The Management of Acute Decompensated Heart Failure

Transcription

1 The Management of Acute Decompensated Heart Failure José A. Tallaj, Robert C. Bourge The University of Alabama, Birmingham, USA SUMMARY The acute management of decompensated heart failure includes the initial stabilization of the patient, assessment of volume status, and tailored treatment, using a variety of therapeutic choices based upon the patient's clinical and hemodynamic status. Current parenteral therapies include the sympathomimetic amines dobutamine and dopamine, which have positive inotropic effects, the phosphodiesterase inhibitors amrinone and milrinone, which have both vasodilatory and positive inotropic properties, as well as the vasodilators nitroglycerin and nitroprusside. There is much debate about the routine use of inotropic agents in decompensated heart failure, especially for intermittent or long-term use. Several new or future agents, which address the concerns about the potential negative effects of inotropic therapy and the positive influence of neurohormonal modulation on outcomes, are also reviewed. One such agent, nesiritide (hbnp), has both vasodilatory and diuretic effects, positive neurohormonal effects, no direct inotropic activity, no effect on heart rate, and no pro-arrhythmic effect. Introduction There are several therapeutic options currently available for the management of acute decompensated heart failure, a complex clinical syndrome requiring a multitude of interventions. No new parenteral agents have come to market for the management of acute decompensation for over a decade. Despite currently available therapeutic agents and approaches to therapy patients with decompensated heart failure continue to have high re-admission and mortality rates [1]. Thus, there is an opportunity for newer, more effective and safer parenteral agents to have a favorable impact on patient outcomes. Many factors, including uncontrolled hypertension and inadequate chronic therapy, may contribute to decompensation (see Table 1), but clinicians should not overlook other possible causes, such as side effects from concomitant medications. If, for example, a patient with cardiac arrhythmias who takes amiodarone presents with decompensated heart failure, the determination of thyroid hormone levels may be a useful measurement to determine if the amiodarone had caused hypo or hyperthyroidism. It is also helpful to consider that sedentary patients with heart failure are at high risk for pulmonary embolus and pulmonary infarction. It is important to remember that multiple co-morbidities may influence or give rise to the decompensated state. Importantly, it is very important that all patients with new onset heart failure be referred for an urgent diagnostic evaluation. Potentially reversible causes of heart failure must be excluded during this evaluation, including importantly, ischemic heart disease and stenotic valvular heart disease. This is because even with significant LV dysfunction, a revascularization procedure or correction of underlying structural cardiac pathology may stabilize or reverse significant LV dysfunction [2].

