The role of ultrafiltration in the management of heart failure

Opinion statement In the United States, 90% of one million annual hospitalizations for heart failure are due to symptoms of volume overload. Hypervolemia contributes to heart failure progression and mortality. Treatment guidelines recommend that therapy for patients with heart failure be aimed at achieving euvolemia. Intravenous loop diuretics induce a rapid diuresis that reduces lung congestion and dyspnea. However, loop diuretics’ effectiveness declines with repeated exposure. Unresolved congestion may contribute to high re-hospitalization rates. Furthermore, loop diuretics may be associated with increased morbidity and mortality due to deleterious effects on neurohormonal activation, electrolyte balance, and cardiac and renal function. Ultrafiltration is an alternative method of sodium and water removal, which safely improves hemodynamics in patients with heart failure. Application of this technology has been limited by the need for high flow rates, large extracorporeal blood volumes, and large-bore central venous catheters. A modified ultrafiltration device has overcome these limitations. Ultrafiltration may be a safe and effective alternative to intravenous diuretics in the treatment of decompensated heart failure.     

超滤在心力衰竭治疗中的价值和展望

容量负荷过重是心力衰竭患者反复住院的主要原因，钠潴留是核心的病理生理环节。血液超滤是治疗液体潴留的“金标准”。现有证据表明超滤能改善心力衰竭转归，降低再住院率。现综述超滤治疗心力衰竭的机制、有效性、安全性、适应证以及未来的研究方向。     

心力衰竭的血液超滤治疗

心脏的体外血液超滤治疗是终末期心力衰竭体液潴留、利尿剂抵抗的有效治疗模式,为心力衰竭指南Ⅱa类适应证。现就心力衰竭体外血液超滤治疗的发展、安全性、适应证、具体操作过程以及成本/疗效比等进行综述。     

Large volume ultrafiltration for acute decompensated heart failure using standard peripheral intravenous catheters

BackgroundUltrafiltration for decompensated heart failure has recently generated significant clinical interest with the development of a portable machine that does not require an intensive care or dialysis unit. This case series was designed to demonstrate the feasibility and effectiveness of performing large volume ultrafiltration via peripherally inserted standard intravenous (IV) catheters in patients with acute decompensated heart failure.Methods and ResultsNine hospitalized patients with decompensated heart failure underwent peripheral ultrafiltration (PUF) therapy with peripheral IV catheters. The mean length of time of PUF therapy was 33.3 ± 20.0 hours with a mean volume removed of 7.0 ± 4.9 L. All patients experienced a statistically significant mean weight loss of 6.2 ± 5.0 kg, P = .01. There was no statistically significant change in renal function.ConclusionWe report the first successful implementation of ultrafiltration via standard peripheral IV catheters to remove a large volume of fluid over an extended period of time reliably in a small group of patients. The ability to use PUF therapy via peripheral IV catheters will potentially allow this therapy to be implemented more easily in a variety of care settings to treat patients with resistant heart failure.     

Ultrafiltration versus usual care for hospitalized patients with heart failure: the Relief for Acutely Fluid-Overloaded Patients With Decompensated Congestive Heart Failure (RAPID-CHF) trial.

OBJECTIVES: The purpose of this research was to assess the safety and efficacy of ultrafiltration (UF) in patients admitted with decompensated congestive heart failure (CHF). BACKGROUND: Ultrafiltration for CHF is usually reserved for patients with renal failure or those unresponsive to pharmacologic management. We performed a randomized trial of UF versus usual medical care using a simple UF device that does not require special monitoring or central intravenous access. METHODS: Patients admitted for CHF with evidence of volume overload were randomized to a single, 8 h UF session in addition to usual care or usual care alone. The primary end point was weight loss 24 h after the time of enrollment. RESULTS: Forty patients were enrolled (20 UF, 20 usual care). Ultrafiltration was successful in 18 of the 20 patients in the UF group. Fluid removal after 24 h was 4,650 ml and 2,838 ml in the UF and usual care groups, respectively (p = 0.001). Weight loss after 24 h, the primary end point, was 2.5 kg and 1.86 kg in the UF and usual care groups, respectively (p = 0.240). Patients tolerated UF well. CONCLUSIONS: The early application of UF for patients with CHF was feasible, well-tolerated, and resulted in significant weight loss and fluid removal. A larger trial is underway to determine the relative efficacy of UF versus standard care in acute decompensated heart failure.     

