ACCORDING to the American Heart Association (AHA), congestive heart failure (CHF) affects approximately 5 million people in the United States. There are 550 000 new cases diagnosed each year, and 6.5 million hospital days are used for management of the disease yearly. These numbers are expected to increase with the growth in our elderly population over the next decade.1
The Joint Commission, the Centers for Medicare and Medicaid Services, and the Institute for Healthcare Improvement (IHI) have collectively agreed that evidence-based medicine is the best method for standardizing healthcare practices that have demonstrated improvement of morbidity and mortality rates for specific diseases common in the United States. These standards of care are evaluated by core measures or indicators used to benchmark an institution's performance in providing disease specific care. These data will be collected by the Joint Commission and the Centers for Medicare and Medicaid Services and publicly reported. Future reimbursement to healthcare organizations will be based on the institution's ability to meet these standards. Because of the increased prevalence rate and heightened awareness of CHF, the IHI has included "Improved care for the patients with CHF" as part of its Five Million Lives campaign.2 This campaign is a national initiative to improve quality of American healthcare by shielding patients from 5 million incidents of medical harm. Part of this effort utilizes evidence-based practices and the guidelines for the care of patients with CHF in conjunction with the American College of Cardiology (ACC) and the AHA 2005 Clinical Performance Measures for Adults with Chronic Heart Failure.2
In the 2006, the IHI has identified 7 key indicators of quality measures: left ventricular systolic heart function assessment; angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) at discharge for HF patients with left ventricular systolic dysfunction; anticoagulant for CHF patients with chronic or recurrent atrial fibrillation; record of influenza; pneumococcal immunization; smoking cessation counseling; and discharge instructions including activity level, diet, discharge medications, follow-up appointment, weight monitoring, and what to do if symptoms worsen.2 Although it is important for nurses to have knowledge of these 7 key indicators and the rational behind the medical treatment of this population set, this article focuses on the pharmacological treatments used for symptoms of HF and reduced left ventricular ejection fraction (LVEF).
PATHOPHYSIOLOGY OF HF
Current therapies for the treatment of HF are aimed at regression and prevention of left ventricular dysfunction. HF is currently defined as a clinical syndrome characterized by symptoms of pump failure secondary to structural and functional disorders that impairs the ability of the ventricle to fill or eject blood.3,4 Alterations in hemodynamics and neurohumoral balance are the major culprits in the development of ventricular dysfunction. HF can affect both ventricles; however, this article focuses on reduced LVEF and its pharmacological approach to treatment. It is important to understand the type of HF the patient has, as therapeutic goals may differ for individuals who do not have reduced LVEF.
Depending on the primary etiology, HF can manifest itself as systolic or diastolic dysfunction. Systolic dysfunction is characterized by changes in left ventricular contractility in which LVEF is less than 0.40; this is characterized by the thinning of the heart wall and dilation of filling chamber. The end result is the elevated left ventricular filling pressure, which leads to fluid overload and elevated pressures in left atrium and pulmonary vasculature. Increased left heart and pulmonary pressures cause fluids to escape into the pulmonary interstitial spaces, leading to pulmonary congestion. The elevation of pulmonary pressure leads to increased right-sided heart pressures, and subsequently symptoms of right-sided HF.3
Diastolic dysfunction is the impairment of left ventricular relaxation, which decreases filling of the ventricle during diastole. Ventricular contractility and LVEF are usually normal; the problem is a filling defect. Diastolic dysfunction is characterized by concentric wall thickness, which leads to decreased compliance in wall motion and decreased size of the filling chamber.4
The contributing factors that lead to the development of HF are considered the precursor to the vicious cycle of events that cause the remodeling of the heart muscle. These events include uncontrolled hypertension, myocardial infarction, valvular disease, and atrial fibrillation. Essentially, any insult that results in a compensatory rise in the left ventricular end diastolic filling pressure can lead to the activation of neurohumoral responses.3,4
Activation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system causes the retention of sodium and water by the release of rennin from the distal tubules of the kidney. This process triggers vasoconstriction, which continues to perpetuate the release of hormones that contributes to the development of HF. Renin converts angiotensinogen to angiotensin I. Angiotensin I is converted to angiotensin II by ACE, which potentates vasoconstriction. The increased level of angiotensin II triggers the adrenals glands to release aldosterone, an antidiuretic hormone. Aldosterone, in turn, causes the kidneys to retain more sodium and water, which continues to increase the circulating volume. As the cardiac output decreases and the circulating levels of angiotensin II increase, the posterior pituitary gland is stimulated to release vasopressin. Vasopressin promotes vasoconstriction and fluid retention; in response to impaired release of nitric oxide, the endothelial lining of the vessels releases an endothelin hormone, which increases vasoconstriction.
