I. Stage B Heart Failure: What every physician needs to know.

Stage B heart failure (HF) encompasses patients with known cardiac structural or functional abnormalities in the absence of HF symptoms. Patients with Stage B HF do not have the HF syndrome (which requires the presence of symptoms); rather, they have a subclinical condition that predisposes them to the development of HF.

The recognition of stage B HF was born out of an awareness that patients in this group are at high risk for adverse cardiovascular events; as such, the American College of Cardiology/American Heart Association (ACC/AHA) HF guidelines have placed patients with stage B HF along the spectrum of HF in an effort to increase appreciation of subclinical HF and the need to prevent overt HF.

Further, the ACC/AHA HF staging system highlights the following: progression to HF often happens in a predictable fashion, cardiac structural and functional abnormalities occur early in the sequence to HF, and development of HF symptoms heralds an advanced stage at which time treatment is difficult (i.e., prevention of symptomatic HF is key).

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The characteristics of patients that fall into stage B HF are diverse, as the presence of several structural and/or functional cardiac abnormalities have been included in this diagnosis. In most cases of stage B HF, risk factors for HF are present, and over time these factors induce cardiac structural and/or functional changes that lead to the HF syndrome.

Examples include a patient with systemic hypertension who develops left ventricular (LV) hypertrophy or a patient with a history of coronary artery disease who suffers a myocardial infarction (MI) that results in wall motion abnormalities and a reduced LV ejection fraction.

The number of patients with stage B HF continues to climb as a result of an aging population, increasing prevalence of comorbidities that predispose to cardiac remodeling, and widespread use of therapies such as angiotensin converting enzyme (ACE)-inhibitors and beta-blockers, both of which improve survival post-MI. As such, the economic burden of stage B HF is high and will likely continue to grow over time.

Recognition of stage B HF is critical: abnormal cardiac structure and/or function increases the risk for overt HF development (up to 10% per year) and also confers a higher mortality risk. Pharmacological therapies, particularly in those with LV systolic dysfunction, have been well studied and prevent progression and mortality in a substantial percentage of patients.

Therefore, early and appropriate identification of stage B HF is crucial to improving outcomes. The current focus of HF diagnosis and treatment, unfortunately, continues to center on stages C and D HF, as these patients are often more easily identified, perceived to have greater “urgency” for treatment, and are more readily referred to specialized centers for care. However, in order to continue to improve morbidity and mortality, the need to focus on earlier stages in order to prevent HF is clear.

II. Diagnostic Confirmation: Are you sure your patient has stage B heart failure?

Key to the diagnosis of stage B HF is evidence of cardiac structural remodeling or functional abnormalities in the absence of any HF symptoms. Examples include LV hypertrophy, LV dilation, LV systolic dysfunction, LV diastolic dysfunction, history of MI (typically with a wall motion abnormality), and valvular heart disease (particularly valvular regurgitation). Presence of HF symptoms automatically moves the patient forward in the spectrum of HF to stage C.

A thorough history and physical exam are helpful in the evaluation of a patient with possible stage B HF. History alone can provide clues to the presence of stage B HF patients (examples include prior MI, history of cardiomyopathy, pertinent family history, or risk factors for HF). Most importantly, the history and physical exam are critical in excluding symptoms or signs of HF which would indicate the presence of stage C (symptomatic) HF.

A. History Part I: Pattern Recognition:

By definition, patients with stage B HF have no prior history of symptomatic HF, and do not have current (or prior) symptoms (or signs) of HF. Thus, as stated previously, the history is important for the exclusion of symptomatic HF. Patients who have exercise intolerance, dyspnea, orthopnea, paroxysmal nocturnal dyspnea, or leg swelling in the presence of risk factors of HF or evidence of structural or functional heart disease should be evaluated for stage C (symptomatic) HF.

