In heart failure (HF), congestion is a key pathophysiologic hallmark and a major contributor to morbidity and mortality. However, the presence of congestion is often overlooked in both acute and chronic settings, particularly when it is not clinically evident, which can have important clinical consequences. Ultrasound (US) is a widely available, non-invasive, sensitive tool that might enable clinicians to detect and quantify the presence of (subclinical) congestion in different organs and tissues and guide therapeutic strategies. In particular, left ventricular filling pressures and pulmonary pressures can be estimated using transthoracic echocardiography; extravascular lung water accumulation can be evaluated by lung US; finally, systemic venous congestion can be assessed at the level of the inferior vena cava or internal jugular vein. The Doppler evaluation of renal, hepatic and portal venous flow can provide additional valuable information. This review aims to describe US techniques allowing multi-organ evaluation of congestion, underlining their role in detecting, monitoring, and treating volume overload more objectively.

UNASSIGNED: Continuous ultrafiltration consists a decongestion method for patients with refractory decompensated heart failure with diuretic resistance as it enables the energetic withdrawal of isotonic fluid under controlled rate according to the patient\'s vital signs, offering decongestion without exceeding plasma refill rate.
UNASSIGNED: A 62-year-old male with history of Holt-Oram syndrome with Eisenmenger physiology presented with worsening dyspnoea. Patient initial clinical and laboratory examination, renal vein ultrasound, and echocardiogram were consistent with significant congestion. A combined strategy of intravenous furosemide with early initiation of continuous ultrafiltration at an adjustable rate for 4 days was finally selected. Patient remained haemodynamically stable during the total treatment time and exhibited significant clinical and laboratory improvement. Consecutive renal vein ultrasounds and echocardiograms demonstrated a continuous and steady recession of congestion. During the 4 days of ultrafiltration, total fluid loss was estimated at 42 L. Patient remained asymptomatic without signs of worsened congestion at 1, 3, and 5 months follow-up.
UNASSIGNED: Our case depicts that continuous ultrafiltration without exceeding plasma refill rate allows an impaired right ventricle to maintain significant preload. This suggests that it might be considered for patients in whom a session of short classic ultrafiltration might have detrimental results regarding cardiac output.

Congestion is a common cause of clinical deterioration and the most common clinical presentation at admission in acute heart failure (HF). Therefore, finding effective and sustainable ways to alleviate congestion has become a crucial goal for treating HF patients. Congestion is a result of complex underlying pathophysiology; therefore, it is not a direct cause of the disease but its consequence. Any therapy that directly promotes sodium/water removal only, thus targeting only clinical symptoms, neither modifies the natural course of the disease nor improves prognosis. This review aims to provide a comprehensive evaluation of the current decongestive therapies and propose a new (not diuretic-centred) paradigm of long-term congestion management in HF that attempts to correct the underlying pathophysiology, thus improving congestion, preventing its development, and favourably altering the natural course of the disease rather than merely treating its symptoms.

OBJECTIVE: Congestion is a major determinant of outcomes in acute heart failure. Its assessment is complex, making sufficient decongestive therapy a challenge. Residual congestion is frequent at discharge, increasing the risk of re-hospitalization and death. Mid-regional pro-adrenomedullin mirrors vascular integrity and may therefore be an objective marker to quantify congestion and to guide decongestive therapies in patients with acute heart failure.
RESULTS: Observational, prospective, single-centre study in unselected patients presenting with acute heart failure. This study aimed to assess adrenomedullin\'s association with congestion and clinical outcomes: in-hospital death, post-discharge mortality and in-hospital worsening heart failure according to RELAX-AHF-2 trial criteria. Pro-adrenomedullin was quantified at baseline and at discharge. Congestion was assessed applying clinical scores. Cox and logistic regression models with adjustment for clinical features were fitted. N = 233, median age 77 years (IQR 67, 83), 148 male (63.5%). Median pro-adrenomedullin 2.0 nmol/L (IQR 1.4, 2.9). Eight patients (3.5%) died in hospital and 100 (44.1%) experienced in-hospital worsening heart failure. After discharge, 60 patients (36.6%) died over a median follow-up of 1.92 years (95% CI: 1.76, 2.46). Pro-adrenomedullin concentrations (logarithmized) were significantly associated with congestion, both at enrolment (β = 0.36 and 0.81 depending on score, each P < 0.05) and at discharge (β = 1.12, P < 0.001). Enrolment of pro-adrenomedullin was associated with in-hospital worsening heart failure [OR 4.23 (95% CI: 1.87, 9.58), P < 0.001], and pro-adrenomedullin at discharge was associated with post-discharge death [HR 3.93 (1.86, 8.67), P < 0.001].
CONCLUSIONS: Elevated pro-adrenomedullin is associated with in-hospital worsening heart failure and with death during follow-up in patients with acute heart failure. Further research is needed to validate this finding and to explore the ability of pro-adrenomedullin to guide decongestive treatment.

