The goal of this program is to provide nurses with information about the incidence, etiology, pathophysiology, diagnosis, and pharmacologic management of heart failure, including the use of B-type natriuretic peptide (BNP) assay levels.  After studying the information presented here, you will be able to:

• Describe the pathophysiology of heart failure.
• Discuss the use of B-type natriuretic peptide assay levels in the management of heart failure.
• Discuss three medications used in the management of heart failure.

Heart failure - a major health, social, and economic problem-affects 5 million Americans, with 550,000 new cases in 2002, the most recent year for which figures are available.¹ In the same year, 970,000 patients were discharged with a diagnosis of HF. The estimated cost to treat HF in 2005 was nearly $28 billion.¹ The B-type natriuretic peptide (BNP) assay is a new tool in the HF diagnosis and management. This blood test measures the amount of circulating BNP - a cardiac neurohormone - secreted from the ventricle in response to HF. It's beneficial in differentiating the cause of dyspnea and monitoring the effects of diuretic therapy.

New diagnostic and treatment modalities for HF, such as the BNP assay, are emerging. Nurses need to be aware of the latest treatment for HF to help them care for the growing number of HF patients.

The causes of HF include acute myocardial infarction; hypertension; valvular dysfunction, such as aortic stenosis and mitral regurgitation; and cardiomyopathy (disease of the heart muscle). HF is due to impaired ventricular contractility resulting in a reduction in cardiac output (CO) and tissue perfusion. HF is a clinical syndrome characterized by dyspnea and fatigue at rest or with exertion. Other signs and symptoms of left ventricular HF include tachycardia, tachypnea, lung crackles This link is provided courtesy of UCLA Medical Center, cough, S3 gallop This link is provided courtesy of UCLA Medical Center (third heart sound created by a stiff or noncompliant ventricle), hypoxia, and dysrhythmias (abnormal heart rhythms such as premature ventricular contractions, ventricular tachycardia, and ventricular fibrillation).

HF can manifest as systolic or diastolic dysfunction. Systolic dysfunction causes impaired ventricular contractility with an ejection fraction (EF) - the percent of blood ejected from the ventricle with each heart beat-of under 0.45. Diastolic dysfunction is evidenced by impaired ventricular relaxation and an EF greater than 0.45.² An EF of 0.45 means that the left ventricle ejects 45% of its volume each time it contracts. An EF of 0.45 is borderline between normal and abnormal ventricular function.

The normal EF is between 0.50-0.65 and can be measured by an echocardiogram. This noninvasive test uses ultrasound to evaluate the function of the heart, including chamber size, wall motion, pumping function (as measured by EF), and valvular function. The echocardiogram can differentiate between systolic and diastolic dysfunction.

The sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) are activated as compensatory mechanisms for the failing ventricle. The sympathetic nervous system is part of the autonomic nervous system that regulates internal processes within the body, and the RAAS is a mechanism for regulating blood pressure (BP). As the CO decreases, the sympathetic nervous system releases catecholamines, such as epinephrine and norepinephrine, which increase the heart rate, contractility, and vasoconstriction. As renal perfusion decreases, renin is released by the kidneys. Renin stimulates angiotensin I, which is converted by the enzyme angiotensinase to angiotensin II, a powerful vasoconstrictor, which increases systemic vascular resistance. The SVR is the resistance against which the ventricle ejects blood into the aorta and arterial vascular bed. Angiotensin also stimulates the secretion of aldosterone, which causes reabsorption of sodium and water, increasing plasma volume. Initially, these mechanisms increase the BP and CO, but they become maladaptive in the long term, and HF progresses.

What's the BNP connection?

As the left ventricle fails, ventricular contractility decreases and the ventricle cannot eject a normal volume of blood. This additional volume causes the myocardium to stretch. BNP is secreted from the ventricular myocardium in response to the increase in volume and pressure. BNP exerts the following effects: natriuresis (excretion of abnormal amounts of sodium in the urine), which causes a decrease in circulating volume. It also causes vasodilatation that reduces the volume of blood returning to the ventricle, thereby reducing the volume of blood that the ventricle ejects. Vasodilatation causes a decrease in BP.

Vasodilatation reduces the volume of blood returning to the ventricle, thereby reducing the volume of blood that the ventricle ejects. Vasodilatation causes a decrease in BP. Natriuresis promotes the excretion of sodium and water, thereby reducing circulating volume. The vasodilatory and natriuretic properties of BNP counteract the vasoconstriction and sodium and water retention caused by activation of the sympathetic nervous system and the RAAS, providing a favorable effect on the failing ventricle in HF.³

Debut of the BNP assay

The level of circulating BNP can be measured in serum plasma, referred to as the BNP assay, developed in 2000 as a diagnostic tool in HF. A venous blood sample is collected and should be analyzed within four hours.³ The turnaround time for this rapid assay is 15 minutes.

The BNP assay helps in the diagnosis of HF since it can differentiate cardiac from pulmonary causes of dyspnea.⁴ The BNP assay can guide HF therapy and predict postdischarge outcomes (death/readmission) of patients with HF.^5-6 But to date there have been no studies that evaluate the practical everyday use of BNP levels in HF.