In patients at high risk for HF (e.g., history of coronary artery disease, hypertension, or diabetes) who have nonspecific symptoms (e.g., fatigue) the clinician should have a high index of suspicion and should evaluate closely for the diagnosis of symptomatic HF. It is important to identify patients with symptomatic HF as early as possible to expedite appropriate evaluation and treatment.

Most patients with stage B HF will have identifiable risk factors for cardiac structural or functional abnormalities. Risk factors to inquire about include systemic hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, sleep apnea, alcoholism, illicit drug use, smoking, exposure to cardiotoxic agents (e.g., doxorubicin, cyclophosphamide, or trastuzumab), infection-related cardiac disease (e.g., viral myocarditis, rheumatic fever), or systemic disorders which have a high prevalence of cardiovascular involvement (e.g., connective tissue disorders, amyloidosis, or hemochromatosis).

Family history may be notable for early onset HF or coronary artery disease, cardiomyopathies, and sudden cardiac death.

In patients with a known history of MI, congenital heart disease, rheumatic heart disease, or significant valvular heart disease, the diagnosis of stage B HF is appropriate if there are no symptoms or signs of HF and no prior history of HF.

B. History Part 2: Prevalence:

The earlier the stage of HF, the higher the prevalence. Thus, stage B HF is more common than stage C, but not nearly as common as stage A which is defined as the presence of risk factors for heart failure in the absence of cardiac structural or functional abnormalities.

In a community study of approximately 2,000 participants, nearly 5% of individuals had evidence of LV systolic dysfunction (i.e., reduced LV ejection fraction) and 21% had any grade of diastolic dysfunction without evidence of HF (nearly 7% of patients aged ≥45 years had at least moderate diastolic dysfunction). During a follow-up period of 6 years, the risk for developing HF was nearly 25% in those with at least moderate diastolic dysfunction.

The burden of systolic dysfunction is also high. The total number of patients with asymptomatic LV systolic dysfunction is estimated to be three to four times as prevalent as the sum of all patients in stages C and D systolic HF. Figure 1 displays the increased risk of developing HF in patients with LV systolic dysfunction and in those with LV diastolic dysfunction.

Figure 1:

A) Kaplan-Meier curves for survival free of heart failure according to ejection fraction. B) Incidence of heart failure according to diastolic function.

In the Framingham Heart Study, the prevalence of LV hypertrophy (determined by echocardiography) was 17.5%. Several studies, including the Multi-Ethnic Study of Atherosclerosis, have found a strong association between increased LV mass and the development of symptomatic (stage C) HF.

C. History Part 3: Competing diagnoses that can mimic stage B heart failure.

Stage B HF can be readily distinguished from other stages along the HF spectrum by history, physical exam, and imaging.

Stage A HF, which represents risk factors for HF in the absence of cardiac structural or functional changes, can be differentiated by history (i.e., no previous MI, no valvular disease) and imaging (i.e., no structural or functional echocardiographic abnormality).

Stage C HF is differentiated from stage B HF if symptoms or signs of HF are present, or if the patient has a prior history of symptomatic HF.

D. Physical Examination Findings.

Typically, patients in stage B HF will have a fairly unremarkable cardiovascular exam. Thus, the physical exam serves primarily to exclude the presence of overt HF, advancing patients to stage C HF. The physical exam, however, can provide clues to the presence of structural heart disease in the asymptomatic patient (examples include a laterally displaced, diffuse, or sustained point of maximal impulse in a patient with dilated cardiomyopathy who has LV systolic dysfunction or an audible (and occasionally palpable) S4 in a patient with systemic hypertension and concentric LV hypertrophy.

Vital signs

Abnormal vital signs, such as hypotension, tachycardia, or tachypnea, increase the likelihood of symptomatic stage C HF. Patients with stage B HF are, by definition, asymptomatic, and typically have normal vital signs (except for patients with systemic hypertension who may have elevated blood pressure).


