Heart failure is a progressive disease that results in the heart being unable to pump enough blood and thereby supply oxygen to support other organs in the body. The American Heart Association estimates that 6.5 million adults in the United States age 20 and over are affected by heart failure and that number is expected to rise to 8.0 million adults by 2030. Source
Causes of heart failure include coronary artery disease, heart attacks, high blood pressure and faulty heart valves.
Heart failure can disturb the normal functioning of the kidney, weakening its ability to excrete sodium from the body and triggering mechanisms that cause water retention resulting in volume overload. Patients with heart failure commonly experience shortness of breath, fatigue, difficulty exercising and swelling of the legs. The increase in fluid volume increases the burden on the weakened heart, further exacerbating the problem.
Volume overload is a major clinical problem and the leading cause of hospitalisations for patients suffering from heart failure. There are approximately 1 million people in the U.S. admitted annually to hospital for heart failure, and 90% of these admissions are due to symptoms of volume overload. Source
In addition, 1 in 4 patients are readmitted within 30 days, and 1 in 2 patients are readmitted within 6 months from discharge. Source
The cost of heart failure-related hospitalisations in the U.S. is estimated at $13 billion a year. Source
Volume overload is currently treated through the administration of diuretics, which frequently cause patients to develop kidney failure and an estimated 40% of heart failure patients experience diuretic resistance or intolerance. Source
Once patients become resistant or intolerant to diuretics or begin to experience kidney failure, clinical alternatives are limited and have significant limitations.
Maintaining a constant concentration of sodium in the body is a key physiological parameter that is vital to patient health. A concentration that is too high will result in hypernatremia and a concentration that is too low will result in hyponatremia.
The body’s response to heart failure causes sodium levels to increase.
To restore the balance, the body retains water, leading to volume overload and an increased burden on the heart.
Challenges of diuretic therapy
The key challenge in addressing volume overload is that removal of water from the body without the removal of the associated amount of sodium only results in a temporary reduction in fluid volumes.
Resistance to diuretics are common and toxicity is well described. Also, traditional diuretic approaches primarily remove hypotonic urine, and the resulting loss of sodium is low. As a result, the sodium concentration in the body increases and to restore this, the body either adds more fluid through eating or drinking, or reduces fluid loss through urination. In most cases, the body will retain its sodium reserves, as sodium is regarded by the body as a scarce resource.
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