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With more than 60 million patients worldwide, heart failure is the only category of cardiovascular disease that continues to grow due to the aging population, increased incidence of diabetes, and persistent non-fatal myocardial infarction. Pulmonary congestion is recognized as the main symptom triggering unscheduled inpatient hospitalizations or outpatient visits to diuresis clinics.

Congestion is not always associated with low cardiac output, rather it is related to the stimulation of neuro-endocrine hormones that leads to excessive renal sodium and water reabsorption. Elevated fluid retention is aggravated in patients with pre-existing chronic kidney disease. Excess body fluid retention not only instigates pulmonary congestion and breathing difficulty, it also causes pulmonary hypertension and impairs the function of the skin, liver, kidney and intestine. A rapid onset of congestion results in acute decompensated heart failure, whereas a gradual development of congestion is associated with the worsening of signs and symptoms of heart failure and currently both conditions have high unmet medical needs.