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Volume 2, Supplement 2, 2001

Volume 2, Supplement 2, 2001

Table of Contents

Pathophysiology and Clinical Spectrum of Acute Congestive Heart Failure
This article reviews the current understanding of the pathophysiology and clinical spectrum of heart failure. A cascade of hemodynamic and neurohormonal derangements result from a decrease in ventricular performance or cardiac output. Because neurohormonal activation has become a target for intervention in heart failure, the role of selected systems (sympathetic nervous, renin–angiotensin–aldosterone) and of natriuretic peptides is detailed. The spectrum (from compensated to acute decompensated) within which congestive heart failure patients present is reviewed, with special attention paid to the intermediate, transitional group of patients, who pose unique diagnostic and therapeutic challenges. Given these variable presentations, there is an obligation to tailor therapy accordingly. [Rev Cardiovasc Med. 2001;2(suppl 2):S2–S6]
Pathophysiology of Radiocontrast Nephropathy and Use of Fenoldopam for Its Prevention
There are no proven therapeutic agents for the prevention or treatment of acute renal failure. Radiocontrast agents induce intense vasoconstriction in the renal medulla, which is hypoxic even in normal physiologic states, thereby aggravating the imbalance of medullary oxygen supply and demand. Fenoldopam specifically i n c reases blood flow to the renal medulla through selective agonism of dopamine-1 receptors and has been found to prevent radiocontrast nephropathy in several investigations, including one randomized, double-blind, placebo-controlled trial. [Rev Cardiovasc Med. 2001;2(suppl 1):S4–S8]
The Treatment Targets in Acute Decompensated Heart Failure
Acute decompensated heart failure is characterized by hemodynamic abnormalities as well as neuroendocrine activation, which contribute to heart failure symptoms, progressive cardiac dysfunction, and sudden death. The therapeutic goals in patients hospitalized with decompensated heart failure are to reverse acute hemodynamic abnormalities, relieve symptoms, and initiate treatment that will slow disease progression and improve long-term survival. Traditional hemodynamic targets in acute heart failure have been reduction in left and right ventricular filling pressures, reduction in systemic vascular resistance, and increase in cardiac output. Treatments aimed at these targets in patients with acute decompensated heart failure include diuretics, vasodilators, and inotropic agents. In patients hospitalized with acute decompensated heart failure, persistently elevated left ventricular filling pressure has been shown to be highly predictive of an increased risk of fatal decompensation and sudden death. Measures of systemic perfusion, arterial pressure, and vascular resistance have not. Thus, there is a more compelling physiologic rationale for the use of vasodilators than for inotropic agents in these patients. An ideal agent for acute decompensated heart failure would be one that rapidly reduces pulmonary wedge pressure, results in balanced arterial and venous dilation, promotes naturiesis, lacks direct positive inotropic effects, and does not result in reflex neuroendocrine activation. [Rev Cardiovasc Med. 2001;2(suppl 2):S7–S12.]
Radiocontrast-Induced Acute Renal Failure: Allocations and Outcomes
Radiocontrast-induced nephropathy causes significant morbidity and mortality with increase in hospital length of stay and costs. It can be largely prevented by identifying the patients at risk before the procedure. Once the at-risk patient is identified, ways to prevent the development of acute renal failure are: avoiding volume depletion, aggressive saline hydration with the aim of keeping the urine output over 150 mL/hour, and the use of low-osmolality contrast agents, with as little volume used as possible. There is theoretical potential for the dopamine D A1 agonist fenoldopam as a preventive agent, and this is currently being tested in randomized trials. [Rev Cardiovasc Med. 2001;2(suppl 1):S9–S13] .
