Management of Heart Failure and Treatment Algorithm

Article Outline

• Abstract
• Pathophysiology
• Clinical Presentation
• Initial Diagnostic Evaluation
  • Plasma BNP
  • Echocardiography
  • Chest X-ray
  • Electrocardiogram
  • Biochemistry
• Additional Diagnostic Tests
• Pharmacologic Treatment
  • Diuretics
  • Clinical Use of Diuretics
  • β-Blockers
  • Clinical Use of β-Blockers
  • ACE Inhibitors and Angiotensin Receptor Blockers
  • Clinical Use of ACE inhibitor and ARBs
  • Aldosterone Antagonists
  • Clinical Use of Aldosterone Antagonists
  • Combination of Nitrates and Hydralazine
  • Clinical use of Combined Nitrate and Hydralazine
  • Digitalis
  • Clinical Use of Digitalis
• Other Treatment
• Clinical Pathway
• Summary
• References
• Copyright

Abstract 

The prevalence of heart failure is increasing among patients seen in primary care settings. Proper diagnosis is essential, given that many treatment conditions may mimic symptoms of heart failure. Early diagnosis and treatment not only can increase a patient's overall quality of life, but they can also significantly reduce rates of mortality and morbidity. Many pharmacologic options are available to treat heart failure. Use of each medication in heart failure management needs to be carefully considered in selected patients. Close monitoring of efficacy and side effects of each medication is vital.

Keywords:  Diagnosis , heart failure , pathophysiology , pharmacologic treatment , treatment algorithm

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As the age of the general population increases, the prevalence and incidence of heart failure (HF) are also on the rise.¹, ², ³ HF is often a progressive condition associated with significant rates of mortality and morbidity that affects mainly the elderly. Five-year mortality rates range from 35% in mild-to-moderate HF to up to 50% in advanced HF. The financial burden of direct HF care in 2006 was estimated at $29.6 billion in the United States.¹

Management of HF should include early identification of persons at risk of developing HF (Table 1) as well as measures to improve quality of life among persons with the disease.⁴, ⁵ This article focuses on the management of chronic HF in ambulatory care settings because most HF care is being provided by primary care clinicians.

Table 1. Factors that Increase Risk of Developing Heart Failure⁴

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Pathophysiology 

Left ventricular (LV) dysfunction usually occurs as a result of myocardial infarction, chronic hypertension, cardiomyopathy, or valvular heart disease.⁴, ⁵, ⁶, ⁷ To maintain adequate tissue perfusion in the presence of LV dysfunction, several physiologic compensatory mechanisms are activated. The two main compensatory mechanisms involve the sympathetic nervous system (SNS) and the rennin-angiotensin-aldosterone system (RAAS). In an acute setting, these mechanisms are important to maintain homeostasis. However, in chronic HF, these neurohormones can cause damaging effects that lead to worsening of the HF symptoms.⁸, ⁹

The activation of the SNS causes arterial vasoconstriction, which leads to increased blood pressure, heart rate, and cardiac afterload. As a result, cardiac workload and oxygen demand are increased, causing further cardiac ischemia. In addition, increased renal vascular resistance by activation of the SNS also reduces renal perfusion and increases renin secretion. Furthermore, the release of renin leads to increased angiotensin II and aldosterone and, subsequently, activates the RAAS. The RAAS increases overall sodium retention and edema. It also reduces the effects of brain natriuretic peptide (BNP). BNP has vasodilatory and diuretic properties and is secreted by ventricles when the tension of the ventricular walls is increased. In acute HF, BNP is initially secreted to maintain sodium balance and to increase vasorelaxation. Therefore, activation of the RAAS blunts the compensatory mechanisms of BNP in the early stage of HF. In addition, aldosterone, which is increased by the RAAS, can cause further reabsorption of sodium. Aldosterone also was reported to increase tissue fibrosis, cause vascular remodeling, reduce heart rate variability, and have predysrhythmic properties, all of which can lead of progression of HF.⁸, ⁹

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Clinical Presentation 

Depending on the severity of the disease and its cause, HF may present with various combinations of the following symptoms⁴, ⁹:

The New York Heart Association (NYHA) classification is widely used to classify severity of the disease by assessing patients' HF functional status (Table 2).

Table 2. NYHA Functional Classification⁴

Many conditions may mimic HF symptoms; therefore, it is important first to rule out other possible causes of the symptoms. Differential diagnoses for HF include coronary ischemia, anemia, physical deconditioning, obesity, hepatic failure, renal failure, hypoalbuminemia, venous stasis, anxiety, and hyperventilation.⁴ The Framingham Heart Study criteria were reported to be 100% sensitive and 78% specific for identifying persons with definite congestive HF (Table 3).¹⁰

Table 3. Framingham Heart Failure Criteria¹⁰

Diagnosis of CHF requires the simultaneous presence of at least 2 major criteria or 1 major criterion in conjunction with 2 minor criteria.

