Abstract
Background
We evaluated the effects of sustained low-efficiency dialysis (SLED) as an alternative to palliative care in persistently congested patients with advanced heart failure unsuitable for mechanical circulatory support or heart transplantation.
Methods
In this single-centre, non-randomised retrospective cohort study, we included patients hospitalised with advanced heart failure, persistent congestion, and renal dysfunction between September 2002 and December 2024. The index date was defined as the time SLED was considered clinically indicated. Patients who were treated with SLED formed the SLED group; patients who declined SLED and continued with standard medical therapy only were assigned to the standard-therapy group. Outcomes included the number and duration of heart failure-related and all-cause hospitalisations 1 year before and after the index date, heart failure medication use, and mortality.
Results
We compared 107 patients treated with SLED (mean age 75 ± 10 years, 48% male, 58% HFpEF) with 32 patients in the standard-therapy group (mean age 79 ± 18 years, 34% male, 53% HFpEF). During the first year after the index date, heart failure hospitalisation occurred in 13% of SLED patients compared to 78% of standard-therapy patients. In the SLED group, the annual heart failure hospitalisation rate decreased from 1.5 to 0.3 events (p < 0.001), and duration of hospital stay from 21.4 to 2.5 days (p < 0.001). No significant change was observed in the standard-therapy group (1.7–1.6 events; 16.3 to 16.3 days). All-cause hospitalisation rates were unchanged in both groups, but the duration of an all-cause hospital stay (25.1–11.5 days, p < 0.001) was significantly reduced in the SLED group. Use and titration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid receptor antagonists, and β-blockers improved significantly in the SLED group but remained largely unchanged with standard therapy. Median survival was longer in the SLED group (23 months, 95% CI: 17 to 29) compared with standard therapy (3 months, 95% CI: 1 to 7; p < 0.001).
Conclusions
In patients with advanced heart failure and persistent congestion, SLED was associated with fewer heart failure-related hospitalisations, enhanced optimisation of pharmacological heart failure therapy, and prolonged survival relative to standard therapy only.
Keywords: Advanced heart failure, Congestion, Cardiorenal syndrome, Sustained low-efficiency dialysis
Introduction
Heart failure is a major global public health concern, characterised by high rates of morbidity and mortality, reduced functional capacity, and diminished quality of life, all contributing to significant healthcare costs [1]. Despite advancements in evidence-based treatments and emerging data, many patients eventually progress to advanced stages of the disease where conventional therapies prove inadequate [2]. Advanced treatment options, such as mechanical circulatory support and heart transplantation, are often not viable for the majority of patients due to factors like advanced age and comorbid conditions [3, 4]. Consequently, these patients are typically referred to palliative care to relieve symptoms and improve their quality of life [1]. Congestion is a defining feature of chronic heart failure and the leading cause of heart failure-related hospital admissions [5]. Hypervolaemia is frequently complicated by kidney dysfunction, diuretic resistance, and electrolyte imbalances [6], making effective congestion management exceptionally challenging. Studies have consistently shown residual congestion is associated with poor outcomes [7], including increased morbidity and mortality if present at initial presentation [8], on discharge [3], and following the index hospitalisation [6, 8, 9]. Loop diuretics represent the cornerstone in congestion management, with 80% of patients being treated with these agents [4]. However, most pharmacological strategies to relieve congestion have not consistently demonstrated long-term benefits, such as reduced heart failure events or improved survival [5, 9, 10]. This unmet need highlights the interest in non-pharmacological fluid removal techniques as potential therapeutic options, especially in patients with cardiorenal syndrome [11], where advanced heart failure therapies often become unsuitable due to renal impairment and severe diuretic-resistant congestion [12, 13]. Current guidelines suggest ultrafiltration as a reasonable approach in patients with congestion unresponsive to medical therapy [3, 4]. Chronic renal replacement therapy is another potential strategy to address persistent volume overload, but the current evidence regarding its long-term safety, survival benefits, and overall outcomes remains limited [14–18]. In this study, we aimed to evaluate the effects of sustained low-efficiency dialysis (SLED), beyond ultrafiltration alone, on all-cause and heart failure-related hospitalisations and long-term outcomes in patients with cardiorenal syndrome and persistent, diuretic-resistant congestion.
