The rapid and sustained beneficial hemodynamic effects of nesiritide observed in this study support its use as a first-line IV therapy for patients with symptomatic decompensated HF.

The optimal use of diuretics in decompensated heart failure remains uncertain. We analyzed data from the ADHERE registry to look at the impact of diuretic dosing. 62,866 patients receiving <160 mg and 19,674 patients ≥160 mg of furosemide were analyzed. The patients receiving the lower doses had a lower risk for in-hospital mortality, ICU stay, prolonged hospitalization, or adverse renal effects. These findings suggest that future studies should evaluate strategies for minimizing exposure to high doses of diuretics.

To assess possible coronary vasoconstriction in patients with ischemic heart disease, we measured coronary vascular resistance in 12 patients with normal hearts and 12 with coronary disease before and during the initial 50 seconds of cold pressor test, a stimulus known to produce systemic vasoconstriction. Control coronary vascular resistance was similar in the two groups, and although it did not change in patients with normal vessels, it rose by 27 per cent (P less than 0.005) in the group with coronary disease during the cold pressor test. In three of 12 patients with coronary disease coronary flow actually declined despite an increase in arterial pressure; in four, angina was precipitated. Phentolamine abolished increases in arterial pressure and coronary vascular resistance during the test in three patients with coronary disease. Adrenergically mediated coronary vascular tone may be an important determinant of coronary blood flow and may contribute to ischemia in patients with coronary disease.

Nitroprusside rapidly and markedly improves cardiac function in patients with decompensated heart failure due to severe left ventricular systolic dysfunction and severe aortic stenosis. It provides a safe and effective bridge to aortic-valve replacement or oral vasodilator therapy in these critically ill patients.

Background: This study aimed to characterize the single-dose pharmacokinetic (PK) and pharmacodynamic (PD) profile of rivaroxaban 15 mg administered before and after dialysis in subjects with end-stage renal disease (ESRD), and to compare this profile in subjects with ESRD to that in healthy control subjects (creatinine clearance ≥80 ml/min). Methods: This was an open-label, single-dose, single-center, parallel-group study of rivaroxaban in ESRD subjects who had been clinically stable on maintenance hemodialysis for ≥3 months. In 8 subjects with ESRD, a 15-mg dose of rivaroxaban was administered 2 ± 0.5 h before a hemodialysis session and repeated 7-14 days later at 3 h after a 4-h hemodialysis session. Eight healthy control subjects, matched for age, sex, and body mass index, received one 15-mg rivaroxaban dose. Results: Compared to healthy subjects, area under the rivaroxaban plasma concentration versus time curve (AUC) increased by 56% following post-dialysis administration. Assuming similar bioavailability between groups, this reflects an approximate 35% decrease in overall drug clearance in ESRD subjects. Pre-dialysis dosing resulted in only 5% lowering of AUC versus post-dialysis dosing, confirming the minimal impact of dialysis on the PK of rivaroxaban. PD effects, as assessed by change in prothrombin time, percent factor Xa inhibition, and anti-Xa activity, were generally concordant with observed changes in plasma PK. Conclusions: Changes in PK and PD parameters in chronic dialysis patients were generally comparable to changes observed previously in patients with moderate-to-severe renal impairment who were not undergoing dialysis, and support use of a 15-mg dose in this patient population.

Heart failure (HF) with normal ejection fraction (EF) is an increasingly common presentation of acute decompensated heart failure (ADHF). Differences between patients with HF and truly normal EF and those with mildly impaired EF have not been described. The Acute Decompensated Heart Failure Registry (ADHERE) contains information on over 100,000 heart failure hospitalizations and may provide insight into this distinction. The ADHERE database was used to investigate differences between patients hospitalized with heart failure and severely (EF < 25%), moderately (EF 25-40%) and mildly reduced ejection fraction (EF 40-55%) vs. those with normal ejection fraction (EF ≥ 55%). The group with normal EF was 69% female with a mean age of 74 (p<0.017 vs. all other groups). Coronary artery disease was less frequent in the normal EF group, and hypertension played a larger role. Patients with EF ≥ 55% had elevated pulse pressure, suggesting a role for arterial stiffening. Treatment differed by ejection fraction. Creatinine increased ≥ 0.5 mg/dl more often in the group with HF and normal EF than the group with HF and severely reduced EF. In-hospital mortality and intensive care unit length of stay varied inversely with ejection fraction; overall length of stay was similar. In conclusion, patients with HF and normal EF are more likely to be female, have a history of high pulse pressure hypertension, less coronary artery disease and a lower risk of inpatient death but a higher likelihood of deterioration in renal function during hospitalization. These observations may be important considerations in the design of future clinical trials. Studies of heart failure with normal ejection fraction (EF) utilize widely varying EF definitions from ≥ 40% to >55%. 1-3 This broad range may obscure important results by mixing different patient populations, particularly because patients with an EF in the 40-55% range may have both left ventricular (LV) systolic and diastolic abnormalities. Even patients with heart failure (HF) and normal EF, long thought to have normal LV systolic function with a primary

In the ED setting, delayed measurement of iBNP levels and delay in treatment for ADHF were strongly associated. These delays were linked with modestly increased in-hospital mortality, independent of other prognostic variables. The adverse impact of delay was most notable in patients with greater iBNP levels (Registry for Acute Decompensated Heart Failure Patients; NCT00366639).

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