UNLOAD FAQs

Q: Is there additional data to support the use of ultrafiltration (UF)?¹
A: There is over 50 years of clinical data supporting ultrafiltration and documenting its benefits to safely and effectively remove excess fluid from volume overloaded patients. UNLOAD is just the most recent and the largest to date. For a complete bibliography, visit the Clinical Background section of this website.

Q: Is UF supported by leading heart health organizations?²
A: For years, UF has been recommended in the published heart failure guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), and the Heart Failure Society of America (HFSA). In fact, in the most recent HFSA 2006 Comprehensive Heart Failure Practice Guideline , UF was recommended to be used as soon as congestion fails to improve in response to diuretic therapy and prior to vasodilator therapy.

Q: How widely is ultrafiltration used in heart failure treatment?³
A: The benefits of UF to fluid overloaded heart failure patients are very well known and understood by nephrologists and renal professionals worldwide . In fact, the foremost renal experts often publish and recommend the use of UF for fluid overload - Drs. Schrier, Paganini, Ronco, Agostoni, Marenzi all have published multiple studies on UF and continuously add to its large and ever-growing clinical database. Although supported by clinical data, the design of current UF devices has been cited as one of the limiting factors to its more widespread use.

Q: Did the UNLOAD study diurese the standard care group to the fullest possible extent?⁴
A: “Aggressive diureses” was ensured by requiring that, at a minimum, IV diuretics be administered at doses at least 2 times daily PO dose for the first 48 hours after randomization. Since there are currently no widely recognized or accepted guidelines for diuretic dosing nonetheless for maximal or aggressive diuretic dosing, the exact diuretic dosing was left to the discretion of the investigator. Aggressive diureses is supported by the fact that 43% of patients in the UNLOAD standard care arm loss more than 4.6 Kg (10.12 lbs) and this is higher than nearly 80% of patients documented in the Adhere Registry.

Q: Is Aquapheresis Therapy using Aquadex FlexFlow more expensive than the standard care use of diuretics?⁵
A: While the initial cost is higher, UNLOAD investigators believe that the sustained benefits and the significant reductions in rehospitalization and in length of stay shown by the trial will translate to sustained benefits to patients and payers alike and greatly outweight any additional cost of providing the therapy.

Q: Was UNLOAD a blinded study? / How was bias minimized with the readmission data?
A: During treatment, blinding was logistically impractical to implement as is common in many medical device trials. During the 90 day follow-up period, potential bias was minimized by the fact that the physicians who admitted the patients upon readmission were ED physicians and not the trial investigators nor involved in the trial.

Q: Can repeated ultrafiltrations cause peripheral venous challenges into the future? How are those concerns handled now?⁶
A: Continuous or bolus IV diuretics and vasodilators also require peripheral venous access, often and unfortunately, repeatedly. UNLOAD’s readmission data show that ultrafiltration can actually reduce the total number and frequency of treatments that need venous access out to 90 days and potentially reduce venous access challenges into the future.

Q: Were rate and duration of volume removal specified in the study protocol?⁷
A: No. To be as clinically representative as possible, these were left to the discretion of the investigator. The rate and duration were set appropriately for each patient based on their diverse needs. The average rate of UF was 237 mL/hour.

Q: Was total sodium removed documented?⁸
A: UNLOAD didn’t document it, but because the UF device removed sodium and water isotonic to plasma, the math used to determine how much total sodium is removed is easy to calculate. All that is required is the patient’s baseline blood sodium level (in mEq/L) and the total amount of fluid removed over therapy (in Liters) and then you can calculate how much sodium was removed.

[grams Na+ removed] = Na atomic weight x (Na level in blood / total fluid removed)
[grams Na+ removed] = 22.98977 x (140 mEq/L / 1 Liter)
[grams Na+ removed] = 3.2 grams / Liter removed

Q: What UF device was used to treat patients in the ultrafiltration arm?
A: The Aquadex FlexFlow device made by CHF Solutions, Inc.

Q: What causes fluid overload?
A: Many health conditions can cause fluid overload, including renal failure, post-surgical fluid overload, metabolic disease, and congestive heart failure. Congestive heart failure is the leading cause of fluid overload.

Q: How common is fluid overload?
A: Good statistics for fluid overload do not exist. But they do exist for the leading cause of fluid overload, congestive heart failure (CHF). Nearly five million Americans are currently diagnosed with congestive heart failure. Approximately 550,000 new cases are diagnosed each year. Congestive heart failure affects people of all ages, from children and young adults to senior citizens. According to the American Heart Association, the condition is more common among the elderly, affecting approximately 10 out of every 1,000 persons over age 65. Medicare data reveals that congestive heart failure is the most common diagnosis among persons over 65 years of age admitted to the hospital. Congestive heart failure diagnoses are increasing eight percent annually, driven largely by the aging American population.

