the following criteria | 31 (100%) |
| LVMI ≥ 95 (female) or ≥115 (male) g/m2, LAVI > 34 mL/m2 (or >40 in) | |
| Patients with AF, RWT > 0.42, E/e′ > 9, NT‐proBNP > 125 pg/mL (or) | |
| Inpatients with AF PASP (mmHg) TR velocity (ms) | |
| HFpEF according to the ESC guidelines | 20 (64.5%) |
| HFpEF or HFmrEF according to ESC guidelines | 22 (71.0%) |
| HFpEF/HFmrEF eligibility criteria of the FINEARTS‐HF trial fulfilled | |
| Age ≥ 40 years | 30 (96.8%) |
| NYHA class ≥ 2 | 20 (64.5%) |
| LVEF ≥ 40% and evidence of structural heart disease defined as at least one of the following criteria (n = 30) | 30 (100%) |
| LVMI ≥ 95 (female) or ≥115 (male) g/m2, LAVI > 30 mL/m2 | |
| LAD > 3.8 cm, LAA ≥ 20 cm2, LV wall thickness ≥ 11 mm | |
| NT‐proBNP ≥ 300 pg/mL (or ≥900 pg/mL in patients presenting with AF) | 8 (25.8%) |
| Diuretic pretreatment | 19 (61.3%) |
| FINEARTS‐HF eligibility criteria fulfilled | 5 (16.1%) |
Abbreviations: AF, atrial fibrillation; ESC, European Society of Cardiology; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; LAVI, left atrial volume index; LV, left ventricle; LVMI, LV mass index; NT‐proBNP, N‐terminal pro B‐type natriuretic peptide; RWT, relative wall thickness; TR, tricuspid regurgitation.
The median value of NT‐proBNP was 150.8 mmol/L (54.5–325.7). Seventeen patients (54.8%) had an NT‐proBNP value above 125 ng/L (or above 365 ng/L in patients with atrial fibrillation).
One patient missed echocardiographic examination at baseline. Of the remaining 30 patients, all patients had morphological and/or functional signs of HFpEF on echocardiography. The HFA‐PEFF Score was 4 (3.0–5.3), and 11 patients (36.7%) had a value of at least 5 points (which allows diagnosing HFpEF without further investigations).
Following the definition of the HF guideline from the European Society of Cardiology (ESC), 20 patients (64.5%) had HFpEF, and 2 patients (6.5%) had HFmrEF at baseline. Only five patients (16.1%) fulfilled inclusion criteria and eligibility criteria of the FINEARTS‐HF trial. Importantly, all patients fulfilling the FINEARTS criteria had also the diagnosis of HFpEF or HFmrEF according to the ESC guideline criteria.
Cardiac impact of finerenone treatment in patients with chronic diabetic kidney disease and HF with preserved or mildly reduced (LV) ejection fraction
LAVI decreased slightly from baseline [31.2 (26.8–39.7) mL/m2] to 4 weeks follow‐up [29.7 (20.8–33.6) mL/m2, P = 0.027] and decreased further at 6 months follow‐up [26.6 (20.8–34.9) mL/m2, P = 0.029 as compared with baseline] (Figure 2). Similarly, in the subgroup of patients with HFpEF or HFmrEF, LAVI decreased from baseline [37.0 (29.3–41.4) mL/m2] to the follow‐up visit after 4 weeks [30.3 (25.9–34.0), P = 0.019]. No significant change in LAVI was observed in the HFpEF/HFmrEF subgroup from baseline to the follow‐up visit after 6 months [33.8 (25.2–36.4) mL/m2, P = 0.140].
Figure 2.
Functional and structural echocardiographic parameters during treatment with finerenone. (A) Left atrial volume index (LAVI) in the overall cohort. (B) LAVI in the subgroup of patients with heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). (C) Change of E/e′ in the overall cohort. (D) Change of E/e′ in the subgroup of patients with HFpEF/HFmrEF.
In the overall cohort, E/e′ did not change significantly during follow‐up (baseline vs. 4 weeks: P = 0.484; baseline vs. 6 months: P = 0.264). However, in the subgroup of patients with HFpEF or HFmrEF, E/e′ showed a numerical decrease from baseline to the 4 week follow‐up [11.9 (8.7–14.5) vs. 11.2 (9.2–15.0), P = 0.605] and decreased further and significantly to the follow‐up visit after 6 months [9.9 (8.0–12.4), P = 0.043 and P = 0.010 as compared with baseline values and to the values from the follow‐up after 4 weeks, respectively] (Figure 2).