Methods
Study Design
We conducted a single-centre, non-randomised, retrospective cohort study at Trbovlje General Hospital. The study included patients hospitalised with advanced heart failure, persistent congestion, and renal dysfunction between September 2002 and December 2024. All enrolled patients were offered treatment with SLED. Patients who accepted the treatment formed the SLED group, while patients who declined SLED due to personal or family preference were assigned to the standard-therapy group. All patients were treated with standard therapy, according to the guidelines [3], including loop diuretics. Baseline characteristics included sex, age, heart failure phenotype, frailty score (assessed using the Rockwood Frailty Scale [19]), echocardiographic parameters, comorbidities, type of haemodialysis vascular access, baseline laboratory values, and clinical signs of congestion. Serum creatinine levels were monitored throughout the observation period in both groups. We evaluated key clinical outcomes, including hospital admissions, survival rates, and the use of pharmacological therapy.
The study protocol was reviewed and approved by the National Medical Ethics Committee of the Republic of Slovenia, Ministry of Health, Republic of Slovenia (Approval No. KME-0120-358/2023/3). The study was conducted in accordance with the Declaration of Helsinki. The requirement for informed consent was waived by the National Medical Ethics Committee of Republic of Slovenia, Ministry of Health, the Republic of Slovenia.
Inclusion and Exclusion Criteria
Heart failure was diagnosed according to ESC (European Society of Cardiology) guidelines [3], and chronic kidney disease was defined using KDIGO (Kidney Disease Improving Global Outcomes) guidelines [20].
The inclusion criteria were as follows:
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1.
at least one previous hospital admission for acute worsening of chronic heart failure;
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2.
NYHA IV functional class on admission;
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3.
advanced heart failure with persistent congestion despite maximal diuretic therapy with loop diuretics and/or metabolic acidosis and/or hyperkalaemia (potassium >5.5 mmol/L);
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4.
unsuitability for advanced heart failure therapies (mechanical circulatory support or heart transplant) due to poor functional status or other comorbidities; and
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5.
inability to initiate or up-titrate guideline-directed medical therapy due to symptomatic hypotension and/or hyperkalaemia and/or worsening renal function.
The exclusion criteria were as follows:
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1.
age less than 18 years;
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2.
pregnancy;
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3.
comorbidity (e.g., malignancy, neurologic disease) with an expected survival of less than 3 months; nd
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4.
pre-existing end stage kidney disease of alternative aetiology (e.g., diabetic nephropathy, glomerulonephritides, etc.).
The index hospitalisation was defined as the admission during which initiation of SLED was clinically indicated, with the index date corresponding to the date of this decision. Patients who received SLED on that date were assigned to the SLED group. Patients who declined SLED and continued with standard therapy formed the standard-therapy group, with the same date recorded as the index date.
Haemodialysis/SLED Protocol
In the acute phase, SLED was performed 4–6 times weekly using low-efficiency bicarbonate dialysis with small-size, low-flux polyamide or cellulose triacetate membranes (surface area 1.3–1.7 m2). Session duration was 6–12 h with a blood flow of 150–200 mL/min, and a dialysate flow of 300 mL/h. In the more chronic phase (after 1–2 weeks), treatment frequency was reduced to 3 sessions per week with a duration of 4–6 h. Ultrafiltration was initiated at 100 mL/h during the first 3–6 sessions to minimise symptomatic hypotension, and then gradually increased to 400 mL/h until clinical recompensation was achieved. Ultrafiltration targets were then based on estimated dry weight. During the initial sessions, albumin was replaced when serum concentrations were below 30 g/L, and noradrenaline (0.01–0.15 μg/kg/min) was administered as needed to prevent cardiogenic shock secondary to severe interdialytic hypotension.
Vascular access consisted of dual-lumen permanent retrograde central venous catheters for patients with reduced left ventricular ejection fraction, and either permanent catheters or arteriovenous fistulas in patients with preserved left ventricular ejection fraction. All patients were managed by physicians specialising in heart failure and cardiorenal syndrome, with additional expertise in chronic haemodialysis treatment. Management protocols included close clinical monitoring, rigorous electrolyte and acid-base balance control, and weekly full blood count and iron studies. The haemodialysis/SLED protocol was dynamically adapted to support the optimal titration of heart failure medications.
Hospital Management and Outcomes
We analysed all-cause and heart failure-related hospitalisations and duration of hospital stay in the year before and after the index date, as well as annually during the observation period. Long-term survival was assessed and compared between groups.