Q: What is congestive heart failure (CHF)?
A: In the medical world, the term “heart failure” does not mean the heart has stopped working, but rather that it is not pumping as efficiently as it should. Congestive heart failure refers to the state in which ineffective pumping of the heart results in a buildup of fluid in the lungs and elsewhere in the body. Different diseases can cause the condition, including coronary artery disease, heart attacks and diseases of the heart valves.

Q: What are the symptoms?
A: Common warning signs and symptoms of fluid overload include:

• Fatigue
• Shortness of breath
• Edema, or swelling in the lower limbs (i.e., legs, ankles and/or feet)
• Rapid weight gain from fluid retention
• Swelling or pain in the abdomen
• Frequent dry, hacking cough
• Difficulty breathing when lying flat

Q: How does it progress?
A: As heart failure progresses, the effects can become quite severe and patients often lose the ability to perform even modest physical activity. The heart becomes less efficient and the body will try to compensate for it. One way the body compensates is to increase “blood volume” by retaining fluid. This is exacerbated by the fact that the kidneys respond to reduced blood flow by retaining fluid as well. Excess fluid retention will lead to swelling throughout the body and collectively this retention and collection of fluid throughout the patient’s body is referred to as fluid or volume overload. Eventually this fluid collects in the lungs (pulmonary edema) and causes shortness of breath and is the leading cause of hospitalizations associated with congestive heart failure.

Different professional societies and associations have various classifications for congestive heart failure patients. The New York Heart Association categorizes congestive heart failure patients in four classes, depending on the severity of symptoms and the degree to which the condition restricts their physical activity.

Q: What are the standard treatment options?
A: In its early stages, congestive heart failure is commonly treated through a program of proper diet, modified daily activities and medications to reduce the symptoms of the disease. Unfortunately, drug therapy typically becomes less effective over time.

Many congestive heart failure patients eventually experience deterioration and require treatment in a hospital. This accounts for more than two million hospital admissions each year in the United States and is the most frequent cause of hospitalization among Medicare patients.

Typically, an in-hospital treatment includes intravenous drug therapy to stabilize the acute condition and remove excess fluid from the body. Commonly used medications include:

• diuretics, which help the body eliminate excess sodium and water through increased urination
• vasodilator drugs, which cause blood vessels to expand, thereby increasing blood flow
• inotropic drugs, which stimulate the heart to expel more blood with each beat;

Such intravenous drug therapy requires a hospital stay of around six days, on average.

Patients in the later stages of congestive heart failure may need to be treated with more invasive options while being considered a heart transplant candidate. More invasive treatment options include angioplasty, coronary artery bypass surgery, heart valve replacement or implantation of a defibrillator to keep the heart beating in a regular rhythm. Other treatment options include left ventricular assist devices and investigational artificial hearts.

Q: What is Aquapheresis and the Aquadex FlexFlow Fluid Removal System?
A: Aquapheresis is the name of the therapy that the Aquadex FlexFlow delivers. It literally means “removal of water” and uses an advanced form of ultrafiltration to filter the excess fluid from the patient. This fluid (primarily salt and water) is removed from the patient at a physician prescribed rate and helps to alleviate the symptoms of fluid overload. Using the Aquadex FlexFlow, up to 500 milliters per hour (or 1 pound) can be safely removed from patients with no clinically significant impact on heart rate, blood pressure, or electrolytes.

Aquapheresis with the Aquadex FlexFlow system - safe, predictable, and effective salt and water removal for patients with fluid overload.

Q: How does the Aquapheresis and the Aquadex FlexFlow Fluid Removal system work?
A: Aquapheresis with the Aquadex FlexFlow uses an advanced and highly automated form of a filtering technique called ultrafiltration.

Ultrafiltration is a process by which blood containing excess fluid is withdrawn and passed through a special filter (hemofilter). The filter removes the excess fluid from the patient’s blood and this blood is returned to the patient and the fluid is collected in a bag for later disposal.

The therapy is composed of three basic components: the electromechanical console (the blue machine with the two pumps), the blood filter circuit, and the venous catheter(s). For a complete explanation and interactive animation of the system in operation, visit http://www.chfsolutions.com.

Q: Does the Aquadex FlexFlow Fluid Removal System “cure” congestive heart failure or fluid overload?
A: Congestive heart failure and fluid overload are progressive conditions (see “How does it progress?” above). Most treatment options do not “cure” but target relieving the severity of the symptoms and seek to provide relief to the patient. Current treatment options may delay further progression of the condition, but there is no known “cure” for congestive heart failure.

