Applied Evidence

Shoulder pain is a common problem that can pose difficult diagnostic and therapeutic challenges for the family physician. It is the third most common musculoskeletal complaint in the general population, and accounts for 5% of all general practitioner musculoskeletal consults.^1,2 The incidence of shoulder pain is 6.6 to 25 cases per 1000 patients, with a peak incidence in the fourth through sixth decades.^3-6 Shoulder pain is second only to knee pain for referrals to orthopedic surgery or primary care sports medicine clinics.^7,8 Furthermore, 8% to 13% of athletic injuries involve the shoulder and account for up to 3.9% of new emergency department visits.^9,10

Differential diagnosis

The challenge for the physician evaluating shoulder pain is the myriad of etiologies and the potential for multiple disorders. Compounding the challenge is a lack of uniformity in the literature regarding diagnostic classification.¹¹ As Table 1 shows, the age of the patient will help focus the differential diagnosis. Patients younger than 30 years old tend to have biomechanical or mild inflammatory etiologies for their pain such as atraumatic instability, tendinosis, and arthropathies. Less than 1% of shoulder injuries in persons younger than 30 years are complete rotator cuff tears, which occur in 35% of patients older than 45 years with shoulder pain.^12,13

The rotator cuff is the most commonly affected structure in the shoulder, and subacromial impingement syndrome is the leading cause of rotator cuff injury.^4,12,14-16 Neer¹⁴ described 3 stages of shoulder impingement that he estimated lead to 95% of rotator cuff tears. Impingement can be caused by repetitive overhead activities, acute trauma, or subtle instability (atraumatic instability). The current theory is that inflammation of the rotator cuff tendons and/or bursa, caused by irritation against the coracoacromial arch, can progress to a complete rotator cuff tear over time.

Referred sources of shoulder pain should be included in the differential diagnosis of shoulder pain. Potential sources include cervical spondylolysis, cervical arthritis, cervical disc disease, myocardial ischemia, reflex sympathetic dystrophy, diaphragmatic irritation, thoracic outlet syndrome, and gallbladder disease.

TABLE 1
Differential diagnosis of shoulder pain

Using the history and physical examination

As noted above, the likelihood of specific conditions such as a complete rotator cuff tear varies with the setting, age of the patient, and specialty of the physi-cian.^4,13,17,18 It is important to keep this pretest probability in mind while interpreting the history and physical examination. For example, a positive empty can test in a 50-year-old patient almost certainly represents a rotator cuff tear, whereas many younger patients with this finding will not have a tear. Moreover, certain components of the history and physical examination are more indicative of disorders while others are better at ruling them out. This concept is represented by the positive and negative likelihood ratios listed in Table 2.

The clinical evaluation begins with identification of the chief complaint and a thorough history. Common complaints include pain, weakness, stiffness, instability, locking, catching, and deformity.²⁶ Determining the duration of symptoms and mechanism of injury will narrow the differential diagnosis. If trauma occurred, the mechanism can determine radiological needs. Aggravating and alleviating factors should be reviewed, including work, recreation, sports, or hobbies. Night pain when lying on the affected side and a history of trauma in a patient older than 65 years both suggest a rotator cuff tear, but no individual symptom is definitive for the diagnosis (Table 2).¹⁹ Pain with overhead work may indicate impingement syndrome, especially if the patient is symptomatic through the arc of 60 to 120 degrees.

The physical examination should include observation, palpation, range of motion (ROM), and provocative testing. Observation requires adequate exposure of the shoulders bilaterally to identify any gross deformities or abnormalities, including muscle atrophy, acromioclavicular joint disparity, or evidence of trauma. Muscle atrophy of either the supraspinatus or infraspinatus muscles is moderately predictive of rotator cuff tears in the elderly population, with a positive predictive value of 81%. However, this sign is not useful if absent, with a negative predictive value of only 43%.¹⁹ No studies have assessed the role of palpation in the evaluation of shoulder pain. Nevertheless, the role of palpation in discerning acromioclavicular joint pathology from shoulder and neck makes it a useful part of the examination.

The shoulder’s ROM should be evaluated both actively and passively. The shoulder is a mobile joint with a complexity of movements. These include flexion to 180 degrees, extension to 40 degrees, abduction to 120 degrees with palms down and 180 degrees with palms up, internal rotation to 55 degrees, and external rotation to 45 degrees with arms at the side. Although determining abduction ROM is consistent among examiners,²⁷ interrater reliability is poor for assessment of external rotation ROM. Lack of full ROM that is equally limited with both passive and active examination is found in arthropathies and adhesive capsulitis.

Pain between 60 and 120 degrees of abduction “the painful arc”) is associated with subacromial impingement, whereas pain after 120 degrees is an indication of acromioclavicular joint origin. However, Calis and coworkers¹⁷ found that the presence of subacromial impingement has a positive likelihood ratio of only 1.7.

After assessing the ROM, the next steps are to evaluate the rotator cuff and biceps tendon, perform impingement testing, check for instability, and finally assess the acromioclavicular joint. The tests are listed in Table 2 in our preferred order of examination and represent the tests best supported by the evidence; the results are based on a literature search of Medline, PubMed, DARE, and Sports Discuss. The technique of each examination maneuver has been published elsewhere and is not described in detail here. Figure 1 through 4 illustrate several common examination maneuvers described below. A Web site that demonstrates the physical examination more thoroughly can be found at http://www.nismat.org/orthocor/exam/shoulder.html#Evaluation.

TABLE 2
Use of history and physical examination to diagnose shoulder pain

Figure 1
The empty can test

Rotator cuff tests

The drop arm test assesses the integrity of the rotator cuff, predominantly the supraspinatus muscle. The empty can test (Figure 1) isolates the supraspinatus against resistance. The lift off test (Figure 2) assesses the subscapularis integrity.

Figure 2
The lift off test

Impingement syndrome

Hawkin’s sign (Figure 3) is a test for evidence of impingement by re-creation of its symptoms.

Figures 3A & 3B
Hawkin’s sign

Glenohumeral joint stability

The augmented anterior apprehension test evaluates anterior shoulder instability. The relocation test, which helps confirm anterior instability, is carried out immediately after a positive anterior apprehension test.

Labral tears

The crank test is used to identify chronic labral injury, whereas the active compression test²⁵ (Figure 4) indicates labral injury if pain is deep in the shoulder.

Figure 4
The active compression test

Acromioclavicular joint

The active compression test²⁵ (Figure 4) indicates acromioclavicular joint inflammation, arthritis, or injury if pain is localized to the top of the shoulder.

Diagnostic tests

Imaging studies used in the evaluation of shoulder pain include plain radiographs, arthrography, computed tomography (CT), ultrasound (US), and magnetic resonance imaging (MRI). Often no imaging is required, or plain radiographs are the sole imaging study needed. Soft tissue injuries are best identified by MRI or US, whereas bony pathology is seen best with plain radiographs or CT. Indications for imaging include severe injury, uncontrolled pain, failure of conservative therapy, return to play considerations, and examiner discretion. Table 3 outlines the accuracy of imaging modalities organized by diagnosis.

TABLE 3
Imaging tests to diagnose shoulder pain

Plain radiographs

Plain radiographs are the first step in diagnostic imaging. They can reveal fractures, dislocation, subluxation, bony lesions, outlet obstruction, acromioclavicular joint pathology, and arthritic changes. No definitive clinical studies on the needs of radiographs have been done. Plain radiographs should be taken when ROM is lost, especially when there is abduction of less than 90 degrees, severe pain, and after trauma. Our preferred x-rays include a glenohumeral anteroposterior (AP) view, a supraspinatus outlet view, and an axillary view. Anteroposterior views with internal and external rotation are added in cases of trauma to help rule out fracture. Positive acromioclavicular joint tests (crossover or palpation) should be followed by acromioclavicular joint radiographs because a shoulder series does not give a clear view of this joint. Additional views of the neck as well as a chest x-ray or abdominal imaging should be considered if a referred source of shoulder pain remains a possibility.

Arthrography

Arthrography was the diagnostic test of choice before MRI. It is specific for rotator cuff tears but lacks sensitivity¹⁵ because it cannot detect partial-thickness or associated soft tissue injuries of the shoulder. Arthrography still has a role in evaluating adhesive capsulitis by demonstrating decreased intracapsular volume.²⁶ The test can be therapeutic if the capsule is dilated during the procedure. Additionally, patients with claustrophobia may be good candidates for arthrography if a full-thickness tear is suspected and MRI is not possible.

Computed tomography

Computed tomography may be used to evaluate bony lesions, including glenoid rim fractures, humoral fractures, and acromioclavicular joint disease. Computed tomography arthrograms may have a role in assessing labral tears and full-thickness rotator cuff tears.³⁵ The use of CT arthrography has fallen into disfavor compared with MRI because of the risks associated with contrast exposure and poor sensitivity for partial-thickness rotator cuff tears or associated soft tissue injury.

Ultrasound

Ultrasound has been used in the evaluation of rotator cuff tears with varying degrees of sensitivity and specificity.^12,29,34 This inconsistency may be related to variation in operator skill. Advantages of US include relatively low cost, speed, and noninvasiveness.

Magnetic resonance imaging

Magnetic resonance imaging has become the gold standard for diagnostic imaging of the shoulder related to soft tissue injury. The advantages include its noninvasive nature, lack of contrast exposure, nonionizing radiation, high degree of resolution, and the ability to evaluate multiple potential pathologic processes.³⁶ Magnetic resonance imaging is the preferred test for evaluating impingement syndrome and rotator cuff pathology. A normal MRI greatly reduces the chances of a rotator cuff tear, with a negative likelihood ratio of 0.08.^16,29,30 Magnetic resonance imaging is also useful in the evaluation of avascular necrosis, biceps tendon disorders, inflammatory processes, and tumors.¹³ The diagnosis of labral lesions can be challenging given the relatively low sensitivity and negative predictive value noted in several trials.^16,28,31 Finally, it is important to note that up to one third of all asymptomatic patients and more than half of those older than 60 years demonstrate asymptomatic rotator cuff tears on MRI.³⁷

Approach to the patient

A general approach to the patient with shoulder pain is summarized in Figure 5. Pre- and posttest probabilities are included to give an understanding of how tests may help diagnose or rule out a complete rotator cuff tear. A recent prospective study combining multiple examination maneuvers demonstrated that a combination of 3 physical examination findings (supraspinatus weakness, weakness in external rotation, and impingement) along with the patient’s age can often diagnose or rule out a rotator cuff tear.³⁸ This group of tests did not distinguish full versus partial thickness tears. This approach is summarized in Figure 6.

Figure 5
Basic approach to assess for complete rotator cuff tear

Figure 6
Alternative approach to a suspected rotator cuff tear

Shoulder pain is a common problem that can pose difficult diagnostic and therapeutic challenges for the family physician. It is the third most common musculoskeletal complaint in the general population, and accounts for 5% of all general practitioner musculoskeletal consults.^1,2 The incidence of shoulder pain is 6.6 to 25 cases per 1000 patients, with a peak incidence in the fourth through sixth decades.^3-6 Shoulder pain is second only to knee pain for referrals to orthopedic surgery or primary care sports medicine clinics.^7,8 Furthermore, 8% to 13% of athletic injuries involve the shoulder and account for up to 3.9% of new emergency department visits.^9,10

Differential diagnosis

The challenge for the physician evaluating shoulder pain is the myriad of etiologies and the potential for multiple disorders. Compounding the challenge is a lack of uniformity in the literature regarding diagnostic classification.¹¹ As Table 1 shows, the age of the patient will help focus the differential diagnosis. Patients younger than 30 years old tend to have biomechanical or mild inflammatory etiologies for their pain such as atraumatic instability, tendinosis, and arthropathies. Less than 1% of shoulder injuries in persons younger than 30 years are complete rotator cuff tears, which occur in 35% of patients older than 45 years with shoulder pain.^12,13

The rotator cuff is the most commonly affected structure in the shoulder, and subacromial impingement syndrome is the leading cause of rotator cuff injury.^4,12,14-16 Neer¹⁴ described 3 stages of shoulder impingement that he estimated lead to 95% of rotator cuff tears. Impingement can be caused by repetitive overhead activities, acute trauma, or subtle instability (atraumatic instability). The current theory is that inflammation of the rotator cuff tendons and/or bursa, caused by irritation against the coracoacromial arch, can progress to a complete rotator cuff tear over time.

Referred sources of shoulder pain should be included in the differential diagnosis of shoulder pain. Potential sources include cervical spondylolysis, cervical arthritis, cervical disc disease, myocardial ischemia, reflex sympathetic dystrophy, diaphragmatic irritation, thoracic outlet syndrome, and gallbladder disease.

TABLE 1
Differential diagnosis of shoulder pain

Using the history and physical examination

As noted above, the likelihood of specific conditions such as a complete rotator cuff tear varies with the setting, age of the patient, and specialty of the physi-cian.^4,13,17,18 It is important to keep this pretest probability in mind while interpreting the history and physical examination. For example, a positive empty can test in a 50-year-old patient almost certainly represents a rotator cuff tear, whereas many younger patients with this finding will not have a tear. Moreover, certain components of the history and physical examination are more indicative of disorders while others are better at ruling them out. This concept is represented by the positive and negative likelihood ratios listed in Table 2.

The clinical evaluation begins with identification of the chief complaint and a thorough history. Common complaints include pain, weakness, stiffness, instability, locking, catching, and deformity.²⁶ Determining the duration of symptoms and mechanism of injury will narrow the differential diagnosis. If trauma occurred, the mechanism can determine radiological needs. Aggravating and alleviating factors should be reviewed, including work, recreation, sports, or hobbies. Night pain when lying on the affected side and a history of trauma in a patient older than 65 years both suggest a rotator cuff tear, but no individual symptom is definitive for the diagnosis (Table 2).¹⁹ Pain with overhead work may indicate impingement syndrome, especially if the patient is symptomatic through the arc of 60 to 120 degrees.

The physical examination should include observation, palpation, range of motion (ROM), and provocative testing. Observation requires adequate exposure of the shoulders bilaterally to identify any gross deformities or abnormalities, including muscle atrophy, acromioclavicular joint disparity, or evidence of trauma. Muscle atrophy of either the supraspinatus or infraspinatus muscles is moderately predictive of rotator cuff tears in the elderly population, with a positive predictive value of 81%. However, this sign is not useful if absent, with a negative predictive value of only 43%.¹⁹ No studies have assessed the role of palpation in the evaluation of shoulder pain. Nevertheless, the role of palpation in discerning acromioclavicular joint pathology from shoulder and neck makes it a useful part of the examination.