2 Acute Management of Heart Failure There are three major tasks involved in the acute management of such patients. First, and most importantly, if a patient is in extremis, the acute situation must be stabilized. A brief medical history and physical examination should be performed. The patient should be normally oxygenated and have adequate blood pressure and peripheral perfusion. As an example, the patient with decompensated heart failure who enters the Emergency Department with a systolic blood pressure of 60 mm Hg should first have his SBP raised to mm Hg, before doing invasive procedures such as putting in an arterial line or a Swan-Ganz catheter. (The target blood pressure depends on the chronic BP of a patient with chronic heart failure as a systolic BP of 80 may be appropriate and even desirable in some patients.) Second, an early clinical assessment of volume status and some non-invasive testing, if available, should be performed before any invasive procedures. Figure 1 illustrates an approach to the categorization of the volume and perfusion status of patients based on signs and symptoms. Lastly, appropriate therapy should be initiated. Therapies currently used in the acute management of severe heart failure include oxygen, diuretics, vasodilators, inotropic agents, and mechanical assist, which can be lifesaving. Figure 1: Rapid Assessment of Hemodynamic Status in Heart Failure [Adapted From Stevenson L.W., Tailored therapy to hemodynamic goals for advanced heart failure, European Journal of Heart Failure 1999, 1:251-25]: Before initiating parenteral therapy, the determinants of cardiac function (preload, afterload, heart rate, and contractility) should be measured and/or estimated. (See again Figure 1) In addition, it is important to assess an individual patient's systolic and diastolic function. While echocardiography or another measure of left ventricular ejection fraction is not necessary before treating a patient, data from patient records should be reviewed. For example, a patient with an LVEF of 60% may need to be treated differently than one with an LVEF of 15%. The clinical estimation of an individual patient's volume status can be difficult. The right heart catheterization utilizing the insertion of a Swan Ganz catheter is the gold standard method to measure intracardiac pressures and cardiac output, and the hemodynamic response to therapy in patients with advanced heart failure. Unfortunately, it is an invasive procedure that can be associated with significant complications.. Despite widespread use of the pulmonary artery catheterization for over 30 years, there is not yet a published randomized trial evaluating its safety or clinical efficacy. Some large observational studies have suggested an excess morbidity and mortality with the use of the pulmonary artery catheterization in critical, noncardiac patients. The SUPPORT study was a case-matched, prospective study examining the 30-day survival rate with and without the use of a pulmonary artery catheter in the intensive care unit setting in five teaching hospitals. The results demonstrated that patients who had pulmonary artery catheterization had a significant increase in ICU stay, morbidity and mortality compared with similar individuals who did have right heart catheterization [3] This was true even after an attempt towards adjustment for selection bias. It is important to note, however, that this study included patients in the critical care setting with multi-organ failure and only a minority of these patients had HF as the primary admission. An large multi-center US-NIH sponsored trial (The ESCAPE trial) is currently underway to evaluate the long-term efficacy of treatment guided by hemodynamic monitoring and clinical assessment versus that guided by clinical assessment alone in hospitalized patients with class IV HF [4]. In the future, we will have the capability of precisely measuring intracardiac filling pressures on both an ongoing and chronic basis using implanted hemodynamic monitoring

3 devices such as the Chronicle System (Medtronic, Inc.). Early work with this device illustrates the fact that major shifts in intracardiac filling pressures that occur throughout the day in patients with chronic heart failure [5]. The measurement of serum BNP levels, also offers great promise to assist the clinician in the assessment and acute management of heart failure patients [6] Table 2 outlines the range of serum BNP levels and their association with clinical situations. Parenteral Therapy for Management of Decompensated Heart Failure Current Therapies Table 3 shows an overview of conventional and promising intravenous agents for the acute therapy of heart failure. There are several parenteral sympathomimetic amines used in the management of acute heart failure, two of which are dopamine and dobutamine. Beta-adrenergic receptors are stimulated by both dopamine and dobutamine. Both dopamine and dobutamine have positive inotropic effects at lower doses. Dopamine has dopamine-1 (DA-1) receptor stimulatory properties that may increase renal blood flow. At higher doses, however, the vasoconstrictive properties of dopamine due to alpha-1 receptor stimulation offset the mild beta- 2 vasodilatory effects, increasing systemic vascular resistance which may lower cardiac output. Of the two agents, dobutamine is the better choice for patients with an adequate blood pressure who need a positive inotropic agent. Dobutamine has mild peripheral vasodilatory effects, and at higher doses doesn't cause vasoconstriction like dopamine. It is also relatively inexpensive compared to other newer IV inotropic agents. Other sympathomimetic amines are used for specialized cases and include epinephrine (effective in severe shock, especially anaphylactic and septic shock), norepinephrine, (a very potent vasoconstrictor) and isoproterenol (used to increase heart rate with Beta-1 receptor stimulation). The phosphodiesterase inhibitors work by increasing cellular cyclic AMP. In general, the direct inotropic effects of milrinone and amrinone, which are bipyridine derivatives, are less than their vasodilatory properties. Other phosphodiesterase inhibitors are enoximone and piroximone, which are imidazoline derivatives. These newer agents are generally of much higher cost than the sympathomimetic amines. The traditional parenteral vasodilators are nitroglycerin, nitroprusside, and enalaprilat. Although they work by different mechanisms, are all veno- and arterio-vasodilators.