As stated previously, most patients with stage B HF will have a relatively benign physical exam. The cardiac exam can provide clues to the presence of abnormal cardiac structure and function in an asymptomatic patient. Besides the typical abnormal heart sounds and murmurs associated with various cardiac diseases, Kussmaul’s sign (paradoxical increase in jugular venous pressure during inspiration) can be particularly helpful in identifying underlying significant cardiac disease. Kussmaul’s sign is easy to elicit on physical examination and can be found in constrictive pericarditis, restrictive cardiomyopathy, right heart failure from any cause (e.g., pulmonary hypertension, right ventricular MI), or severe tricuspid regurgitation.

Signs of poor perfusion or fluid overload on physical examination, such as weak carotid upstrokes, cool extremities, elevated jugular venous pressure, rales, ascites, and leg swelling, should alert the clinician to the possibility of stage C HF. If patients with these signs deny symptoms, further objective testing should be obtained to exclude the presence of symptomatic HF.

E. What diagnostic tests should be performed?

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

The purpose of laboratory testing is to gauge the severity of risk factors, monitor for side effects of current treatment, and to ascertain whether end organ dysfunction is present (which would signal stage C HF). Standard tests to consider include a complete blood count, serum electrolytes (including calcium and magnesium), kidney function tests, urinalysis, urine microalbumin, hemoglobin A1c, thyroid function tests, liver function tests, fasting lipid panel, and 12-lead electrocardiogram.

Routine measurement of serum B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) in asymptomatic patients is controversial, but we believe that in high-risk patients, it is reasonable to use BNP or NT-proBNP as screening tests which increase the likelihood of stage B HF. Studies have shown that adding BNP or NT-proBNP to clinical risk factors for HF increases the diagnostic accuracy for identifying patients with stage B HF.

In addition, both BNP and NT-proBNP have been shown to be powerful predictors of cardiac events and outcomes. Thus, we recommend using BNP (or NT-proBNP) in patients with risk factors for HF in whom the diagnosis of stage B HF is suspected. If BNP (or NT-proBNP) is elevated, echocardiography should be the next diagnostic test.

Finally, a high BNP level (or NT-proBNP) in an asymptomatic patient should prompt consideration of objective exercise testing to determine functional limitation and clinically overt (stage C) HF. The exact cut off for elevated natriuretic peptide levels is not known. Plasma BNP levels greater than 45 to 50pg/mL in both men and women have 95% specificity in detecting LV systolic dysfunction and elevated LV mass, but sensitivity is poor.

Using age and sex-specific reference limits (95th percentile values) yields a better combination of sensitivity and specificity at the expense of greater (inappropriate) referrals for echocardiography. Given the inadequacy of current knowledge in using natriuretic peptides in stage B HF, we believe a more conservative approach, in high-risk populations, using higher thresholds for elevated BNP levels is warranted and most cost-effective. High risk individuals can be determined by clinical prediction scoring systems, such as the Association of Health Aging and Body Composition (ABC) HF score.

Younger patients with cardiac abnormalities out of proportion to what might be expected based on age and prior risk factors should undergo a more thorough workup to exclude less common diagnoses. For instance, a 50-year-old woman with severe diastolic dysfunction, increased LV wall thickness, and low voltage on the electrocardiogram, should prompt the clinician to consider the diagnosis of an infiltrative cardiomyopathy such as cardiac amyloidosis.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Transthoracic echocardiography is the best first test for patients in whom the diagnosis of stage B HF is considered. Routine echocardiography, with Doppler and tissue Doppler imaging, can readily diagnose stage B HF if any of the following are present: reduced LV ejection fraction (typically defined as ejection fraction [EF] <50%, although most studies of patients with global LV systolic dysfunction use a cut-off of EF <40%); LV dilation; LV hypertrophy; wall motion abnormalities; right ventricular [RV] enlargement/dysfunction; severe valvular disease; pericardial disease; evidence of congenital heart disease.