The shoulder’s ROM should be evaluated both actively and passively. The shoulder is a mobile joint with a complexity of movements. These include flexion to 180 degrees, extension to 40 degrees, abduction to 120 degrees with palms down and 180 degrees with palms up, internal rotation to 55 degrees, and external rotation to 45 degrees with arms at the side. Although determining abduction ROM is consistent among examiners,²⁷ interrater reliability is poor for assessment of external rotation ROM. Lack of full ROM that is equally limited with both passive and active examination is found in arthropathies and adhesive capsulitis.

Pain between 60 and 120 degrees of abduction “the painful arc”) is associated with subacromial impingement, whereas pain after 120 degrees is an indication of acromioclavicular joint origin. However, Calis and coworkers¹⁷ found that the presence of subacromial impingement has a positive likelihood ratio of only 1.7.

After assessing the ROM, the next steps are to evaluate the rotator cuff and biceps tendon, perform impingement testing, check for instability, and finally assess the acromioclavicular joint. The tests are listed in Table 2 in our preferred order of examination and represent the tests best supported by the evidence; the results are based on a literature search of Medline, PubMed, DARE, and Sports Discuss. The technique of each examination maneuver has been published elsewhere and is not described in detail here. Figure 1 through 4 illustrate several common examination maneuvers described below. A Web site that demonstrates the physical examination more thoroughly can be found at http://www.nismat.org/orthocor/exam/shoulder.html#Evaluation.

TABLE 2
Use of history and physical examination to diagnose shoulder pain

Figure 1
The empty can test

Rotator cuff tests

The drop arm test assesses the integrity of the rotator cuff, predominantly the supraspinatus muscle. The empty can test (Figure 1) isolates the supraspinatus against resistance. The lift off test (Figure 2) assesses the subscapularis integrity.

Figure 2
The lift off test

Impingement syndrome

Hawkin’s sign (Figure 3) is a test for evidence of impingement by re-creation of its symptoms.

Figures 3A & 3B
Hawkin’s sign

Glenohumeral joint stability

The augmented anterior apprehension test evaluates anterior shoulder instability. The relocation test, which helps confirm anterior instability, is carried out immediately after a positive anterior apprehension test.

Labral tears

The crank test is used to identify chronic labral injury, whereas the active compression test²⁵ (Figure 4) indicates labral injury if pain is deep in the shoulder.

Figure 4
The active compression test

Acromioclavicular joint

The active compression test²⁵ (Figure 4) indicates acromioclavicular joint inflammation, arthritis, or injury if pain is localized to the top of the shoulder.

Diagnostic tests

Imaging studies used in the evaluation of shoulder pain include plain radiographs, arthrography, computed tomography (CT), ultrasound (US), and magnetic resonance imaging (MRI). Often no imaging is required, or plain radiographs are the sole imaging study needed. Soft tissue injuries are best identified by MRI or US, whereas bony pathology is seen best with plain radiographs or CT. Indications for imaging include severe injury, uncontrolled pain, failure of conservative therapy, return to play considerations, and examiner discretion. Table 3 outlines the accuracy of imaging modalities organized by diagnosis.

TABLE 3
Imaging tests to diagnose shoulder pain

Plain radiographs

Plain radiographs are the first step in diagnostic imaging. They can reveal fractures, dislocation, subluxation, bony lesions, outlet obstruction, acromioclavicular joint pathology, and arthritic changes. No definitive clinical studies on the needs of radiographs have been done. Plain radiographs should be taken when ROM is lost, especially when there is abduction of less than 90 degrees, severe pain, and after trauma. Our preferred x-rays include a glenohumeral anteroposterior (AP) view, a supraspinatus outlet view, and an axillary view. Anteroposterior views with internal and external rotation are added in cases of trauma to help rule out fracture. Positive acromioclavicular joint tests (crossover or palpation) should be followed by acromioclavicular joint radiographs because a shoulder series does not give a clear view of this joint. Additional views of the neck as well as a chest x-ray or abdominal imaging should be considered if a referred source of shoulder pain remains a possibility.

Arthrography

Arthrography was the diagnostic test of choice before MRI. It is specific for rotator cuff tears but lacks sensitivity¹⁵ because it cannot detect partial-thickness or associated soft tissue injuries of the shoulder. Arthrography still has a role in evaluating adhesive capsulitis by demonstrating decreased intracapsular volume.²⁶ The test can be therapeutic if the capsule is dilated during the procedure. Additionally, patients with claustrophobia may be good candidates for arthrography if a full-thickness tear is suspected and MRI is not possible.

Computed tomography

Computed tomography may be used to evaluate bony lesions, including glenoid rim fractures, humoral fractures, and acromioclavicular joint disease. Computed tomography arthrograms may have a role in assessing labral tears and full-thickness rotator cuff tears.³⁵ The use of CT arthrography has fallen into disfavor compared with MRI because of the risks associated with contrast exposure and poor sensitivity for partial-thickness rotator cuff tears or associated soft tissue injury.

Ultrasound

Ultrasound has been used in the evaluation of rotator cuff tears with varying degrees of sensitivity and specificity.^12,29,34 This inconsistency may be related to variation in operator skill. Advantages of US include relatively low cost, speed, and noninvasiveness.

Magnetic resonance imaging

Magnetic resonance imaging has become the gold standard for diagnostic imaging of the shoulder related to soft tissue injury. The advantages include its noninvasive nature, lack of contrast exposure, nonionizing radiation, high degree of resolution, and the ability to evaluate multiple potential pathologic processes.³⁶ Magnetic resonance imaging is the preferred test for evaluating impingement syndrome and rotator cuff pathology. A normal MRI greatly reduces the chances of a rotator cuff tear, with a negative likelihood ratio of 0.08.^16,29,30 Magnetic resonance imaging is also useful in the evaluation of avascular necrosis, biceps tendon disorders, inflammatory processes, and tumors.¹³ The diagnosis of labral lesions can be challenging given the relatively low sensitivity and negative predictive value noted in several trials.^16,28,31 Finally, it is important to note that up to one third of all asymptomatic patients and more than half of those older than 60 years demonstrate asymptomatic rotator cuff tears on MRI.³⁷

Approach to the patient

A general approach to the patient with shoulder pain is summarized in Figure 5. Pre- and posttest probabilities are included to give an understanding of how tests may help diagnose or rule out a complete rotator cuff tear. A recent prospective study combining multiple examination maneuvers demonstrated that a combination of 3 physical examination findings (supraspinatus weakness, weakness in external rotation, and impingement) along with the patient’s age can often diagnose or rule out a rotator cuff tear.³⁸ This group of tests did not distinguish full versus partial thickness tears. This approach is summarized in Figure 6.

Figure 5
Basic approach to assess for complete rotator cuff tear

Figure 6
Alternative approach to a suspected rotator cuff tear

Shoulder pain is a common problem that can pose difficult diagnostic and therapeutic challenges for the family physician. It is the third most common musculoskeletal complaint in the general population, and accounts for 5% of all general practitioner musculoskeletal consults.^1,2 The incidence of shoulder pain is 6.6 to 25 cases per 1000 patients, with a peak incidence in the fourth through sixth decades.^3-6 Shoulder pain is second only to knee pain for referrals to orthopedic surgery or primary care sports medicine clinics.^7,8 Furthermore, 8% to 13% of athletic injuries involve the shoulder and account for up to 3.9% of new emergency department visits.^9,10

Differential diagnosis

The challenge for the physician evaluating shoulder pain is the myriad of etiologies and the potential for multiple disorders. Compounding the challenge is a lack of uniformity in the literature regarding diagnostic classification.¹¹ As Table 1 shows, the age of the patient will help focus the differential diagnosis. Patients younger than 30 years old tend to have biomechanical or mild inflammatory etiologies for their pain such as atraumatic instability, tendinosis, and arthropathies. Less than 1% of shoulder injuries in persons younger than 30 years are complete rotator cuff tears, which occur in 35% of patients older than 45 years with shoulder pain.^12,13

The rotator cuff is the most commonly affected structure in the shoulder, and subacromial impingement syndrome is the leading cause of rotator cuff injury.^4,12,14-16 Neer¹⁴ described 3 stages of shoulder impingement that he estimated lead to 95% of rotator cuff tears. Impingement can be caused by repetitive overhead activities, acute trauma, or subtle instability (atraumatic instability). The current theory is that inflammation of the rotator cuff tendons and/or bursa, caused by irritation against the coracoacromial arch, can progress to a complete rotator cuff tear over time.

Referred sources of shoulder pain should be included in the differential diagnosis of shoulder pain. Potential sources include cervical spondylolysis, cervical arthritis, cervical disc disease, myocardial ischemia, reflex sympathetic dystrophy, diaphragmatic irritation, thoracic outlet syndrome, and gallbladder disease.

TABLE 1
Differential diagnosis of shoulder pain

Using the history and physical examination

As noted above, the likelihood of specific conditions such as a complete rotator cuff tear varies with the setting, age of the patient, and specialty of the physi-cian.^4,13,17,18 It is important to keep this pretest probability in mind while interpreting the history and physical examination. For example, a positive empty can test in a 50-year-old patient almost certainly represents a rotator cuff tear, whereas many younger patients with this finding will not have a tear. Moreover, certain components of the history and physical examination are more indicative of disorders while others are better at ruling them out. This concept is represented by the positive and negative likelihood ratios listed in Table 2.

The clinical evaluation begins with identification of the chief complaint and a thorough history. Common complaints include pain, weakness, stiffness, instability, locking, catching, and deformity.²⁶ Determining the duration of symptoms and mechanism of injury will narrow the differential diagnosis. If trauma occurred, the mechanism can determine radiological needs. Aggravating and alleviating factors should be reviewed, including work, recreation, sports, or hobbies. Night pain when lying on the affected side and a history of trauma in a patient older than 65 years both suggest a rotator cuff tear, but no individual symptom is definitive for the diagnosis (Table 2).¹⁹ Pain with overhead work may indicate impingement syndrome, especially if the patient is symptomatic through the arc of 60 to 120 degrees.

The physical examination should include observation, palpation, range of motion (ROM), and provocative testing. Observation requires adequate exposure of the shoulders bilaterally to identify any gross deformities or abnormalities, including muscle atrophy, acromioclavicular joint disparity, or evidence of trauma. Muscle atrophy of either the supraspinatus or infraspinatus muscles is moderately predictive of rotator cuff tears in the elderly population, with a positive predictive value of 81%. However, this sign is not useful if absent, with a negative predictive value of only 43%.¹⁹ No studies have assessed the role of palpation in the evaluation of shoulder pain. Nevertheless, the role of palpation in discerning acromioclavicular joint pathology from shoulder and neck makes it a useful part of the examination.

The shoulder’s ROM should be evaluated both actively and passively. The shoulder is a mobile joint with a complexity of movements. These include flexion to 180 degrees, extension to 40 degrees, abduction to 120 degrees with palms down and 180 degrees with palms up, internal rotation to 55 degrees, and external rotation to 45 degrees with arms at the side. Although determining abduction ROM is consistent among examiners,²⁷ interrater reliability is poor for assessment of external rotation ROM. Lack of full ROM that is equally limited with both passive and active examination is found in arthropathies and adhesive capsulitis.

Pain between 60 and 120 degrees of abduction “the painful arc”) is associated with subacromial impingement, whereas pain after 120 degrees is an indication of acromioclavicular joint origin. However, Calis and coworkers¹⁷ found that the presence of subacromial impingement has a positive likelihood ratio of only 1.7.

After assessing the ROM, the next steps are to evaluate the rotator cuff and biceps tendon, perform impingement testing, check for instability, and finally assess the acromioclavicular joint. The tests are listed in Table 2 in our preferred order of examination and represent the tests best supported by the evidence; the results are based on a literature search of Medline, PubMed, DARE, and Sports Discuss. The technique of each examination maneuver has been published elsewhere and is not described in detail here. Figure 1 through 4 illustrate several common examination maneuvers described below. A Web site that demonstrates the physical examination more thoroughly can be found at http://www.nismat.org/orthocor/exam/shoulder.html#Evaluation.

TABLE 2
Use of history and physical examination to diagnose shoulder pain

Figure 1
The empty can test

Rotator cuff tests

The drop arm test assesses the integrity of the rotator cuff, predominantly the supraspinatus muscle. The empty can test (Figure 1) isolates the supraspinatus against resistance. The lift off test (Figure 2) assesses the subscapularis integrity.

Figure 2
The lift off test

Impingement syndrome

Hawkin’s sign (Figure 3) is a test for evidence of impingement by re-creation of its symptoms.

Figures 3A & 3B
Hawkin’s sign

Glenohumeral joint stability

The augmented anterior apprehension test evaluates anterior shoulder instability. The relocation test, which helps confirm anterior instability, is carried out immediately after a positive anterior apprehension test.

Labral tears

The crank test is used to identify chronic labral injury, whereas the active compression test²⁵ (Figure 4) indicates labral injury if pain is deep in the shoulder.

Figure 4
The active compression test

Acromioclavicular joint

The active compression test²⁵ (Figure 4) indicates acromioclavicular joint inflammation, arthritis, or injury if pain is localized to the top of the shoulder.

Diagnostic tests

Imaging studies used in the evaluation of shoulder pain include plain radiographs, arthrography, computed tomography (CT), ultrasound (US), and magnetic resonance imaging (MRI). Often no imaging is required, or plain radiographs are the sole imaging study needed. Soft tissue injuries are best identified by MRI or US, whereas bony pathology is seen best with plain radiographs or CT. Indications for imaging include severe injury, uncontrolled pain, failure of conservative therapy, return to play considerations, and examiner discretion. Table 3 outlines the accuracy of imaging modalities organized by diagnosis.

TABLE 3
Imaging tests to diagnose shoulder pain

Plain radiographs

Plain radiographs are the first step in diagnostic imaging. They can reveal fractures, dislocation, subluxation, bony lesions, outlet obstruction, acromioclavicular joint pathology, and arthritic changes. No definitive clinical studies on the needs of radiographs have been done. Plain radiographs should be taken when ROM is lost, especially when there is abduction of less than 90 degrees, severe pain, and after trauma. Our preferred x-rays include a glenohumeral anteroposterior (AP) view, a supraspinatus outlet view, and an axillary view. Anteroposterior views with internal and external rotation are added in cases of trauma to help rule out fracture. Positive acromioclavicular joint tests (crossover or palpation) should be followed by acromioclavicular joint radiographs because a shoulder series does not give a clear view of this joint. Additional views of the neck as well as a chest x-ray or abdominal imaging should be considered if a referred source of shoulder pain remains a possibility.

Arthrography

Arthrography was the diagnostic test of choice before MRI. It is specific for rotator cuff tears but lacks sensitivity¹⁵ because it cannot detect partial-thickness or associated soft tissue injuries of the shoulder. Arthrography still has a role in evaluating adhesive capsulitis by demonstrating decreased intracapsular volume.²⁶ The test can be therapeutic if the capsule is dilated during the procedure. Additionally, patients with claustrophobia may be good candidates for arthrography if a full-thickness tear is suspected and MRI is not possible.