4 Table 4 summarizes the hemodynamic and direct diuretic effects of the intravenous agents used for the management of decompensated HF. These agents work via different mechanism, and have different hemodynamic properties, thus illustrating once again the need for tailored therapy based upon the underlying hemodynamic milieu and underlying disease, if known.

5 In the classic study by Colluci and colleagues, which compared the inotropic and vasodilatory effects of dobutamine, milrinone, and nitroprusside, dobutamine was found to have a more positive inotropic effect than milrinone, as demonstrated by the ratio of the change in pressure to change in time (dpdt, an index of contractility) versus the percent change in systemic vascular resistance [7]. Milrinone had a greater vasodilatory effect than dobutamine, and as shown in Figure 2, nitroprusside (like intravenous nitroglycerin) has an almost purely vasodilatory effect. Figure 2: Relative Effects of Dobutamine, Milrinone, and Nitroprusside on +dp/dt and SVR in Patients with Severe Heart Failure [from Colucci, WS, et.al. Circulation, 1986; 73; ]: The use of currently available inotropic agents, should, in general, be limited to those situations where, in the opinion of an experienced clinician, they are definitely warranted. The recently published "Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure" (OPTIME-CHF) study investigated the routine use of milrinone in patients admitted with decompensated heart failure not thought to necessarily require intravenous vasodilator or inotropic drug therapy [8,9]. This was a prospective, multicenter, double-blind, randomized, placebo -controlled study in 951 patients designed to assess whether the routine use of milrinone early (within 48 hours of admission) would reduce the number of hospital days for cardiac events within the 60 days following therapy. The results of the study showed that there was no difference between groups in the primary end point, days of hospitalization for cardiac events. Also, there were no differences between groups in discharge date, length of hospitalization, dose of ACE inhibitor, or progression of CHF. In OPTIME-CHF, treatment failures during infusion were significantly higher with milrinone, which may have been due to the significantly higher incidence of adverse events, including sustained hypotension, in the milrinone group. While it appears that the incidence of sustained hypotension was the driver of the overall difference in adverse events between the groups, there was also a trend toward a higher incidence of

