NDT Advance Access originally published online on March 16, 2009
Nephrology Dialysis Transplantation 2009 24(7):2024-2026; doi:10.1093/ndt/gfp109
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A critical look at acute decompensated heart failure from a nephrologist's perspective
Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Canada
Correspondence and offprint requests to: Christopher T. Chan; E-mail: christopher.chan{at}uhn.on.ca
Keywords: acute decompensated heart failure; kidney function; prognosis; treatment
Acutely decompensated heart failure is associated with significant morbidity and mortality. It is responsible for $30 billion overall annual cost in the United States alone [1]. Recent evidence has demonstrated the clinical importance of kidney function in the risk stratification, clinical presentation and prognostication of patients with heart failure. Despite great anticipation that the clinical use of aquaretics and natriuretic peptides would turn out to be beneficial, these therapies have failed to improve survival in patients with heart failure. Against this background adjunct approaches, e.g. ultrafiltration and continuous positive airway pressure (CPAP) ventilation, are gaining increasing interest as a treatment strategy. In the following update, we review the emerging appreciation of the role kidney function plays in heart failure and address the challenges and opportunities for nephrologists in the contemporary management of acutely decompensated heart failure.
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Renal function and outcome of heart failure |
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 Top Renal function and outcome... Systolic versus diastolic heart...Pharmacological intervention-...Novel interventions on the...References |
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The pathophysiology of acutely decompensated heart failure has been reviewed elsewhere [2] and is beyond the scope of the present comment. In brief, neurohormonal activation, inflammatory/fibrotic cascades and haemodynamic compromise lead to a reduction in glomerular filtration rate and renal plasma flow. It had been known for some time that baseline serum creatinine in conjunction with NT-proBNP >4.65 pg/ml [3] and even a small increase in serum creatinine during the follow-up [4,5] predict a poor outcome in patients with decompensated acute heart failure. In the cardiac patient it should also be remembered that Dronedarone (the successor of amiodarone) causes a spurious increase of serum creatinine by blocking tubular secretion of creatinine [6].
For the assessment of acutely decompensated heart failure, the practical risk stratification tool that Fonarow [7] derived from the data of the ‘Acute Decompensated Heart Failure National Registry’ (ADEHERE) is of considerable interest. In a total population of >100 000 patients, the best single predictor of mortality was a blood urea nitrogen level of >15.35 mmol/L. The high predictive value of urea is due to the fact that in decompensated heart failure more urea is reabsorbed in the collecting duct via increased numbers of aquaporin channels. The other two predictive variables included systolic hypotension (<115 mmHg) and high serum creatinine concentration (>243.1 µmol/L). Based on the investigators’ regression model, a patient who presented with all three poor prognostic parameters had an in-hospital mortality of >20%. In a follow-up study, the same group of investigators demonstrated a dose relationship between renal function and in-hospital mortality. In addition, in patients with worsening of renal function higher doses of diuretics had been used as well as more inotropes and the inotropic agent nesiritide, whereas they received less angiotensin-converting enzyme inhibitors or angiotensin blockers [8].
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Systolic versus diastolic heart failure—equally poor prognosis |
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TopRenal function and outcome...Systolic versus diastolic heart...Pharmacological intervention-...Novel interventions on the...References |
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It has recently been recognized that heart failure with preserved systolic function, i.e. diastolic heart failure, has an equally poor prognosis as does systolic heart failure. It is therefore relevant that renal dysfunction is equally prevalent in both types of heart failure as recently documented by Yancy et al. [9]. They demonstrated in more than 50 000 patients that a serum creatinine concentration >176 µmol/L was present in 17% of patients with preserved systolic function (diastolic heart failure) as compared with 18% of patients with reduced systolic function (systolic heart failure).
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Pharmacological intervention—efficacy of novel agents |
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TopRenal function and outcome...Systolic versus diastolic heart...Pharmacological intervention-...Novel interventions on the...References |
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Although there had been great expectations when developing novel pharmacotherapeutic agents (e.g. aquaretics and nesiritide) in the treatment of acutely decompensated heart failure, there is to date no definite proof that these medications provide a survival advantage in the long run.
What is the available evidence? The EVEREST study [10] examined the short-term clinical effects of selective vasopressin V2 receptor blockade by the aquaretic tolvaptan that selectively increases water excretion. Overall, more than 4000 patients with acutely decompensated heart failure were randomized to receive either tolvaptan (30 mg/day) or placebo in addition to standard therapy. The patients receiving the active drug experienced an improvement in global clinical status. However, there was no change in long-term survival in patients treated with tolvaptan.
The use of the intravenously administered recombinant natriuretic peptide nesiritide in patients with heart failure has yielded controversial results. Although observational data suggest a clinical advantage with a signal towards survival benefit, a recent meta-analysis [11] came to the conclusion that the use of nesiritide in heart failure is associated with negative outcomes especially in regards to renal function. Given the high impact of renal dysfunction on clinical outcomes in heart failure, it appears undesirable to use medications that aggravate renal dysfunction.
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Novel interventions on the horizon—ultrafiltration and CPAP |
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TopRenal function and outcome...Systolic versus diastolic heart...Pharmacological intervention-...Novel interventions on the...References |
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Given the above unsatisfactory data, adjunct strategies have become attractive alternatives in the contemporary management of heart failure. Specifically, the promising results of ultrafiltration and CPAP ventilation in patients with heart failure have renewed the interest in their use. In the recently published UNLOAD study [12], 200 patients with acutely decompensated heart failure were randomized to ultrafiltration versus intravenous diuretics. Rehospitalization was lower with the use of ultrafiltration, but the duration of hospitalization was not different between the two groups. The authors concluded that in such patients, ultrafiltration safely produces greater weight and fluid loss than intravenous diuretics, reduces 90-day resource utilization for heart failure and is an effective alternative therapy. It is important, however, to note that the two treatment arms were not titrated to the same reduction of target weight. Furthermore, the study was not powered to find out whether ultrafiltration provides better kidney function or survival. Future studies must assess underlying pathomechanisms, and larger longitudinal studies will be required to get a better grasp on the clinical utility of ultrafiltration in heart failure.
Obstructive and central sleep apnoea are more prevalent in patients with heart failure compared to normal controls. Recently, a randomized study on the use of CPAP in patients with heart failure documented improved cardiac geometry and systolic function [13]. A recent study addressed the clinical benefit of CPAP in patients with heart failure and central sleep apnoea [14]. Although no significant benefit of CPAP treatment could be documented, the study may in fact have been underpowered.
Common to both of the above-mentioned non-pharmacological therapies is their potential to improve cardiac geometry and function through diastolic ventricular interaction that has been identified recently [15]. It is plausible to assume that this mechanism may have a beneficial effect on renal plasma flow and glomerular filtration rate in patients with heart failure [16,17]. Further clinical research and additional innovation in technology is needed prior to the routine application of these adjunct therapies.
It has recently become clear that kidney function is of central importance in the assessment, treatment and outcomes of patients with acutely decompensated heart failure. In future pharmacological and non-pharmacological interventions (i.e. ultrafiltration and CPAP), in patients with heart failure renal endpoints must be included. For decades, nephrologists have learned that cardiac endpoints are among the most relevant clinical outcomes in patients with kidney failure; it would seem that the reciprocal notion is true in patients with heart failure. A combined cardio-renal approach will yield the greatest advances in the contemporary management of acutely decompensated heart failure.
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Acknowledgments |
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Dr C Chan holds the R Fraser Elliott Chair in Home Dialysis.
Conflict of interest statement. None declared.
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References |
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Accepted in revised form: 23. 2.09
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