The normal BNP level is 0-100 pg/ml. The unit of measure, the pico gram, is abbreviated as "pg." A pico gram is one trillionth of a gram (10-12 g). In patients with BNP levels between 101 and 400 pg/ml, left ventricle dysfunction without volume overload, pulmonary embolism, and cor pulmonale. (right-sided HF) must be excluded as possible causes of dyspnea.³ The BNP levels are elevated in HF, greater than 400 pg/ml, and correlate to the severity of left ventricle dysfunction. The higher the BNP level, the greater is the severity of HF. BNP levels are elevated in both diastolic and systolic dysfunction, but BNP levels cannot differentiate between systolic and diastolic failure.³

BNP levels are beneficial in the differential diagnosis of dyspnea. HF, asthma, and COPD symptoms are overlapping; therefore, these syndromes are often difficult to differentiate. BNP levels can identify acute HF and help to differentiate from asthma and COPD in patients presenting to the ED with acute dyspnea.⁴ HF as the cause of dyspnea has levels ranging between 401 and 5000 pg/ml.

The use of BNP levels is well-established in HF, but levels may be elevated in other conditions and populations (stroke, severe sepsis or septic shock, the elderly, hyperthyroidism, and subarachnoid hemorrhage).^7-11 Like any diagnostic tool, the BNP assay has limitations, and nurses should focus on clinical assessment, pharmacological management, and evaluation of a patient's response to therapy.

The mainstays

Diuretics and salt reduction are mainstays in the management of HF. Furosemide, a loop diuretic, blocks the reabsorption of sodium and water within the nephron's ascending loop of Henle and promotes the excretion of excess volume. Loop diuretics also excrete potassium, which may lead to hypokalemia. Potassium chloride supplements may be required to maintain the serum potassium within normal limits (3.5-5.5 mEq/L). Hypokalemia predisposes the patient to developing dysrhythmias, which may be life-threatening.

BNP levels can also be used to monitor and manage HF. Elevated levels indicate an increase in intracardiac volume and pressure due to decompensated HF. Diuretic therapy reduces circulating volume through fluid elimination. As circulating volume is reduced, there is less blood returning to the right side of the heart, the pulmonary vascular bed, and the left ventricle. As a result, there is a reduction in intracardiac volume, with a decrease in heart size and improvement in contractility.¹² As intracardiac volume decreases, BNP levels fall. Serial levels can indicate the effectiveness of diuretic therapy. Increasing levels of BNP despite optimal therapy may also be indicative of patients at a higher risk of mortality associated with HF.³

Nurses can help evaluate the patient's response to diuretic therapy by monitoring the vital signs, lung sounds, SpO2, urine output, body weight, BNP, and potassium levels. Effective diuresis will result in an improvement in the patient's signs and symptoms (a decrease in dyspnea, heart rate, and respiratory rate and an increase in oxygenation). As fluid is eliminated, the urine output increases, resulting in a decrease in body weight and BNP and potassium levels.

ACE inhibitors, ARBs, and beta blockers

Unless contraindicated (as with heart block, potassium-sparing diuretics, and bilateral renal artery stenosis), all HF patients with an EF of 0.40 or lower should be treated with an angiotensin-converting enzyme (ACE) inhibitor such as captopril (Capoten).¹³ ACE inhibitors block the conversion of angiotensin I to angiotensin II, producing vasodilatation. Venous vasodilatation reduces the amount of blood volume returning to the ventricle, and arterial vasodilatation reduces the resistance to ventricular contraction, thereby reducing the workload on the failing ventricle. ACE inhibitors increase bradykinin levels that may produce a cough (known as the ACE inhibitor cough), which patients may not be able to tolerate.

Angiotensin receptor blockers (ARBs), such as valsartan (Diovan), are recommended for HF patients with a reduced EF who are ACE inhibitor intolerant.¹³ ACE inhibitors and ARBs are usually not prescribed in combination. ARBs block the vasoconstrictor and aldosterone-secreting effects of angiotensin II. Since ACE inhibitors and ARBs produce vasodilatation, nurses need to monitor the patient's BP upon initiation and throughout therapy. ACE inhibitors and ARBs may cause hyperkalemia and should be used with caution in patients with renal insufficiency or failure.

Beta blockers, such as carvedilol (Coreg), are recommended for the treatment of HF patients with a reduced EF unless contraindicated (second- or third-degree heart block, cardiogenic shock, severe bradycardia).¹³ Beta-blockers blunt the effect of catecholamines, decreasing the heart rate and contractility and reducing the workload on the failing ventricle. Due to the effects of beta-blockers, nurses should monitor patient BP and heart rate. Note that with the initiation of beta blocker therapy, HF symptoms may worsen as a result of decreased contractility associated with beta blockers. However, symptoms usually improve over time with continued use. ACE inhibitors and beta blockers reduce mortality associated with HF.¹³ Typically, physicians may write orders to hold ACE inhibitors, ARBs, (i.e. systolic BP less than 90 or 100 mm Hg), and beta blockers (i.e. systolic BP less than 90 or 100 mm Hg and/or heart rate less than 50/min). RNs should consult the health care provider about any concerns on administration of these medications.