6 ventricular fibrillation and ventricular tachycardia in the milrinone group. New onset atrial fibrillation was statistically higher in the milrinone versus placebo group. The results of the study suggest that routine use of milrinone in all patients admitted with decompensated heart failure is not advisable. However, this study does not address the effect of inotropic agents in patients with clear evidence of low cardiac output (cold) and hypervolemia (wet). Milrinone is still used in this clinical situation. New or Future Parenteral Therapies Several new agents are either now available or soon to be available for the management of acute decompensated heart failure. Agents being investigated or nearing approval for the therapy of acute heart failure include: Levosimendan (Investigational in the US) Levosimendan increases calcium sensitivity of troponin C and also has some phosphodiesterase III inhibitor properties, i.e., it is a positive inotrope and a vasodilator. It also has positive lusitropic effects, thus relaxing the myocardium. Levosimendan seems to improve both systolic and diastolic function, but its effects appear even greater in diastolic dysfunction [10]. A recent multicenter randomized study showed a dose dependent improvement in cardiovascular hemodynamics in patients randomized to a 6 hour infusion of Levosimendan [11]. A large multicenter study of the effects of Levosimendan is currently underway in the US (the REVIVE study). Endothelin Receptor Antagonists (Investigational in the US for the therapy of heart failure) The endothelin receptor blockers, bosentan (oral) and tezosentan (IV) are 2 new agents currently being investigated in large HF trials. These agents cause both arterial and venous vasodilation, with no significant change in heart rate. Data from a small study (n=36) in men with NYHA Class III HF showed that bosentan versus placebo increased cardiac index and decreased SVR [12] In a multicenter randomized trial, the longterm administration of bosentan in patients with CHF was associated with worse heart disease, probable due to a early fluid retention [13]. Tezosentan administered as a 6-hour infusion to 61 patients with NYHA Class III or IV HF demonstrated dose-dependent increases in cardiac index [14]. Despite these beneficial hemodynamic effects, a recently published randomized trial of a 24-hour infusion of Tezosentan, in addition to conventional therapy with diuretics and nitrates, in patients with pulmonary edema, did not affect the outcome in a positive or negative way. However, there was a trend towards improved outcomes (measured as combined death, mechanical ventilation, recurrent pulmonary edema and MI) in the group of patients treated with the lower dose of Tezosentan [15]. A large, international, multicenter study is currently underway evaluating the effect of a short term intravenous infusion of tezosentan on morbidity and mortality in patients with severe HF (the VERITAS study). Vasopressin Receptor Antagonists (Investigational in the US) Another new class of drugs is the vasopressin receptor antagonists, which may be available soon. It has been know for some time that vasopressin levels are inappropriately elevated in patients with heart failure. OPC , which is in development by Otsuka, blocks the antidiuretic action of endogenous vasopressin, thus increasing free water clearance [16]. This drug was studied as an oral addition to the therapy of patients admitted with volume overload in the large, multi-center ACTIV-CHF study. The results of this study should be available in the near future. Adenosine A 1 Receptor Antagonists (Investigational in the US) The adenosine A 1 receptor antagonists is another class of agents under investigation. One example, the second generation of BG9719, is being investigated by Biogen. This class of agents increases vasodilation of the afferent renal arterioles, thus increasing GFR and improving renal function. Sodium reabsorption at the proximal tubule is decreased, causing natriuresis. Additionally, sodium reabsorption at the distal tubule and chloride reabsorption at the collecting duct are decreased, causing a potassium neutral natriuresis. In a randomized, double-blind, crossover study, the parenteral adenosine A1 receptor antagonist, BG9719, was administered in combination with furosemide compared to furosemide alone in 79 patients with NYHA Class II or III heart failure with edema. The combination of furosemide and BG9719 caused a significantly greater diuresis than furosemide alone, and improved creatinine clearance. When patients received furosemide alone, there was a decrease in creatinine clearance. These new agents hold the promise to induce diuresis without causing worsening renal dysfunction, especially in patients with pre-existing renal insufficiency. Nesiritide: Nesiritide or BNP (b-type natruretic peptide, Natrecor ) is a new intravenous agent approved for use in the United States in 2001 for the therapy of acute decompensated HF [18,19]. It binds to cell surface receptors, causing an increase in cellular cgmp with a resultant modest diuretic and natriuretic effect, as well as vasodilatory properties. Nesiritide dilates veins and arteries, as well as coronary arteries. It also has some positive neurohormonal effects, in that it decreases aldosterone [20]. Many small and large clinical studies