The retention of fluids increases the stretching of myocardial tissue, which stimulates the release of natriuretic peptides.3,4
There are 2 natriuretic peptides that are released by the heart in response to the increased filling pressures or stimulation of stretch receptors located in the heart. One is human atrial natriuretic hormone (hANP), which is released by receptors located in the atria, and the other is human brain natriuretic hormone (hBNP) released from receptors located in the ventricles. Both of these hormones stimulate the kidneys to increase the excretion of sodium and water in an effort to decrease the circulating volume. The release of hBNP also promotes vasodilatation of veins, arteries, and coronary arteries, which decreases preload and afterload, which, in turn, reduces blood pressure.3,4
Over time the body's compensatory responses fail, which leads to stiffening of the endothelial layer of blood vessels and the heart, causing the tissue to become noncompliant, which promotes ventricular remodeling. As the cycle of events continues, it perpetuates the signs and symptoms of HF, which can lead to repeated hospital admissions for the treatment of acute symptoms. Understanding the underlying mechanisms that lead to HF can help demystify the current evidence-based guidelines. It will allow nurses to understand the rational behind the drug therapy and treatment standards recommended by the ACC/AHA and the IHI, while improving care for HF patients.
PHARMACOLOGICAL TREATMENT OF HF
To understand recommendations for drug treatment, it is necessary to have knowledge of the classification of recommendations and levels of evidence system that have been assigned by the ACC/AHA guidelines. These recommendations are based on multiple clinical trials and are relevant to the size of the population studied.5
Classification of recommendations assigns an estimated value to the effectiveness of the treatments. The ACC/AHA classification system ranks treatment effectiveness from class I to class III. Class I recommendations support the use of a particular procedure or treatment as being beneficial, useful, and/or effective based on the evidence and/or general agreement of the data. Class II recommendations indicate that there is conflicting evidence and/or a divergence of opinion about the usefulness or efficacy of a procedure or therapy. Class II has 2 subdivisions: class IIa states that the evidence or opinion is in favor of the usefulness or efficacy of the data. Class IIb states that the evidence or opinions are not well established. Class III recommendations do not support use, since the procedure or therapy is not effective, and may be harmful.5
Levels of evidence examine the number of study groups involved in the clinical trials or analyses, which determines the generalized application of the recommendations on the size and types of populations studied. Levels of evidence are graded from A through C. Level A means that the data are derived from multiple random clinical trials or meta-analyses. This level of evidence provides more validity across diverse population sets. Level B data are obtained from a single random trial or nonrandomized studies; these studies are limited to the population used to conduct the research. Level C states that recommendations are based on the consensus opinion of experts, case studies, or standards of care.5
CURRENT PHARMACOLOGICAL TREATMENT
Lifestyle changes and the use of medications are the primary means for prevention and regression of left ventricular dysfunction. The frequency of rehospitalizations can be decreased if patients are compliant with their medication and monitoring based on their plan of care. Patients need to be educated on their medications prior to discharge from the hospital, with nurses playing an intricate part in this process.