The NT‐proBNP value did neither change from baseline to 4 week follow‐up [150.8 (54.5–325.7) vs. 136.0 (39.3–344.8) ng/L, P = 0.5] nor from baseline to 6 month follow‐up [159.7 (54.0–358.8), P = 0.6]. Patients with HFpEF or HFmrEF according to ESC criteria had higher NT‐proBNP values at baseline compared with patients without HFpEF or HFmrEF [164.4 (79.0–341.6) vs. 54.9 (27.1–126.1) ng/L, P = 0.041]. As in the overall cohort, the NT‐proBNP value remained stable over time in the subgroup of patients with HFmrEF or HFpEF according to ESC criteria [4 weeks follow‐up: 163.2 (79.0–402.4), P = 0.355; 6 months follow‐up: 200.1 (65.1–423.5), P = 0.527].
In the overall cohort, LVMI did neither change significantly from baseline [93.5 (77.1–110.9) g/m2] to 4 weeks follow‐up [92.6 (79.8–117.0) g/m2, P = 0.802] nor to 6 months follow‐up [97.1 (77.7–120.1) g/m2, P = 0.737]. Likewise, in the subgroup of patients with HFpEF or HFmrEF, LVMI remained stable over time [98.3 (80.7–111.7) g/m2 vs. 94.8 (82.0–126.5) g/m2 vs. 98.1 (80.5–123.1) g/m2, P = 0.983 and P = 0.557; baseline vs. 4 weeks vs. 6 months, respectively]. Two patients (6.4%) had documented intermittent atrial fibrillation at baseline, and no new‐onset atrial fibrillation occurred during follow‐up. At baseline, all patients had a urine albumin‐to‐creatinine ratio (UACR) ≥ 30 m/g creatinine with a median UACR of 190.7 mg/g creatinine (45.2–397.3). After 6 months of treatment with finerenone, the median reduction in UACR was −29.8 mg/g creatinine (−251.2 to −6.9) (P < 0.001).
Change in concomitant cardiometabolic medication
There was no significant change in the number of cardiometabolic medications prescribed between baseline and the 6 month follow‐up (Table 3). Specifically, the number of patients receiving loop diuretics or thiazide diuretics remained unchanged (P = 0.99 and P = 0.58, respectively). While thiazide diuretic dosages remained stable throughout the observation period, loop diuretic dosages were either reduced or increased in one patient each between baseline and follow‐up.
Table 3.
Change in medication between baseline and Month 6.
| Baseline | Month 6 | P | |
|---|---|---|---|
| ACE inhibitor | 11 (35%) | 12 (39%) | 0.99 |
| ARB | 21 (68%) | 19 (61%) | 0.79 |
| Beta‐blocker | 21 (68%) | 20 (65%) | 0.99 |
| Thazid | 8 (26%) | 11 (35%) | 0.58 |
| Loop diuretic | 11 (35%) | 11 (35%) | 0.99 |
| CCB | 18 (58%) | 17 (55%) | 0.99 |
| SGLT2 inhibitor | 29 (94%) | 29 (94%) | 0.99 |
| Aspirin (low‐dose) | 10 (0.99) | 10 (32%) | 0.99 |
Note: Change in medication between baseline and Month 6.
Abbreviations: SGLT2, sodium‐glucose cotransporter 2; CCB, calcium channel blocker; ACE, angiotensin‐converting enzyme; ARB, angiotensin receptor blockers.
Discussion
This prospective single‐centre study has four major findings 1 : (1) in a real‐world setting, treatment with finerenone was well‐tolerated and safe in patients with DKD. (2) HFpEF is commonly observed in patients with DKD, although its prevalence varies depending on the diagnostic criteria and algorithms applied. (3) While laboratory markers such as NT‐proBNP remained stable—potentially due to the limited sample size and the mild HFpEF stage in this cohort—significant reductions in structural (LAVI) and functional (E/e′ in the subgroup of patients with HFpEF or HFmrEF) parameters suggest a potential role of finerenone in promoting cardiac reverse remodelling. (4) The improvements in cardiac parameters were observed in patients who were all receiving RAAS inhibitors and nearly all were on SGLT2 inhibitor therapy. These findings support finerenone as a promising additional therapeutic option in this patient population, warranting further investigation in larger cohorts.
Safety of finerenone treatment in a real‐world setting
In randomized controlled trials (RCTs) in patients with CKD and type 2 diabetes 1 , 2 and in patients with HFmrEF or HFpEF, 11 treatment with finerenone was safe, and the overall number of serious adverse events was lower compared with placebo. 17 Similarly, in our real‐world cohort, finerenone was well‐tolerated and the majority of patients were receiving the full dose of finerenone after 4 weeks (77.4%) and after 6 months (71.0%). None of the patients died, and only one patient had an unplanned hospitalization within the study period (see below).
