Klein L, Massie BM, Leimberger JD, O'Connor CM, Pina IL, Adams KF Jr, Califf RM, Gheorghiade M. Admission or changes in renal function during hospitalization for worsening heart failure predict postdischarge survival: results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF)

Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Circulation Heart Failure (Impact Factor: 5.89). 05/2008; 1(1):25-33. DOI: 10.1161/CIRCHEARTFAILURE.107.746933
Source: PubMed


Admission measures of renal function (blood urea nitrogen [BUN], estimated glomerular filtration rate [eGFR]) in patients hospitalized for worsening heart failure are predictors of in-hospital outcomes. Less is known about the changes and relationships among these variables and the postdischarge survival rate.
In a retrospective analysis of 949 patients from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure, we investigated the relation between admission values and changes in BUN and eGFR and rate of death by 60 days after discharge. On admission, median eGFR was 51 mL min(-1) 1.73 m(-2) (interquartile range, 37 to 70 mL min(-1) 1.73 m(-2)), and BUN was 25 mg/dL (interquartile range, 17 to 41 mg/dL). On average, there was a 1.1-mL min(-1) 1.73 m(-2) decrease in eGFR and a 4.7-mg/dL increase in BUN from admission to discharge. By discharge, 12% of patients had a >25% decrease in eGFR, and 39% had a >25% increase in BUN. Although both lower admission eGFR and higher admission BUN were associated with higher risk of death by 60 days after discharge, multivariable-adjusted Cox proportional-hazards analysis showed that BUN was a stronger predictor of death by 60 days than was eGFR (chi(2), 11.6 and 0.6 for BUN and eGFR, respectively). Independently of admission values, an increase of >or=10 mg/dL in BUN during hospitalization was associated with worse 60-day survival rate: BUN (per 5-mg/dL increase) had a hazard ratio of 1.08 (95% CI, 1.01 to 1.16). Although milrinone treatment led to a minor improvement in renal function by discharge, the 60-day death and readmission rates were similar between the milrinone and placebo groups.
A substantial number of patients admitted with heart failure have worsening renal function during hospitalization. Higher admission BUN and increasing BUN during hospitalization, independently of admission values, are associated with a worse survival rate. Use of milrinone in these high-risk patients does not improve outcomes despite minor improvements in the renal function.

114 Reads
  • Source
    • "The Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of a Chronic Heart Failure (OPTIME-HF) trial reported that milrinone did not improve kidney function or overall survival in acute decompensated heart failure (ADHF) patients7). Low-dose dopamine (<5 µg·min-1·kg-1), commonly combined with diuretics, is believed to increase renal vasodilatation and renal blood flow, attenuate the effects of norepinephrine and aldosterone, and promote natriuresis via effects on dopamine-1 and 2 receptors8). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cardio-renal syndromes are disorders of the heart and kidney wherein acute or long-term dysfunction in one organ may induce acute or long-term dysfunction of the other. Because of this complex organ interaction, management of cardiorenal syndrome must be tailored to the underlying pathophysiology. Clinical guidelines exist for the treatment of heart failure or renal failure as separate conditions. Thus far, however, there has been no consensus about managing patients with cardio-renal and reno-cardiac syndromes. Pharmacologic treatment remains a controversial subject. Standard cardiac drugs such as diuretics and inotropes may have limited effect because resistance often develops after long-term use. Recent studies of patients with acute cardio-renal syndromes have focused on newer therapies, including phosphodiesterase inhibitors, vasopressin antagonists, adenosine A1 receptor antagonists, and renal protective dopamine. Initial clinical trials of these agents have shown encouraging results in some patients with heart failure, but have failed to demonstrate a clear superiority over more conventional treatments. Similarly, the benefits of diuretics, aspirin, erythropoietin agents, and iron supplements for management of chronic cardiorenal syndromes are unknown.
    Electrolyte & blood pressure: E & BP 06/2013; 11(1):17-23. DOI:10.5049/EBP.2013.11.1.17
  • Source
    • "Although, it is well established that patients who are admitted with AHF and renal dysfunction have worse outcomes, there is limited data for evidence-based therapeutic approaches.6-8) This is most likely because AHF is not a specific clinical-pathologic event and is not caused by a well-defined pathophysiologic mechanism (like acute coronary thrombosis), but instead results from various factors. "
    [Show abstract] [Hide abstract]
    ABSTRACT: During treatment of acute heart failure (AHF), worsening renal function is often complicated and results in a complex clinical course. Furthermore, renal dysfunction is a strong independent predictor of long-term adverse outcomes in patients with AHF. Traditionally, the predominant cause of renal dysfunction has been attributed to impairment of cardiac output and relative underfilling of arterial perfusion. Recently, emerging data have led to the importance of venous congestion and elevated intra-abdominal pressure rather than confining it to impaired forward cardiac output as the primary driver of renal impairment. Relief of congestion is a major objective of AHF treatment but therapy is still based on the administration of loop diuretics. The results of the recently performed controlled studies for the assessment of new treatments to overcome resistance to diuretic treatment to protect kidneys from untoward effects have been mostly neutral. Better treatment of congestion in heart failure remains a major problem.
    Korean Circulation Journal 10/2011; 41(10):565-74. DOI:10.4070/kcj.2011.41.10.565 · 0.75 Impact Factor
  • Source
    • "CRS type 1, or acute CRS, is determined by any of the acute HF syndromes [2] causing AKI. This type of CRS is frequent, with acute HF syndromes being the most common and the most expensive diagnosis-related group for Medicare patients [15] and worsening renal function occurring in 30–45% of patients during hospitalisation [16, 17]. The mechanisms contributing to worsening renal function after an episode of acute HF are multiple and complex. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cardio-renal syndromes (CRS) are defined as disorders of the heart and kidney whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. CRS have been classified into five categories, where types 2 and 4 represent respectively chronic cardio-renal and chronic reno-cardiac syndromes. In these conditions, the chronic disorder of either the heart or kidney has been shown to induce some degree of cachexia. At the same time, cachexia has been proposed as a possible mechanism contributing to the worsening of such pathological organ cross talk. Common pathogenetic mechanisms underlie body wasting in cachectic states of different chronic heart and kidney diseases. In these circumstances, a vicious circle could arise, in which cachexia associated with either heart failure or chronic kidney disease may contribute to further damage of the other organ. In chronic CRS, activation of the immune and neuroendocrine systems contributes to the genesis of cachexia, which in turn can negatively affect the heart and kidney function. In patients with cardiac sustained activation of the immune and neuroendocrine systems and oxidative stress, renal vascular resistance can increase and therefore impair renal perfusion, leading to worsening kidney function. Similarly, in renal cachexia, increased levels of pro-inflammatory cytokines can cause progressive left ventricular systolic dysfunction, myocardial cell death, endothelial dysfunction and increased myocardial fibrosis, with consequent impairment of the chronic reno-cardiac syndrome type 4. Thus, we speculate that the occurrence of different types of chronic CRS could represent a fundamental step in the genesis of cachexia, being renal and cardiac dysfunction closely related to the occurrence of systemic disorders leading to a final common pathway. Therefore, the heart and kidney and cachexia represent a triad causing a vicious circle that increases mortality and morbidity: In such circumstances, we may plausibly talk about cardio-renal cachexia syndrome. Complex interrelations may explain the transition from CRS to cachexia and from cachexia to CRS. Identification of the exact mechanisms occurring in these conditions could potentially help in preventing and treating this deadly combination.
    09/2011; 2(3):135-142. DOI:10.1007/s13539-011-0038-2
Show more