Pharmacological Therapy
We evaluated the use of non-diuretic pharmacological therapies for heart failure, comparing their use at the index date with that at the end of the observation period. Medications assessed included angiotensin receptor-neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARBs), mineralocorticoid receptor antagonists (MRAs), β-blockers, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. Use of high-dose loop diuretic therapy at baseline was required for inclusion in both groups (a total daily dose of furosemide 1,000 mg), and changes in diuretic dosing were documented during follow-up.
Statistical Analysis
Statistical analyses were performed using Stata 18.0 for Mac (2023, StataCorp LLC). Data were appraised for normality of distribution using the Kolmogorov-Smirnov test. Continuous variables were summarised as means (with standard deviation) for normally distributed data or medians (interquartile range) for non-normally continuous variables. Categorical variables were presented as counts and percentages. Group comparisons for normally distributed continuous variables were performed using the two-sample t test. Categorical variables were analysed with the chi-square test. Percentages were compared using the two-sample test of proportions. Statistical significance was set at two-tailed p < 0.05. A linear mixed-effects model with maximum likelihood estimation was used to compare the variables over time. Long-term survival was assessed using Kaplan-Meier analysis, and survival differences between groups were evaluated using the log-rank test.
Results
Baseline Characteristics
A total of 139 patients hospitalised with advanced heart failure between September 2002 and March 2023 were included in the study. Of these, 107 were treated with SLED, and 32 with standard therapy only (Fig. 1). As shown in Table 1, both groups were comparable in age (75 vs. 79 years), sex (48% vs. 34% men), left ventricular ejection fraction (50% vs. 50%, heart failure with preserved ejection fraction in 58% and 53%) and heart failure aetiology (hypertensive heart disease being the most common at 47% and 34%). All patients had markedly elevated NT-proBNP concentrations (17,052 pmol/L vs. 18,670 pmol/L). Clinical signs of congestion did not differ between the groups, but acute respiratory failure was more frequent in the SLED group.
Fig. 1.
The study flow diagram.
Table 1.
Baseline patients’ characteristics
| | Standard therapy + SLED (N = 107) | Standard therapy only (N = 32) | p value |
|---|---|---|---|
| Males | 51 (48) | 11 (34) | 0.185 |
| Age, years | 75±10 | 79±18 | 0.116 |
| Median Clinical Frailty Scale score | 6 | 7 | 0.005 |
| Echocardiographic parameters | |||
| Median LVOT VTI, cm | 19±6 | 17±4 | 0.075 |
| Median LVEF, % | 50±15 | 50±12 | 0.879 |
| Heart failure phenotype | | | 0.737 |
| HFrEF | 25 (23) | 7 (22) | |
| HFmrEF | 20 (19) | 8 (25) | |
| HFpEF | 62 (58) | 17 (53) | |
| Heart failure aetiology | | | 0.055 |
| Hypertensive | 50 (47) | 11 (34) | |
| Ischaemic | 39 (36) | 9 (28) | |
| Valvular | 12 (11) | 10 (31) | |
| Dilatative | 6 (6) | 2 (6) | |
| Haemodialysis vascular access | |||
| Central venous catheter | 80 (75) | | |
| Arteriovenous fistula | 27 (25) | | |
| Comorbidities | |||
| Arterial hypertension | 87 (81) | 23 (72) | 0.247 |
| Hyperlipoproteinemia | 41 (38) | 14 (44) | 0.581 |
| Diabetes mellitus | 61 (57) | 11 (34) | 0.025 |
| Myocardial infarction | 49 (46) | 11 (34) | 0.253 |
| Cerebrovascular insult | 17 (16) | 3 (9) | 0.357 |
| Peripheral arterial disease | 27 (25) | 2 (6) | 0.020 |
| Atrial fibrillation | 66 (62) | 25 (78) | 0.086 |
| Baseline laboratory findings | |||
| Mean creatinine, μmol/L | 383±191 | 217±67 | 0.000 |
| Mean potassium, mmol/L | 4.7±0.9 | 4.8±0.6 | 0.782 |
| Mean NT-proBNP, pmol/L | 17,052±11,835 | 18,670±12,943 | 0.514 |
| Baseline signs of congestion | |||
| Elevated central venous pressure | 103 (96) | 32 (100) | 0.267 |
| Pleural effusion | 82 (77) | 28 (88) | 0.184 |
| Hepatomegaly | 103 (96) | 31 (97) | 0.870 |
| Congestive hepatopathy | 102 (95) | 31 (97) | 0.705 |
| Peripheral oedema | 104 (97) | 31 (97) | 0.924 |
| Acute respiratory failure | 57 (53) | 26 (81) | 0.005 |
| Baseline diuretics | |||
| Furosemide | 107 (100) | 32 (100) | 1.000 |
| Furosemide dose, mg | 1,000 | 1,000 | 1.000 |
| Thiazide diuretic/acetazolamide | 0 (0) | 0 (0) | 1.000 |
Values are presented as means ± SD or numbers (%) unless otherwise stated. SLED, sustained low-efficiency dialysis; SD, standard deviation; LVOT VTI, left ventricular outflow tract velocity time integral; IQR, interquartile range; LVEF, left ventricular ejection fraction; HFrEF, heart failure with reduced ejection fraction; HFmrEF, heart failure with mid-range ejection fraction; HFpEF, heart failure with preserved ejection fraction.