ACE inhibitors
The first-line drug of choice is an ACE inhibitor, with a class I, level A of evidence recommendation, which causes a positive effect on cardiac function by reducing preload and afterload, while increasing cardiac output and ejection fraction.5 The mechanism of action is vasodilation of both the venous and arterial sides of the heart. ACE inhibitors are effective in managing HF by interrupting the stimulation of renin-angiotensin-aldosterone system. The specific properties of ACE inhibitors allow them to bind to active sites of ACE, which block the conversion of angiotensin I to angiotensin II, both of which are potent vasoconstrictors. The inhibition of angiotensin II decreases aldosterone-mediated sodium and water retention by the kidneys, which decreases the circulating volume. The reduction in volume decreases ventricular end diastolic pressure (preload), which indirectly produces vasodilation and decreases systemic vascular resistance (afterload). In turn, cardiac output increases and patients experience a decrease of their HF symptoms.4
ACE inhibitors are initiated at low doses followed by gradual increases if lower doses are well tolerated. Renal function and serum potassium level should be monitored 1 to 2 weeks after starting therapy and then periodically (Table 1). ACE inhibitors should be used with caution in patients with very low systemic blood pressures (systolic pressure <80 mm Hg), increased serum creatinine level above 3 mg/dL, bilateral renal artery stenosis, and serum potassium levels above 5.5 mmol/L. Patients should not receive an ACE inhibitor if they have experienced angioedema or renal failure symptoms with previous use of the drug, or if they are pregnant.4,6
The most common adverse effects of ACE inhibitors are headaches, dizziness, fatigue, diarrhea, coughing, and hypotension. The most frequent of these adverse effects is coughing. Patients describe their cough as dry and nagging, which is reversible once the drug has been discontinued. If the side effects can be tolerated the patient should be encouraged to stay on the ACE inhibitor, as its benefits outweigh the adverse effects.4,6
[beta]-Blockers
[beta]-Blockers, specifically carvedilol, bisoprolol, and metoprolol, are recommended as a class I, level A of evidence for the treatment of HF with reduced LVEF.5 Historically, [beta]-blockers had been contraindicated for the treatment of HF. The combination of their negative inotropic effect, bradycardia, and peripheral vascular constriction can exacerbate signs and symptoms of HF. However, the results from recent experimental and controlled clinical trails suggest that prolonged activation of the SNS can accelerate the progression of HF, which is where [beta]-blockers are helpful.7
These agents decrease the effects of the SNS on the heart and blood vessels. Activation of the SNS causes the release of catecholamines, which triggers cellular changes that promote the loss of myocardial cells. These cells lead to cell death (apoptosis). [beta]-Blockers decrease the adrenergic effects generated by this process. Both carvedilol and metoprolol have been shown to improve left ventricular function, hemodynamics, and symptoms of HF.8 Multiple clinical trials demonstrated a 65% reduction in death rates when using carvedilol versus placebo.8 The clinical trials on [beta]-blockers were performed on patients receiving ACE inhibitor therapy. ACE inhibitors are still the preferred first-line agent, however, evidence supports the combined use of both agents.7,8
Initiation of [beta]-blockers therapy starts with the lowest dose possible to prevent symptoms of excessive vasodilation such as hypotension, dizziness, or lightheadedness. Blood pressure should be closely monitored during treatment. Drug titration should be done slowly, doubling the dose each time. [beta]-Blockers may cause fluid retention after 3 to 5 days of starting initial dose (Table 1). Diuretic therapy can be added or adjusted to treat this initial fluid retention until weight returns to pretreatment levels. Taking the [beta]-blocker, ACE inhibitor, or vasodilator at different times during the day can reduce the risk of developing hypotension.5,6
[beta]-Blockers are contraindicated in patients who experience bronchospasm, symptomatic bradycardia, or advanced heart blockage without pacemaker backup. Liver functions need monitoring, as rare cases of hepatic injury have been reported with carvedilol. It is important for patients to understand that initial effects of early therapy usually do not preclude the long-term use of the drug, because the benefits of [beta]-blocker outweigh the side effects. Most symptoms improve within 2 to 3 months of initial treatment.5,6
Angiotensin II receptor blockers
ARBs inhibit stimulation of the renin-angiotensin-aldosterone system by blocking the physiologic effect at the level of angiotensin receptors. They do not block degradation of vasoactive chemicals such as bradykinin and substance P; they are not associated with the adverse effects caused by ACE inhibitors from the accumulation of bradykinin. ARBs are an acceptable alternative for treatment of HF patients who cannot tolerate ACE inhibitors, and are assigned a class I, level A of evidence recommendation.5
Initial doses of the drug start out low to prevent hypotension and then increased according to the patient's tolerance levels (Table 1). Patient's renal function and blood pressure need monitoring during treatment to prevent renal impairment and hypotension. The most common adverse effect of ARBs is hypotension, with patients suffering from hyponatremia, hypovolemia, renal impairment, and low baseline blood pressures are more at risk for developing hypotension. ARBs can worsen renal function as well as hyperkalemia, and are contraindicated in pregnancy.5,6