Computed tomography

Computed tomography may be used to evaluate bony lesions, including glenoid rim fractures, humoral fractures, and acromioclavicular joint disease. Computed tomography arthrograms may have a role in assessing labral tears and full-thickness rotator cuff tears.³⁵ The use of CT arthrography has fallen into disfavor compared with MRI because of the risks associated with contrast exposure and poor sensitivity for partial-thickness rotator cuff tears or associated soft tissue injury.

Ultrasound

Ultrasound has been used in the evaluation of rotator cuff tears with varying degrees of sensitivity and specificity.^12,29,34 This inconsistency may be related to variation in operator skill. Advantages of US include relatively low cost, speed, and noninvasiveness.

Magnetic resonance imaging

Magnetic resonance imaging has become the gold standard for diagnostic imaging of the shoulder related to soft tissue injury. The advantages include its noninvasive nature, lack of contrast exposure, nonionizing radiation, high degree of resolution, and the ability to evaluate multiple potential pathologic processes.³⁶ Magnetic resonance imaging is the preferred test for evaluating impingement syndrome and rotator cuff pathology. A normal MRI greatly reduces the chances of a rotator cuff tear, with a negative likelihood ratio of 0.08.^16,29,30 Magnetic resonance imaging is also useful in the evaluation of avascular necrosis, biceps tendon disorders, inflammatory processes, and tumors.¹³ The diagnosis of labral lesions can be challenging given the relatively low sensitivity and negative predictive value noted in several trials.^16,28,31 Finally, it is important to note that up to one third of all asymptomatic patients and more than half of those older than 60 years demonstrate asymptomatic rotator cuff tears on MRI.³⁷

Approach to the patient

A general approach to the patient with shoulder pain is summarized in Figure 5. Pre- and posttest probabilities are included to give an understanding of how tests may help diagnose or rule out a complete rotator cuff tear. A recent prospective study combining multiple examination maneuvers demonstrated that a combination of 3 physical examination findings (supraspinatus weakness, weakness in external rotation, and impingement) along with the patient’s age can often diagnose or rule out a rotator cuff tear.³⁸ This group of tests did not distinguish full versus partial thickness tears. This approach is summarized in Figure 6.

Figure 5
Basic approach to assess for complete rotator cuff tear

Figure 6
Alternative approach to a suspected rotator cuff tear

Heart failure (HF) affects more than 2 million adults in the United States.¹ This common, costly, and disabling disorder mainly affects the elderly, with prevalence rates of up to 10% in patients older than 65 years.^2,3 The management of HF is responsible for millions of outpatient visits per year,⁴ is the most common discharge diagnosis for Medicare beneficiaries,⁵ and accounts for more than 5% of total health care dollars spent.⁶

Treatment

Major advances in the pharmacologic treatment of heart failure (HF) have emerged in recent years. An approach to the diagnosis and evaluation of HF is described elsewhere.⁷ This article summarizes the evidence for outpatient treatment of HF. Current intervention trials do not distinguish between systolic and diastolic heart failure; it is therefore unknown whether or how drug therapy should be tailored according to the type of HF. The treatment of cardiac dysrhythmias in the setting of HF is beyond the scope of this article and is presented elsewhere.⁸Table 1 compares the available outpatient treatments of HF and includes the levels of evidence, numbers needed to treat, and appropriate situations for use. In the remainder of this article, we will discuss pharmacologic and nonpharmacologic management, including identification of ineffective treatments.

TABLE 1
Treatment options in heart failure

Pharmacologic treatment

Angiotensin-converting enzyme inhibitors. A systematic review⁹ of 32 trials with a total of 7105 patients demonstrated that mortality rates were lower in patients taking an angiotensin-converting enzyme (ACE) inhibitor than in those not taking one (number needed to treat [NNT] = 24 for > 90 days, meaning that 1 fewer death occurs for every 24 patients who take an ACE inhibitor for more than 90 days). In addition, there is a reduction in the combined endpoints of death and hospitalization because of HF (NNT = 11). Although most of this benefit was realized in the first 90 days of therapy, benefits lasted for 4 to 5 years and were more pronounced in patients categorized in more severe New York Heart Association (NYHA) HF classes¹⁰ (class I: no limitation of activities; class II: slight limitation of activity; class III: marked limitation of activity and comfortable only at rest; class IV: symptoms at rest).

Dosage comparison studies demonstrate that HF patients can benefit from even moderate doses of ACE inhibitors. A recent multicenter trial comparing moderate dose enalapril (10 mg twice a day) with a higher dose (30 mg twice a day) in patients with a left ventricular ejection fraction (LVEF) of less than 20% found no differences in mortality at 1 year between the 2 groups.¹¹ In addition, both groups achieved similar increases in functional status and LVEF.

Several trials have demonstrated good tolerability of ACE inhibitors.^12-14 Dropout rates of 15% to 30% were similar between patients in the ACE inhibitor and placebo groups, mainly because of side effects, including dizziness, altered taste, hypotension, hyperkalemia, and cough.

Angiotensin-receptor blockers. Angiotensin-receptor blockers (ARBs) reduce all-cause mortality and HF-related hospitalizations in patients with NYHA class II and III HF at rates comparable with those of ACE inhibitors.^15,16 Cough is not a side effect of ARBs. Although they are more expensive, ARBs offer a reasonable alternative for patients who do not tolerate ACE inhibitors.

Beta-blockers. The beta-blockers carvedilol, metoprolol, and bisoprolol have a proven mortality benefit for patients with HF.^17-19 Pooled results of 6 randomized controlled trials (RCTs), including more than 9000 patients already taking ACE inhibitors, showed a significant reduction in total mortality (NNT = 24 over 1–2 years) and sudden death (NNT = 35), regardless of NYHA classification.²⁰ The average dropout rate of 16% was similar in the betablocker and placebo groups.

Early beta-blocker studies included few NYHA class IV patients until a recent study of the use of carvedilol in severe chronic HF.²¹ In this study, all patients were taking diuretics plus either an ACE inhibitor or ARB and were permitted to take digoxin, nitrates, hydralazine, spironolactone, or amiodarone. Carvedilol at an average dose of 37 mg per day decreased mortality (NNT = 18 for 10 months) and lowered combined mortality and hospitalization for worsening HF (NNT = 13). Study patients taking carvedilol withdrew from the study at a lower rate (approximately 15%) than placebo.

Because the pharmacologic properties of betablockers vary, clinicians have wondered which are most beneficial. The investigators in a study comparing metoprolol (a beta-1 antagonist) with carvedilol (a beta-1, beta-2, and alpha-1 antagonist) in NYHA class II or III patients found no differences in quality-of-life measures or changes in NYHA classification.²²

Spironolactone. The addition of spironolactone to standard care can help patients with severe HF.²³ In NYHA class III and IV HF patients, spironolactone at doses ranging from 25 mg every other day to 50 mg per day reduces mortality (NNT = 9 for 2 years), reduces hospitalization from all cardiac causes (NNT = 4), and reduces hospitalization for worsening HF (NNT = 3). The most common serious adverse event in the spironolactone group was severe hyperkalemia (number needed to harm [NNH] = 195). Ten percent of men taking spironolactone experienced breast pain and gynecomastia.

Hydralazine and isosorbide dinitrate. The combination of hydralazine and isosorbide dinitrate (ISDN) reduces mortality in HF patients, but tolerability is an issue. In earlier trials, men with HF symptoms that were optimally controlled with digoxin and diuretics and treated with hydralazine (average dose = 270 mg/day) plus ISDN (average dose = 136 mg/day) had a decrease in all-cause mortality of 28% (NNT = 19 for 6 years).²⁴ A more recent trial comparing hydralazine plus ISDN with enalapril²⁵ (average daily doses of hydralazine = 300 mg/day; ISDN = 160 mg/day; enalapril = 20 mg/day) in NYHA class II–III patients showed no differences in mortality between the 2 groups over 3 years. Tolerability was a problem in these trials; more than 30% of patients stopped taking hydralazine, nitrate, or both.

Digoxin. Digoxin is effective for treating the symptoms of HF in the absence of dysrhythmias but there are no data demonstrating a mortality benefit. Digoxin increases functional capacity in NYHA class II–III patients and heart failure symptoms worsen if digoxin is withdrawn.²⁶ Although there are no differences in all-cause mortality with the use of digoxin, there are fewer hospitalizations due to worsening HF (NNT = 27–114 over 3 years) and a lower rate of clinical deterioration (NNT = 4–75).²⁷ In a randomized trial comparing digoxin and placebo, patients taking digoxin were twice as likely to be hospitalized for suspected digoxin toxicity (2.0% vs 0.9%; P < .001; NNH = 52).²⁸

Diuretics. Diuretics are a mainstay of the symptomatic treatment of heart failure. Short-term studies have shown that diuretics improve the symptoms of sodium and fluid retention and increase exercise tolerance and cardiac function regardless of NYHA classification.^29-32 No studies that examine their effects on morbidity and mortality are available.

Antiplatelet therapy and anticoagulation. Patients with HF have an increased risk for thromboembolic events of 1.6% to 3.2% per year.³³ One systematic review concluded that antiplatelet therapy is not useful in preventing thromboembolism in patients with HF in sinus rhythm and may even be harmful.³⁴ Another systematic review also concluded that the data do not support the routine use of anticoagulants (eg, warfarin) in patients with HF and sinus rhythm.³⁵ Anticoagulation may be beneficial, however, if there is echocardiographic visualization of a left ventricular thrombus or in cases of “severe” HF or concomitant atrial fibrillation.³⁵

Nonpharmacologic management

Dietary sodium restriction. There is consensus that dietary sodium restriction is important in the treatment of HF³⁶ and is recommended in published guidelines.^8,37 Sodium restriction assists with fluid volume control and minimizes the dosages of HF drugs used. These recommendations are based on the retention of sodium and water in symptomatic HF. No studies, however, have examined the effect of dietary sodium restriction on morbidity or mortality, either alone or in combination with pharmacologic treatments.

Exercise training. Moderate exercise training improves quality of life and decreases mortality in patients with stable chronic HF. A recent RCT demonstrated a decrease in mortality (NNT = 4 for 14 months) and hospital readmission for HF (NNT = 5) with only moderate exercise on a stationary bicycle (60% of maximum exercise capacity) for 2 to 3 hours per week.³⁸ Other studies have demonstrated improvements in physiologic markers³⁹ and in quality-of-life ratings with short-term, symptom-limited exercise.⁴⁰

Multidisciplinary or case-management approach. A case-based or disease-management approach to patients with HF decreases the frequency of unplanned and repeat hospitalizations, increases functional status, and increases quality of life.⁴¹ Even a single in-home visit by a clinical pharmacist and a nurse results in fewer unplanned readmissions and fewer days of hospitalization up to 18 months after discharge.^42,43 A small study of 27 patients in a Veterans Affairs hospital demonstrated that patient instruction in the self-monitoring of weight and blood pressure, combined with frequent telephone follow-up from a nurse, lowered repeat hospitalizations over 1 year, with the effect more pronounced in patients with more severe NYHA classifications.⁴⁴ A large RCT demonstrated that a multidisciplinary management approach (intensive patient education about HF and its treatment, dietary assessment and instruction, medication analysis and elimination of unnecessary medications, and telephone and home visit follow-up) results in fewer hospitalizations (NNT = 5 for 3 months) and reduced costs of care.⁴⁵

Treatments that have no benefit or are harmful

Calcium-channel blockers. Although some of the newer, longer-acting calcium-channel blockers (CCBs) appear to be safe in the treatment of heart failure,^46-49 no trials are available demonstrating that they lower mortality, decrease hospitalizations, or improve quality of life in patients with a failing heart. Older, short-acting CCBs can worsen HF.⁵⁰

Positive inotropic therapy. Intermittent positive inotropic therapy, either orally (milrinone) or intravenously (dobutamine), should be avoided. Although short-term studies have shown some increase in cardiac function and symptoms,⁵¹ long-term studies demonstrate no mortality benefit.⁵² One RCT of milrinone demonstrated an increase in mortality (NNH = 17 for 5 months), an increased rate of hospitalization for worsening HF (NNH = 20), and more serious side effects (NNH = 25).⁵³

Prognosis

Despite the increased longevity in Western developed nations and increased survival from coronary artery disease over recent decades, the overall prognosis of HF has improved very little.^6,54 Mortality data derived from several different sources, the largest being the Framingham Heart Study,^2,55 have shown that HF remains highly lethal, with a 5-year survival rate of 25% in men and 38% in women with NYHA II–IV heart failure. Mortality data from the placebo arms of intervention trials show an average 1-year mortality of 18%.^{9,17,19,20,56} A recent population-based study of patients with a new diagnosis of HF showed survival rates of only 62% at 12 months and 57% at 18 months.⁵⁷ Despite these dismal population-based data, predicting the likelihood of survival in individuals with HF is largely unreliable.⁸ Estimating individual prognosis is only somewhat useful in making end-of-life care and hospice decisions for patients with very advanced HF. Table 2 summarizes specific prognostic factors for patients with HF.

TABLE 2
Factors that affect prognosis in patients with heart failure (HF)

Suggested management of patients with heart failure

Although the optimal sequence of pharmacologic interventions for treating HF has not been examined in RCTs, recommendations can be made on the basis of existing evidence in HF management (Figure). This approach can be divided into 4 steps performed simultaneously: (1) control risks for the development and progression of HF (treat concomitant diseases); (2) HF treatment; (3) symptom control; (4) close follow-up.

Control risks. Risks for the development and worsening of HF should be addressed as described else-where.⁸ Steps include longitudinal surveillance; identification and treatment of hypertension, diabetes and thyroid diseases; management of atherosclerotic and coronary artery disease and myocardial ischemia; and the elimination of alcohol and tobacco use.

Heart failure treatment. All patients with HF should take a drug or a combination of drugs that affects the disease process. Drugs shown by the preponderance of evidence to decrease morbidity and mortality include ACE inhibitors, beta-blockers, and ARBs. For most HF patients, regardless of NYHA class, ACE inhibitors should be the initial baseline treatment because of their proven track record and the observation that most recent HF trials include patients who are already taking these medications. ARBs are similar in efficacy to ACE inhibitors and, therefore, are an adequate alternative when ACE inhibitors are not tolerated. Beta-blockers (metoprolol and bisoprolol) added to ACE inhibitors are also useful as a baseline treatment in most HF patients and may be especially useful in the case of tachydysrhythmias and in the postmyocardial infarction period.

For severe HF (NYHA III–IV), spironolactone and carvedilol are useful additions to baseline drug therapy. Carvedilol may be added if a beta-blocker is not currently used. If the patient is currently taking a beta-blocker, the drug should be discontinued before the patient is switched to carvedilol.