Patients in the standard-therapy group had higher baseline frailty scores that did not change during the observation period (median baseline and follow-up frailty score both 7; follow-up at a median of 3 months, IQR 1–7). In contrast, patients in the SLED group demonstrated a significant reduction in frailty, with median scores decreasing from 6 at baseline to 5 after a median follow-up of 10 months (IQR 6–34; p = 0.000).
In a mixed-effects model with random intercepts for patients, baseline creatinine was significantly higher in the SLED group (β = 134.64 μmol/L, 95% CI: 71.62 to 197.66, p < 0.001). Creatinine concentration did not change significantly over time in the standard-therapy group (β = 0.28 μmol/L/week, 95% CI: –1.46 to 2.02, p = 0.752). The interaction term indicated a greater weekly increase in creatinine in the SLED group (β = 1.32 μmol/L/week, 95% CI: –0.45 to 3.09), although this difference was not statistically significant (p = 0.144) (Fig. 2).
Fig. 2.
Mean creatinine over time.
The most common vascular access was a permanent central venous catheter (75%). Most patients (80%) remained on the same SLED treatment plan throughout the observation period, while 20% had the number of weekly sessions reduced during the chronic phase.
Hospital Admissions and Duration of Hospital Stay
Tables 2 and 3b summarise hospitalisation outcomes. In the first year after the index date, 14 patients (13%) in the SLED group were hospitalised for heart failure compared with 25 patients (78%) in the standard-therapy group (p < 0.001). In the SLED group, the mean annual number of heart failure-related hospitalisations decreased from 1.5 (95% CI: 1.1 to 1.9) to 0.3 (95% CI: 0.1 to 0.4), and the mean duration of heart failure-related hospital stay decreased from 21.4 days (95% CI: 15.3 to 27.5) to 2.5 days (95% CI: 0.7 to 4.2) (both p < 0.001). Over the entire observation period, the annual average duration of hospital stay was 6.1 days (95% CI: 3.6 to 8.7, p < 0.001). For all-cause hospitalisations in the SLED group, the mean annual admission rate decreased from 1.9 (95% CI: 1.5 to 2.3) to 1.4 (95% CI: 1.2 to 1.7) in the first post-index year (p = 0.080) and remained stable at 1.8 (95% CI: 1.5 to 2.1, p = 0.640). The mean duration of all-cause hospital stays decreased from 25.1 days (95% CI: 18.8 to 31.4) to 11.5 days (95% CI: 8.6 to 14.4) after SLED (p < 0.001). The average over the observation period was 18.7 days (95% CI: 14.8 to 22.6), which was not statistically different from baseline (p = 0.101).
Table 2.
Hospital admissions and duration of hospital stay – patients treated with SLED
| | 1 year before the start of SLED (mean, 95% CI) | 1 year after the start of SLED (mean, 95% CI) | Annually during the whole observation period (mean, 95% CI) | p value |
|---|---|---|---|---|
| All-cause hospitalisations | ||||
| Per year | 1.9 (1.5–2.3) | 1.4 (1.2–1.7) | | 0.080 |
| | 1.8 (1.5–2.1) | 0.640 | ||
| Duration of hospital stay | 25.1 (18.8–31.4) | 11.5 (8.6–14.4) | | 0.000 |
| | 18.7 (14.8–22.6) | 0.101 | ||
| Hospitalisations for heart failure | ||||
| Per year | 1.5 (1.1–1.9) | 0.3 (0.1–0.4) | | 0.000 |
| | 0.4 (0.3–0.6) | 0.000 | ||
| Duration of hospital stay | 21.4 (15.3–27.5) | 2.5 (0.7–4.2) | | 0.000 |
| | 6.1 (3.6–8.7) | 0.000 | ||
SLED, sustained low-efficiency dialysis; CI, confidence interval.