Rubbing Salt into Wounds: Hypertonic Saline to Assist with Volume Removal in Heart Failure

Traditionally accepted management strategies for patients with heart failure include sodium and fluid restriction, neurohormonal blockade, and the use of loop diuretics to achieve and maintain euvolemia. Despite continued advances in medical and device therapy, fluid management remains a significant problem in patients with the cardiorenal syndrome (manifested as diuretic resistance and worsening renal function with more aggressive attempts at volume removal). This article examines the counterintuitive use of hypertonic saline as a potential therapy to facilitate diuresis in patients with decompensated heart failure and diuretic resistance. Low-volume hypertonic saline administration offsets counterproductive neurohormonal upregulation, transiently improves hemodynamics, and promotes renal sodium excretion with accompanied net water loss and preservation of renal function. This “new” therapeutic tool should be explored further as an adjunct to current medical therapies in the management of patients with refractory volume overload.     

Treatment of congestion in heart failure with diuretics and extracorporeal therapies: effects on symptoms, renal function, and prognosis

In the United States and Europe, approximately 90% of heart failure hospitalizations are due to symptoms and signs of sodium and fluid excess. Congestion is associated with heart failure progression. Venous congestion, rather than a reduced cardiac output, may be the primary hemodynamic factor driving worsening renal function in patients with acutely decompensated heart failure. According to data from large national registries, approximately 40% of hospitalized heart failure patients are discharged with unresolved congestion, which may contribute to unacceptably high re-hospitalization rates. Diuretics reduce the symptoms and signs of fluid overload, but their effectiveness can be reduced by excess salt intake, underlying chronic kidney disease, renal adaptation to their action, and neurohormonal activation. In addition, the production of hypotonic urine limits the ability of loop diuretics to reduce total body sodium. Ultrafiltration is the mechanical removal of fluid from the vasculature. Hydrostatic pressure is applied to blood across a semipermeable membrane to separate isotonic plasma water from blood. Because solutes in blood freely cross the semipermeable membrane, fluid can be removed without causing significant changes in the serum concentration of electrolytes and other solutes. Relatively small, mostly single-center clinical studies of ultrafiltration have shown that removal of isotonic fluid may relieve symptoms of congestion and restore diuretic responsiveness in patients with diuretic resistance. These studies have also shown a favorable effect on neurohormonal activation. When compared with intravenous diuretics, ultrafiltration similarly changed dyspnea scores but reduced re-hospitalizations (28 of 87 patients (32%) versus 16 of 89 patients (18%), P < 0.037) in a randomized controlled trial of patients with decompensated heart failure. Future larger controlled clinical trials should evaluate further the effect of ultrafiltration on patients’ outcomes, including survival.     

Redefining the therapeutic objective in decompensated heart failure: hemoconcentration as a surrogate for plasma refill rate

BackgroundAcute decompensated heart failure is a growing epidemiologic problem about which little consensus exists on guidelines and recommendations for therapy.Methods and ResultsAvailable databases suggest that a large percentage of patients are being inadequately decongested while hospitalized, resulting in poor clinical outcomes. This is partly from a lack of an appropriate target to define therapeutic success. The demonstration of a prerenal state by blood work does not indicate adequate decongestion but rather means that the rate of fluid removal has exceeded the plasma refill rate. Hemoconcentration, as evidenced by a rising hematocrit is an appropriate surrogate to indicate that the plasma refill rate has been exceeded by the rate of fluid removal. This surrogate of plasma refill rate can be easily and continuously measured by using an in-line hematocrit sensor during ultrafiltration therapy.ConclusionWe propose that the therapeutic objective in acute decompensated heart failure should be redefined and that the rate of volume extraction should be adjusted to approximate the plasma refill rate and that complete decongestion will have occurred only once hemoconcentration is observed at minimal rates of volume extraction.     

Therapeutic Dilemmas in Mixed Septic-Cardiogenic Shock

Sepsis is an increasing cause of decompensation in patients with chronic heart failure with reduced or preserved ejection fraction. Sepsis and decompensated heart failure results in a mixed septic-cardiogenic shock that poses several therapeutic dilemmas: Rapid fluid resuscitation is the cornerstone of sepsis management, while loop diuretics are the main stay of decompensated heart failure treatment. Whether inotropic therapy with dobutamine or inodilators improves microvascular alterations remains unsettled in sepsis. When to resume loop diuretic therapy in patients with sepsis and decompensated heart failure is unclear. In the absence of relevant guidelines, we review vasopressor therapy, the timing and volume of fluid resuscitation, and the need for inotropic therapy in patients who, with sepsis and decompensated heart failure, present with a mixed septic-cardiogenic shock.     

Ultrafiltration in decompensated heart failure

Fluid congestion is the hallmark of decompensated heart failure. As heart failure progresses, reduced response to diuretics is common. In these patients, ultrafiltration has been found to alleviate excess volume and improve diuretic sensitivity. Compared with diuretics, ultrafiltration provides a more predictable and safer way to achieve euvolemia with minimal electrolyte abnormalities and neurohormonal activation. The emerging familiarity and ease of use of ultrafiltration suggests that in the future this will be an important therapy for the treatment of acute and chronic volume overload associated with decompensated heart failure.     

Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure: Nesiritide Redux

Nesiritide, a synthetic drug form of human B-type natriuretic peptide, is approved for the early treatment of dyspnea in acute decompensated heart failure. Meta-analyses suggested a risk of worsening renal insufficiency and mortality with its use. Therefore, the Acute Study of Clinical Effectiveness in Decompensated Heart Failure (ASCEND-HF) was designed as a prospective, multicenter, double-blind, randomized trial to examine the use of nesiritide in this common, morbid, and often lethal clinical condition. Two coprimary end points, dyspnea and 30-day hospital readmission or death, were chosen to examine symptomatic response and objective outcomes, respectively. Preliminary reports from ASCEND-HF investigators suggest no significant improvement in symptoms or clinical outcomes, although no adverse effect on mortality or renal function was noted. We recommend the continued use of nesiritide in acute decompensated heart failure as an individualized case-based therapy to those patients who meet criteria for treatment and are expected to receive benefit from its use.     

Ultrafiltration for the management of acute decompensated heart failure

Heart failure is a major public health problem and is increasing in incidence throughout the industrialized world. Despite recent advances in pharmacotherapy, the overall mortality remains high and largely unchanged. Ultrafiltration has received increased attention in the treatment of acute decompensated congestive heart failure, and recent clinical trials suggest its usefulness in removing volume while preserving renal function. This review will focus on the background of ultrafiltration in the treatment of acute decompensated heart failure as well as the current evidence regarding its efficacy and safety.     

The regulation and measurement of plasma volume in heart failure

Plasma volume, the intravascular portion of the extracellular fluid volume, can be measured using standard dilution techniques with radiolabeled tracer molecules. In healthy persons, plasma volume remains relatively constant as a result of tight regulation by the complex interaction between neurohormonal systems involved in sodium and water homeostasis. Although chronic heart failure (CHF) is characterized by activation of many of these neurohormonal systems, few studies have evaluated plasma volume in this condition under treatment. Untreated edematous decompensated heart failure (HF) is associated with a significant expansion of plasma volume. Patients with stable CHF, receiving conventional therapy, appear to have a contracted plasma volume, a concept that is in contrast to the widely held belief that CHF is associated with long-term hypervolemia. It is likely that significant changes in plasma volume occur during intensification of medical therapy or during transition from the edematous to the stable state. Clinical assessment of plasma volume may be of particular value during treatment in patients with decompensated HF, in whom the plasma volume is contracted despite an increase in total extracellular fluid volume. Under these circumstances, treatment with inotropes or renal vasodilators may be more appropriate than intravenous diuretics alone. Further studies evaluating plasma volume in HF may help to improve our understanding of the pathophysiologic mechanisms occurring in the development and progression of this complex condition.     

A rapid bedside test for B-type peptide predicts treatment outcomes in patients admitted for decompensated heart failure: a pilot study

OBJECTIVES: The goal of this study was to determine if B-type natriuretic peptide (BNP) levels predict outcomes of patients admitted with decompensated heart failure. BACKGROUND: Treatment of decompensated congestive heart failure (CHF) has often been based on titration of drugs to relieve patient's symptoms, a case that could be made for attempting to also treat neurohormonal abnormalities. Because BNP reflects both elevated left ventricular pressure as well as neurohormonal modulation, we hypothesized that BNP might be useful in assessing outcomes in patients admitted with decompensated CHF. METHODS: We followed 72 patients admitted with decompensated New York Heart Association class III to IV CHF, measuring daily BNP levels. We then determined the association between initial BNP measurement and the predischarge or premoribund BNP measurement and subsequent adverse outcomes (death and 30-day readmission). RESULTS: Of the 72 patients admitted with decompensated CHF, 22 end points occurred (death: n = 13, readmission: n = 9). In these patients, BNP levels increased during hospitalization (mean increase, 233 pg/ml, p < 0.001). In patients without end points, BNP decreased (mean decrease 215 pg/ml). Univariate analysis revealed that the last measured BNP was strongly associated with the combined end point. In patients surviving hospitalization, BNP discharge concentrations were strong predictors of subsequent readmission (area under the receiver operator curve of 0.73). CONCLUSIONS: In patients admitted with decompensated CHF, changes in BNP levels during treatment are strong predictors for mortality and early readmission. The results suggest that BNP levels might be used successfully to guide treatment of patients admitted for decompensated CHF.     