The hydralazine–nitrate combination has been proved effective, but tolerability and ease-of-use issues limit its usefulness. No data are available to support the use of nitrates other than isosorbide dinitrate. Nitrates may be useful, however, for concomitant chronic myocardial ischemia.

Patients with stable HF should be encouraged to begin and maintain a regular aerobic exercise program. The level of exercise can range from brief, symptom-limited exercise to moderate exercise (60% capacity) for 3 or more hours per week.

The use of antiplatelet therapy or the routine use of anticoagulation in patients with HF who are in sinus rhythm provides no benefit. Anticoagulation may be useful if the patient has severe HF or has a known mural thrombus. HF patients with atrial fibrillation should be considered for antiplatelet or anticoagulation therapy as described elsewhere.⁵⁸

Short-acting CCBs may worsen HF. No data support the use of any CCB in the primary treatment of HF. Similarly, intermittent use of milrinone or dobutamine is not indicated.

Symptom control. The symptomatic treatment of HF includes the use of diuretics and dietary sodium restriction to control sodium levels and volume status. Symptom control should be accomplished along with the pharmacologic disease management outlined above.

The role of digoxin in the failing heart without dysrhythmias is unclear. Digoxin may be most useful in symptom control, as it reduces hospitalizations attributed to worsening HF. This benefit must be balanced against an increased risk of hospitalization caused by digoxin toxicity. Patients who are already taking digoxin should probably continue to do so. The role of digoxin in newly diagnosed HF patients is unknown.

Close follow-up. Comprehensive follow-up, with the patient as a more active participant and in which care is extended beyond the hospital or office to the home, is a key strategy in the long-term care of HF patients. This aspect of HF management should include educating patients about their disease process and their dietary and pharmacologic treatments; teaching them how to monitor their weight, symptoms, and blood pressure and to understand when to seek care; and following up periodically by telephone between scheduled office visits.

FIGURE
Management of adults with heart failure

Heart failure (HF) affects more than 2 million adults in the United States.¹ This common, costly, and disabling disorder mainly affects the elderly, with prevalence rates of up to 10% in patients older than 65 years.^2,3 The management of HF is responsible for millions of outpatient visits per year,⁴ is the most common discharge diagnosis for Medicare beneficiaries,⁵ and accounts for more than 5% of total health care dollars spent.⁶

Treatment

Major advances in the pharmacologic treatment of heart failure (HF) have emerged in recent years. An approach to the diagnosis and evaluation of HF is described elsewhere.⁷ This article summarizes the evidence for outpatient treatment of HF. Current intervention trials do not distinguish between systolic and diastolic heart failure; it is therefore unknown whether or how drug therapy should be tailored according to the type of HF. The treatment of cardiac dysrhythmias in the setting of HF is beyond the scope of this article and is presented elsewhere.⁸Table 1 compares the available outpatient treatments of HF and includes the levels of evidence, numbers needed to treat, and appropriate situations for use. In the remainder of this article, we will discuss pharmacologic and nonpharmacologic management, including identification of ineffective treatments.

TABLE 1
Treatment options in heart failure

Pharmacologic treatment

Angiotensin-converting enzyme inhibitors. A systematic review⁹ of 32 trials with a total of 7105 patients demonstrated that mortality rates were lower in patients taking an angiotensin-converting enzyme (ACE) inhibitor than in those not taking one (number needed to treat [NNT] = 24 for > 90 days, meaning that 1 fewer death occurs for every 24 patients who take an ACE inhibitor for more than 90 days). In addition, there is a reduction in the combined endpoints of death and hospitalization because of HF (NNT = 11). Although most of this benefit was realized in the first 90 days of therapy, benefits lasted for 4 to 5 years and were more pronounced in patients categorized in more severe New York Heart Association (NYHA) HF classes¹⁰ (class I: no limitation of activities; class II: slight limitation of activity; class III: marked limitation of activity and comfortable only at rest; class IV: symptoms at rest).

Dosage comparison studies demonstrate that HF patients can benefit from even moderate doses of ACE inhibitors. A recent multicenter trial comparing moderate dose enalapril (10 mg twice a day) with a higher dose (30 mg twice a day) in patients with a left ventricular ejection fraction (LVEF) of less than 20% found no differences in mortality at 1 year between the 2 groups.¹¹ In addition, both groups achieved similar increases in functional status and LVEF.

Several trials have demonstrated good tolerability of ACE inhibitors.^12-14 Dropout rates of 15% to 30% were similar between patients in the ACE inhibitor and placebo groups, mainly because of side effects, including dizziness, altered taste, hypotension, hyperkalemia, and cough.

Angiotensin-receptor blockers. Angiotensin-receptor blockers (ARBs) reduce all-cause mortality and HF-related hospitalizations in patients with NYHA class II and III HF at rates comparable with those of ACE inhibitors.^15,16 Cough is not a side effect of ARBs. Although they are more expensive, ARBs offer a reasonable alternative for patients who do not tolerate ACE inhibitors.

Beta-blockers. The beta-blockers carvedilol, metoprolol, and bisoprolol have a proven mortality benefit for patients with HF.^17-19 Pooled results of 6 randomized controlled trials (RCTs), including more than 9000 patients already taking ACE inhibitors, showed a significant reduction in total mortality (NNT = 24 over 1–2 years) and sudden death (NNT = 35), regardless of NYHA classification.²⁰ The average dropout rate of 16% was similar in the betablocker and placebo groups.

Early beta-blocker studies included few NYHA class IV patients until a recent study of the use of carvedilol in severe chronic HF.²¹ In this study, all patients were taking diuretics plus either an ACE inhibitor or ARB and were permitted to take digoxin, nitrates, hydralazine, spironolactone, or amiodarone. Carvedilol at an average dose of 37 mg per day decreased mortality (NNT = 18 for 10 months) and lowered combined mortality and hospitalization for worsening HF (NNT = 13). Study patients taking carvedilol withdrew from the study at a lower rate (approximately 15%) than placebo.

Because the pharmacologic properties of betablockers vary, clinicians have wondered which are most beneficial. The investigators in a study comparing metoprolol (a beta-1 antagonist) with carvedilol (a beta-1, beta-2, and alpha-1 antagonist) in NYHA class II or III patients found no differences in quality-of-life measures or changes in NYHA classification.²²

Spironolactone. The addition of spironolactone to standard care can help patients with severe HF.²³ In NYHA class III and IV HF patients, spironolactone at doses ranging from 25 mg every other day to 50 mg per day reduces mortality (NNT = 9 for 2 years), reduces hospitalization from all cardiac causes (NNT = 4), and reduces hospitalization for worsening HF (NNT = 3). The most common serious adverse event in the spironolactone group was severe hyperkalemia (number needed to harm [NNH] = 195). Ten percent of men taking spironolactone experienced breast pain and gynecomastia.

Hydralazine and isosorbide dinitrate. The combination of hydralazine and isosorbide dinitrate (ISDN) reduces mortality in HF patients, but tolerability is an issue. In earlier trials, men with HF symptoms that were optimally controlled with digoxin and diuretics and treated with hydralazine (average dose = 270 mg/day) plus ISDN (average dose = 136 mg/day) had a decrease in all-cause mortality of 28% (NNT = 19 for 6 years).²⁴ A more recent trial comparing hydralazine plus ISDN with enalapril²⁵ (average daily doses of hydralazine = 300 mg/day; ISDN = 160 mg/day; enalapril = 20 mg/day) in NYHA class II–III patients showed no differences in mortality between the 2 groups over 3 years. Tolerability was a problem in these trials; more than 30% of patients stopped taking hydralazine, nitrate, or both.

Digoxin. Digoxin is effective for treating the symptoms of HF in the absence of dysrhythmias but there are no data demonstrating a mortality benefit. Digoxin increases functional capacity in NYHA class II–III patients and heart failure symptoms worsen if digoxin is withdrawn.²⁶ Although there are no differences in all-cause mortality with the use of digoxin, there are fewer hospitalizations due to worsening HF (NNT = 27–114 over 3 years) and a lower rate of clinical deterioration (NNT = 4–75).²⁷ In a randomized trial comparing digoxin and placebo, patients taking digoxin were twice as likely to be hospitalized for suspected digoxin toxicity (2.0% vs 0.9%; P < .001; NNH = 52).²⁸

Diuretics. Diuretics are a mainstay of the symptomatic treatment of heart failure. Short-term studies have shown that diuretics improve the symptoms of sodium and fluid retention and increase exercise tolerance and cardiac function regardless of NYHA classification.^29-32 No studies that examine their effects on morbidity and mortality are available.

Antiplatelet therapy and anticoagulation. Patients with HF have an increased risk for thromboembolic events of 1.6% to 3.2% per year.³³ One systematic review concluded that antiplatelet therapy is not useful in preventing thromboembolism in patients with HF in sinus rhythm and may even be harmful.³⁴ Another systematic review also concluded that the data do not support the routine use of anticoagulants (eg, warfarin) in patients with HF and sinus rhythm.³⁵ Anticoagulation may be beneficial, however, if there is echocardiographic visualization of a left ventricular thrombus or in cases of “severe” HF or concomitant atrial fibrillation.³⁵

Nonpharmacologic management

Dietary sodium restriction. There is consensus that dietary sodium restriction is important in the treatment of HF³⁶ and is recommended in published guidelines.^8,37 Sodium restriction assists with fluid volume control and minimizes the dosages of HF drugs used. These recommendations are based on the retention of sodium and water in symptomatic HF. No studies, however, have examined the effect of dietary sodium restriction on morbidity or mortality, either alone or in combination with pharmacologic treatments.

Exercise training. Moderate exercise training improves quality of life and decreases mortality in patients with stable chronic HF. A recent RCT demonstrated a decrease in mortality (NNT = 4 for 14 months) and hospital readmission for HF (NNT = 5) with only moderate exercise on a stationary bicycle (60% of maximum exercise capacity) for 2 to 3 hours per week.³⁸ Other studies have demonstrated improvements in physiologic markers³⁹ and in quality-of-life ratings with short-term, symptom-limited exercise.⁴⁰

Multidisciplinary or case-management approach. A case-based or disease-management approach to patients with HF decreases the frequency of unplanned and repeat hospitalizations, increases functional status, and increases quality of life.⁴¹ Even a single in-home visit by a clinical pharmacist and a nurse results in fewer unplanned readmissions and fewer days of hospitalization up to 18 months after discharge.^42,43 A small study of 27 patients in a Veterans Affairs hospital demonstrated that patient instruction in the self-monitoring of weight and blood pressure, combined with frequent telephone follow-up from a nurse, lowered repeat hospitalizations over 1 year, with the effect more pronounced in patients with more severe NYHA classifications.⁴⁴ A large RCT demonstrated that a multidisciplinary management approach (intensive patient education about HF and its treatment, dietary assessment and instruction, medication analysis and elimination of unnecessary medications, and telephone and home visit follow-up) results in fewer hospitalizations (NNT = 5 for 3 months) and reduced costs of care.⁴⁵

Treatments that have no benefit or are harmful

Calcium-channel blockers. Although some of the newer, longer-acting calcium-channel blockers (CCBs) appear to be safe in the treatment of heart failure,^46-49 no trials are available demonstrating that they lower mortality, decrease hospitalizations, or improve quality of life in patients with a failing heart. Older, short-acting CCBs can worsen HF.⁵⁰

Positive inotropic therapy. Intermittent positive inotropic therapy, either orally (milrinone) or intravenously (dobutamine), should be avoided. Although short-term studies have shown some increase in cardiac function and symptoms,⁵¹ long-term studies demonstrate no mortality benefit.⁵² One RCT of milrinone demonstrated an increase in mortality (NNH = 17 for 5 months), an increased rate of hospitalization for worsening HF (NNH = 20), and more serious side effects (NNH = 25).⁵³

Prognosis

Despite the increased longevity in Western developed nations and increased survival from coronary artery disease over recent decades, the overall prognosis of HF has improved very little.^6,54 Mortality data derived from several different sources, the largest being the Framingham Heart Study,^2,55 have shown that HF remains highly lethal, with a 5-year survival rate of 25% in men and 38% in women with NYHA II–IV heart failure. Mortality data from the placebo arms of intervention trials show an average 1-year mortality of 18%.^{9,17,19,20,56} A recent population-based study of patients with a new diagnosis of HF showed survival rates of only 62% at 12 months and 57% at 18 months.⁵⁷ Despite these dismal population-based data, predicting the likelihood of survival in individuals with HF is largely unreliable.⁸ Estimating individual prognosis is only somewhat useful in making end-of-life care and hospice decisions for patients with very advanced HF. Table 2 summarizes specific prognostic factors for patients with HF.

TABLE 2
Factors that affect prognosis in patients with heart failure (HF)

Suggested management of patients with heart failure

Although the optimal sequence of pharmacologic interventions for treating HF has not been examined in RCTs, recommendations can be made on the basis of existing evidence in HF management (Figure). This approach can be divided into 4 steps performed simultaneously: (1) control risks for the development and progression of HF (treat concomitant diseases); (2) HF treatment; (3) symptom control; (4) close follow-up.

Control risks. Risks for the development and worsening of HF should be addressed as described else-where.⁸ Steps include longitudinal surveillance; identification and treatment of hypertension, diabetes and thyroid diseases; management of atherosclerotic and coronary artery disease and myocardial ischemia; and the elimination of alcohol and tobacco use.

Heart failure treatment. All patients with HF should take a drug or a combination of drugs that affects the disease process. Drugs shown by the preponderance of evidence to decrease morbidity and mortality include ACE inhibitors, beta-blockers, and ARBs. For most HF patients, regardless of NYHA class, ACE inhibitors should be the initial baseline treatment because of their proven track record and the observation that most recent HF trials include patients who are already taking these medications. ARBs are similar in efficacy to ACE inhibitors and, therefore, are an adequate alternative when ACE inhibitors are not tolerated. Beta-blockers (metoprolol and bisoprolol) added to ACE inhibitors are also useful as a baseline treatment in most HF patients and may be especially useful in the case of tachydysrhythmias and in the postmyocardial infarction period.

For severe HF (NYHA III–IV), spironolactone and carvedilol are useful additions to baseline drug therapy. Carvedilol may be added if a beta-blocker is not currently used. If the patient is currently taking a beta-blocker, the drug should be discontinued before the patient is switched to carvedilol.

The hydralazine–nitrate combination has been proved effective, but tolerability and ease-of-use issues limit its usefulness. No data are available to support the use of nitrates other than isosorbide dinitrate. Nitrates may be useful, however, for concomitant chronic myocardial ischemia.

Patients with stable HF should be encouraged to begin and maintain a regular aerobic exercise program. The level of exercise can range from brief, symptom-limited exercise to moderate exercise (60% capacity) for 3 or more hours per week.