Table 3.
Hospital admissions and duration of hospital stay – patients who declined SLED (standard therapy only)
| | 1 year before the predicted start of SLED (mean, 95% CI) | 1 year after the predicted start of SLED (mean, 95% CI) | Annually during the whole observation period (mean, 95% CI) | p value |
|---|---|---|---|---|
| All-cause hospitalisations | ||||
| Per year | 1.8 (1.3–2.3) | 1.7 (1.2–2.1) | | 0.793 |
| | 6.8 (4.3–9.4) | 0.001 | ||
| Duration of hospital stay | 17 (11.5–22.5) | 16.8 (10.7–22.8) | | 0.952 |
| | 74.8 (40.1–109.5) | 0.004 | ||
| Hospitalisations for heart failure | ||||
| Per year | 1.7 (1.2–2.2) | 1.6 (1.1–2.0) | | 0.712 |
| | 6.6 (4.1–9.1) | 0.001 | ||
| Duration of hospital stay | 16.3 (11.3–21.3) | 16.3 (10.3–22.3) | | 0.952 |
| | 74.1 (39.4–108.7) | 0.004 | ||
SLED, sustained low-efficiency dialysis; CI, confidence interval.
In the standard-therapy group, no significant changes were observed in the year following the index date. The annual number of heart failure-related hospitalisations was 1.7 (95% CI: 1.2 to 2.2) before and 1.6 (95% CI: 1.1 to 2.0) after (p = 0.712), and the mean duration of hospital stay was unchanged, at 16.3 days (95% CI: 11.3 to 21.3) before and after (p = 0.952). For all-cause hospitalisations in the standard-therapy group, the annual admission rate was stable in the pre- and post-index year (1.8, 95% CI: 1.3 to 2.3 vs. 1.7, 95% CI: 1.2 to 2.1; p = 0.793) but increased significantly to 6.8 per year (95% CI: 4.3 to 9.4) during the observation period (p = 0.001). The mean duration of all-cause hospital stay was similar before and after the index date (17.0 days, 95% CI: 11.5 to 22.5 vs. 16.8 days, 95% CI: 10.7 to 22.8; p = 0.952) but increased markedly to 74.8 days (95% CI: 40.1 to 109.5, p = 0.004) over the full observation period.
Use of Non-Diuretic Pharmacological Heart Failure Therapies
Tables 4 and 5 outline the use of non-diuretic pharmacological therapies for heart failure in both groups at baseline (at the index date) and at the end of the observation period. In the SLED group, ACEi/ARBs use declined from 47% to 39% (p = 0.269), although the proportion of patients receiving titrated (target) doses of ACEi/ARB increased significantly from 12% to 25% (p = 0.014). MRA use increased significantly from 20% to 50% (p < 0.001), with target dosing rising from 7% to 25% (p < 0.001). β-blocker therapy increased from 58% to 76% (p = 0.006), accompanied with a significant increase in the proportion of patients reaching target doses from 9% to 26% (p = 0.001). Use of SGLT2 inhibitors and ARNI demonstrated modest but non-significant increases (7–12%, p = 0.251; and 3–7%, p = 0.195, respectively). In the standard-therapy group, no significant changes were observed in either drug use or titration over the observation period.
Table 4.
Implementation and titration of non-diuretic pharmacological heart failure therapies – patients treated with SLED
| | Before SLED (% of patients) | After SLED (% of patients) | p value |
|---|---|---|---|
| MRA | 20 | 50 | 0.000 |
| MRA, titrated dose | 7 | 25 | 0.000 |
| ACE inhibitor/ARB | 47 | 39 | 0.269 |
| ACE inhibitor/ARB, titrated dose | 12 | 25 | 0.014 |
| ARNI | 3 | 7 | 0.195 |
| ARNI, titrated dose | 2 | 2 | 1.000 |
| SGLT2 inhibitor | 7 | 12 | 0.251 |
| Beta blocker | 58 | 76 | 0.006 |
| Beta blocker, titrated dose | 9 | 26 | 0.001 |
SLED, sustained low-efficiency dialysis; MRA, mineralocorticoid receptor antagonist; ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor/neprilysin inhibitor; SGLT2, sodium-glucose co-transporter-2.
Table 5.
