ABOUT ACUTE HEART FAILURE

Acute heart failure (AHF) is the most common cause for hospital admission in patients over 65 years old. It is the leading cause of HF-related morbidity, mortality and health economic costs. In the United States alone, there are more than one million annual hospitalizations for AHF. The mortality rate for AHF at 30-days is 12% and at one-year it is 33%. Despite much research, there have been no improvements in the mortality rate over many decades.

The Acute Decompensated Heart Failure National Registry (ADHERE) collects detailed hospitalization data of AHF patients from initial presentation in the hospital or emergency department until discharge, transfer, or death. It is an observational database which reflects real-world treatment patterns and in-hospital outcomes for these patients. While most physiological studies and the substantial majority of prior clinical trials of AHF have focused on patients with left ventricular systolic dysfunction and either normal or reduced blood pressure, ADHERE shows that patients with this type of HF constitute only a minority of those admitted with AHF (Adams, 2005). In fact, patients with AHF are most commonly hypertensive at the time of admission and often have preserved (normal), not depressed, left ventricular contractile function. Georghiade et al. (Gheorghiade, 2006) concluded that ADHERE, systolic hypertension is common in patients hospitalized for HF, that the mean SBP at admission was 143 mm Hg and that 51% of patients had preserved systolic function. In a smaller registry that captured all emergency room admissions with AHF for 3 months, the first blood pressure recorded was found to be even higher, i.e. > 160 mmHg systolic (Milo-Cotter, 2007). General understanding of how to treat patients with AHF with hypertension, the most common patient population hospitalized for HF, is severely limited.

In chronic HF patients, the presence of concomitant chronic renal failure has been one of the strongest risk factors for mortality. This risk becomes evident even at a serum creatinine of 1.3 mg/dL and estimated creatinine clearance values of 60 mL/min are at least as powerful an adverse prognostic factor as ejection fraction and New York Heart Association (NYHA) class (Krumholz, 2000; Gottlieb, 2002; Hillege, 2006). In the setting of hospitalization for AHF, a recent analysis of ADHERE has demonstrated that renal dysfunction in the form of increased BUN and creatinine is one of the strongest predictors of adverse outcome (Fonarow, 2005). Although any increase in creatinine is associated with poorer survival rates, longer hospitalization, and more frequent readmission, several studies have used a threshold of a 0.3 mg/dL rise in serum creatinine over baseline to define this phenomenon of worsening renal function (Krumholz, 2000). Changes of this magnitude generally occur in about 1/3 of patients admitted for AHF and are associated with a prolonged and more complicated hospital course, as well as high rates of morbidity and mortality (Rev. in Shlipak, 2004). In one multicenter cohort study, a creatinine increase of 0.3 mg/dL had a sensitivity of 81% and specificity of 62% for predicting in-hospital mortality (Gottlieb, 2002).

Vasodilators are standard therapy for HF. Orally acting agents have been shown to reduce mortality and improve patient symptoms and quality of life during chronic administration. Multiple vasodilators have been tested for their benefits when given via intravenous administration to patients with AHF. There remains an unmet medical need for an intravenous vasodilator in the treatment of AHF, especially in patients with hypertension and preserved systolic function.