The use of antiplatelet therapy or the routine use of anticoagulation in patients with HF who are in sinus rhythm provides no benefit. Anticoagulation may be useful if the patient has severe HF or has a known mural thrombus. HF patients with atrial fibrillation should be considered for antiplatelet or anticoagulation therapy as described elsewhere.⁵⁸

Short-acting CCBs may worsen HF. No data support the use of any CCB in the primary treatment of HF. Similarly, intermittent use of milrinone or dobutamine is not indicated.

Symptom control. The symptomatic treatment of HF includes the use of diuretics and dietary sodium restriction to control sodium levels and volume status. Symptom control should be accomplished along with the pharmacologic disease management outlined above.

The role of digoxin in the failing heart without dysrhythmias is unclear. Digoxin may be most useful in symptom control, as it reduces hospitalizations attributed to worsening HF. This benefit must be balanced against an increased risk of hospitalization caused by digoxin toxicity. Patients who are already taking digoxin should probably continue to do so. The role of digoxin in newly diagnosed HF patients is unknown.

Close follow-up. Comprehensive follow-up, with the patient as a more active participant and in which care is extended beyond the hospital or office to the home, is a key strategy in the long-term care of HF patients. This aspect of HF management should include educating patients about their disease process and their dietary and pharmacologic treatments; teaching them how to monitor their weight, symptoms, and blood pressure and to understand when to seek care; and following up periodically by telephone between scheduled office visits.

FIGURE
Management of adults with heart failure

Heart failure (HF) affects more than 2 million adults in the United States.¹ This common, costly, and disabling disorder mainly affects the elderly, with prevalence rates of up to 10% in patients older than 65 years.^2,3 The management of HF is responsible for millions of outpatient visits per year,⁴ is the most common discharge diagnosis for Medicare beneficiaries,⁵ and accounts for more than 5% of total health care dollars spent.⁶

Treatment

Major advances in the pharmacologic treatment of heart failure (HF) have emerged in recent years. An approach to the diagnosis and evaluation of HF is described elsewhere.⁷ This article summarizes the evidence for outpatient treatment of HF. Current intervention trials do not distinguish between systolic and diastolic heart failure; it is therefore unknown whether or how drug therapy should be tailored according to the type of HF. The treatment of cardiac dysrhythmias in the setting of HF is beyond the scope of this article and is presented elsewhere.⁸Table 1 compares the available outpatient treatments of HF and includes the levels of evidence, numbers needed to treat, and appropriate situations for use. In the remainder of this article, we will discuss pharmacologic and nonpharmacologic management, including identification of ineffective treatments.

TABLE 1
Treatment options in heart failure

Pharmacologic treatment

Angiotensin-converting enzyme inhibitors. A systematic review⁹ of 32 trials with a total of 7105 patients demonstrated that mortality rates were lower in patients taking an angiotensin-converting enzyme (ACE) inhibitor than in those not taking one (number needed to treat [NNT] = 24 for > 90 days, meaning that 1 fewer death occurs for every 24 patients who take an ACE inhibitor for more than 90 days). In addition, there is a reduction in the combined endpoints of death and hospitalization because of HF (NNT = 11). Although most of this benefit was realized in the first 90 days of therapy, benefits lasted for 4 to 5 years and were more pronounced in patients categorized in more severe New York Heart Association (NYHA) HF classes¹⁰ (class I: no limitation of activities; class II: slight limitation of activity; class III: marked limitation of activity and comfortable only at rest; class IV: symptoms at rest).

Dosage comparison studies demonstrate that HF patients can benefit from even moderate doses of ACE inhibitors. A recent multicenter trial comparing moderate dose enalapril (10 mg twice a day) with a higher dose (30 mg twice a day) in patients with a left ventricular ejection fraction (LVEF) of less than 20% found no differences in mortality at 1 year between the 2 groups.¹¹ In addition, both groups achieved similar increases in functional status and LVEF.

Several trials have demonstrated good tolerability of ACE inhibitors.^12-14 Dropout rates of 15% to 30% were similar between patients in the ACE inhibitor and placebo groups, mainly because of side effects, including dizziness, altered taste, hypotension, hyperkalemia, and cough.

Angiotensin-receptor blockers. Angiotensin-receptor blockers (ARBs) reduce all-cause mortality and HF-related hospitalizations in patients with NYHA class II and III HF at rates comparable with those of ACE inhibitors.^15,16 Cough is not a side effect of ARBs. Although they are more expensive, ARBs offer a reasonable alternative for patients who do not tolerate ACE inhibitors.

Beta-blockers. The beta-blockers carvedilol, metoprolol, and bisoprolol have a proven mortality benefit for patients with HF.^17-19 Pooled results of 6 randomized controlled trials (RCTs), including more than 9000 patients already taking ACE inhibitors, showed a significant reduction in total mortality (NNT = 24 over 1–2 years) and sudden death (NNT = 35), regardless of NYHA classification.²⁰ The average dropout rate of 16% was similar in the betablocker and placebo groups.

Early beta-blocker studies included few NYHA class IV patients until a recent study of the use of carvedilol in severe chronic HF.²¹ In this study, all patients were taking diuretics plus either an ACE inhibitor or ARB and were permitted to take digoxin, nitrates, hydralazine, spironolactone, or amiodarone. Carvedilol at an average dose of 37 mg per day decreased mortality (NNT = 18 for 10 months) and lowered combined mortality and hospitalization for worsening HF (NNT = 13). Study patients taking carvedilol withdrew from the study at a lower rate (approximately 15%) than placebo.

Because the pharmacologic properties of betablockers vary, clinicians have wondered which are most beneficial. The investigators in a study comparing metoprolol (a beta-1 antagonist) with carvedilol (a beta-1, beta-2, and alpha-1 antagonist) in NYHA class II or III patients found no differences in quality-of-life measures or changes in NYHA classification.²²

Spironolactone. The addition of spironolactone to standard care can help patients with severe HF.²³ In NYHA class III and IV HF patients, spironolactone at doses ranging from 25 mg every other day to 50 mg per day reduces mortality (NNT = 9 for 2 years), reduces hospitalization from all cardiac causes (NNT = 4), and reduces hospitalization for worsening HF (NNT = 3). The most common serious adverse event in the spironolactone group was severe hyperkalemia (number needed to harm [NNH] = 195). Ten percent of men taking spironolactone experienced breast pain and gynecomastia.

Hydralazine and isosorbide dinitrate. The combination of hydralazine and isosorbide dinitrate (ISDN) reduces mortality in HF patients, but tolerability is an issue. In earlier trials, men with HF symptoms that were optimally controlled with digoxin and diuretics and treated with hydralazine (average dose = 270 mg/day) plus ISDN (average dose = 136 mg/day) had a decrease in all-cause mortality of 28% (NNT = 19 for 6 years).²⁴ A more recent trial comparing hydralazine plus ISDN with enalapril²⁵ (average daily doses of hydralazine = 300 mg/day; ISDN = 160 mg/day; enalapril = 20 mg/day) in NYHA class II–III patients showed no differences in mortality between the 2 groups over 3 years. Tolerability was a problem in these trials; more than 30% of patients stopped taking hydralazine, nitrate, or both.

Digoxin. Digoxin is effective for treating the symptoms of HF in the absence of dysrhythmias but there are no data demonstrating a mortality benefit. Digoxin increases functional capacity in NYHA class II–III patients and heart failure symptoms worsen if digoxin is withdrawn.²⁶ Although there are no differences in all-cause mortality with the use of digoxin, there are fewer hospitalizations due to worsening HF (NNT = 27–114 over 3 years) and a lower rate of clinical deterioration (NNT = 4–75).²⁷ In a randomized trial comparing digoxin and placebo, patients taking digoxin were twice as likely to be hospitalized for suspected digoxin toxicity (2.0% vs 0.9%; P < .001; NNH = 52).²⁸

Diuretics. Diuretics are a mainstay of the symptomatic treatment of heart failure. Short-term studies have shown that diuretics improve the symptoms of sodium and fluid retention and increase exercise tolerance and cardiac function regardless of NYHA classification.^29-32 No studies that examine their effects on morbidity and mortality are available.

Antiplatelet therapy and anticoagulation. Patients with HF have an increased risk for thromboembolic events of 1.6% to 3.2% per year.³³ One systematic review concluded that antiplatelet therapy is not useful in preventing thromboembolism in patients with HF in sinus rhythm and may even be harmful.³⁴ Another systematic review also concluded that the data do not support the routine use of anticoagulants (eg, warfarin) in patients with HF and sinus rhythm.³⁵ Anticoagulation may be beneficial, however, if there is echocardiographic visualization of a left ventricular thrombus or in cases of “severe” HF or concomitant atrial fibrillation.³⁵

Nonpharmacologic management

Dietary sodium restriction. There is consensus that dietary sodium restriction is important in the treatment of HF³⁶ and is recommended in published guidelines.^8,37 Sodium restriction assists with fluid volume control and minimizes the dosages of HF drugs used. These recommendations are based on the retention of sodium and water in symptomatic HF. No studies, however, have examined the effect of dietary sodium restriction on morbidity or mortality, either alone or in combination with pharmacologic treatments.

Exercise training. Moderate exercise training improves quality of life and decreases mortality in patients with stable chronic HF. A recent RCT demonstrated a decrease in mortality (NNT = 4 for 14 months) and hospital readmission for HF (NNT = 5) with only moderate exercise on a stationary bicycle (60% of maximum exercise capacity) for 2 to 3 hours per week.³⁸ Other studies have demonstrated improvements in physiologic markers³⁹ and in quality-of-life ratings with short-term, symptom-limited exercise.⁴⁰

Multidisciplinary or case-management approach. A case-based or disease-management approach to patients with HF decreases the frequency of unplanned and repeat hospitalizations, increases functional status, and increases quality of life.⁴¹ Even a single in-home visit by a clinical pharmacist and a nurse results in fewer unplanned readmissions and fewer days of hospitalization up to 18 months after discharge.^42,43 A small study of 27 patients in a Veterans Affairs hospital demonstrated that patient instruction in the self-monitoring of weight and blood pressure, combined with frequent telephone follow-up from a nurse, lowered repeat hospitalizations over 1 year, with the effect more pronounced in patients with more severe NYHA classifications.⁴⁴ A large RCT demonstrated that a multidisciplinary management approach (intensive patient education about HF and its treatment, dietary assessment and instruction, medication analysis and elimination of unnecessary medications, and telephone and home visit follow-up) results in fewer hospitalizations (NNT = 5 for 3 months) and reduced costs of care.⁴⁵

Treatments that have no benefit or are harmful

Calcium-channel blockers. Although some of the newer, longer-acting calcium-channel blockers (CCBs) appear to be safe in the treatment of heart failure,^46-49 no trials are available demonstrating that they lower mortality, decrease hospitalizations, or improve quality of life in patients with a failing heart. Older, short-acting CCBs can worsen HF.⁵⁰

Positive inotropic therapy. Intermittent positive inotropic therapy, either orally (milrinone) or intravenously (dobutamine), should be avoided. Although short-term studies have shown some increase in cardiac function and symptoms,⁵¹ long-term studies demonstrate no mortality benefit.⁵² One RCT of milrinone demonstrated an increase in mortality (NNH = 17 for 5 months), an increased rate of hospitalization for worsening HF (NNH = 20), and more serious side effects (NNH = 25).⁵³

Prognosis

Despite the increased longevity in Western developed nations and increased survival from coronary artery disease over recent decades, the overall prognosis of HF has improved very little.^6,54 Mortality data derived from several different sources, the largest being the Framingham Heart Study,^2,55 have shown that HF remains highly lethal, with a 5-year survival rate of 25% in men and 38% in women with NYHA II–IV heart failure. Mortality data from the placebo arms of intervention trials show an average 1-year mortality of 18%.^{9,17,19,20,56} A recent population-based study of patients with a new diagnosis of HF showed survival rates of only 62% at 12 months and 57% at 18 months.⁵⁷ Despite these dismal population-based data, predicting the likelihood of survival in individuals with HF is largely unreliable.⁸ Estimating individual prognosis is only somewhat useful in making end-of-life care and hospice decisions for patients with very advanced HF. Table 2 summarizes specific prognostic factors for patients with HF.

TABLE 2
Factors that affect prognosis in patients with heart failure (HF)

Suggested management of patients with heart failure

Although the optimal sequence of pharmacologic interventions for treating HF has not been examined in RCTs, recommendations can be made on the basis of existing evidence in HF management (Figure). This approach can be divided into 4 steps performed simultaneously: (1) control risks for the development and progression of HF (treat concomitant diseases); (2) HF treatment; (3) symptom control; (4) close follow-up.

Control risks. Risks for the development and worsening of HF should be addressed as described else-where.⁸ Steps include longitudinal surveillance; identification and treatment of hypertension, diabetes and thyroid diseases; management of atherosclerotic and coronary artery disease and myocardial ischemia; and the elimination of alcohol and tobacco use.

Heart failure treatment. All patients with HF should take a drug or a combination of drugs that affects the disease process. Drugs shown by the preponderance of evidence to decrease morbidity and mortality include ACE inhibitors, beta-blockers, and ARBs. For most HF patients, regardless of NYHA class, ACE inhibitors should be the initial baseline treatment because of their proven track record and the observation that most recent HF trials include patients who are already taking these medications. ARBs are similar in efficacy to ACE inhibitors and, therefore, are an adequate alternative when ACE inhibitors are not tolerated. Beta-blockers (metoprolol and bisoprolol) added to ACE inhibitors are also useful as a baseline treatment in most HF patients and may be especially useful in the case of tachydysrhythmias and in the postmyocardial infarction period.

For severe HF (NYHA III–IV), spironolactone and carvedilol are useful additions to baseline drug therapy. Carvedilol may be added if a beta-blocker is not currently used. If the patient is currently taking a beta-blocker, the drug should be discontinued before the patient is switched to carvedilol.

The hydralazine–nitrate combination has been proved effective, but tolerability and ease-of-use issues limit its usefulness. No data are available to support the use of nitrates other than isosorbide dinitrate. Nitrates may be useful, however, for concomitant chronic myocardial ischemia.

Patients with stable HF should be encouraged to begin and maintain a regular aerobic exercise program. The level of exercise can range from brief, symptom-limited exercise to moderate exercise (60% capacity) for 3 or more hours per week.

The use of antiplatelet therapy or the routine use of anticoagulation in patients with HF who are in sinus rhythm provides no benefit. Anticoagulation may be useful if the patient has severe HF or has a known mural thrombus. HF patients with atrial fibrillation should be considered for antiplatelet or anticoagulation therapy as described elsewhere.⁵⁸

Short-acting CCBs may worsen HF. No data support the use of any CCB in the primary treatment of HF. Similarly, intermittent use of milrinone or dobutamine is not indicated.