Implementation and titration of non-diuretic pharmacological heart failure therapies – patients who declined SLED (standard treatment only)
| | Before predicted SLED (% of patients) | After predicted SLED (% of patients) | p value |
|---|---|---|---|
| MRA | 56 | 65 | 0.503 |
| MRA, titrated dose | 13 | 29 | 0.105 |
| ACE inhibitor/ARB | 41 | 42 | 0.916 |
| ACE inhibitor/ARB, titrated dose | 19 | 19 | 0.951 |
| ARNI | 22 | 19 | 0.805 |
| ARNI, titrated dose | 9 | 10 | 0.967 |
| SGLT2 inhibitor | 28 | 39 | 0.373 |
| Beta blocker | 78 | 87 | 0.348 |
| Beta blocker, titrated dose | 28 | 32 | 0.721 |
SLED, sustained low-efficiency dialysis; MRA, mineralocorticoid receptor antagonist; ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor/neprilysin inhibitor; SGLT2, sodium-glucose co-transporter-2.
Use of Loop Diuretics
At the index date, all patients were receiving furosemide 1,000 mg daily to ensure comparability across both groups (Table 1). At the time of admission for the index hospitalisation, the mean furosemide dose was 573 mg (SLED group 604 mg; standard-therapy group 441 mg; p = 0.0896) and had to be escalated during the hospital stay to manage congestion. With the exception of SGLT2 inhibitors and MRA, no patients were treated with other types of diuretics (such as thiazide diuretics and acetazolamide), reflecting local clinical practice and national prescribing policy. During follow-up (median 11 months, IQR 4–26), all patients in the standard-therapy group continued on the same high-dose of furosemide without any dose modification. In contrast, in the SLED group, only 60% of patients remained on furosemide (p < 0.001) by the end of the observation period. Among these, the mean daily dose decreased from 1,000 mg at baseline to 365 ± 41 mg after a median of 10 months (IQR 6–37; p < 0.001). Overall, in the SLED group, 40% of patients discontinued furosemide completely, 35% underwent dose reduction, and 25% remained on the predefined maximal dose.
Long-Term Survival
The median survival time was 3 months in the standard-therapy group (95% CI: 1–7 months) and 23 months (95% CI: 17 to 29 months; log-rank p < 0.001) in the SLED group (Fig. 3).
Fig. 3.
Kaplan-Meier survival analysis.
Safety Outcomes
SLED was not associated with any serious adverse events. Clinically significant electrolyte disturbances were not observed as these were prevented through close monitoring. Symptomatic hypotension occurred in 5 patients during the initial sessions and was attributed to excessive ultrafiltration in the acute phase. These episodes were managed, and subsequently prevented, by a stepwise escalation of ultrafiltration from near-zero net removal at initiation to effective levels in the chronic phase with interdialytic noradrenaline given when needed. No vascular access related infections, thrombosis or major bleeding were reported.
Discussion
To the best of our knowledge, this is the first study to investigate the long-term effects of SLED in congested patients with advanced heart failure outside of intensive care settings. Several observations are relevant to clinical practice. First, in patients treated with SLED, we observed a reduction in heart failure-related hospitalisations and the length of hospital stay for all-cause hospitalisations. Second, SLED facilitated the enhanced use and titration of non-diuretic pharmacological therapies. Lastly, survival in patients treated with SLED was prolonged.