In RCTs, hyperkalaemia occurred more frequently in patients receiving finerenone, although none of the hyperkalaemia events resulted in death. 1 , 2 , 11 In a meta‐analysis comprising all the three aforementioned RCTs, hyperkalaemia leading to treatment discontinuation occurred in 1.3% and hyperkalaemia leading to hospitalization occurred in 0.8% of patients treated with finerenone (vs. 0.5% and 0.2%, respectively, in the placebo groups). 17 Similarly, in our real‐world study, finerenone led to higher potassium values during follow‐up, although the extent of the increase was only moderate [4.2 (3.8–4.5) vs. 4.4 (4.2–4.8) mmol/L from baseline to 4 weeks follow‐up, P = 0.017]. Importantly, within the study period, only one patient had an unplanned hospitalization due to hyperkalaemia (up to 6.0 mmol/L) following acute kidney injury caused by dehydration following a gastrointestinal infection. This patient was treated with a potassium‐binding agent thereafter, and finerenone treatment was re‐started after a pause. Interestingly, in our cohort, baseline potassium values were slightly lower compared with the RCT. 17 This might be due to the fact that in our study, most patients were treated with SGLT2 inhibitors (29 of 31 patients, 93.5%), whereas in the aforementioned RCTs, the rate of SGLT2 inhibitor treatment was between 4.6% and 13.6%, only. 1 , 2 , 11 This is an important difference, and the results provided in our real‐world cohort indicate that finerenone is well tolerated even (and may be especially) in combination with an SGLT2 inhibitor.
The pooled analysis of RCTs showed a slight decrease of SBP in patients treated with finerenone leading to a higher rate of patients with SBP below 100 mmHg (11.1% vs. 7.0%). 15 In comparison, in our study, we observed no effects on blood pressure after 6 months of treatment, and the number of patients with SBP below 100 mmHg was low at baseline (0%) and at the follow‐up visits (2 of 27 patients, 7.4%).
After 4 weeks of treatment, we observed a decrease of eGFR from 52.0 (43.0–78.0) mL/min/1.73 m2 to 48.0 (39.0–71.0) mL/min/1.73 m2 (P = 0.002). However, thereafter, eGFR stabilized [51.5 (40.3–84.3) mL/min/1.73 m2 at 6 months follow‐up]. This finding is in line with a previously observed temporary decrease in the eGFR after initiation of MRA treatment, which may be due to vasodilation of the efferent arteriole mediated by MRA antagonists and, at least in the case of diabetic patients, due to a reduction of an aldosterone‐mediated hyperfiltration. 18 Importantly, this temporary decrease of eGFR is not equivalent to worsening of clinical outcome and may even lead to a long‐term renal protective effect by a reduction of glomerular filtration pressure. 18 Accordingly, in the EVALUATE (Eplerenone Combination Versus Conventional Agent to Lower Blood Pressure on Urinary Antialbuminuric Treatment Effect) trial, the urinary albumin excretion rate after 52 weeks was significantly reduced in the eplerenone group despite the fact that a significant decrease in eGFR was observed 8 weeks after treatment with eplerenone. 19 Similarly, in patients with diabetes and CKD, a decrease of the UACR was observed in patients treated with finerenone, and treatment with finerenone led to a lower risk of CKD progression during longer‐term follow‐up. 1 Of note, in a crossover study, treatment with the MRA eplerenone and treatment with the SGLT2 inhibitor dapagliflozin both reduced UACR as compared with baseline. Interestingly, the effect was even greater when both substances were combined. 8 Thus, regarding beneficial renal effects, the combination of MRA and SGLT2 inhibitor treatment seems to be promising. Further studies are required to confirm long‐term safety and efficacy of this treatment combination. In line with these findings, we observed a significant reduction in UACR after 6 months of finerenone treatment in our real‐world cohort. This supports the antiproteinuric effect of finerenone and reinforces its role in cardio‐renal risk reduction in patients with DKD.