Symptom control. The symptomatic treatment of HF includes the use of diuretics and dietary sodium restriction to control sodium levels and volume status. Symptom control should be accomplished along with the pharmacologic disease management outlined above.

The role of digoxin in the failing heart without dysrhythmias is unclear. Digoxin may be most useful in symptom control, as it reduces hospitalizations attributed to worsening HF. This benefit must be balanced against an increased risk of hospitalization caused by digoxin toxicity. Patients who are already taking digoxin should probably continue to do so. The role of digoxin in newly diagnosed HF patients is unknown.

Close follow-up. Comprehensive follow-up, with the patient as a more active participant and in which care is extended beyond the hospital or office to the home, is a key strategy in the long-term care of HF patients. This aspect of HF management should include educating patients about their disease process and their dietary and pharmacologic treatments; teaching them how to monitor their weight, symptoms, and blood pressure and to understand when to seek care; and following up periodically by telephone between scheduled office visits.

FIGURE
Management of adults with heart failure

Heart failure is increasing in incidence and prevalence; it currently affects 0.4% to 2% of the general population and 8% to 10% of the elderly.^1,2 In the United States, heart failure is the second most common cardiovascular reason for an outpatient visit in the ambulatory care setting and remains the most common cause for hospitalization among patients older than 65 years.³ The total cost for heart failure management in 1999 was estimated to approach $56 billion.⁴ Those suffering with this illness experience high levels of morbidity and mortality⁵ that are reflected in the workloads of both primary and secondary care. Heart failure admission rates are rising, and the prognosis of heart failure has been compared with that of malignancy, with a 6-year mortality rate of 84% in men and 77% in women.^6,7

A number of heart failure guidelines^8-14 provide direction regarding “best practice” with regard to diagnosis and management. These guidelines have all been produced by expert panels and base their evidence on systematic critical reviews of the literature, plus expert consensus opinion. The evidence underlying the development of these guidelines ranges from well-conducted randomized controlled trials to expert opinion. These guidelines all emphasize the ways in which approaches to the diagnosis and management of heart failure have altered substantially in recent years and are continuing to change rapidly. The need to detect heart failure at an early stage to slow the progression of left ventricular systolic dysfunction (LVSD) is now well accepted.¹⁵

The following provides an overview of the current recommended approaches to diagnosis, focusing specifically on LVSD, the most common type of heart failure and also the usual focus of most guidelines. Accurate diagnosis of LVSD is the single most important step in management.¹⁶ An adequate diagnosis should establish the existence of heart failure, differentiate systolic from diastolic dysfunction, and identify the main underlying cause and any subsidiary diagnoses that may exacerbate heart failure. The etiology of heart failure and the presence of exacerbating factors or other diseases need to be carefully considered in all patients. Coronary artery disease remains the most common potentially reversible etiologic factor in heart failure.⁸

Using the history and physical examination

The major symptoms of heart failure are fatigue, exercise intolerance, exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and dependent edema. However, such symptoms are similar to those of many other diseases, particularly pulmonary diseases. For example, exertional dypsnea is a common symptom in heart failure but can be due to a wide range of other causes, such as chronic obstructive pulmonary disease, interstitial lung disease, asthma, respiratory infection, deconditioning, or obesity. Many patients with impaired left ventricular function may have no obvious symptoms.¹⁷ This highlights the importance of exploring past medical and medication history as these contribute to the overall clinical assessment.

Physical findings that may support a diagnosis of heart failure include raised jugular venous pressure, peripheral edema not due to venous insufficiency, presence of a third heart sound, gallop rhythm, laterally displaced apical impulse, tachycardia, and pulmonary rales that do not clear with coughing. Although clinical findings are particularly useful in acute severe heart failure at the time of hospitalization,¹⁸ it is difficult to accurately diagnose mild heart failure in the community on the basis of clinical grounds alone.^2,9 The value of different symptoms and aspects of the medical history and use of medications in the evaluation of potential heart failure patients have been examined by researchers.^{18, 20-23} Similarly, the utility of physical examination has also undergone investigation.^18,20,22-28Table 1 summarizes the study findings with regard to clinical symptoms and signs.

Davie and colleagues²⁰ assessed the value of symptoms, past history, medications, and signs in the evaluation of patients who may have LVSD. No one clinical feature predicted LVSD, as assessed by echocardiography with sensitivity, specificity, and a high positive and negative predictive value. Absence of dyspnea on exertion essentially ruled out heart failure (negative likelihood ratio [LR-] = 0.06), while gallop rhythm (positive likelihood ratio [LR+] = 24.0), laterally displaced apical impulse (LR+ 16.4), and elevated jugular venous pulsation (LR+ = 8.9) are strong evidence in favor of the diagnosis. Furthermore, the combination of history of myocardial infarction and displaced apex on physical examination, although not particularly sensitive (39% sensitivity) was very specific (99% specificity) with high positive (89%) and negative (89%) predictive values. The authors also suggest that a breathless patient with a past history of myocardial infarction and a displaced apex beat on physical examination will almost certainly have heart failure and, if resources are limited, may not need echocardiography to confirm the diagnosis. However, less than 50% of breathless patients will have this combination, and the other half would therefore need echocardiography as the gold standard diagnostic tool for LVSD.

Morgan and coworkers²⁸ assessed the prevalence and clinical characteristics of LVSD among elderly patients (those aged 70 years to 84 years) in a primary care setting by echocardiographic assessment of ventricular function. They found that no single clinical symptom or sign was both sensitive and specific, and concluded that diagnosis should not be based on clinical history and examination alone. They found that a substantial number of elderly individuals had asymptomatic or misdiagnosed LVSD, and suggested this might be due to the extremely limited sensitivity and specificity of clinical history taking and examination. For example, only 11% of patients with LVSD had a raised jugular venous pressure, and bilateral ankle edema was common but nonspecific. Researchers have therefore concluded that although these clinical findings are useful in acute severe heart failure, they have only a small role in detecting LVSD in the community.¹⁸

TABLE 1
The use of clinical symptoms and signs to diagnose heart failure, by study

Laboratory and imaging evaluation

Although an important and valuable part of the evaluation, the history and physical examination alone are insufficient to confirm a diagnosis in most cases. Recommended initial tests for patients with signs or symptoms of heart failure include complete blood count (CBC), serum electrolytes, serum creatinine, serum albumin, liver function tests, urinalysis, electrocardiogram, and chest x-ray (Figure).

Blood tests. For those older than 65 years or with atrial fibrillation or evidence of thyroid disease, thyroid function tests should also be performed because heart failure due to thyrotoxicosis is frequently associated with rapid atrial fibrillation and hypothyroidism may also present as heart failure.^8,10 The other routine blood tests are important as a way to exclude alternative diagnoses; they also help with the search for predisposing or exacerbating causes of the heart failure. These baseline tests also help guide future therapeutic decision making. For example, electrolyte and renal function results are pertinent when initiating angiotensin-converting enzyme (ACE) inhibitors. Anemia can exacerbate pre-existing heart failure, and measurement of renal function is essential to distinguish fluid overload due to heart failure from renal failure. Liver enzymes may be affected by hepatic congestion. Urinalysis is valuable in the detection of underlying renal disease or diabetes.⁸

Electrocardiography. An electrocardiogram (ECG) is another recommended part of the evaluation of the suspected heart failure patient.^8-14 Considerable attention has been paid to examining the value of this test in the diagnosis of LVSD.^29-32 Davie and colleagues²⁹ assessed the value of the ECG in identifying patients with possible heart failure by examining referrals for echocardiography by primary care practitioners. A total of 534 patients were referred for echocardiography for possible heart failure, of whom 18% (n = 96) had LVSD. They showed that LVSD was extremely unlikely if the ECG result was normal, but that 1 in 3 patients with an abnormal result had significant LVSD. Thus, a normal ECG result virtually excludes chronic heart failure due to LVSD. However, the ECG is not a substitute for echocardiography, as an abnormal result does not accurately predict the presence of LVSD (Table 2).

Others have confirmed these findings.^30,32 Talreja and colleagues³⁰ found that of 330 consecutive in-patients referred for echocardiographic assessment of left ventricular function, 124 (41%) had LVSD. Only 2 of 124 patients with LVSD had a normal electrocardiogram result. When the ECG result is normal, the authors suggest that echocardiography is not needed. However, they concede that physicians are unlikely to adhere to this because many may not be as sophisticated in interpreting the ECG and may feel it important to get an accurate measure of ejection fraction. Guidelines published by the European Society of Cardiology¹⁰ state that a normal ECG result in patients with suspected heart failure should lead us to doubt the accuracy of the diagnosis.

Chest x-ray. The chest x-ray is most valuable as a test to exclude pulmonary causes. However, the existing evidence suggests it is not a reliable way to exclude LVSD.^24,26,33,34 (Table 2) provides information about the value of radiography in predicting LVSD. A systematic review of the literature concluded that redistribution and cardiomegaly were the best chest radiographic findings for diagnosing increased preload and reduced ejection fraction, respectively.³⁴ However, neither finding alone could adequately exclude or confirm LVSD. Studies published since that review have confirmed this finding.³³ Although part of the evaluation of the heart failure patient, radiography is only one part of the diagnostic process and cannot be used to provide definitive diagnostic information.

Echocardiography. The most important step in the evaluation of the heart failure patient is the assessment of left ventricular systolic function. Both echocardiography and radionuclide ventriculography have been advocated.^8-14 However, echocardiography is preferred as it is widely available, simple, noninvasive, safe, usually less expensive, and provides more information about valve function and left ventricular hypertrophy. Table 2 demonstrates the high sensitivity and specificity of echocardiography.³⁵ In view of this, it is recommended as a standard adjunct to the clinical diagnosis of patients with dyspnea on exertion and suspected heart failure. Between 8% and 18% of patients will have inadequate echocardiograms, in which case radionuclide ventriculography is advocated.⁸

Neurohormonal markers. In recent years there has been increasing interest in the potential role of neurohormonal markers, such as B-type natriuretic peptide (BNP), atrial natriuretic peptide (ANP), N-terminal pro-ANP (N-ANP), and N-terminal pro-BNP (N-BNP) as indices of LVSD.^36-42 Most of the data relating to these markers are relatively recent; therefore their use is not addressed in any detail in any of the aforementioned guidelines.

Some studies^41,42 suggest that BNP and N-BNP are useful for diagnosing LVSD even when the positive predictive values are low, because of their high negative predictive values. One of the most recent studies⁴⁴ examined the utility of BNP in an urgent care setting and suggested that BNP was an extremely reliable indicator of LVSD. In this population of patients with acute dyspnea where 39% had a final diagnosis of heart failure, 90% with a positive BNP had heart failure and 98% of those with a negative BNP did not. Although there appears to be a growing body of evidence supporting the role of these neurohormonal markers in the evaluation of the patient with LVSD, Table 2 illustrates that there have also been conflicting findings. This is partly because of differences in study design, study populations, cut-off points for ANP and BNP, and the definition of LVSD. Most studies agree that assessment of BNP, in particular, may be a cost-effective method for initial screening for LVSD, but should still be followed by an echocardiogram to confirm the diagnosis.

Management follows diagnosis. Making the correct diagnosis is the crucial first step in the management of chronic heart failure. Figure 1 summarizes the steps currently recommended for the evaluation of the patient with LVSD. A confirmation of a diagnosis of LVSD, however, is not the end of the story. Management will then need to include initiation of appropriate therapies and consideration of treatable and reversible etiologies, a subject to be addressed in the June 2002 issue of this journal.

TABLE 2
Key investigations used for the diagnosis of left ventricular systolic dysfunction

Figure
Steps in the assessment of the patient with suspected heart failure

ACKNOWLEDGMENTS

We wish to thank Mr Chris Shiels at the Department of Primary Care, University of Liverpool, for his valuable advice regarding this manuscript.

Heart failure is increasing in incidence and prevalence; it currently affects 0.4% to 2% of the general population and 8% to 10% of the elderly.^1,2 In the United States, heart failure is the second most common cardiovascular reason for an outpatient visit in the ambulatory care setting and remains the most common cause for hospitalization among patients older than 65 years.³ The total cost for heart failure management in 1999 was estimated to approach $56 billion.⁴ Those suffering with this illness experience high levels of morbidity and mortality⁵ that are reflected in the workloads of both primary and secondary care. Heart failure admission rates are rising, and the prognosis of heart failure has been compared with that of malignancy, with a 6-year mortality rate of 84% in men and 77% in women.^6,7

A number of heart failure guidelines^8-14 provide direction regarding “best practice” with regard to diagnosis and management. These guidelines have all been produced by expert panels and base their evidence on systematic critical reviews of the literature, plus expert consensus opinion. The evidence underlying the development of these guidelines ranges from well-conducted randomized controlled trials to expert opinion. These guidelines all emphasize the ways in which approaches to the diagnosis and management of heart failure have altered substantially in recent years and are continuing to change rapidly. The need to detect heart failure at an early stage to slow the progression of left ventricular systolic dysfunction (LVSD) is now well accepted.¹⁵

The following provides an overview of the current recommended approaches to diagnosis, focusing specifically on LVSD, the most common type of heart failure and also the usual focus of most guidelines. Accurate diagnosis of LVSD is the single most important step in management.¹⁶ An adequate diagnosis should establish the existence of heart failure, differentiate systolic from diastolic dysfunction, and identify the main underlying cause and any subsidiary diagnoses that may exacerbate heart failure. The etiology of heart failure and the presence of exacerbating factors or other diseases need to be carefully considered in all patients. Coronary artery disease remains the most common potentially reversible etiologic factor in heart failure.⁸

Using the history and physical examination

The major symptoms of heart failure are fatigue, exercise intolerance, exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and dependent edema. However, such symptoms are similar to those of many other diseases, particularly pulmonary diseases. For example, exertional dypsnea is a common symptom in heart failure but can be due to a wide range of other causes, such as chronic obstructive pulmonary disease, interstitial lung disease, asthma, respiratory infection, deconditioning, or obesity. Many patients with impaired left ventricular function may have no obvious symptoms.¹⁷ This highlights the importance of exploring past medical and medication history as these contribute to the overall clinical assessment.

Physical findings that may support a diagnosis of heart failure include raised jugular venous pressure, peripheral edema not due to venous insufficiency, presence of a third heart sound, gallop rhythm, laterally displaced apical impulse, tachycardia, and pulmonary rales that do not clear with coughing. Although clinical findings are particularly useful in acute severe heart failure at the time of hospitalization,¹⁸ it is difficult to accurately diagnose mild heart failure in the community on the basis of clinical grounds alone.^2,9 The value of different symptoms and aspects of the medical history and use of medications in the evaluation of potential heart failure patients have been examined by researchers.^{18, 20-23} Similarly, the utility of physical examination has also undergone investigation.^18,20,22-28Table 1 summarizes the study findings with regard to clinical symptoms and signs.