B-Type Natriuretic Peptide (BNP) Levels: Diagnostic and Therapeutic Potential
Finding a simple blood test that would aid in the diagnosis and management of patients with CHF would clearly have a favorable impact on the staggering costs associated with the disease. B-type natriuretic peptide (BNP) may be the first potential “white count” for heart failure. The fact that a point-of-care, rapid assay for BNP has recently been approved by the FDA gives the clinician an opportunity to explore its potential usefulness. Data suggest that serial point-of-care testing of BNP will be of immense help in patients presenting to urgent care clinics with dyspnea. Additionally, BNP might serve as a screen for patients referred for echocardiography, and might also be an effective way to improve the in-hospital management of patients admitted with decompensated CHF. Finally, the role of BNP in the outpatient cardiac or primary care clinic may be one of critical importance in titration of therapies as well as assessment of the state of the patient’s neurohormonal compensation. [Rev Cardiovasc Med. 2001;2(suppl 2):S13–S18]
Past and Present Attempts to Prevent Radiocontrast Nephropathy
Radiocontrast nephropathy is an under-recognized event after coronary and radiographic angiography, with major morbidity and mort a l i t y. Patients at greatest risk for RCN can be defined prior to the procedure based on age, presence of diabetes, and presence of preexisting renal dysfunction. Despite attempts to alter pre p ro c e d u r a l hydration, amount of dye administered, and postprocedural therapies, this clinical event continues to affect over 25% of patients at high risk. This discussion will review the literature in order to understand the attempts that have been made to p revent radiocontrast nephro p a t h y. [Rev Cardiovasc Med. 2001;2(suppl 1):S14–S18]
Managing the High-Risk Patient: Experience with Fenoldopam, a Selective Dopamine Receptor Agonist, in Prevention of Radiocontrast Nephropathy During Percutaneous Coronary Intervention
Acute worsening of renal function due to contrast agents occurs in 15% to 40% of patients with baseline renal insufficiency undergoing percutaneous coronary i n t e rvention. Radiocontrast nephropathy is associated with increased morbidity, p rolonged hospitalization, and higher in-hospital mort a l i t y. Our nonrandomized data suggest that in adequately hydrated patients, the dopamine-1 receptor agon i s t fenoldopam is a useful adjunct during PCI for prevention of RCN, reducing its incidence to less than 5%. This renoprotective effect of fenoldopam was more p ronounced in diabetics, with moderate renal failure, in whom no agent has been shown so far to be beneficial. [Rev Cardiovasc Med. 2001;2(suppl 1):S19–S25]
New Therapeutic Choices in the Management of Acute Congestive Heart Failure
Patients with acute congestive heart failure generally present with profound fluid retention states and dyspnea due to pulmonary edema. If the condition is not aggressively and appropriately treated, irreversible cardiac decompensation may ensue, leading to cardiogenic shock, multiorgan failure, and death. Intravenous inotropic, vasopressor, and vasodilator therapies have proved effective in initial stabilization of acute heart failure decompensation, but these agents, particularly the traditionally used ones, are generally limited by side effects that can be egregious and include substantive ventricular arrhythmias. Dobutamine has largely replaced agents with rather profound toxicity, such as isoproterenol and epinephrine. The phosphodiesterase-inhibiting agent milrinone, having both vasodilator and inotropic properties, can produce tachycardia and significant ventricular arrhythmias, but has proven quite useful for seriously ill patients. Clinical trials of levosimendan have found a positive inotropic response when the drug is given parenterally; vasodilating properties are also evident. Clinical trials are under way to evaluate the potential benefits of endothelin receptor antagonists when given intravenously. Intravenous administration of nesiritide, a recombinant human B-type natriuretic peptide, has been shown to produce favorable hemodynamic effects, including balanced vasodilation associated with a rapid improvement in clinical symptoms. [Rev Cardiovasc Med. 2001;2(suppl 2):S19–S24].