ADJUNCTIVE TREATMENT
Alternative vasodilator therapy
Alternative vasodilation therapy is an appropriate option for patients with contraindications or intolerance to ACE inhibitors and/or ARBs. The ACC/AHA has ranked them as a class IIa recommendation, with a level A of evidence.5 They can be used in addition to ACE inhibitors when a patient requires more systemic vasodilation to reduce preload and after load. This, in turn, improves cardiac output and hemodynamic parameters without direct inotropic effect.9 Hydralazine and isosorbide dimitrate combinations are the favored drugs for this type of therapy. Vasodilators are classified by their mechanism of action; they can be a venodilator, arteriolar dilator, or a balanced vasodilator. Isosorbide is a venodilator that redistributes blood from the venous side of the heart to systemic circulation, which causes a decrease in preload. Hydralazine is an arteriolar dilator, as it causes a decrease in afterload. ACE inhibitors and ARBs are considered balanced vasodilators, as they exert their effect on both the venous and arterial sides of the heart.5,6
Diuretics
In HF patients, significant volume overload should be treated with diuretics in conjunction with an ACE inhibitor and a [beta]-blocker. This drug classification is ranked a class I, level C of evidence and is recommended for patients with symptoms of fluid retention.4 Diuretics promote an increase of sodium and water excretion by the kidneys. Thiazide-type diuretics effects occur in the distal tubules of the kidneys. Loop diuretics work at the loop of Henle as well as at the proximal and distal tubules. Diuretics decrease preload by reducing volume overload.6
Dosages are commonly prescribed at the lowest fixed dose possible (Table 2). Administrations of intravenous loop diuretics are used for patients in the acute care setting who may require aggressive therapy to control onset of severe symptoms. Diuretics are titrated to achieve maximum improvement of volume overload. Overuse of diuretics should be avoided before starting ACE inhibitors, as volume depletion can lead to hypotension and renal insuffiency.5
Calcium channel blockers
First-generation calcium channel blockers (CCBs) are not recommended because of their myocardial depressant effect. Newer vascular selective dihydrpyridine CCBs, such as amlodipine and felodipine, have fewer myocardial depressant effects and are used in adjunct to standard HF therapy for treatment of resistant hypertension and angina.9 Amlodipine and flodipine are prescribed for the treatment of hypertension or angina at a dosage of 5 to 10 mg daily. The most common side effects are hypotension, flushing, headaches, and edema.5,6
Digoxin
The use of digoxin for the treatment of HF remains controversial, as clinical trials have not shown a decrease in the mortality rate in HF patients who were taking digoxin in combination with diuretics and ACE inhibitors.6 However, digoxin is associated with the improvement of symptoms when administered with standard therapy for HF caused by systolic dysfunction. It has a class IIa, level B of evidence.5 Digoxin has an inotropic effect that is caused by inhibiting the cell membrane sodium-potassium adenosine triphosphatase activity, which increases calcium entry into the cell. Calcium has been shown to improve contractility of myocardium.4
Loading doses of digoxin are not usually required in the treatment of HF. The dosing is based on renal function, age, and body weight, with recommended doses ranging from 0.125 to 0.25 mg daily. A serum digoxin level should be drawn approximately 1 to 2 weeks after initial treatment. Once a steady state is reached, the patient should be monitored periodically for symptoms of toxicity, including serum electrolytes, serum urea nitrogen, creatinine, and serum digoxin level.6
Digoxin toxicity is an adverse effect that is manifested by central nervous system and gastrointestinal symptoms. Central nervous system adverse effects include headaches, fatigue, malaise, disorientation, confusion, delirium, seizures, and visual disturbances.6
Aldosterone antagonists
Aldosterone antagonists have a class I, level B of evidence; they should be used carefully in selected patient populations.5 These drugs are classified as aldosterone receptor blockers. Some HF patients may continue to have high levels of circulating aldosterone even if they are on an ACE inhibitor or an ARB. This is the reason the recommendations support low dose use of aldosterone antagonists in patients with moderately severe to severe symptoms of HF and reduced LVEF. Patients need monitoring for renal function and potassium concentration during treatment with these agents. Baseline creatinine and potassium levels are required prior to initial dosing. Therapy can be initiated if creatinine is less than or equal to 2.5 mg/dL in men or less than or equal to 2.0 mg/dL in women and a potassium level of less than 5.0 mEq/dL.6
CONCLUSION
The ACC/AHA published its first guidelines for evaluation and management of HF in 1995, with subsequent revisions in 2001 and 2005.5 These guidelines will continue to be revised as new evidence emerges from our academic centers. Understanding the current guidelines will provide the knowledge to support their use in other clinical settings. This will allow nursing staff to promote quality patient outcomes and assist their healthcare institutions and participating healthcare providers to meet the core indicators set by the IHI and the ACC/AHA.
Knowledge of the current recommendations for drug therapy, mechanism of action, adverse effects, precautions, and recommended dosing schedule allows nurses to collaborate with physicians about the patient's plan of care, educate patients and their families, and provide vigilance of the IHI core standard.
REFERENCES