Davie and colleagues²⁰ assessed the value of symptoms, past history, medications, and signs in the evaluation of patients who may have LVSD. No one clinical feature predicted LVSD, as assessed by echocardiography with sensitivity, specificity, and a high positive and negative predictive value. Absence of dyspnea on exertion essentially ruled out heart failure (negative likelihood ratio [LR-] = 0.06), while gallop rhythm (positive likelihood ratio [LR+] = 24.0), laterally displaced apical impulse (LR+ 16.4), and elevated jugular venous pulsation (LR+ = 8.9) are strong evidence in favor of the diagnosis. Furthermore, the combination of history of myocardial infarction and displaced apex on physical examination, although not particularly sensitive (39% sensitivity) was very specific (99% specificity) with high positive (89%) and negative (89%) predictive values. The authors also suggest that a breathless patient with a past history of myocardial infarction and a displaced apex beat on physical examination will almost certainly have heart failure and, if resources are limited, may not need echocardiography to confirm the diagnosis. However, less than 50% of breathless patients will have this combination, and the other half would therefore need echocardiography as the gold standard diagnostic tool for LVSD.

Morgan and coworkers²⁸ assessed the prevalence and clinical characteristics of LVSD among elderly patients (those aged 70 years to 84 years) in a primary care setting by echocardiographic assessment of ventricular function. They found that no single clinical symptom or sign was both sensitive and specific, and concluded that diagnosis should not be based on clinical history and examination alone. They found that a substantial number of elderly individuals had asymptomatic or misdiagnosed LVSD, and suggested this might be due to the extremely limited sensitivity and specificity of clinical history taking and examination. For example, only 11% of patients with LVSD had a raised jugular venous pressure, and bilateral ankle edema was common but nonspecific. Researchers have therefore concluded that although these clinical findings are useful in acute severe heart failure, they have only a small role in detecting LVSD in the community.¹⁸

TABLE 1
The use of clinical symptoms and signs to diagnose heart failure, by study

Laboratory and imaging evaluation

Although an important and valuable part of the evaluation, the history and physical examination alone are insufficient to confirm a diagnosis in most cases. Recommended initial tests for patients with signs or symptoms of heart failure include complete blood count (CBC), serum electrolytes, serum creatinine, serum albumin, liver function tests, urinalysis, electrocardiogram, and chest x-ray (Figure).

Blood tests. For those older than 65 years or with atrial fibrillation or evidence of thyroid disease, thyroid function tests should also be performed because heart failure due to thyrotoxicosis is frequently associated with rapid atrial fibrillation and hypothyroidism may also present as heart failure.^8,10 The other routine blood tests are important as a way to exclude alternative diagnoses; they also help with the search for predisposing or exacerbating causes of the heart failure. These baseline tests also help guide future therapeutic decision making. For example, electrolyte and renal function results are pertinent when initiating angiotensin-converting enzyme (ACE) inhibitors. Anemia can exacerbate pre-existing heart failure, and measurement of renal function is essential to distinguish fluid overload due to heart failure from renal failure. Liver enzymes may be affected by hepatic congestion. Urinalysis is valuable in the detection of underlying renal disease or diabetes.⁸

Electrocardiography. An electrocardiogram (ECG) is another recommended part of the evaluation of the suspected heart failure patient.^8-14 Considerable attention has been paid to examining the value of this test in the diagnosis of LVSD.^29-32 Davie and colleagues²⁹ assessed the value of the ECG in identifying patients with possible heart failure by examining referrals for echocardiography by primary care practitioners. A total of 534 patients were referred for echocardiography for possible heart failure, of whom 18% (n = 96) had LVSD. They showed that LVSD was extremely unlikely if the ECG result was normal, but that 1 in 3 patients with an abnormal result had significant LVSD. Thus, a normal ECG result virtually excludes chronic heart failure due to LVSD. However, the ECG is not a substitute for echocardiography, as an abnormal result does not accurately predict the presence of LVSD (Table 2).

Others have confirmed these findings.^30,32 Talreja and colleagues³⁰ found that of 330 consecutive in-patients referred for echocardiographic assessment of left ventricular function, 124 (41%) had LVSD. Only 2 of 124 patients with LVSD had a normal electrocardiogram result. When the ECG result is normal, the authors suggest that echocardiography is not needed. However, they concede that physicians are unlikely to adhere to this because many may not be as sophisticated in interpreting the ECG and may feel it important to get an accurate measure of ejection fraction. Guidelines published by the European Society of Cardiology¹⁰ state that a normal ECG result in patients with suspected heart failure should lead us to doubt the accuracy of the diagnosis.

Chest x-ray. The chest x-ray is most valuable as a test to exclude pulmonary causes. However, the existing evidence suggests it is not a reliable way to exclude LVSD.^24,26,33,34 (Table 2) provides information about the value of radiography in predicting LVSD. A systematic review of the literature concluded that redistribution and cardiomegaly were the best chest radiographic findings for diagnosing increased preload and reduced ejection fraction, respectively.³⁴ However, neither finding alone could adequately exclude or confirm LVSD. Studies published since that review have confirmed this finding.³³ Although part of the evaluation of the heart failure patient, radiography is only one part of the diagnostic process and cannot be used to provide definitive diagnostic information.

Echocardiography. The most important step in the evaluation of the heart failure patient is the assessment of left ventricular systolic function. Both echocardiography and radionuclide ventriculography have been advocated.^8-14 However, echocardiography is preferred as it is widely available, simple, noninvasive, safe, usually less expensive, and provides more information about valve function and left ventricular hypertrophy. Table 2 demonstrates the high sensitivity and specificity of echocardiography.³⁵ In view of this, it is recommended as a standard adjunct to the clinical diagnosis of patients with dyspnea on exertion and suspected heart failure. Between 8% and 18% of patients will have inadequate echocardiograms, in which case radionuclide ventriculography is advocated.⁸

Neurohormonal markers. In recent years there has been increasing interest in the potential role of neurohormonal markers, such as B-type natriuretic peptide (BNP), atrial natriuretic peptide (ANP), N-terminal pro-ANP (N-ANP), and N-terminal pro-BNP (N-BNP) as indices of LVSD.^36-42 Most of the data relating to these markers are relatively recent; therefore their use is not addressed in any detail in any of the aforementioned guidelines.

Some studies^41,42 suggest that BNP and N-BNP are useful for diagnosing LVSD even when the positive predictive values are low, because of their high negative predictive values. One of the most recent studies⁴⁴ examined the utility of BNP in an urgent care setting and suggested that BNP was an extremely reliable indicator of LVSD. In this population of patients with acute dyspnea where 39% had a final diagnosis of heart failure, 90% with a positive BNP had heart failure and 98% of those with a negative BNP did not. Although there appears to be a growing body of evidence supporting the role of these neurohormonal markers in the evaluation of the patient with LVSD, Table 2 illustrates that there have also been conflicting findings. This is partly because of differences in study design, study populations, cut-off points for ANP and BNP, and the definition of LVSD. Most studies agree that assessment of BNP, in particular, may be a cost-effective method for initial screening for LVSD, but should still be followed by an echocardiogram to confirm the diagnosis.

Management follows diagnosis. Making the correct diagnosis is the crucial first step in the management of chronic heart failure. Figure 1 summarizes the steps currently recommended for the evaluation of the patient with LVSD. A confirmation of a diagnosis of LVSD, however, is not the end of the story. Management will then need to include initiation of appropriate therapies and consideration of treatable and reversible etiologies, a subject to be addressed in the June 2002 issue of this journal.

TABLE 2
Key investigations used for the diagnosis of left ventricular systolic dysfunction

Figure
Steps in the assessment of the patient with suspected heart failure

ACKNOWLEDGMENTS

We wish to thank Mr Chris Shiels at the Department of Primary Care, University of Liverpool, for his valuable advice regarding this manuscript.

Heart failure is increasing in incidence and prevalence; it currently affects 0.4% to 2% of the general population and 8% to 10% of the elderly.^1,2 In the United States, heart failure is the second most common cardiovascular reason for an outpatient visit in the ambulatory care setting and remains the most common cause for hospitalization among patients older than 65 years.³ The total cost for heart failure management in 1999 was estimated to approach $56 billion.⁴ Those suffering with this illness experience high levels of morbidity and mortality⁵ that are reflected in the workloads of both primary and secondary care. Heart failure admission rates are rising, and the prognosis of heart failure has been compared with that of malignancy, with a 6-year mortality rate of 84% in men and 77% in women.^6,7

A number of heart failure guidelines^8-14 provide direction regarding “best practice” with regard to diagnosis and management. These guidelines have all been produced by expert panels and base their evidence on systematic critical reviews of the literature, plus expert consensus opinion. The evidence underlying the development of these guidelines ranges from well-conducted randomized controlled trials to expert opinion. These guidelines all emphasize the ways in which approaches to the diagnosis and management of heart failure have altered substantially in recent years and are continuing to change rapidly. The need to detect heart failure at an early stage to slow the progression of left ventricular systolic dysfunction (LVSD) is now well accepted.¹⁵

The following provides an overview of the current recommended approaches to diagnosis, focusing specifically on LVSD, the most common type of heart failure and also the usual focus of most guidelines. Accurate diagnosis of LVSD is the single most important step in management.¹⁶ An adequate diagnosis should establish the existence of heart failure, differentiate systolic from diastolic dysfunction, and identify the main underlying cause and any subsidiary diagnoses that may exacerbate heart failure. The etiology of heart failure and the presence of exacerbating factors or other diseases need to be carefully considered in all patients. Coronary artery disease remains the most common potentially reversible etiologic factor in heart failure.⁸

Using the history and physical examination

The major symptoms of heart failure are fatigue, exercise intolerance, exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and dependent edema. However, such symptoms are similar to those of many other diseases, particularly pulmonary diseases. For example, exertional dypsnea is a common symptom in heart failure but can be due to a wide range of other causes, such as chronic obstructive pulmonary disease, interstitial lung disease, asthma, respiratory infection, deconditioning, or obesity. Many patients with impaired left ventricular function may have no obvious symptoms.¹⁷ This highlights the importance of exploring past medical and medication history as these contribute to the overall clinical assessment.

Physical findings that may support a diagnosis of heart failure include raised jugular venous pressure, peripheral edema not due to venous insufficiency, presence of a third heart sound, gallop rhythm, laterally displaced apical impulse, tachycardia, and pulmonary rales that do not clear with coughing. Although clinical findings are particularly useful in acute severe heart failure at the time of hospitalization,¹⁸ it is difficult to accurately diagnose mild heart failure in the community on the basis of clinical grounds alone.^2,9 The value of different symptoms and aspects of the medical history and use of medications in the evaluation of potential heart failure patients have been examined by researchers.^{18, 20-23} Similarly, the utility of physical examination has also undergone investigation.^18,20,22-28Table 1 summarizes the study findings with regard to clinical symptoms and signs.

Davie and colleagues²⁰ assessed the value of symptoms, past history, medications, and signs in the evaluation of patients who may have LVSD. No one clinical feature predicted LVSD, as assessed by echocardiography with sensitivity, specificity, and a high positive and negative predictive value. Absence of dyspnea on exertion essentially ruled out heart failure (negative likelihood ratio [LR-] = 0.06), while gallop rhythm (positive likelihood ratio [LR+] = 24.0), laterally displaced apical impulse (LR+ 16.4), and elevated jugular venous pulsation (LR+ = 8.9) are strong evidence in favor of the diagnosis. Furthermore, the combination of history of myocardial infarction and displaced apex on physical examination, although not particularly sensitive (39% sensitivity) was very specific (99% specificity) with high positive (89%) and negative (89%) predictive values. The authors also suggest that a breathless patient with a past history of myocardial infarction and a displaced apex beat on physical examination will almost certainly have heart failure and, if resources are limited, may not need echocardiography to confirm the diagnosis. However, less than 50% of breathless patients will have this combination, and the other half would therefore need echocardiography as the gold standard diagnostic tool for LVSD.

Morgan and coworkers²⁸ assessed the prevalence and clinical characteristics of LVSD among elderly patients (those aged 70 years to 84 years) in a primary care setting by echocardiographic assessment of ventricular function. They found that no single clinical symptom or sign was both sensitive and specific, and concluded that diagnosis should not be based on clinical history and examination alone. They found that a substantial number of elderly individuals had asymptomatic or misdiagnosed LVSD, and suggested this might be due to the extremely limited sensitivity and specificity of clinical history taking and examination. For example, only 11% of patients with LVSD had a raised jugular venous pressure, and bilateral ankle edema was common but nonspecific. Researchers have therefore concluded that although these clinical findings are useful in acute severe heart failure, they have only a small role in detecting LVSD in the community.¹⁸

TABLE 1
The use of clinical symptoms and signs to diagnose heart failure, by study

Laboratory and imaging evaluation

Although an important and valuable part of the evaluation, the history and physical examination alone are insufficient to confirm a diagnosis in most cases. Recommended initial tests for patients with signs or symptoms of heart failure include complete blood count (CBC), serum electrolytes, serum creatinine, serum albumin, liver function tests, urinalysis, electrocardiogram, and chest x-ray (Figure).

Blood tests. For those older than 65 years or with atrial fibrillation or evidence of thyroid disease, thyroid function tests should also be performed because heart failure due to thyrotoxicosis is frequently associated with rapid atrial fibrillation and hypothyroidism may also present as heart failure.^8,10 The other routine blood tests are important as a way to exclude alternative diagnoses; they also help with the search for predisposing or exacerbating causes of the heart failure. These baseline tests also help guide future therapeutic decision making. For example, electrolyte and renal function results are pertinent when initiating angiotensin-converting enzyme (ACE) inhibitors. Anemia can exacerbate pre-existing heart failure, and measurement of renal function is essential to distinguish fluid overload due to heart failure from renal failure. Liver enzymes may be affected by hepatic congestion. Urinalysis is valuable in the detection of underlying renal disease or diabetes.⁸

Electrocardiography. An electrocardiogram (ECG) is another recommended part of the evaluation of the suspected heart failure patient.^8-14 Considerable attention has been paid to examining the value of this test in the diagnosis of LVSD.^29-32 Davie and colleagues²⁹ assessed the value of the ECG in identifying patients with possible heart failure by examining referrals for echocardiography by primary care practitioners. A total of 534 patients were referred for echocardiography for possible heart failure, of whom 18% (n = 96) had LVSD. They showed that LVSD was extremely unlikely if the ECG result was normal, but that 1 in 3 patients with an abnormal result had significant LVSD. Thus, a normal ECG result virtually excludes chronic heart failure due to LVSD. However, the ECG is not a substitute for echocardiography, as an abnormal result does not accurately predict the presence of LVSD (Table 2).