Q: How is aquapheresis with the Aquadex FlexFlow different from other available therapies?
A: Aquapheresis with the Aquadex FlexFlow by CHF Solutions empowers physicians and nurses to treat fluid overloaded patients like never before.

Whether it’s in an inpatient or outpatient clinical setting, whether the patient has peripheral or central venous access, the Aquadex FlexFlow’s low blood flow (10-40 ml/min), low extracorporeal blood volume (33 ml), and precise removal rates (10 to 500 ml/hr), allow physicians and nurses to remove the salt and water they need to, where and when they want to… with no clinically significant impact on electrolytes, heart rate, or blood pressure.

Q: Where can I find more information?

Sources:

1. Selected Study Highlights of Ultrafiltration (UF) and Aquapheresis in Heart Failure document (http://www.chfsolutions.com/clinical_highlights.html). Schrier J Am Coll Cardiol 2006;47:1– 8.

2. Recommendation

12.11 When congestion fails to improve in response to diuretic therapy, the following options should be considered:

• Sodium and fluid restriction,
• Increasing doses of loop diuretic,
• Continuous infusion of a loop diuretic, or
• Addition of a second type of diuretic orally (metolazone or spironolactone) or intravenously (chlorothiazide).A fifth option, ultrafiltration, may be considered.
• Ultrafiltration. Mechanical methods of fluid removal are being actively investigated as potential alternatives to pharmacologic diuresis. Small uncontrolled studies have long suggested the utility of this approach using not only traditional dialysis but hemofiltration methods. More recently, 2 studies examined the utility of a peripheral venovenous system. Randomized controlled clinical trials are underway to evaluate the potential use of this treatment modality in patients with acute HF.”
  Reference(s): Adams, KF, Lindenfeld J, Arnold JMO, Baker DW, Barnard DH, Baughman KL, Boehmer JP, Deedwania P, Dunbar SB, Elkayam U, Gheorghiade M, Howlett JG, Konstam MA, Kronenberg MW, Massie BM, Mehra MR, Miller AB, Moser DK, Patterson JH, Rodeheffer RJ, Sackner-Bernstein J, Silver MA, Starling RC, Stevenson LW, Wagoner LE. Executive Summary: HFSA 2006 Comprehensive Heart Failure Practice Guideline. J Cardiac Failure 2006;12:10–38.
  Available at: http://www.hfsa.org/hf_guidelines.asp
  4.4.1. Management of Fluid Status “If the degree of renal dysfunction is severe or if the edema becomes resistant to treatment, ultrafiltration or hemofiltration may be needed to achieve adequate control of fluid retention. The use of such mechanical methods of fluid removal can produce meaningful clinical benefits in patients with diuretic-resistant HF and may restore responsiveness to conventional doses of loop diuretics. In general, patients should not be discharged from the hospital until a stable and effective diuretic regimen is established, and ideally, not until euvolemia is achieved. Patients who are sent home before these goals are reached are at high risk of recurrence of fluid retention and early readmission, because unresolved edema may itself attenuate the response to diuretics. Once euvolemia is achieved, the patient’s dry weight can be defined and used as a continuing target for the adjustment of diuretic doses.”
  Reference(s): Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). American College of Cardiology. Available at: http://www.acc.org/clinical/guidelines/failure/index.pdf

3. Reference(s): Go to the National Library of Medicine’s PubMed database (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=Display&DB=pubmed), search on “ultrafiltration heart failure” and read any of the currently available 477 citations.

4. Reference(s): UNLOAD protocol; Costanzo MR. Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure (UNLOAD), ACC.06 Smaller Trial Late-Breaking Clinical Trials II, American College of Cardiology 2006 Scientific Sessions; March 12, 2006; Atlanta, GA.
Reference(s): Brater NEJM 1998 339; 6:387-395.

5. Reference(s): Drs. Costanzo, Massie, Carson, Teerlink as quoted in the 2006 ACC Newsletter - March 15 2006.

6. Reference(s): Costanzo MR. Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure (UNLOAD), ACC.06 Smaller Trial Late-Breaking Clinical Trials II, American College of Cardiology 2006 Scientific Sessions; March 12, 2006; Atlanta, GA.

7. Reference(s): Costanzo MR. Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure (UNLOAD), ACC.06 Smaller Trial Late-Breaking Clinical Trials II, American College of Cardiology 2006 Scientific Sessions; March 12, 2006; Atlanta, GA. Available from http://acc06online.acc.org/Lectures.aspx?sessionId=24&date=14

8. http://www.nephron.com/cgi-bin/SI.cgi