In June, the FDA approved the combination drug hydralazine and isosorbide dinitrate (BiDil) for HF in African Americans.¹⁴ This new HF drug produces vasodilatation and reduces the workload on the failing ventricle. The approval was based on the results of the African-American Heart Failure Trial, conducted after two previous clinical trials in the general population of HF patients found no drug benefit, but suggested a benefit in African-American patients. Patients experienced a 43% reduction in mortality and a 39% reduction in hospitalization for HF. This is the first drug to be approved for a specific ethnic population.¹⁴

First in class: nesiritide

Nesiritide (Natrecor) is the first member of a new drug class, a recombinant form of human BNP. The FDA approved this drug in 2001 for patients with acutely decompensated HF, New York Heart Association Class III and IV (moderate and severe stages of HF).³

Its mechanism of action is vasodilatation. Nesiritide decreases pulmonary capillary wedge pressure (PCWP) or volume and systemic vascular resistance. The PCWP is measured by a balloon-tipped catheter that is inserted through a central vein (i.e., internal jugular, subclavian) into the right side of the heart and positioned in the pulmonary artery. The catheter is connected to a bedside monitor, where it displays the pulmonary artery pressure and waveform. When the balloon is inflated, the catheter floats into the pulmonary capillary bed, where it becomes "wedged" and measures the forward pressure (left side of the heart). Therefore, it is an indirect measurement of the pressure or volume of blood in the left ventricle. The normal PCWP is 6-12 mm Hg. As volume increases in the left ventricle, the PCWP increases, indicating HF. Vasodilators are beneficial in HF since they decrease PCWP. Nesiritide has both safety and therapeutic benefits over traditional vasodilators, such as nitroglycerine and nitroprusside (Nipride). The use of both nitroglycerine and nitroprusside result in neurohormonal activation of potent vasoconstrictors such as norepinephrine and angiotensin II, which counteract the vasodilatory effect of these drugs.¹⁵

Nesiritide is administered as a 2 mcg/kg bolus over 60 seconds and followed by a continuous infusion of 0.01 mcg/kg/min for up to 48 hours. Nesiritide reduces the PCWP in 15 minutes after starting the infusion. The drug is not titrated. It may be increased to 0.03 mcg/kg/min for desired effect. Since nesiritide produces vasodilatation, the nurse should monitor the patient's BP and PCWP.¹⁶

The major adverse effect is hypotension. For symptomatic hypotension, the infusion should be reduced or discontinued and other measures to support BP instituted. It has a short half-life of 18 minutes. Once the BP is stabilized, the infusion may be restarted at a dose that is reduced by 30% without the bolus dose. Nesiritide is contraindicated in patients hypersensitive to any of its components and in patients with cardiogenic shock, systolic BP of less than 90 mm Hg, significant valvular stenosis, restrictive or obstructive cardiomyopathy, constrictive pericarditis (inflammation of the pericardium or sac surrounding the heart), or pericardial tamponade (excess fluid in the pericardial sac that compresses or constricts the heart).¹⁶

Due to incompatibility, nesiritide should not be administered with drugs such as heparin, insulin, bumetanide (Bumex), enalapril (Vasotec), hydralazine (Apresoline), and furosemide. Note that these drugs are often prescribed in the management of patients with HF. Nesiritide should not be infused through a heparin-coated intravenous catheter.¹⁶ Plasma BNP levels will be falsely elevated since the BNP assay cannot differentiate between endogenous BNP and the recombinant drug form.³

Recent reports have questioned whether nesiritide may have adverse effects on survival and renal function. An expert panel has recommended additional clinical trials.¹⁷ The panel also made recommendations about the appropriate use of nesiritide, which is now approved only for inpatient settings for acute HF, not as an outpatient preventive or maintenance therapy. The FDA recently approved updated labeling for nesiritide.¹⁷

A happy ending

What happened to Mrs. Holland? She was discharged after three days on a low-sodium diet, furosemide, a potassium chloride supplement, captopril, carvedilol, activity as tolerated, and daily weight monitoring with instructions to contact her physician for a weight gain of more than 2 pounds a day. Vital signs are 130/70; 98.2-84-20. Lungs are clear. Oxygen saturation is 93% on room air. Her discharge BNP is 350 pg/ml. She has a follow-up appointment with her cardiologist.

HF affects millions and is the most common cause of hospitalization for people over 65. Patients with HF as the cause of dyspnea have BNP levels greater than 400 pg/ml. Diuretics cause a rapid fall in BNP levels because of a decrease in circulating volume. In addition to diuretics, ACE inhibitors and beta blockers are used in the management of HF and decrease mortality associated with it. The drug nesiritide (a form of human BNP) is used for patients with moderate and severe HF.

Clinicians caring for patients with HF should be knowledgeable about the BNP assay- normal values, abnormal values, and the pharmacological management of HF--and should fine tune their history-taking and physical assessment skills to provide optimum evidence-based care.

*Patient's name has been changed.