7 involving a total of over 1200 patients with decompensated heart failure have been reported. The first two seminal clinical trials utilizing nesiritide were reported by Colucci et al. in a single publication which included the results of a double blind, placebo controlled efficacy trial in 127 patients and an open label comparator trial (blinded to dose of nesiritide only) in 305 patients [21]. Entry criteria for both trials included patients with chronic heart failure requiring admission to the hospital for treatment of decompensation. A Swan Ganz catheter was required in the efficacy trial with specific hemodynamic entry criteria and was allowed in the comparator trial at the discretion of the treating physician. In the efficacy trial, patients received a 6 hours infusion of either placebo or nesiritide at a dose of or 0.03 mcg/kg/min after an appropriate bolus and in the comparator trial they received open label "standard" therapy vs. an infusion of nesiritide at or 0.03 mcg/kg/min after an appropriate bolus for up to seven days. The results of the efficacy trial are summarized in figure 3. There was a significant decrease in the pulmonary capillary wedge pressure (PCWP), right atrial pressure, systemic vascular resistance and mean pulmonary artery pressure with a modest but significant increase in the cardiac index in both treatment arms (an increase of 0.2 and 0.4 L/min/m 2 respectively). In the comparator trial there was no significant difference between the nesiritide groups and the standard therapy group. A smaller group in the nesiritide groups required IV diuretic therapy. Figure 3: Nesiritide Efficacy Trial, Hemodynamic Effects The Prospective Randomized Evaluation of Cardiac Ectopy with DobutaminE or Natrecor Therapy (PRECEDENT) study was a multicenter, randomized trial that compared the effects of Natrecor and dobutamine on heart rate and ventricular arrhythmias in 255 severe heart failure patients who required intravenous vasoactive therapy [22]. After a 24-hour baseline Holter monitoring period, patients were randomized to nesiritide at.015 or.030 mcg/kg/min or dobutamine at 5 mcg/kg/min. Dobutamine increased all primary end points of ventricular beats per hour, repetitive beats per hour and average heart rate (p 0.05). There was also a significantly higher incidence of episodes of ventricular tachycardia, couplets and triplets with dobutamine compared to nesiritide (p<0.05). The results of this study demonstrated that dobutamine increases heart rate and is significantly more pro-arrhythmic in patients with decompensated heart failure. Further, induction of new episodes of ventricular tachycardia and aggravation of existing ectopy occurred more often in the dobutamine treatment group. The results of a large pivotal study, the Vasodilator in the Management of Acute CHF (VMAC) was recently published [ 23] The VMAC trial was a unique trial involving 489 patients with acutely decompensated, severe CHF from a wide variety of causes including acute coronary syndromes, CHF due to diastolic dysfunction as well as patients with renal insufficiency and a history of arrhythmias. Patients were stratified based on the investigator's decision to use invasive hemodynamic monitoring. The 246 patients who received a Swan Ganz catheter were randomized to placebo, IV nitroglycerin (NTG, dosed per investigator discretion), fixed dose nesiritide (2 mcg/kg bolus followed by a 0.01 mcg/kg/min drip) or adjustable dose nesiritide (same starting dose but allowed to increase up to 0.03 mcg/kg/min after 3 hours). Patients initially randomized to placebo were reassigned after the first three hours to either nitroglycerin or fixed dose nesiritide. Background therapy could include standard heart failure medications including IV dobutamine. The 243 patients not catheterized were randomized to placebo, IV NTG (dosed at the investigator's discretion) or fixed dose nesiritide and again the placebo group were reassigned after three hours. The key findings included a more rapid and a significantly greater drop in the PCWP at 3 and 24 hours with nesiritide vs. nitroglycerin (see Figure 4). Nesiritide resulted in improved dyspnea at 3 hours vs. placebo, but no statistically significant improvement

8 compared to nitroglycerin was noted. More importantly, there was no appreciable tolerance with the use of nesiritide when compared to NTG (see Figure 5). Nesiritide appears to be well tolerated. The primary adverse event reported in the use of nesiritide is hypotension. In the early trials a higher dose of nesiritide was used and the incidence of hypotension was 6-12%. In the VMAC trial, where the currently recommended doses of nesiritide were used, the incidence of symptomatic hypotension with nesiritide was approximately 4% and was similar in patients that received nitroglycerin [23]. One obvious concern in this acutely ill population is the possibility of the induction of arrhythmias with the use of positive inotropic agents. Nesiritide has no apparent pro-arrhythmic effect, as documented in early studies, and inthe PRECEDENT trial as described earlier. Clinical Utility of Nesiritide: Nesiritide is currently indicated in the US for the therapy of acute decompensated heart failure. The use of a vasodilatory agent such as nesiritide should be limited to patients with volume overload. The goals of the acute therapy (and chronic therapy for that matter) are to improve survival and to improve symptoms. Symptomatic improvement is accomplished by adjusting the individual patient's perfusion status into the "warm" (optimally perfused) state and volume status into the "dry" (not congested) state. Indeed, the optimal "dry" state for a patient can be referred to as the "optivolemic" state rather than the euvolemic state. This is because, for a particular patient, the ventricular filling pressure necessary to optimize cardiac output without excessive congestion may not be within a normal range (that is, a patient may not be euvolemic when that individuals volume status is optimized). In general, a vasodilator drug with diuretic properties (like nesiritide) should be given to the decompensated heart failure patient that is