Nesiritide: A Unique Therapeutic Cardiac Peptide
Nesiritide is the generic name for recombinant human B-type natriuretic peptide. This drug represents the first of a new class of agents for the treatment of decompensated congestive heart failure. The properties of B-type natriuretic peptide include a balanced arterial and venous vasodilatation and a marked natriuresis and diuresis, making it an excellent drug for the management of heart failure. We review the physiology and pathophysiology of the natriuretic peptides and the clinical data for nesiritide. In addition, the hemodynamic effects of the drug as well as its efficacy and safety in the treatment of heart failure are critiqued. Nesiritide is a new class of therapeutic peptide for the treatment of heart failure that appears to offer unique and safe hemodynamic properties. [Rev Cardiovasc Med. 2001;2(suppl 2):S25–S31]
Clinical Experience with the Use of Fenoldopam for Prevention of Radiocontrast Nephropathy in High-Risk Patients
A protocol for using fenoldopam, an FDA-approved intravenous agent for the t reatment of severe hypertension with a newly available renal vasodilatory effect, was adopted to prevent radiocontrast nephropathy in high-risk patients undergoi n g angiographic pro c e d u res. Fenoldopam is a selective dopamine-receptor agonist with renoprotective properties. The results of 46 consecutive procedures were re t rospectively reviewed in both diabetic and nondiabetic patients and compare d to a prior published cohort of similarly at-risk patients. The incidence of radiocontrast nephropathy was 13% in the group treated with fenoldopam, compare d to an expected 38% based on historical controls. The percentage change in seru m c reatinine was also very favorable. In this clinical experience of a high-volume c o ro n a ry and peripheral vascular laboratory, the use of fenoldopam in high-risk patients appeared to minimize the likelihood of radiocontrast nephropathy. [Rev Cardiovasc Med. 2001;2(suppl 1):S26–S30]
Design and Rationale of CONTRAST--A Prospective, Randomized, Placebo-Controlled Trial of Fenoldopam Mesylate for the Prevention of Radiocontrast Nephropathy
Radiocontrast-induced nephropathy develops in approximately 10% to 20% of patients following administration of iodine-based dye and is one of the most prognostically detrimental complications that invasive cardiologists and radiologists encounter. Preexisting renal dysfunction and diabetes mellitus are two of the most powerful predictors of the likelihood of developing acute renal insufficiency after contrast delivery. To date, only adequate preprocedural hydration and postprocedural hydration to offset dehydration from contrast-induced diuresis have been shown to be effective in preventing this condition. Fenoldopam mesylate, a systemic vasodilator curre n t l y F D A - a p p roved for short - t e rm, in-hospital management of severe hypertension, has been shown to i n c rease renal plasma flow in patients with and without chronic renal insufficiency. As a selective agonist of the dopamine-1 receptor, fenoldopam may preserve outer medullary renal blood flow and thereby attenuate radiocontrast-induced nephro p a t h y. Small studies with fenoldopam prior to iodine-based dye administration have demonstrated low rates of radiocontrast nephro p a t h y, and a larger, randomized trial has found that renal blood flow 1 hour after angiography rose in the fenoldopam group compared to a decline in the placebo group. The CONTRAST study has been designed to determine whether fenoldopam is indeed effective in diminishing the occurrence of radiocontrast-induced nephropathy. [Rev Cardiovasc Med. 2001;2(suppl 1):S31–S36]
Nesiritide: Practical Guide to Its Safe and Effective Use
The therapeutic goals for patients hospitalized with acute decompensated heart failure are to reverse acute hemodynamic abnormalities, relieve symptoms, and provide the ability to initiate early treatment, which will decrease disease progression and improve long-term survival. The use of nesiritide on top of standard care, such as diuretic therapy, has been proven to lead to meaningful clinical benefits in a broad range of acutely decompensated heart failure patients. Nesiritide is an attractive therapeutic option because of its more rapid and sustained hemodynamic profile with less adverse effects than alternative heart failure treatments, such as nitroglycerine or dobutamine. The use of nesiritide represents an entirely new treatment approach to reverse acutely decompensated heart failure and to facilitate optimization of the heart failure medical regimen. [Rev Cardiovasc Med. 2(suppl 2):S32–S35]