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Initial Diagnostic Evaluation 

Plasma BNP 

B-type natriuretic peptide is a cardiac neurohormone secreted by the ventricles and is a significant predictor of HF. The likelihood of a diagnosis of HF is small when BNP is less than 100 pg/mL.⁴, ¹¹ Therefore, it would be helpful to establish a BNP baseline for patients with chronic HF.

Echocardiography 

Echocardiography is the most useful noninvasive tool to diagnose HF. It reliably provides information on measurements of cardiac chambers, wall thickness, LV function, valvular function, and estimates of hemodynamic pressures.¹², ¹³

Most patients with HF have systolic HF.⁶ In systolic HF, patients usually have global hypokinesis causing a reduction of LV ejection fraction (LVEF) to less than 40%. Additional findings include elevated ventricular filling pressure and increased pulmonary pressure.

Patients with diastolic HF usually have normal or near normal LVEF. Left atrial enlargement in the absence of mitral valve disease is highly indicative of LV diastolic dysfunction. In addition, abnormal blood flow across the mitral valve can be detected when impaired LV relaxation is present.¹⁴

Chest X-ray 

Chest X-ray can be used as a screening tool to rule out pneumonia as a source of a patient's symptoms. It also allows an assessment of heart size, although it is a poor indicator for ventricular function or dilatation. Presence of cardiomegaly supports the diagnosis of HF, especially when upper lobe pulmonary venous congestion is present.¹³ However, chest X-ray is not recommended for routine HF follow-up.

Electrocardiogram 

Electrocardiogram (EKG) is an important part of HF evaluation, although there are no specific EKG findings that are diagnostic for HF. Presence of a Q wave would suggest a history of myocardial infarction and ischemic heart disease. In addition, heart rate and rhythm can provide overall assessment of cardiac function. Most importantly, LV hypertrophy is a common finding among patients with HF.⁴, ¹² Furthermore, prolongation of the QRS duration is considered as an indication of poor prognosis in patients with HF.³

Biochemistry 

In addition to BNP, it is essential to perform other laboratory tests to identify possible correctable triggering factors for a patient's HF exacerbation. These laboratory tests include complete blood count to rule out anemia and infection; thyroid function test to rule out thyrotoxicosis; serum creatinine to assess renal function; electrolytes to assess potassium, sodium, and glucose status; and liver function test to rule out hepatic congestion as a result of HF.⁴, ⁶, ¹²

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Additional Diagnostic Tests 

The following secondary diagnostic tests may be considered for some, but not all, patients to help identify HF management options.⁴, ⁵, ⁶, ¹²

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Pharmacologic Treatment 

Because of the complexity of the disease, most patients with HF are routinely treated with polypharmacy. Most experts recommend that medications be adjusted to dosages used in research protocols that have shown clinical benefits. Close monitoring of these medications is essential to avoid complications and to maximize their clinical effects.

Diuretics 

Symptoms of HF usually result from fluid and sodium retention. Diuretics can effectively reduce the symptoms of pulmonary and systemic congestion and restore euvolemia. However, diuretics were not shown to improve mortality and should not be used alone in management of chronic HF.⁵, ⁷ In addition, many patients may exhibit HF symptoms without any signs of overt fluid overload; diuretics should not be used as the first-line treatment for these patients and those remain asymptomatic. There are three main categories of diuretics, and each works at a different site in the renal tubule.

Thiazides. Thiazide diuretics block sodium transport in the distal convoluted tubule. When used alone, thiazides are effective for treatment of hypertension but not of HF. In addition, the effects of thiazides are reduced when the glomerular filtration rate is below 30 mL/min,⁶, ⁷ and they would not be helpful to many patients with HF who already have compromised kidney function. However, metolazone (Zaroxolyn), a potent thiazide, is effective when used along with a loop diuretic to synergize the diuretic effect in patients with severe HF.⁹ When given in combination, metolazone usually is given 30 minutes before the loop diuretic.

Loop diuretics. The loop diuretics are the diuretic of choice for treatment of HF. The site of action for loop diuretics is in the ascending limb of the loop of Henle. Patients with chronic HF may develop loop diuretic resistance that will require either increasing the dosage of the loop diuretic or adding metolazone to the regimen.

Potassium-sparing diuretics. These diuretics inhibit sodium reabsorption in the collecting duct of the nephron and have mild direct diuretic and antihypertensive effects. They are often used as an adjunct agent to maintain normokalemia.⁹ However, spironolactone (Aldactone) is also used as a neurohormonal antagonist for patients with advanced HF. The use of spironolactone is discussed in a later section. Renal insufficiency and hyperkalemia are contraindications for its use.

