Acute decompensated heart failure (ADHF) is one of the leading causes of hospital admissions and a significant burden on the healthcare system. It can be attributed to medication noncompliance, comorbidities, diet, modifiable risk factors, disease progression, and/or treatment failure. The standard treatment is usually pharmacologic involving intravenous (IV) diuresis, mainly with loop diuretics. However, chronic diuretic therapy use is associated with negative neuro-hormonal effects which may lead to diuretic resistance and worsening renal function which in turn can lead to increased morbidity and mortality. There has been a growing interest in alternative strategies to manage volume overload in ADHF patients. The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) guidelines recommend pharmacological and non-pharmacological interventions to treat volume overload. Extracorporeal ultrafiltration (UF) is, therefore, an emerging alternative therapy of interest for treating volume overload in ADHF patients. 
Loop diuretics administered intravenously remain the first-line therapy for hospitalized ADHF patients. Loop diuretics inhibit Na+/2Cl-/K+ cotransporter in the ascending limb of the loop of Henle which causes decreased sodium and chloride reabsorption and results in natriuresis and diuresis. Loop diuretics also increase the synthesis of prostaglandins, which cause renal and pulmonary vasodilation. This leads to a reduction in pulmonary wedge pressure. This overall causes improvement of dyspnea and decreases ventricular filling pressures.
Recent studies have suggested that the lack of adequate decongestion achieved by loop diuretics is more common than previously known. In patients with renal insufficiency (as seen in >50% of HF patients), anions compete with receptor sites for tubular transporters and these patients need higher diuretic doses to achieve effect. As heart failure (HF) worsens, the dose-response curve for loop diuretics shifts downwards and to the right causing a need for higher doses of diuretic to achieve the same effect. This is one of the mechanisms that can lead to an effect known as diuretic resistance in some patients. Dose escalation beyond a previously recognized dose ceiling or dose beyond the recommended maximum daily dose suggests diuretic resistance. Long term administration of loop diuretics can cause a mechanism known as the “braking phenomenon.” This results due to extracellular volume contraction causing an overactivation of the RAAS and sympathetic responses as well as adaptive epithelial hypertrophy and hyperfunction in the distal nephron resulting in reduced delivery of solute to the proximal tubule.
There are several strategies to overcome this diuretic resistance, one of them including ultrafiltration. Studies suggest that peripheral venovenous ultrafiltration is one of the most promising approaches in management of ADHF patients.
In patients with refractory ADHF, which is severe in nature, who do not respond to standard pharmacological treatment including the use of IV diuretics due to mechanisms discussed above, volume overload can be reversed through the use of UF. UF has been shown to produce an overall positive nitrogen balance and may also be indicated in patients with the fluid overload that need to increase their caloric intake. In patients undergoing cardiopulmonary bypass with evidence of excess body water, UF may be used to prevent the additional accumulation of fluid.
UF is contraindicated in any patient with evidence of hemodynamic instability. It is also contraindicated in patients with acute coronary syndrome including myocardial infarction or unstable angina. Patients with serum creatinine greater than 3.0 mg/dL should not undergo UF. UF is also contraindicated in patients with a hematocrit of over 45%. Lastly, adequate venous access is necessary for UF, thus if there is a contraindication for vascular access, then UF cannot be started.
UF equipment is similar to that for hemodialysis. The apparatus used to conduct UF consists of a dialyzer, dialysate, tubing for the transport of blood and of the dialysis solution, and a machine to power and mechanically monitor the procedure. Dialyzers are usually made of polyurethane with hollow fibers membranes that are suspended in the dialysate.
There are studies evaluating the differences among methods of vascular access for ultrafiltration that is done long term and intermittently. Issues related to cost and technical difficulty should be considered when choosing the access site. Central venous access is required with a preference for internal jugular access. Access, especially long-term, for UF patients increases the risks of adverse events. An arteriovenous communication is usually used in chronic dialysis patients but is also used in UF and can be associated with an increased risk of high output HF and right ventricular HF. Peritoneal dialysis access is also an option but can cause a rare complication of peritonitis.
Dialyzer fibers are hollow membranes that are suspended in dialysate through which blood can flow, dialysate flows in the opposite direction of blood to create a cross-current exchange. Solute clearance is usually achieved through diffusion and convection. Ultrafiltration and fluid removal occurs due to a hydrostatic pressure gradient across the dialyzer membrane (called a transmembrane pressure) which is created by the dialysis machine. Cell-free Fluid then diffuses from a high-pressure system (blood) to that of a low-pressure system (dialysate). The pressure gradient is achieved by positive pressurization of the blood compartment and negative pressure via suction applied to the dialysate compartment.
Adverse events associated with UF include clotting of UF filters, transient discomfort at the venous access site, central venous catheter infection, catheter malfunction, hypotension, bleeding events, and renal injury. A very small percentage of patients had volume overload refractory to UF. Early studies suggest that UF is unsafe. A recent systematic review and meta-analysis by Siddiqui et al. concluded that UF is safe and effective in ADHF and that there were no significant adverse events in UF in comparison to IV diuretics. There were fewer bleeding events with UF than with standard therapy. The increased events of hypotension in UF noted in the studies were clinically insignificant. In addition, the incidence of acute kidney injury in UF and diuretic therapy were comparable. The Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) trial by Bart et al. compared the effect of UF with diuretic therapy on renal function in patients with heart failure who have persistent volume overload and renal function that is declining. The study found that, although UF is associated with a higher increase in serum creatine initially, long-term the serum creatinine is lower when compared to patients on standard diuretic therapy.
UF therapy is a mechanical modality of fluid removal. It reduces central venous pressure (CVP) without impacting circulating volume. This is accomplished by the creation of a hydrostatic pressure gradient that triggers a mechanical extraction of fluid across a filter which subsequently results in separation and removal of isotonic plasma water. Studies show that it can be used effectively to reduce volume overload in patients resistant to conventional diuretic therapy. The UNLOAD (UF versus Intravenous Diuretics for Patients Hospitalized for ADHF) trial found that UF is not only an effective alternative therapy for refractory HF but also safely produces greater weight and fluid loss than intravenous diuretics and reduces 90-day HF readmissions and cumulative hospital readmissions. Three recent meta-analyses evaluating the comparative outcomes of UF versus conventional diuretic therapy in reducing volume overload in patients with ADHF found that patients that were able to tolerate UF had a significant reduction in volume overload and weight in comparison to conventional diuretics alone.
UF can show great benefits for patients in ADHF refractory to standard therapy with diuretics. It also causes iso-osmotic volume loss without changing or creating any electrolyte abnormalities. It can lead to maximum sodium loss per unit of volume removal compared to IV diuretics. UF can also lead to change in the neurohormonal milieu which may have clinical significance in heart disease, and it has also been shown to restore diuretic sensitivity.
The use of UF to manage CHF patients is done with an interprofessional team that includes a cardiologist, nephrologist, intensivist, hemodialysis nurses, an internist, and a vascular surgeon. Ultrafiltration requires a careful assessment of the patient to determine the goal of fluid removal. Vital signs must be monitored closely and periodically. A team of extensively trained hemodialysis nurses is required. While acutely the treatment can reduce the fluid in the body, the long term outcomes remain unknown. UF is also an expensive endeavor and not everyone benefits from it- hence patient selection is the key. 
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