Diastolic dysfunction (Figure 2) can also be readily diagnosed by comprehensive echocardiography and can be included in the definition of stage B HF. However, it appears that patients with moderate or greater (grade 2 or higher) diastolic dysfunction are at highest risk for developing HF; therefore, patients with more advanced diastolic dysfunction are the ones that fit the diagnosis of stage B HF best. The diagnosis of diastolic dysfunction is complex, and should not rely on any one criteria.

Figure 2:

Echocardiographic patterns of diastolic dysfunction.

Furthermore, an algorithmic approach, including ones included in guidelines on the diagnosis of diastolic dysfunction, may not be ideal. When diagnosing diastolic dysfunction, the following factors should be taken into consideration: age, mitral inflow parameters (early mitral inflow [E], late [atrial] mitral inflow [A], E/A ratio, E deceleration time), pulmonary venous flow, tissue Doppler e’ velocity, E/e’ ratio, and left atrial volume. In addition, factors such as the presence of LV systolic dysfunction and LV hypertrophy are also helpful for the diagnosis and categorization of diastolic dysfunction.

Finally, diastolic stress testing (i.e., determination of E/e’ ratio, a surrogate for LV filling pressures, at peak exercise) can assist with the diagnosis of diastolic dysfunction in patients who have indeterminate or conflicting indices during evaluation on resting echocardiography.

Although not routinely measured on transthoracic echocardiography, several other simple echocardiographic indices may provide clues to underlying cardiac dysfunction. These include tricuspid annular plane systolic excursion (TAPSE), tissue Doppler LV and right ventricular systolic (s’) velocities, and peak global longitudinal LV systolic strain. Each of these indices has been associated with adverse cardiovascular outcomes in at-risk patients.

Additional imaging tests (including cardiac magnetic resonance imaging and transesophageal echocardiography) may be warranted based on the initial results from transthoracic echocardiography. However, routine transthoracic echocardiography is the first test for the evaluation of underlying cardiac structural and functional abnormalities in patients suspected of having stage B HF.

III. Management.

For patients with asymptomatic LV systolic dysfunction and those with evidence of prior MI, the mainstays of therapy are beta-blockers and ACE-inhibitors (or angiotensin receptor blockers).

Neurohormonal activation in response to LV systolic dysfunction is a key intermediary in the progression to HF and provides the rationale for the use of these agents. For instance, activation of the renin-angiotensin-aldosterone system leads to increased vasoconstriction, fibrosis, thrombosis, and remodeling.

Thus, ACE-inhibitors (or angiotensin receptor blockers) have antihypertensive, antifibrotic, and antithrombotic properties and can also inhibit/reverse maladaptive remodeling. Clinical trials in patients with asymptomatic LV systolic dysfunction, such as Studies of Left Ventricular Dysfunction (SOLVD)-Prevention, Survival And Ventricular Enlargement Study Group (SAVE), and Valsartan in Acute Myocardial Infarction (VALIANT), have shown that ACE-inhibitors (and angiotensin receptor blockers) decrease mortality and prevent progression to symptomatic HF.

Likewise, adrenergic activation plays a critical role in HF development by increasing oxygen demand, upregulating the renin-angiotensin-aldosterone pathway, increasing fibrosis and cell size, and increasing blood pressure. Beta-blockade therefore has several beneficial effects in patients with asymptomatic LV systolic dysfunction.

In SOLVD-Prevention, beta-blockers and ACE-inhibitors were synergistic for the prevention of adverse outcomes. Other trials demonstrating the benefit of beta-blockers include Carvedilol Post-Infarction Survival Control in LV Dysfunction (CAPRICORN), which showed that carvedilol improved outcomes in patients with EF less than 40% (34% of whom were asymptomatic), and Reversal of Ventricular Remodeling with Toprol-XL (REVERT), which showed that treatment with long-acting metoprolol was associated with beneficial reverse remodeling and improvements in EF.

Select patients with asymptomatic LV systolic dysfunction, particularly from an ischemic etiology, may also benefit from an implantable cardioverter-defibrillator (ICD) as illustrated in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II).