HF with preserved LV ejection fraction (HFpEF) in patients with diabetes mellitus and CKD
HFpEF was frequently present in included patients with diabetes and CKD. However, the amount of patients with HFpEF varies largely depending on the diagnostic algorithms that are applied. According to the HF guidelines of the ESC, the diagnosis of HFpEF requires three criteria: (1) signs and symptoms of HF, (2) LVEF ≥ 50% and (3) echocardiographic signs of increased LV filling pressures or an increased NT‐proBNP value. 16 When the ESC criteria were applied, HFpEF or HFmrEF was present in 22 of 31 patients (71.0%) in our cohort, indicating a broad overlap of patients with diabetes, CKD and HFpEF. However, only three patients (9.7%) had a previously known HF diagnosis and the only slightly elevated NT‐proBNP value at baseline [median 142.6 (54.2–329.7) pg/mL] points to a rather early stage of HFpEF in most patients included in our study. In comparison, inclusion in the FINEARTS‐HF trial required an NT‐proBNP value of at least 300 pg/mL (or at least 900 pg/mL in patients presenting with atrial fibrillation) and the median NT‐proBNP level in the FINEARTS‐HF trial was larger than 1000 pg/mL at baseline. 11 Accordingly, only five patients (16.1%) included in our study fulfilled the inclusion criteria of the FINEARTS‐HF trial.
Cardiac impact of finerenone treatment in patients with diabetes, CKD and HF with preserved (LV) ejection fraction
In our study, no reduction of NT‐proBNP was observed during treatment with finerenone. This was true in the overall cohort and in the subgroup of patients with HFpEF or HFmrEF. In contrast, in 422 ambulatory patients with symptomatic HFpEF included in the Aldo‐DHF trial, the steroidal MRA spironolactone reduced E/e′ and NT‐proBNP. 20 These differences regarding the effect of MRA treatment on natriuretic peptide levels may in part be due to the rather mild stages of HF and the rather low baseline value of NT‐proBNP, which may limit the chance of treatment effects in our study. Additionally, relatively small potential effects may remain undetected due to the limited sample size. However, in our study, treatment with finerenone led to an improvement of the functional echocardiographic parameter E/e′ in the subgroup of patients with HFpEF or HFmrEF. This may reflect a reduction of LV filling pressures 21 mediated by MRAs and is in line with the results of the Aldo‐DHF trial 20 and with the results of a meta‐analysis including a total of 984 patients treated with the steroidal MRA spironolactone. 22 In contrast to the subgroup of patients with HFpEF or HFmrEF, we observed no reduction of E/e′ in the overall cohort of our study. However, in the overall cohort, baseline E/e′ was rather low, providing lower margin for reduction with finerenone. Interestingly, the randomized controlled ‘heart “OMics” in AGEing’ (HOMAGE) trial, 9 which compared the effects of spironolactone versus placebo in people with, or at high risk of, coronary disease and raised plasma B‐type natriuretic peptides (Stage B according to the ACC/AHA HF guidelines 23 ) found no reduction of E/e′ in patients treated with spironolactone. As in our study, patients included in HOMAGE had lower baseline levels of E/e′ as compared with Aldo‐DHF 20 and TOPCAT. 24
Although anti‐fibrotic effects of MRAs are well established in animal models, 25 previous studies with the steroidal MRA spironolactone failed to demonstrate a significant reduction of LVMI as compared with placebo. 9 , 24 Likewise, in our study, LVMI remained stable over the time of treatment with finerenone, although previous results from animal studies 25 would suggest an even stronger anti‐fibrotic effect of the nonsteroidal MRA finerenone compared with steroidal MRAs. Of note, previous studies have shown that cardiovascular and kidney benefits of finerenone were not modified by the presence of LV hypertrophy at baseline in patients with CKD and type 2 diabetes. 26 In contrast to our study, in the Aldo‐DHF trial, LVMI decreased during treatment with spironolactone; however, the effect became significant only after 12 months of treatment. 20 Thus, we cannot exclude that potential effects of finerenone on LVMI remain undetected due to a shorter time of treatment in our study. Importantly, in the present study, LAVI significantly decreased with finerenone treatment, with early improvements at 4 weeks that further progressed by 6 months. In comparison, a reduction of LAVI after treatment with the steroidal MRA spironolactone was previously shown in HOMAGE 9 but not in Aldo‐DHF 20 nor in the echocardiographic substudy of TOPCAT. 24 The LAVI reduction observed in the present study may reflect decreased LV filling pressures mediated by finerenone, highlighting its therapeutic potential as a selective nonsteroidal MRA. In this context, it is of relevance to know that left atrial enlargement has been associated with worse outcomes in cardiac diseases 27 , 28 and that clinical outcomes may be improved by inducing left atrial reverse remodelling. 29
Limitations
