Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple approaches have been tried to achieve adequate decongestion rapidly while minimizing adverse effects, no single diuretic strategy has shown superiority, and there is a paucity of data and guidelines to utilize in making these decisions. Observational cohort studies have shown associations between urine sodium excretion and outcomes after hospitalization for ADHF. Urine chemistries (urine sodium ± urine creatinine) may guide diuretic titration during ADHF, and multiple randomized clinical trials have been designed to compare a strategy of urine chemistry-guided diuresis to usual care. This review will summarize current literature for diuretic monitoring and titration strategies, outline evidence gaps, and describe the recently completed and ongoing clinical trials to address these gaps in patients with ADHF with a particular focus on the utility of urine sodium-guided strategies.

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BACKGROUND: Comprehensive uptitration of neurohormonal blockade targets fundamental mechanisms underlying development of congestion and may be an additional approach for decongestion after acute heart failure (AHF).
OBJECTIVE: This hypothesis was tested in the STRONG-HF (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by N-Terminal Pro-Brain Natriuretic Peptide Testing of Heart Failure Therapies) trial.
METHODS: In STRONG-HF, patients with AHF were randomized to the high-intensity care (HIC) arm with fast up-titration of neurohormonal blockade or to usual care (UC). Successful decongestion was defined as an absence of peripheral edema, pulmonary rales, and jugular venous pressure <6 cm.
RESULTS: At baseline, the same proportion of patients in both arms had successful decongestion (HIC 48% vs UC 46%; P = 0.52). At day 90, higher proportion of patients in the HIC arm (75%) experienced successful decongestion vs the UC arm (68%) (P = 0.0001). Each separate component of the congestion score was significantly better in the HIC arm (all, P < 0.05). Additional markers of decongestion also favored the HIC: weight reduction (adjusted mean difference: -1.36 kg; 95% CI: -1.92 to -0.79 kg), N-terminal pro-B-type natriuretic peptide level, and lower orthopnea severity (all, P < 0.001). More effective decongestion was achieved despite a lower mean daily dose of loop diuretics at day 90 in the HIC arm. Among patients with successful decongestion at baseline, those in the HIC arm had a significantly better chance of sustaining decongestion at day 90. Successful decongestion in all subjects was associated with a lower risk of 180-day HF readmission or all-cause death (HR: 0.40; 95% CI: 0.27-0.59; P < 0.0001).
CONCLUSIONS: In STRONG-HF, intensive uptitration of neurohormonal blockade was associated with more efficient and sustained decongestion at day 90 and a lower risk of the primary endpoint.

Loop diuretics are the cornerstone of decongestive therapy in patients presenting with acute heart failure and have been extensively studied in randomized clinical trials. Therefore, in current guidelines, they are the only drug with a class I recommendation to treat signs and symptoms of congestion when present. However, the percentage of patients achieving successful decongestion is suboptimal, and diuretic resistance frequently develops. Patients with a poor response to loop diuretics and those discharged with residual signs of congestion are characterized by a worse prognosis over time. Recently, a renovated interest in different diuretic classes sprouted among heart failure researchers in order to improve decongestion strategies and ameliorate short- and long-term clinical outcomes. Randomized clinical trials investigating associations among diuretic classes and loop diuretics have been performed but yielded variable results. Therefore, despite initial evidence of a possible benefit from some of these compounds, a definite way to approach diuretic resistance via diuretic combination therapy is still missing. The aim of this review is to summarize current clinical evidence on the use of diuretic combination therapy in patients with acute heart failure and to suggest a possible approach to avoid or counteract diuretic resistance.

Acute heart failure (AHF) often leads to unfavorable outcomes due to fluid overload. While diuretics are the cornerstone treatment, acetazolamide may enhance diuretic efficiency by reducing sodium reabsorption. We performed a systematic review and meta-analysis on the effects of acetazolamide as an add-on therapy in patients with AHF compared to diuretic therapy. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCT). A random-effects model was employed to compute mean differences and risk ratios. Statistical analysis was performed using R software. The GRADE approach was used to rate the certainty of the evidence. We included 4 RCTs with 634 patients aged 68 to 81 years. Over a mean follow-up of 3 days to 34 months, acetazolamide significantly increased diuresis (MD 899.2 mL; 95% CI 249.5 to 1549; p < 0.01) and natriuresis (MD 72.44 mmol/L; 95% CI 39.4 to 105.4; p < 0.01) after 48 h of its administration. No association was found between acetazolamide use and WRF (RR 2.4; 95% CI 0.4 to 14.2; p = 0.3) or all-cause mortality (RR 1.2; 95% CI 0.8 to 1.9; p = 0.3). Clinical decongestion was significantly higher in the intervention group (RR 1.35; 95% CI 1.09 to 1.68; p = 0.01). Acetazolamide is an effective add-on therapy in patients with AHF, increasing diuresis, natriuresis, and clinical decongestion, but it was not associated with differences in mortality.