For patients with asymptomatic LV diastolic dysfunction, optimal treatment is less clear. We advocate searching for the underlying cause of diastolic dysfunction in all patients, particularly those who have moderate or severe diastolic dysfunction. Often times, treating the underlying cause will prevent the development of overt HF.

In addition, diastolic dysfunction is often a marker for patients who have multiple comorbidities. Since adverse outcomes in these patients are often due to their comorbidities, we advocate aggressive management of these comorbidities.

Further, because hypertension is common in patients with asymptomatic LV diastolic dysfunction, blood pressure control is particularly important. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), in patients with preserved ejection fraction, chlorthalidone reduced the risk of HF incidence more than both amlodipine and lisinopril. In the very elderly patient with hypertension (age >80 years, systolic blood pressure >160mm Hg), indapamide, a thiazide-like diuretic, reduced the incidence of HF in the Hypertension in the Very Elderly Trial (HYVET).

Patients with LV hypertrophy should be treated according to history and presence of systemic hypertension. If there is a history of hypertension, antihypertensive drugs that have been shown to improve outcomes and/or regress LV hypertrophy should be used. In the Losartan Intervention for Endpoint Reduction (LIFE) study, losartan was associated with regression of LV hypertrophy, which is a strong and independent risk factor for HF development. If LV hypertrophy is present and blood pressure is normal, evaluation for hypertrophic cardiomyopathy or infiltrative cardiomyopathy should be undertaken.

Patients with asymptomatic but severe valvular disease should be treated according to the ACC/AHA guidelines in order to prevent adverse outcomes, including symptomatic HF.

A. Immediate management.

The diagnosis of stage B HF is not a medical emergency. However, control of comorbidities which predispose to subclinical HF (and progression to overt HF) are of utmost importance and should be prioritized.

B. Physical Examination Tips to Guide Management.

The best use of the physical exam in patients with stage B HF is for monitoring over time for the development of symptomatic HF in these at-risk patients. Signs of fluid overload such as elevated jugular venous pressure, basilar rales, dullness and decreased breath sounds at the lung bases (indicative of pleural effusions), ascites, and/or lower extremity edema are all signs that herald the possible development of overt, clinical HF.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Repeat echocardiography after initial treatment can be helpful in determining therapeutic efficacy in terms of reversing or normalizing the cardiac structural or functional abnormality which led to the diagnosis of stage B HF. However, all tests, including echocardiography, should only be done with clear diagnostic or therapeutic rationale.

We advise against the use of echocardiography for routine monitoring. For example, in a patient with known LV systolic dysfunction, after initial treatment and re-evaluation, there is no need for annual echocardiograms to evaluate LV ejection fraction unless there is a change in symptoms or a specific clinical question that needs to be answered.

Laboratory testing can be helpful in the monitoring of medications, particularly ACE-inhibitors, angiotensin receptor blockers, and diuretics. Patients on these drugs should undergo routine laboratory evaluation of electrolytes and renal function.

Some patients will develop worsening symptoms after the initiation of beta-blockers. Etiologies of clinical worsening in response to beta-blockers include: (1) negative inotropy in patients with severe LV systolic dysfunction, and (2) chronotropic incompetence. In these patients, beta-blockers should be down-titrated and additional testing may be warranted (e.g., cardiopulmonary exercise or treadmill testing should be performed in patients with suspected chronotropic incompetence).

The routine use of BNP (or NT-proBNP) to monitor response to therapy and to follow patients to determine the onset of symptomatic HF has not been well defined. Thus, we do not advocate the use of BNP at the present time for this purpose. However, in patients in whom clinical status is equivocal, BNP testing can help determine whether stage B HF is progressing to stage C HF.

D. Long-term management.

All recommendations for stage A HF should be followed for those with stage B HF. These include, when appropriate, controlling blood pressure, encouraging smoking cessation, treating dyslipidemia, and encouraging exercise and dietary discretion (e.g., sodium restriction).