Clinical Use of Diuretics 

Patients should have baseline blood pressure, weight, serum glucose, and serum electrolytes done before starting a diuretic.⁴ Hydrochlorothiazide may be effective for patients with hypertension and minimal fluid retention; otherwise, use a loop diuretic for all patients with HF. Both blood pressure and electrolytes should be repeated in 1 to 2 weeks. Some patients may be taught to increase the loop diuretic dosage for 1 to 2 days if there is a weight gain of 2 pounds in 1 day or with increased HF symptoms. Persons taking higher dosages of loop diuretics are at risk of developing prerenal syndrome if they are overdiuresed, causing elevation in blood urea nitrogen, creatinine, and potassium. If overdiuresis occurs, the diuretics need to be withheld or reduced, and electrolytes and renal functions should be repeated in 1 to 2 days before resuming treatment. To prevent diuretic resistance, patents should always be maintained on the lowest effective loop diuretic dosage and to reduce dietary sodium intake.⁵ When a patient becomes resistant to one loop diuretic, switching to a different loop diuretic may overcome the resistance. If such strategy does not work, adding metolazone 1 to 2 times a day 30 minutes before a loop diuretic is usually effective.⁴ A potassium-sparing diuretic can also be considered along with a loop diuretic, especially in the presence of hypokalemia.

β-Blockers 

After a myocardial infarction, β-blockers may reduce mortality, LV remodeling, and hospital readmission.⁵, ⁷ They suppress both SNS and RAAS to provide cardiac protection. However, only three β-blockers, bisoprolol (Zebeta), carvedilol (Coreg), and sustained-release metoprolol XL (Toprol XL), have been approved for the management of HF.⁹ β-Blockers should be used with caution in patients with diabetes, asthma, peripheral vascular disease, hypotension, and bradycardia. The combination of a β-blocker and an angiotensin-converting enzyme (ACE) inhibitor is recommended for management of patients with chronic HF with LVEF of 40% or less.

Clinical Use of β-Blockers 

Unless contraindicated, patients should be placed on a β-blocker before discharge from the hospital after an MI or stable HF. Patients should be started on a low dose and the dose gradually increased every 2 weeks to reach target doses in 8 to 12 weeks.⁵ If worsening of HF symptoms occurs during increasing dosing of a β-blocker, adjustments of diuretic and other medications may be tried before lowering the dosage of the β-blocker. Patients must avoid abrupt discontinuation of β-blockers because this may cause rebound hypertensive effects.

ACE Inhibitors and Angiotensin Receptor Blockers 

ACE inhibitors and angiotensin receptor blockers (ARBs) reduce the effects of angiotensin II and subsequently decrease aldosterone production. In studies, ACE inhibitors decreased rates of mortality, reduced hospital admissions, and increased functional status in patients with NYHA classes II to IV. They also were shown to benefit patients with asymptomatic systolic dysfunction.⁴, ⁷

Common side effects of ACE inhibitors are cough, hyperkalemia, and, rarely, angioedema.⁴, ⁵, ⁹ They are used with caution when patients are also on a potassium-sparing diuretic. In general, ACE inhibitors are preferred to ARBs because ACE inhibitors were widely found to be efficacious in clinical trials. However, ARBs usually do not cause cough and may be equally effective in management of HF for patients who developed cough from ACE inhibitors. The benefits of ARBs were shown in the CHARM and Val-Heft trials that found significant reduction of cardiovascular mortality in patients with NYHA class II to III HF with the use of candesartan and valsartan.¹⁵, ¹⁶ However, the ELITE II trial revealed nonsignificant increase of sudden death or resuscitated cardiac arrests in patients taking losartan (Cozaar) compared with captopril.¹⁷ Therefore, valsartan (Diovan) and candesartan (Atacand) are the preferred ARBs used in the management of HF.⁵ In addition, combination of an ACE inhibitor and candesartan were shown to reduce overall cardiovascular event in patients with chronic HF in the CHARM-added trial.¹⁵ However, the combination of ACE inhibitor, ARB, and aldactone antagonist should not be used because of increased risks of hyperkalemia.⁵

ACE inhibitors are contraindicated in patients who are pregnant, have a history of angioedema with previous exposure to an ACE inhibitor, or have severe hypotension. Furthermore, caution is required in patients with elevated creatinine (>3 mg/dL), elevated serum potassium (>5.5 mmol/L), or bilateral renal artery stenosis.⁶

Clinical Use of ACE inhibitor and ARBs 

An ACE inhibitor may be used as a monotherapy for patients with mild HF without fluid retention. Start patients on a low dose after obtaining baseline potassium and renal function. Potassium and creatinine must be repeated in 1 to 2 weeks. Stop the medication immediately if there is a significant elevation in potassium or serum creatinine. If there are no contraindications, the dosage can be slowly increased to the target dosage used in clinical trials.⁹ Switch to Atacand or Diovan if cough persists on an ACE inhibitor.⁵