The available evidence supporting renal replacement therapy as a strategy for decongestion in heart failure is limited and inconsistent [14–16, 18, 21–26]. Ultrafiltration and SLED represent distinct renal replacement modalities that differ primarily in their physiological basis and treatment goals. Ultrafiltration focuses predominantly on fluid removal without altering the solute composition [21, 27], and is typically delivered as a relatively rapid, intermittent procedure. It can sometimes precipitate haemodynamic instability and worsening renal function, as observed in the CARESS-HF trial, where safety concerns were raised, including increased adverse events and lack of significant benefit in hospitalisation or mortality compared with diuretic therapy [23]. Other studies, including UNLOAD, CUORE, and AVOID-HF, demonstrated greater weight loss [21, 24] and reductions in heart failure-related hospitalisations [23–25], with no significant impact on mortality [23, 24]. None of these studies used a SLED protocol. In contrast, SLED combines features of intermittent and continuous dialysis, providing gradual ultrafiltration together with effective metabolic and electrolyte control, while generally maintaining greater haemodynamic stability [28]. Our findings align with and extend prior research on renal replacement therapies in advanced heart failure with persistent congestion. Cnossen et al. reported significant reductions in heart failure hospitalisations after initiation of dialysis (including both peritoneal dialysis [PD] and haemodialysis) together with improvements in quality of life [18]. Similarly, Premuzic et al. [14] observed longer survival with continuous veno-venous haemofiltration compared with ultrafiltration in critically ill patients with cardiorenal syndrome, complementing our observation of improved survival with SLED. Recently, Haas et al. [26] highlighted the importance of individualised “low and slow” ultrafiltration rates with multidisciplinary oversight to achieve effective decongestion while preserving haemodynamic stability – principles that are intrinsic to SLED protocols. Collectively, these studies underscore the need for personalised fluid management strategies, with SLED offering a potentially safer and more comprehensive approach to renal replacement therapy in advanced heart failure. Although the available evidence remains limited, the consistency of findings across studies suggests reductions in heart failure-related hospitalisations and a possible trend towards improved survival in patients with advanced heart failure managed with dialysis. Evidence specific to SLED in congestive heart failure is sparse; however, successful use of SLED has been documented in diuretic-resistant patients with NYHA class IV chronic heart failure [29, 30]. Notably, our cohort was substantially larger, older, and followed for a longer duration that those previously reported.
PD shares several features with SLED, and both represent viable renal replacement options for managing refractory congestion in advanced heart failure, each with distinct advantages. PD provides continuous, gentle fluid and solute removal, thereby promoting haemodynamic stability and preserving residual renal function [18]. In a meta-analysis of 20 observational studies including 769 patients with refractory congestive heart failure, PD improved symptoms, led to a reduction of hospitalisation days by approximately 35 days per patient annually, and maintained stable renal function. Although mortality remained high at around 37.2%, this was slightly lower than in previously reported cohorts [15]. Both SLED and PD can be initiated in intensive care and continued in the chronic setting, with meaningful clinical benefits. The choice between modalities is often dictated by patient suitability. SLED may be more appropriate for patients with significant functional impairment or limited capacity for self-care, particularly in a healthcare system without a nurse-supported PD, where patients rely only on themselves or their caregivers. In addition, regular clinical supervision during SLED permits medication titration, parenteral nutritional support, and, when indicated, supervised exercise. By contrast, PD offers greater autonomy and flexibility. Collectively, PD and SLED represent complementary strategies for decongestion and electrolyte control in advanced heart failure, with the choice of modality best guided by individual patient characteristics and clinical context.
Optimising guideline-directed medical therapy (GDMT) in patients with heart failure undergoing dialysis remains challenging. Current KDIGO guidelines advise cautious use of heart failure medications during dialysis because of haemodynamic risks [31]. In our study, initiation and titration of these therapies [3], namely, ACEi/ARBs, MRAs, and β-blockers, in the SLED group improved significantly, and no meaningful changes were observed in the standard-therapy group. This difference likely reflects the haemodynamic stability and electrolyte control achieved and maintained by SLED, which enables safer medication up-titration. Although evidence on GDMT use in dialysis patients is limited, our findings suggest that SLED, when combined with close monitoring, may facilitate broader implementation of these cornerstone therapies, potentially improving clinical outcomes.
Although our study reported significantly longer median survival in the SLED group compared with standard therapy (23 vs. 3 months, p < 0.001), these findings must be interpreted considering baseline characteristics. Most comorbidities and other clinical variables were comparable between groups, except for frailty, a well-established predictor of poor outcomes in heart failure [32], that was greater in the standard-therapy group, which may have contributed to their shorter survival. Accordingly, differences in frailty may partially account for the survival benefit attributed to SLED. Importantly, however, frailty scores improved significantly during the observation period in the SLED group, suggesting that SLED may help stabilise patients sufficiently to reduce vulnerability and enable clinical recovery.
In our study, no major adverse events attributable to SLED were observed, supporting its safety. A non-significant rise in serum creatinine was noted in the SLED group, but this was clinically negligible due to effective renal clearance. By contrast, lower creatinine concentrations in the standard-therapy group likely reflected persistent hypervolaemia due to limited decongestion. With active fluid management, SLED patients achieved dry weight independent of intrinsic renal function. These findings suggest that with careful patient selection and individualised protocols, SLED can be a safe renal replacement strategy ensuring effective decongestion and metabolic control.