Long-term treatment for stage B HF depends on the specific underlying cause that led to the diagnosis:

LV systolic dysfunction: As stated above, most trials that have studied patients with asymptomatic LV systolic dysfunction have included patients with EF less than or equal to 40%. Regardless of etiology, patients with EF less than or equal to 40% should be treated with beta-blockers and ACE-inhibitors.

We also tend to treat patients with EF less than or equal to 50% if other risk factors for HF are present. Our preference for a beta-blocker is to use carvedilol when possible, especially in those with concomitant systemic hypertension. Ramipril and lisinopril are good choices for ACE-inhibitors because of they are dosed once daily. Carvedilol, ramipril, and lisinopril are all generic and thus cost-effective for patients (for dosing, please refer to Common Pitfalls and Side-Effects of Management, section IIIE.)

In patients with ischemic heart disease and EF less than or equal to 30% who are expected to live more than 1 year, ICD therapy has been shown to reduce mortality. There is less data for patients with nonischemic cardiomyopathy; in these patients, placement of an ICD in patients with stage B HF with no evidence of coronary artery disease and EF less than or equal to 30% must be approached on a case-by-case basis.

Further risk stratification with Holter monitoring, electrophysiologic study, and cardiac magnetic resonance imaging (to evaluate for late gadolinium enhancement as evidence of myocardial scar) can be considered. In addition, for certain etiologies of nonischemic cardiomyopathy (e.g., cardiac sarcoidosis) which are known to be arrhythmogenic, we have a low threshold for ICD implantation even in the absence of symptomatic HF.

Post-MI: Regardless of EF, patients who have suffered an MI (particularly those who have echocardiographic wall motion abnormalities or electrocardiogram Q waves consistent with prior MI) should be treated with beta-blockers and ACE-inhibitors (or angiotensin receptor blockers). Mineralocorticoid receptor antagonists (spironolactone, eplerenone) have been shown to reduce mortality in post-MI patients with LV systolic dysfunction; however, these patients had signs and symptoms of HF.

Nevertheless, we consider these agents in stage B HF patients who are post-MI and have LV systolic dysfunction. Coronary revascularization should be undertaken according to established guidelines. Examples include patients with three-vessel coronary artery disease with LV systolic dysfunction and those with left main coronary artery disease.

Valvular heart disease: We treat patients with stage B HF who have severe valvular disease based on ACC/AHA guideline recommendations. Indications for patients with asymptomatic, severe valvular heart disease depend on the type of valve disease:

  • For severe aortic stenosis, class I recommendations (in the ACC/AHA guidelines for management of patients with valvular heart disease) for aortic valve replacement in an asymptomatic patient include those with EF less than 50% and those who are undergoing cardiac surgery for another reason (e.g., coronary artery bypass grafting). Class IIb indications for valve replacement include severe aortic stenosis with abnormal response (e.g., hypotension) to exercise; severe stenosis with high likelihood of rapid progression (e.g., advanced age, severely calcified valve); and extremely severe stenosis (valve area <0.6cm2, mean gradient >60mm Hg, peak aortic velocity >5m/s) who have a less than 1% operative mortality. These recommendations may change in the near future with the advent and success of transcatheter aortic valve replacement.

  • For severe aortic regurgitation, guideline-based recommendations for aortic valve replacement in asymptomatic patients include those who have LV systolic dysfunction at rest (EF <50%) or normal LV systolic function but with severe LV dilation (LV end-diastolic dimension >75mm or LV end-systolic dimension >55mm). Patient size should also be taken into consideration and biplane LV volumes on echocardiography, indexed to body surface area, may provide a better indication of LV remodeling.

  • For severe mitral regurgitation, guideline-based recommendations for mitral valve repair (preferred when possible) or replacement in asymptomatic patients include mild-to-moderate LV systolic dysfunction (defined as EF 30-60%) and/or LV end-systolic dimension greater than 40mm.