Nesiritide for the treatment of diastolic dysfunction

Despite advances in the treatment of left ventricular diastolic dysfunction, therapy is still primarily empiric and readmission rates remain high, with up to half of patients discharged with the diagnosis of congestive heart failure being rehospitalized within 6 months due to recurrent decompensation. Even with this high economic burden, no effective, long-term therapies have been developed. The authors present a patient with recurrent hospitalizations for decompensated congestive heart failure due to left ventricular diastolic dysfunction becoming refractory to parenteral diuretic therapy. The patient exhibited a dramatic response to a 96-hour intravenous infusion of nesiritide and experienced prolonged clinical benefit, remaining in New York Heart Association functional class I for more than 6 months after the infusion.     

Ultrafiltration for acute decompensated heart failure: financial implications

Heart failure is the leading cause of hospitalization in older patients and is considered a public health problem with a significant financial burden on the health care system. Ultrafiltration represents an emerging therapy for patients with heart failure with a number of advantages over the conventional therapy. In this article, a summary of the relevant pathophysiological mechanisms such as removal of inflammatory cytokines are provided that might indeed be associated with a number of financial implications for ultrafiltration. Then practical points such as training of physicians and staff that need to be considered by physicians and medical centers with regards to financial implications of this therapy are reviewed.     

Treatment of persistent cardiac failure by ultrafiltration

Ultrafiltration, a method of extra renal filtering, which accomplishes an iso-osmotic removal of water an sodium from the plasma, was used in twelve patients. It is reserved for terminal persistent heart failures. In one case, it preceded a heart transplant. Simple to carry out, this technique is well tolerated when the pulmonary pressure is elevated, respecting an ultrafiltration output inferior or equal to 500 ml/h. Immediate improvement of the patients is spectacular. A new treatment failure may impose long-term ultrafiltration sessions. Failure of the medical treatment, impossibility of heart transplant, must be an indication for ultrafiltration which improves the comfort, and most likely the life expectancy of patients with persistent heart failure.     

Ultrafiltration in the management of refractory congestive heart failure.

Ultrafiltration was performed in nine patients with congestive cardiac failure that was refractory to conventional medical treatment. A mean of 12 X 7 litres of fluid was removed, and there was a sustained symptomatic improvement in all patients. Weight loss continued after ultrafiltration and a sustained increase in serum sodium concentration was also noted. A transient fall in right atrial pressure was seen only at four hours after ultrafiltration. No adverse haemodynamic effects were seen four and eighteen hours after fluid removal. Intracardiac dimensions measured by echocardiography remained unchanged. Ultrafiltration can be used to relieve symptoms in patients with refractory congestive heart failure and gross oedema.     

Ultrafiltration in the management of refractory congestive heart failure

Ultrafiltration was performed in nine patients with congestive cardiac failure that was refractory to conventional medical treatment. A mean of 12 X 7 litres of fluid was removed, and there was a sustained symptomatic improvement in all patients. Weight loss continued after ultrafiltration and a sustained increase in serum sodium concentration was also noted. A transient fall in right atrial pressure was seen only at four hours after ultrafiltration. No adverse haemodynamic effects were seen four and eighteen hours after fluid removal. Intracardiac dimensions measured by echocardiography remained unchanged. Ultrafiltration can be used to relieve symptoms in patients with refractory congestive heart failure and gross oedema.     

Propeptide of procollagen type I (PIP) and outcomes in decompensated heart failure

BACKGROUND: Changes in extracellular matrix are recognized as a contributing factor in the cardiac remodeling process. Several studies have addressed the value of turnover markers of collagen as predictors of death or new heart failure episodes. The aim of the present study was to evaluate the relationship between peripheral serum concentration of propeptide of procollagen type I (PIP) and outcomes in patients with decompensated heart failure. METHODS: A total of 111 patients admitted to our Unit between September 2000 and May 2003 for decompensated heart failure were analyzed. Death from any cause or due to heart failure and readmission were considered primary endpoints. RESULTS: The mean PIP concentration was 80.84+/-36.40 ng/mL. The PIP serum level was significantly higher among those patients who suffered some endpoint during follow-up (88.12+/-37.31 ng/mL vs 73.13+/-34.06 ng/mL; p=0.029). Twenty-five (22.52%) of the 111 patients died during the 21 months of follow-up, and 54 (48.6%) were readmitted with new bouts of heart failure. Using Cox proportional hazards regression analyses, serum PIP levels, systolic dysfunction, and diabetes mellitus were identified as independent predictors of death. Serum PIP levels, age, and sex were independent predictors of new heart failure episodes and readmission. CONCLUSION: A single serum measurement of PIP seems to have prognostic value in patients with decompensated heart failure. Accordingly, patients with higher values of PIP at decompensation are at a higher risk of death or readmission during follow-up.