Others have confirmed these findings.^30,32 Talreja and colleagues³⁰ found that of 330 consecutive in-patients referred for echocardiographic assessment of left ventricular function, 124 (41%) had LVSD. Only 2 of 124 patients with LVSD had a normal electrocardiogram result. When the ECG result is normal, the authors suggest that echocardiography is not needed. However, they concede that physicians are unlikely to adhere to this because many may not be as sophisticated in interpreting the ECG and may feel it important to get an accurate measure of ejection fraction. Guidelines published by the European Society of Cardiology¹⁰ state that a normal ECG result in patients with suspected heart failure should lead us to doubt the accuracy of the diagnosis.

Chest x-ray. The chest x-ray is most valuable as a test to exclude pulmonary causes. However, the existing evidence suggests it is not a reliable way to exclude LVSD.^24,26,33,34 (Table 2) provides information about the value of radiography in predicting LVSD. A systematic review of the literature concluded that redistribution and cardiomegaly were the best chest radiographic findings for diagnosing increased preload and reduced ejection fraction, respectively.³⁴ However, neither finding alone could adequately exclude or confirm LVSD. Studies published since that review have confirmed this finding.³³ Although part of the evaluation of the heart failure patient, radiography is only one part of the diagnostic process and cannot be used to provide definitive diagnostic information.

Echocardiography. The most important step in the evaluation of the heart failure patient is the assessment of left ventricular systolic function. Both echocardiography and radionuclide ventriculography have been advocated.^8-14 However, echocardiography is preferred as it is widely available, simple, noninvasive, safe, usually less expensive, and provides more information about valve function and left ventricular hypertrophy. Table 2 demonstrates the high sensitivity and specificity of echocardiography.³⁵ In view of this, it is recommended as a standard adjunct to the clinical diagnosis of patients with dyspnea on exertion and suspected heart failure. Between 8% and 18% of patients will have inadequate echocardiograms, in which case radionuclide ventriculography is advocated.⁸

Neurohormonal markers. In recent years there has been increasing interest in the potential role of neurohormonal markers, such as B-type natriuretic peptide (BNP), atrial natriuretic peptide (ANP), N-terminal pro-ANP (N-ANP), and N-terminal pro-BNP (N-BNP) as indices of LVSD.^36-42 Most of the data relating to these markers are relatively recent; therefore their use is not addressed in any detail in any of the aforementioned guidelines.

Some studies^41,42 suggest that BNP and N-BNP are useful for diagnosing LVSD even when the positive predictive values are low, because of their high negative predictive values. One of the most recent studies⁴⁴ examined the utility of BNP in an urgent care setting and suggested that BNP was an extremely reliable indicator of LVSD. In this population of patients with acute dyspnea where 39% had a final diagnosis of heart failure, 90% with a positive BNP had heart failure and 98% of those with a negative BNP did not. Although there appears to be a growing body of evidence supporting the role of these neurohormonal markers in the evaluation of the patient with LVSD, Table 2 illustrates that there have also been conflicting findings. This is partly because of differences in study design, study populations, cut-off points for ANP and BNP, and the definition of LVSD. Most studies agree that assessment of BNP, in particular, may be a cost-effective method for initial screening for LVSD, but should still be followed by an echocardiogram to confirm the diagnosis.

Management follows diagnosis. Making the correct diagnosis is the crucial first step in the management of chronic heart failure. Figure 1 summarizes the steps currently recommended for the evaluation of the patient with LVSD. A confirmation of a diagnosis of LVSD, however, is not the end of the story. Management will then need to include initiation of appropriate therapies and consideration of treatable and reversible etiologies, a subject to be addressed in the June 2002 issue of this journal.

TABLE 2
Key investigations used for the diagnosis of left ventricular systolic dysfunction

Figure
Steps in the assessment of the patient with suspected heart failure

ACKNOWLEDGMENTS

We wish to thank Mr Chris Shiels at the Department of Primary Care, University of Liverpool, for his valuable advice regarding this manuscript.

ABSTRACT

BACKGROUND: While the superiority of proton pump inhibitors (PPIs) over histamine-2 receptor antagonists in symptom control of gastroesophageal reflux disease (GERD) has been well established, limited work has been done comparing the efficacy of different PPIs. Theoretically, differences in pharmacokinetic properties, such as increased bioavailability of lansoprazole, could play a role in efficacy of symptom control. The purpose of this study was to demonstrate a difference between PPIs in GERD symptom control.

POPULATION STUDIED: The patient population for this study consisted of 3510 individuals over age 18 years with endoscopically confirmed erosive esophagitis of grade 2 severity or higher who were gathered through a large multicenter clinical trial. To enter the study, patients had to have experienced at least 1 episode of moderate to very severe heartburn within 3 days before their screening visit. Comparison of treatment groups showed the only significant demographic difference was increased reported tobacco use in the omeprazole group (28%) versus the lansoprazole group (25%).

STUDY DESIGN AND VALIDITY: This study was a double-blind multicenter clinical trial in which participants were randomized to receive either 30 mg lansoprazole or 20 mg omeprazole once daily for 8 weeks. Allocation concealment was not mentioned. Follow-up visits were conducted at the end of weeks 1, 2, and 8 of treatment. Analysis was by intention to treat.

OUTCOMES MEASURED: This study looked primarily at onset and duration of symptom relief and severity as recorded by patients in a diary. Specifically, daytime and nighttime heartburn symptoms were analyzed with regard to percentage of complete heartburn relief as well as average heartburn severity at days 1 to 3 and the end of weeks 1, 2, and 8 of treatment.

RESULTS: The group treated with lansoprazole showed a statistically significant advantage in symptom relief throughout the treatment period. On day 1 of treatment, the lansoprazole group was found to be 33% heartburn free as compared with 25% in the omeprazole group (P < .0001). The number needed to treat (NNT) to see this statistically significant difference was 12.5. Patients receiving lansoprazole versus omeprazole had small but statistically significant decreases in numbers of heartburn-free days (56% vs 49% in first 3 days of treatment, NNT = 14) and nights (NNT = 14) as well as daytime heartburn severity and nighttime severity. The lansoprazoletreated group also showed increased sustained resolution of symptoms over the omeprazole-treated group during the 8-week study period. Overall, however, these differences were extremely small and narrowed as the study progressed to 8 weeks.

ABSTRACT

BACKGROUND: While the superiority of proton pump inhibitors (PPIs) over histamine-2 receptor antagonists in symptom control of gastroesophageal reflux disease (GERD) has been well established, limited work has been done comparing the efficacy of different PPIs. Theoretically, differences in pharmacokinetic properties, such as increased bioavailability of lansoprazole, could play a role in efficacy of symptom control. The purpose of this study was to demonstrate a difference between PPIs in GERD symptom control.

POPULATION STUDIED: The patient population for this study consisted of 3510 individuals over age 18 years with endoscopically confirmed erosive esophagitis of grade 2 severity or higher who were gathered through a large multicenter clinical trial. To enter the study, patients had to have experienced at least 1 episode of moderate to very severe heartburn within 3 days before their screening visit. Comparison of treatment groups showed the only significant demographic difference was increased reported tobacco use in the omeprazole group (28%) versus the lansoprazole group (25%).

STUDY DESIGN AND VALIDITY: This study was a double-blind multicenter clinical trial in which participants were randomized to receive either 30 mg lansoprazole or 20 mg omeprazole once daily for 8 weeks. Allocation concealment was not mentioned. Follow-up visits were conducted at the end of weeks 1, 2, and 8 of treatment. Analysis was by intention to treat.

OUTCOMES MEASURED: This study looked primarily at onset and duration of symptom relief and severity as recorded by patients in a diary. Specifically, daytime and nighttime heartburn symptoms were analyzed with regard to percentage of complete heartburn relief as well as average heartburn severity at days 1 to 3 and the end of weeks 1, 2, and 8 of treatment.

RESULTS: The group treated with lansoprazole showed a statistically significant advantage in symptom relief throughout the treatment period. On day 1 of treatment, the lansoprazole group was found to be 33% heartburn free as compared with 25% in the omeprazole group (P < .0001). The number needed to treat (NNT) to see this statistically significant difference was 12.5. Patients receiving lansoprazole versus omeprazole had small but statistically significant decreases in numbers of heartburn-free days (56% vs 49% in first 3 days of treatment, NNT = 14) and nights (NNT = 14) as well as daytime heartburn severity and nighttime severity. The lansoprazoletreated group also showed increased sustained resolution of symptoms over the omeprazole-treated group during the 8-week study period. Overall, however, these differences were extremely small and narrowed as the study progressed to 8 weeks.

ABSTRACT

BACKGROUND: While the superiority of proton pump inhibitors (PPIs) over histamine-2 receptor antagonists in symptom control of gastroesophageal reflux disease (GERD) has been well established, limited work has been done comparing the efficacy of different PPIs. Theoretically, differences in pharmacokinetic properties, such as increased bioavailability of lansoprazole, could play a role in efficacy of symptom control. The purpose of this study was to demonstrate a difference between PPIs in GERD symptom control.

POPULATION STUDIED: The patient population for this study consisted of 3510 individuals over age 18 years with endoscopically confirmed erosive esophagitis of grade 2 severity or higher who were gathered through a large multicenter clinical trial. To enter the study, patients had to have experienced at least 1 episode of moderate to very severe heartburn within 3 days before their screening visit. Comparison of treatment groups showed the only significant demographic difference was increased reported tobacco use in the omeprazole group (28%) versus the lansoprazole group (25%).

STUDY DESIGN AND VALIDITY: This study was a double-blind multicenter clinical trial in which participants were randomized to receive either 30 mg lansoprazole or 20 mg omeprazole once daily for 8 weeks. Allocation concealment was not mentioned. Follow-up visits were conducted at the end of weeks 1, 2, and 8 of treatment. Analysis was by intention to treat.

OUTCOMES MEASURED: This study looked primarily at onset and duration of symptom relief and severity as recorded by patients in a diary. Specifically, daytime and nighttime heartburn symptoms were analyzed with regard to percentage of complete heartburn relief as well as average heartburn severity at days 1 to 3 and the end of weeks 1, 2, and 8 of treatment.

RESULTS: The group treated with lansoprazole showed a statistically significant advantage in symptom relief throughout the treatment period. On day 1 of treatment, the lansoprazole group was found to be 33% heartburn free as compared with 25% in the omeprazole group (P < .0001). The number needed to treat (NNT) to see this statistically significant difference was 12.5. Patients receiving lansoprazole versus omeprazole had small but statistically significant decreases in numbers of heartburn-free days (56% vs 49% in first 3 days of treatment, NNT = 14) and nights (NNT = 14) as well as daytime heartburn severity and nighttime severity. The lansoprazoletreated group also showed increased sustained resolution of symptoms over the omeprazole-treated group during the 8-week study period. Overall, however, these differences were extremely small and narrowed as the study progressed to 8 weeks.

In 1995 and 1996, US adults made more than 18 million office visits for the evaluation and treatment of hyperlipidemia, including 3.4% of all visits to family physicians. Among visits to family physicians, 4.1% included measurement of cholesterol levels.¹ Overall, mean cholesterol levels decreased from 220 in 1960–1962 to 203 in 1988–1994. During the same time period, the proportion of adults with elevated total cholesterol levels (> 240) decreased from 32% to 19%.² Despite this progress, the availability of more effective drugs, guidelines advocating increasingly aggressive treatment, and populationwide goals established in Healthy People 2010 will continue to increase the number of patients seen by family physicians for screening, diagnosis, and treatment of hyperlipidemia.³

When to treat

The National Cholesterol Education Program (NCEP), a program within the National Institute of Health’s Heart, Lung, and Blood Institute, published a guideline in 1993 for screening and treating hyperlipidemia. Physicians have since become familiar with the NCEP concept of basing treatment decisions on assessment of patient risk factors (smoking, age, diabetes, hypertension, family history of early coronary artery disease [CAD]) and application of algorithms linked to desired low-density lipoprotein (LDL) cholesterol levels. The advantage of this strategy is its simplicity. Physicians assess whether the NCEP risk factors are present and then work with their patients to achieve the desired LDL level through lifestyle modification, drug therapy, or both.

Unfortunately, the NCEP guideline did not assess the individual’s actual risk of CAD. In its recently released Third Report, the NCEP has recognized the value of this strategy by incorporating the Framingham tables to calculate the 10-year risk of developing clinical CAD based on a patient’s individual risk factors, including cholesterol levels (Table 1).⁴ This new NCEP III guideline recommends traditional risk factor counting coupled, in certain situations, with the 10-year risk derived from the Framingham scoring system.

TABLE 1
FRAMINGHAM TABLES FOR CALCULATING CORONARY ARTERY DISEASE RISK

Therapy is based on the individual patient’s risk category and LDL levels (Figure). Patients whose 10-year risk is greater than 20% or those who have CAD-equivalent conditions (ie, diabetes, peripheral arterial disease, abdominal aortic aneurysm, symptomatic carotid artery disease) are considered to have a risk equivalent to that of patients with known CAD; all have an LDL goal of 100 or less.

For those with a 10-year CAD risk less than 20%, the number of positive risk factors determines the LDL goal. This new method allows physicians to communicate with their patients more clearly about individual risk and enhances shared decision making. While the NCEP III report is based on extensive literature review, the recommendations of its expert panel are not characterized according to the strength of the supporting evidence, as is done by the US Preventive Services Task Force.

Figure
TREATMENT STRATEGY BASED ON LDL LEVEL AND RISK CATEGORY

Explaining treatment benefits

The NCEP III report does not make explicit the effect of the treatment on the patient; that is, how much the proposed treatment will reduce the risk of CAD. This determination depends in part on whether the patient being treated has known CAD or a CAD-equivalent condition (secondary prevention) versus no known CAD (primary prevention). The benefits of treatment have been most clearly quantified for drug treatment and are most easily evaluated using the number needed to treat (NNT). The NNT refers to the number of patients who would have to be treated for 5 years to prevent 1 CAD event. Physicians may use the NNTs to assist patients in determining their preferences for treatment, bearing in mind that the NNT refers to an outcome for a population, such as men with high cholesterol levels. For a given individual, their risk of an adverse outcome is all or none. Nonetheless, patients may find the NNT a useful way to assess their personal values in making treatment decisions.

Treatment

Lifestyle modification

Diet modification is the cornerstone of therapy for mild to moderate hyperlipidemia. Modifying the diet is also recommended along with pharmacologic therapy in people at higher risk of CAD. NCEP III recommends a diet for “therapeutic lifestyle changes” that includes < 200 mg cholesterol per day, < 7% saturated fat, 25% to 35% total fat, 50% to 60% carbohydrates, and 15% protein of total calories.⁴