LV hypertrophy due to systemic hypertension: Blood pressure should be controlled to less than 140/90mm Hg. Adequate blood pressure control has been shown to reduce the risk of incident HF (whether or not LV hypertrophy is present) as in ALLHAT and HYVET. Our preference is to use angiotensin receptor blockers as first line agents in these stage B HF patients because of their ability to regress LV hypertrophy.

ACE-inhibitors and calcium channel blockers (e.g., amlodipine) have also been shown to regress LV hypertrophy whereas beta-blockers have minimal effect. Mineralocorticoid antagonists are particularly effective in treating resistant hypertension (hypertension despite three optimally dosed medications, one of which is a diuretic) and also reduce LV hypertrophy. It should be noted, however, that it is unclear whether regression of LV hypertrophy decreases HF incidence. Thus, the choice of antihypertensive drug(s) in these patients should be based on the entire clinical picture.

LV diastolic dysfunction: No specific therapies have been well studied in asymptomatic LV diastolic dysfunction. In these patients, blood pressure should be controlled, comorbidities should be treated, and dietary restriction (low sodium diet) may be beneficial in preventing the development of symptomatic HF.

E. Common Pitfalls and Side-Effects of Management

In patients who are intolerant of ACE-inhibitors (i.e., cough), angiotensin receptor blockers should be used.

In patients with normal or low blood pressure, carvedilol may not be tolerated. In these patients, we typically use long-acting metoprolol (XL).

Digoxin should not be used in patients with stage B HF unless there is a separate indication for its use (e.g., atrial fibrillation).

In patients on spironolactone who develop gynecomastia or breast tenderness, eplerenone can be used.

In patients with LV systolic dysfunction, calcium channel blockers, particularly non-dihydropyridine calcium channel blockers (verapamil, diltiazem) should be avoided. We typically avoid dihydropyridine calcium channel blockers in these patients as well unless there is a specific indication for their use.


  • Ramipril 1.25 to 2.5mg orally every day, up to 10mg orally every day

  • Lisinopril 2.5mg orally every day, up to 20 to 40mg orally every day

  • Enalapril 2.5mg orally twice a day, up to 20mg orally twice a day

  • Captopril 6.25mg orally three times a day, up to 50mg orally three times a day

Angiotensin receptor blockers:

  • Losartan 25 to 50mg orally every day, up to 100mg orally every day

  • Candesartan 4 to 8mg orally every day, up to 32mg orally every day

  • Valsartan 20 to 40mg orally twice a day, up to 160mg orally twice a day

Aldosterone antagonists:

  • Spironolactone 12.5 to 25mg orally every day, up to 25mg orally twice a day

  • Eplerenone 25mg orally every day, up to 50mg orally every day


  • Metoprolol succinate (XL) 12.5 to 25mg orally every day, up to 200mg orally every day

  • Carvedilol 3.125mg orally twice a day, up to 25 to 50mg orally twice a day (50mg dose for patients with weight >85kg)

IV. Management with Comorbidities

Hypertension: in patients with stage B HF who have concomitant hypertension, we typically use ACE-inhibitors (lisinopril or ramipril), carvedilol, chlorthalidone, spironolactone, and amlodipine as agents which are efficacious in controlling blood pressure, improve outcomes, and/or are associated with improvements in cardiac structure and function.

Diabetes: ACE-inhibitors and angiotensin receptor blockers are beneficial in patients with diabetes because of their renal protective effects. These agents can also decrease the incidence of diabetes and proteinuria in patients with LV dysfunction and impaired glucose tolerance. Carvedilol has less of a detrimental effect on glucose control in diabetics compared to short-acting metoprolol. Spironolactone can cause an increase in hemoglobin A1c levels, whereas eplerenone does not.

Chronic kidney disease: electrolytes and renal function should be monitored frequently since many patients with stage B HF will be on ACE-inhibitors or angiotensin receptor blockers.