9 "warm" (relatively well perfused, with an acceptable blood pressure, in general > 90mmHg) and "wet" (hypervolemic, i.e., elevated ventricular filling pressures). The majority of acutely decompensated heart failure patients presenting acutely present in this state making nesiritide a useful and important drug for the management of acutely decompensated heart failure. Nesiritide seems to offer advantages over the use of inotropic agents in that it has no arrhythmogenic effects. It improves hemodynamics faster and with less side effects than intravenous nitroglycerin. As tachyphylaxis to nesiritide does not develop (as occurs with NTG), invasive hemodynamic guidance of drug dosing is not required. The use of nesiritide in other diseases, such as pulmonary arterial hypertension and its intermittent scheduled use in chronic heart failure is under active investigation. Unfortunately, in a patient with chronic heart failure and/or other diseases (i.e. pulmonary disease), the definitive assessment of volume overload can be difficult [24]. The use of new technologies, including point of care measurement of serum BNP levels, may aid in the assessment of an individual patients volume status [25]. An algorithm for the evaluation and management of the acutely decompensated patient is shown in Figure 6. Figure 6: Algorithm for the Assessment and Management of Decompensated Heart Failure Initial Approach to The Patient With Decompensated Heart Failure: The practical application of the various therapeutic options outlined above involve the stepwise approach to the stabilization and evaluation of the individual patient, initial diagnosis, confirmatory testing and review of pertinent records, and then the application of therapeutic measures. On stepwise approach to this task is outlined in Table 5 and Figure 6. It is important to quickly assess the hemodynamic and volume status on the patient and institute the appropriate therapy that will provide the best chances of a favorable outcome in this acutely and severely ill population (see above).the goals of therapy should be to adjust the cardiac output to the normal or warm state and the volume status to the dry or optivolemic range.

10 Conclusion In summary, the acute management of heart failure includes stabilization of the patient, assessment of volume status, and tailored treatment, using a variety of therapeutic options based upon an individual patient's underlying cardiac disease, volume status, renal function, blood pressure, and peripheral perfusion. There are several older therapies still is use and these continue to play an important role in acute HF management. Likewise, there are several newer therapies, including nesiritide, which may provide additional choices and safer and more efficacious treatment options. For some patients, new or investigative therapies for acute or chronic heart failure should be considered (see Table 6 above? Need for this table) [19]. Ongoing studies will serve to further elucidate the therapeutic efficacy and cost effectiveness of these new therapeutic agents or approaches to the therapy of this life threatening disease. References 1. American Heart Association Heart and Stroke Statistical Update. Dallas, Tex.: American Heart Asso., Castro PF, Bourge RC, Foster RE. Evaluation of Hibernating Myocardium in Patients with Ischemic Heart Disease. Am J Med 1998;104: Connors AF, Jr, Speroff T, Dawson NV, et al. The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT investigators. JAMA 1996, 276: Shah MR, O'Connor CM, Sopko G, Hasselblad V, Califf RM, Stevenson LW, for the ESCAPE Investigators. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness (ESCAPE): design and rationale. Am Heart J 2001; 141: Adamson PB, Magalski A, Braunschweig F, Bohm M, Reynolds D, Steinhaus D, Luby A, Linde C, Ryden L, Bremers B, Takle T, and Bennett T. Ongoing Right Ventricular Hemodynamics in Heart Failure: Clinical Value of Measurements Derived From an Implantable Monitoring System. J Amr Coll Card 2003; 41: Maisel A., B-Type Natriuretic Peptide Levels: A Potential Novel "White Count" for Congestive Heart Failure. Journal Cardiac Failure 2001;7: Colucci, WS, et.al. Circulation, 1986;73; Cuffe MS, Califf RM, Adams KF, Bourge RC, et al. Rationale and design of the OPTIME CHF trial: outcomes of a prospective