OBJECTIVE: Incomplete decongestion due to lack of titration of diuretics to effective doses is a common reason for readmission in patients with acute decompensated heart failure (ADHF). The natriuretic response prediction equation (NRPE) is a novel tool that proved to be rapid and accurate to predict natriuretic response and does not need urine collection. However, the NRPE has not been externally validated. The goal of this study was to externally validate the discrimination capacity of the NRPE in patients with ADHF and fluid overload.
RESULTS: Patients admitted with ADHF who required intravenous loop diuretics were included. A spot urine sample was obtained ~2 h following diuretic administration, and a timed 6-h urine collection by study staff was carried out. Urine sodium and urine creatinine from the spot urine sample were used to predict the 6-h natriuretic response using the NRPE. The primary goal was to validate the NRPE to discriminate poor loop diuretic natriuretic response (sodium output <50 mmol in the 6 h following diuretic administration). The NRPE was compared with urine sodium and measured urine output which are the methods currently recommended by international guidelines to assess diuretic response. Eighty-seven diuretic administrations from 49 patients were analysed. Mean age of patients was 57 ± 17 years and 67% were male. Mean estimated glomerular filtration rate was 65 ± 28 mL/min/1.73 m2, and ejection fraction was 35 ± 15%. Median dose of intravenous furosemide equivalents administered the day of the study was 80 mg (IQR 40 - 160). Poor natriuretic response occurred in 39% of the visits. The AUC of the NRPE to predict poor natriuretic response during the 6-h urine collection was 0.91 (95% CI 0.85-0.98). Compared with the NRPE, spot urine sodium concentration (AUC 0.75) and urine output during the corresponding nursing shift (AUC 0.74) showed lower discrimination capacity.
CONCLUSIONS: In this cohort of patients with ADHF, the NRPE outperformed spot urine sodium concentration and all other metrics related to diuretic response to predict poor natriuretic response. Our findings support the use of this equation at other settings to allow rapid and accurate prediction of natriuretic response.

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The lymphatic system plays a crucial, yet often overlooked, role in maintaining fluid homeostasis, and its dysregulation is a key feature of heart failure (HF). Lymphatic dysregulation in patients with HF typically results from a combination of self-perpetuating congestive mechanisms, such as increased fluid filtration, decreased lymph drainage into the central venous system, impaired lymph vessel integrity, dysfunctional lymphatic valves, and dysfunctional renal lymphatic system. These pathomechanisms collectively overwhelm the lymphatic system and hinder its ability to decongest the interstitial space with subsequent manifestation and progression of clinical congestion. Targeting the lymphatic system to counteract these congestive pathomechanisms and facilitate interstitial fluid removal represents a novel pathway to treat congestion in HF. In this study, we discuss the physiological roles of the lymphatic system in fluid homeostasis and the pathophysiological alteration of these roles in HF. We also discuss innovative technologies that aim to use the lymphatic system pathway to treat congestion in HF and provide future directions related to these approaches.

Congestion is the most common manifestation of acute decompensated heart failure (ADHF). Residual congestion despite initial medical therapy is common and is recognized to be associated with worse outcomes; however, there are currently no standardized definition regarding decongestion end point. In the second part of this 2-part review, we provide a critical appraisal of decongestion definitions previously used in ADHF studies, review alternative metrics to define severity of volume overload, and propose a more granular 4-class congestion grading scheme and decongestion end point definitions that could potentially be included in future ADHF trials and consensus definitions.

Despite recent advances in the treatment of patients with chronic heart failure, acute decompensated heart failure remains associated with significant mortality and morbidity because many novel therapies have failed to demonstrate meaningful benefit. Persistent congestion in the setting of escalating diuretic therapy has been repeatedly shown to be a marker of poor prognosis and is currently being targeted by various emerging device-based therapies. Because these therapies inherently carry procedural risk, patient selection is key in the future trial design. However, it remains unclear which patients are at a higher risk of residual congestion or adverse outcomes despite maximally tolerated decongestive therapy. In the first part of this 2-part review, we aimed to outline patient risk factors and summarize current evidence for early recognition of high-risk profile for residual congestion and adverse outcomes. These factors are classified as relating to the following: (1) previous clinical course, (2) severity of congestion, (3) diuretic response, and (4) degree of renal impairment. We also aimed to provide an overview of key inclusion criteria in recent acute decompensated heart failure trials and investigational device studies and propose potential criteria for selection of high-risk patients in future trials.

OBJECTIVE: Congestion is prognostically relevant in cardiac transthyretin amyloidosis (ATTR-CA), but whether congestion has an incremental prognostic value beyond the well-established, congestion-sensitive NT-proBNP is unknown. Therefore, we aimed to comparatively evaluate the prognostic utility of several congestion surrogates over NT-proBNP.
METHODS: We estimated hazard ratios by Cox proportional hazards regressions with time-varying covariates from a panel data set of the local amyloidosis cohort study AmyKoS. Different models were compared by using chi(χ)2-statistics measuring overall model significance.
CONCLUSIONS: 131 ATTR-CA patients (wild-type 84.0%, hereditary 6.9%, without genetic testing 9.2%; median age 78.7 (quartiles 73.3, 82.1) years; 85.5% male) with 566 observations across a median follow-up of 38.2 (30.6; 48.2) months were analyzed. 83.2% received disease-modifying treatment; 20.6% participated concurrently in placebo-controlled gene silencer trials. Information on congestion improved biomarker-driven risk stratification and identified patients at the highest risk. Echocardiographic congestion markers performed better than clinical findings and daily diuretic use/dosage. Relevant adjusters were daily diuretic dosage, disease-modifying treatment, eGFR, and right atrial volume. NT-proBNP and the tricuspid regurgitation peak velocity (tr-vmax) provided an easy-to-use stratification with overall model performance similar to NAC and Mayo staging systems. Further analyses are necessary for validation and to identify the optimal cut points of the congestion markers.