Our study has several limitations that need to be considered: (1) our study is a single‐centre study with a relatively small sample size, and follow‐up was limited to 6 months. Thus, some potential beneficial effects of finerenone treatment may have been undetected. However, the fact that finerenone treatment was safe and, despite the relatively small sample size, led to functional and structural cardiac improvements in our real‐world cohort is promising and underlines the need for future larger studies in this setting. (2) Our study is an observational study in a real‐world setting; thus, we had no placebo group for comparison. However, considering the longitudinal evaluation, each patient served as his or her own control. (3) In our study, finerenone was used in doses of up to 20 mg/day as indicated for patients with DKD. In contrast, a dose of up to a maximum of 40 mg/day was used in the FINEARTS‐HF study for patients with HFpEF. Thus, we cannot exclude that a higher dose may lead to even more pronounced effects of treatment. (4) Although HFpEF was diagnosed in the majority of our patients, our patient cohort was not a dedicated ‘HFpEF cohort’, and most patients included in our study had a rather early stage of disease. The diagnosis of HFpEF in CKD patients is challenging due to the influence of renal function on NT‐proBNP levels. Although we applied guideline‐based clinical and echocardiographic criteria, the relatively low NT‐proBNP values raise the possibility of overdiagnosis in some cases. Therefore, potential beneficial effects of finerenone treatment (e.g., on NT‐proBNP values) may have remained undetected due to an only slightly abnormal baseline value providing only a small margin for improvement. However, even in this cohort with only early stage HF, clinically important beneficial effects of finerenone treatment were present. Additionally, considering the fact that it is very difficult to improve the prognosis of patients with HFpEF, it is of particular interest to examine patients in an early stage of HF. 5 While reductions in LAVI and E/e′ suggest reverse cardiac remodelling and lower filling pressures, NT‐proBNP levels remained unchanged, likely due to the low baseline values and the influence of renal function on this biomarker. The absence of complementary imaging such as cardiac magnetic resonance imaging further limits the assessment of structural changes. These factors highlight the need for multimodal evaluation in future studies. Finally, 6 the study population differed from those enrolled in pivotal RCTs of finerenone, particularly with respect to concomitant use of SGLT2 inhibitors and overall cardiovascular risk profile. These differences may limit the generalizability of our findings to other DKD populations.
Conclusions
In a real‐world scenario, treatment with the selective non‐steroidal MRA finerenone appeared safe and well‐tolerated in patients with diabetes and CKD. HFpEF was common in this population, and finerenone treatment was associated with reductions in E/e′ and left atrial size, suggesting a potential for cardiac reverse remodelling. However, given the small sample size, short follow‐up, frequent co‐treatment with SGLT2 inhibitors and differences from trial populations, these findings should be viewed as preliminary. They may not be generalizable to broader patient groups. Larger, multicentre studies with extended follow‐up are needed to confirm the safety profile and clarify the clinical relevance of the observed echocardiographic changes.
Conflict of interest statement
Kristian Hellenkamp has received speaker honoraria or fees for consultancy from AstraZeneca, Bayer, BDI, Boehringer‐Ingelheim and Novartis. He has received a research grant from AstraZeneca. Stephan von Haehling has received fees for lectures and consultancy from AstraZeneca, Bayer, Boehringer Ingelheim, BRAHMS, Edwards Lifesciences, Novartis, Novo Nordisk, MSD, Pfizer, Pharmacosmos, Respicardia and Vifor. His research at the University of Göttingen was supported by the Innovative Medicines Initiative (IMI), Deutsches Zentrum für Herz‐ und Kreislaufforschung (DZHK), AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Pfizer. Katja Gollisch has received speaker honoraria from Amgen, AstraZeneca and Novartis. Dirk Raddatz has received speaker honoraria from Bayer. Michael J. Koziolek has received speaker honoraria from Astra‐Zeneca and Boehringer‐Ingelheim. Manuel Wallbach has received speaker honoraria from Bayer, CVRX, AstraZeneca and Boehringer‐Ingelheim, as well as research grants from CVRX and Novartis. Sophia Kaebe, Miroslava Valentova, Fani Delistefani and Ann‐Kathrin Schäfer declare that they have no conflict of interest.
Hellenkamp, K. , Kaebe, S. , Valentova, M. , von Haehling, S. , Delistefani, F. , Gollisch, K. , Raddatz, D. , Schäfer, A.‐K. , Koziolek, M. J. , and Wallbach, M. (2025) Finerenone in diabetic chronic kidney disease—Real‐world insights including patients with HFpEF or HFmrEF. ESC Heart Failure, 12: 4219–4229. 10.1002/ehf2.15424.
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