It is important to emphasise that our study population was highly selected and represented an exceptionally high-risk group. All patients had advanced heart failure with persistent hypervolaemia that rendered them ineligible for advanced heart failure therapies. They were profoundly debilitated, frequently bedbound, and were initially considered only suitable for palliative care.
This study has several limitations. First, it was a retrospective, non-randomised, single-centre analysis with a limited sample size. Second, we did not directly compare SLED with other decongestive therapies, such as PD or ultrafiltration alone, which could provide additional insights into relative efficacy. Third, no standardised protocols for guiding haemodialysis/SLED have been established, and treatment decisions were based on clinical assessment and judgement. In addition, baseline frailty was greater in the standard-therapy group and likely contributed to poorer survival independently of treatment. Moreover, the inclusion of patients who voluntarily declined SLED may have introduced an uncontrolled selection bias. A further limitation is that no patients received combination diuretic therapy with a thiazide or acetazolamide at baseline, reflecting local prescribing practices during the study period when acetazolamide was not widely available and thiazides were not used as monotherapy. Moreover, evidence for acetazolamide in chronically congested heart failure remains limited, and thiazides are not recommended in the presence of renal impairment [3, 9, 33].
Prospective, randomised, multicentre studies are needed to address these limitations, account for confounding factors such as frailty, and more definitively establish causality. Future research should also incorporate additional clinical endpoints, such as quality of life and patient-reported outcomes.
Conclusion
This study is the first to evaluate the long-term use of SLED in patients with advanced heart failure and refractory congestion outside intensive care. In this selected population, SLED was associated with reductions in heart failure-related hospitalisations and all-cause length of stay, facilitated initiation and titration of guideline-directed medical therapies, and was linked to prolonged survival compared with standard therapy. SLED was well tolerated with no major adverse events observed, supporting its safety in high-risk patients. Although baseline differences in frailty may have influenced survival outcomes, the haemodynamic stability and metabolic control achieved with SLED likely contributed to its clinical benefits. Although retrospective in nature and derived from a small, highly selected population treated at a single centre, thus limiting generalisability to broader heart failure populations, these findings suggest that SLED could represent a safe and effective renal replacement option for patients with advanced heart failure and persistent congestion. Prospective, randomised studies are needed to confirm these findings, refine treatment protocols, and further examine the effects on quality of life and patient-centred outcomes.
Clinical Perspectives
Our study underscores key clinical considerations in the management of advanced heart failure with persistent congestion, emphasising the role of SLED as a potential therapeutic option for a selected group of patients with diuretic-resistant congestion who are not candidates for advanced therapies. SLED offers a practical, less invasive alternative to palliative care, addressing an important unmet clinical need. Its use was associated with reductions in heart failure-related hospitalisations and duration of hospital stay, outcomes that may enhance patient care while also reducing healthcare costs. In patients treated with SLED, prolonged survival was observed, suggesting a potential survival benefit in high-risk populations. Improved haemodynamic stability and electrolyte balance, achieved with SLED, can facilitate the initiation and optimisation of evidence-based pharmacological heart failure therapies, even in patients with severe decompensations. Finally, the potential role of SLED in the outpatient settings, and its use as an earlier intervention before the development of diuretic resistance, warrants further investigation.
Acknowledgements
The authors thank the Department of Haemodialysis and the Vascular Access and Vascular Disease Unit for their cooperation, desire to learn, and strive for progress.
Statement of Ethics
The study protocol was reviewed and approved by the National Medical Ethics Committee of the Republic of Slovenia, Ministry of Health, Republic of Slovenia (Approval No. KME-0120-358/2023/3). The study was conducted in accordance with the Declaration of Helsinki. The requirement for informed consent was waived by the National Medical Ethics Committee of Republic of Slovenia, Ministry of Health, the Republic of Slovenia.
Conflict of Interest Statement
The authors declare no potential conflicts of interest concerning this article’s research, authorship, and publication.
Funding Sources
M.L. is supported by the Slovenian Research and Innovation Agency (Grant No. P3-0456 and J3-3076).
Author Contributions
B.L. – study design, writing, revision, and supervision. T.F. – data analysis, writing, and revision. G.M. – writing and revision. M.L. – final revision and supervision.
Funding Statement
M.L. is supported by the Slovenian Research and Innovation Agency (Grant No. P3-0456 and J3-3076).
Data Availability Statement
The data that support the findings of this study are not publicly available due to privacy reasons but are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are not publicly available due to privacy reasons but are available from the corresponding author upon reasonable request.