Aldosterone Antagonists 

Spironolactone and Eplerenone suppress the neurohormonal effects that cause the cascade of HF symptoms. Spironolactone was found to significantly reduce rates of mortality, decrease hospitalization, and improve HF symptoms among patients with NYHA class IV HF on standard HF therapy.¹⁸ Renal insufficiency and hyperkalemia are contraindications for their use. Close monitoring of renal function and serum potassium is required, especially when a patient is also on an ACE inhibitor or ARB. An aldosterone antagonist is considered only if patients remain symptomatic after treatment with diuretic, ACE inhibitor or ARB, and β-blocker.

Clinical Use of Aldosterone Antagonists 

Baseline serum potassium and creatinine should be obtained and repeated in 3 days and periodically during treatment.⁴ The medication should be discontinued if any significant elevation of potassium or creatinine is noted.

Combination of Nitrates and Hydralazine 

Combination of nitrates and hydralazine was found to be more effective than placebo but less effective than an ACE inhibitor in HF management. However, in a subsequent African-American Heart Failure Trial (A-HeFT), the combination of nitrate and hydralazine showed significant benefits in African American patients with NYHA class III to IV HF who were already on standard drug treatment with diuretic, ACE inhibitor or ARB and β-blocker.⁴ Headache is a common complaint, and lower dosage should be started with gradual increase in dosage.

Clinical use of Combined Nitrate and Hydralazine 

Given the beneficial finding of the A-HeFT, combined nitrate and hydralazine should be considered in African American patients with NYHA class III and IV HF who are already on the standard ACE inhibitor or ARB, β-blocker, and aldactone.⁴ This is also a possible alternative treatment for patients who are unable to tolerate ACE inhibitors.⁶, ⁷ To prevent nitrate-related headaches, start on a low dose and have the patient take Tylenol 30 minutes before taking nitrate. BiDil is a drug that combines hydralazine 37.5 mg and isosorbide dinitrate 20 mg in one pill. However, separate nitrate and hydralazine can be used if cost is a concern. Patient compliance needs to be monitored because this regimen requires dosing 3 to 4 times a day.

Digitalis 

Use of digoxin in treatment of HF is controversial, especially in patients with low LVEF, normal sinus rhythm, or without history of HF symptoms.⁵ Several studies showed short-term treatment with digoxin improved HF symptoms, quality of life, and exercise tolerance.⁵, ⁷ The Digitalis Investigation Group Trial showed that in patients with LVEF of 45% or less and already on diuretic and ACE inhibitor, when compared with a placebo, patients in the digoxin group were less likely to develop worsening HF and to be hospitalized. However, there was no difference in mortality rate.⁴ Digoxin provides positive inotropic effects and reduces plasma noradrenaline and sympathetic nerve activity. Therefore, digoxin is most beneficial for patients with HF who also have atrial fibrillation. Otherwise, digoxin should be considered only as an add-on therapy for patients remaining symptomatic despite ACE inhibitor, β-blocker, diuretic, and aldosterone antagonist.⁵ Contraindications to the use of digoxin include second- and third-degree atrioventricular block, sick sinus syndrome, and severe bradycardia.

Clinical Use of Digitalis 

Digoxin should not be used as a primary HF therapy. No loading dose is needed for patients with chronic HF.⁶ Baseline EKG, renal function, and electrolytes will need to be obtained. Digoxin levels need to be monitored and kept below 1.0 ng/mL.⁴, ⁵ In addition, serum potassium, magnesium, and renal function should be checked periodically to avoid digoxin toxicity.⁴, ⁵, ⁶

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Other Treatment 

Cardiac resynchronization therapy, such as cardioverter-defibrillators and pacemakers, are increasingly implanted in patients with advanced HF. Outpatient infusion therapy with Lasix also is becoming popular for treatment of refractory HF. However, these treatments are usually managed by cardiology specialists and are beyond the scope of this article. Patients who continue to exhibit HF symptoms despite maximal pharmacologic treatment should be referred to specialists for further interventions.

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Clinical Pathway 

Treatments of diastolic HF are not fully established. Tighter control of both systolic and diastolic blood pressures remains the goal in treating asymptomatic diastolic HF.⁵ However, management of systolic HF is well defined. A step-by-step treatment algorithm for systolic HF management was developed to guide therapeutic approach (Figure 1).

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• Figure 1. 

  HF treatment algorithm for patients without MI.

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Summary 

HF therapies are complex, and they require significant oversight from primary care clinicians. It takes a careful balance to slowly titrate the medications to control the symptoms without causing potentially harmful side effects. Many patients with HF can lead productive lives for many years with proper management of their medical treatment.

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References 

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