11 trial of intravenous milrinone for exacerbations of chronic heart failure. Am Heart J 2000;139: Cuffe MS, Gheorghiade M, O'Connor CM, Califf RM, Benza RL, Bourge RC, Colucci W, Massie B, Pina I, Quigg R, Silver M, Robinson LA, Leimberger J, Gheorghiade M. Short Term Intravenous Milrinone for Acute Exacerbation of Chronic Heart Failure. JAMA 2002; 287: Janssen PM, Datz N, Zeitz O, Hasenfuss G. Levosimendan improves diastolic and systolic function in failing human myocardium. Eur J Pharmacol 2000;404(1-2): Slawsky MT, et al. Acute Hemodynamic and Clinical Effects of Levosimendan in Patients With Severe Heart Failure. Circulation. 2000;102: Sutsch G, Kiowski W, Yan X, et al. Short-term oral endothelin-receptor antagonist therapy in conventionally treated patients with symptomatic severe chronic heart failure. Circulation 1998; 98: Packer, Milton, ENABLE study results, presented at the American College of Cardiology, Torre-Amione G, Young JB, Durand J, et al Hemodynamic effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients with class III to IV congestive heart failure. Circulation 2001;103(7): Kaluski E, Kobrin I, Zimlichman R et al. RITZ-5: randomized intravenous Tezosentan for the treatment of pulmonary edema: a randomized trial. JACC 2003;41: Goldsmith, SR. Vasopressin: A Therapeutic Target in Congestive Heart Failure. J Cardiac Failure 1999;5: Gottlieb S, Brater DC, Thomas I, et al. BG9719 (CVT-124), an A1-Adenosine receptor antagonist, protects against the decline in renal function observed with standard congestive heart failure therapy. J Am Coll Cardiol Rayburn BK, Bourge RC. Nesiritide: A Unique Therapeutic Cardiac Peptide. Reviews in Cardiovascular Medicine 2001; 2 (suppl 2):S25-S Bourge RC & Rayburn BK. New Therapeutic Approaches for Congestive Heart Failure. Textbook of Cardiovascular Medicine Updates, Vol 4(6) Ed. E.J. Topol, Lippincott Williams & Wilkins Healthcare, New York, Abraham WT, et al. Systemic hemodynamic, neurohormonal, and renal effects of a steady-state infusion of human brain natriuretic peptide in patients with hemodynamically decompensated heart failure. J Card Fail 1998;4: Colucci WS, Elkayam U, Horton DP, Abraham WT, Bourge RC, et al, for the Nesiritide Study Group. Intravenous Nesiritide, a Natriuretic Peptide, in the Treatment of Decompensated Congestive Heart Failure New England J Med 2000;343: Burger AJ, Horton DP, Elkayam U, LeJemtel TH, & Ghali JK. Comparison of the Effects of Dobutamine and Nesiritide (B- Type Natriuretic Peptide) on Cardiac Ectopy in Acutely Decompensated Ischemic Versus Non-Ischemic Cardiomyopathies. J Cardiac Failure 1999;5 (Suppl 1): Publication Committee for the VMAC Investigators (Young JB, Abraham WT, Stevenson LW, Horton DP, Elakyam U, & Bourge RC). Intravenous Nesiritide vs Nitroglycerin for Treatment of Decompensated Congestive Heart Failure. JAMA 2002; 287: Stevenson, LW & Perloff JK. The Limited Reliability of Physical Signs for Estimating Hemodynamics in Chronic Heart Failure. JAMA 1989; 261: Maisel A. B-Type Natriuretic Peptide Levels: A Potential Novel "White Count" for Congestive Heart Failure. J Cardiac Failure 2001; 7: Your questions, contributions and commentaries will be answered by the lecturer or experts on the subject in the Heart Failure list. Please fill in the form and press the "Send" button. Question, contribution or commentary: Name and Surname:: Country:: Argentina Send Erase Top Updating: 09/12/2003

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