Acute kidney injury is common in patients with acute decompensated heart failure. It is more common in patients with acute heart failure who suffer from chronic kidney disease. Worsening renal function is often defined as a rise in serum creatinine of more than 0.3 milligrams per deciliter (26.5 µmol/L), which by definition, is acute kidney injury stage one. Perhaps the term acute kidney injury is more appropriate than worsening renal function as it is used universally by nephrologists, internists, and other medical practitioners. In health, the heart and the kidney support each other to maintain body\'s homeostasis. In disease, the heart and the kidney can adversely affect each other\'s function causing further clinical deterioration. In patients presenting with acute heart failure and fluid overload, therapy with diuretics for decongestion often causes a rise in serum creatinine and acute kidney injury. However, in the longer term the decongestion improves survival and prevents hospital admissions despite rising serum creatinine and acute kidney injury. It is important to realize that renal venous congestion due to increased right sided heart pressures in acute heart failure is a major cause of kidney dysfunction and hence decongestion therapy improves kidney function in the longer term. This review provides a perspective on the acceptable acute kidney injury with decongestion therapy which is associated with improved survival; as opposed to acute kidney injury due to tubular injury related to sepsis or nephrotoxic drugs, which is associated with poor survival.

The Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure (PUSH-AHF) study, published in August of 2023, was the first randomized clinical trial to compare natriuresis-guided decongestion (based on spot urinary sodium measurement) to standard of care in patients with acute heart failure with congestion receiving loop diuretic therapy. Based on results from their trial, the authors concluded that natriuresis-guided loop diuretic treatment was safe and improved natriuresis and diuresis without impacting long-term clinical outcomes. The original PUSH-AHF trial included limited information about renal outcomes and left clinicians with important questions about how natriuresis-guided decongestion might affect their patients\' renal function. On May 12, 2024, however, at the 2024 Annual Congress of the HFA-ESC, Dr. Kevin Damman provided an in-depth exploration of renal outcomes from the trial when he presented a pre-specified, secondary analysis, renal function in the PUSH-AHF trial. This review puts the sub-study findings into context by considering the history of the original trial from which they came from and explaining the need for a close study of its renal outcomes particularly. It highlights the potential impact of renal function in PUSH-AHF on clinical practice and future directions that should be considered by the cardiology research community.

Incomplete decongestion is the main cause of readmission in the early post-discharge period of a hospitalization for acute heart failure. Recent heart failure guidelines have highlighted initiation and rapid up-titration of quadruple therapy with angiotensin receptor neprilysin inhibitor, beta adrenergic receptor blocker, mineralocorticoid receptor antagonist, and sodium glucose cotransporter 2 inhibitor to prevent hospitalizations for heart failure with reduced ejection fraction. However, full decongestion remains the foremost therapeutic goal of hospitalization for heart failure. While early addition of sodium glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists may be helpful, the value of the other therapeutics comes after decongestion is complete.

OBJECTIVE: Renal and liver congestion are associated with adverse outcomes in patients with tricuspid regurgitation (TR). Currently, there are no valid sonographic indicators of fluid status in this population. Intra-renal venous Doppler (IRVD) is a novel method for quantifying renal congestion but its interpretation can be challenging in severe TR due to altered haemodynamics. This study explores the potential of portal vein Doppler (PVD) as an alternative marker for decongestion during volume removal in patients with severe TR.
RESULTS: Forty-two patients with severe TR undergoing decongestive therapy were prospectively enrolled. Inferior vena cava diameter, PVD, and IRVD were sequentially assessed during volume removal. Improvement criteria were portal vein pulsatility fraction (PVPF) < 70% and renal venous stasis index (RVSI) < 0.5 for partial improvement, and PVPF < 30% and RVSI < 0.2 for complete improvement. After volume removal, PVPF significantly improved from 130 ± 39% to 47 ± 44% (P < 0.001), while IRVD improved from 0.72 ± 0.08 to 0.54 ± 0.22 (P < 0.001). A higher proportion of patients displayed improvement in PVD compared to IRVD (partial: 38% vs. 29%, complete: 41% vs. 7%) (P < 0.001). Intra-renal venous Doppler only improved in patients with concomitant improvement in severe TR. Portal vein Doppler was the only predictor of achieving ≥5 L of negative fluid balance [area under the ROC curve (AUC) 0.83 P = 0.001].
CONCLUSIONS: This proof-of-concept study suggests that PVD is the only sonographic marker that can track volume removal in severe TR, offering a potential indicator for decongestion in this population. Further intervention trials are warranted to determine if PVD-guided decongestion improves patient outcomes in severe TR.