ACE-inhibitors, angiotensin receptor blockers, and aldosterone antagonists should not be prescribed to patients with hyperkalemia. In addition, potassium and renal function should be checked 7 to 10 days after starting or uptitrating any of these drugs.

Pregnant patients should not be prescribed ACE-inhibitors or angiotensin receptor blockers.

The importance of medication compliance, salt/dietary discretion, smoking cessation, alcohol moderation, weight monitoring, and exercise, when appropriate, should be addressed routinely.

V. Patient Safety and Quality Measures

A. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

By definition, stage B HF patients are asymptomatic. Thus it is important to treat with the measures described above for each specific underlying cardiac structural or functional abnormality which led to the diagnosis of stage B HF so that progression to symptomatic, stage C HF can be prevented.

B. What's the Evidence for specific management and treatment recommendations?

Ammar, KA, Jacobsen, SJ, Mahoney, DW. “Prevalence and prognostic significance of heart failure stages: application of the American College of Cardiology/American Heart Association heart failure staging criteria in the community”. Circulation. vol. 115. 2007. pp. 1563-70. (This community study of 2029 individuals validated the ACC/AHA heart failure staging system. Mortality and B-type natriuretic peptide levels increased, while prevalence decreased, in a "dose-dependent" manner from stage A to stage D HF.)

Bonow, RO, Carabello, BA, Chatterjee, K. “ACC/AHA 2006 Guidelines for the Management of Patients with Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease)”. Circulation. vol. 114. 2006. pp. e84-231. (This report from the ACC/AHA task force summarizes the evaluation, management, and treatment of patients with suspected or known valvular heart disease.)

Correa de Sa, DD, Hodge, DO, Slusser, JP. “Progression of preclinical diastolic dysfunction to the development of symptoms”. Heart. vol. 96. 2010. pp. 528-32. (This study found that patients with at least moderate diastolic dysfunction in the absence of symptoms have significant medical comorbidities. Further, although the rate of progression to clinical HF [defined by Framingham criteria] is low over a 2-year period, the rate of development of HF symptoms [dyspnea, edema, or fatigue] is 31.2%.)

Frigerio, M, Oliva, F, Turazza, FM, Bonow, RO. “Prevention and management of chronic heart failure in management of asymptomatic patients”. Am J Cardiol. vol. 91. 2003. pp. 4F-9F. (This article discusses the identification, diagnosis, and treatment of asymptomatic patients at risk for HF development. The authors review the importance of identifying and treating patients with stage B HF in order to prevent, or at least delay, progression to clinical HF. Though screening in the community may be beneficial, current evidence for electrocardiography, echocardiography, and B-type natriuretic peptide evaluation is not conclusive.)

Goldberg, LR, Jessup, M. “Stage B heart failure: management of asymptomatic left ventricular systolic dysfunction”. Circulation. vol. 113. 2006. pp. 2851-60. (In addition to reviewing the basics of asymptomatic LV systolic dysfunction, including prevalence, etiology, screening, outcomes, and management, this paper also summarizes the relevant clinical trials for treatment. Particular consideration is given to the appropriate use of ACE-inhibitors, angiotensin receptor blockers, beta-blockers, digoxin, aldosterone antagonists, and ICDs.)

Hunt, SA, Abraham, WT, Chin, MH. “2009 Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation”. J Am Coll Cardiol. vol. 53. 2009. pp. e1-e90. (These clinical practice guidelines from the ACC/AHA provide an overview of the evaluation and treatment of the HF stages. A section is devoted to stage B HF and treatment of special populations within this stage.)

Kane, GC, Karon, BL, Mahoney, DW. “Progression of left ventricular diastolic dysfunction and risk of heart failure”. JAMA. vol. 306. 2011. pp. 856-63. (This population-based study complements the findings of Correa et al. and shows the association between longitudinal worsening in diastolic function and heart failure development. Over a 4-year period, diastolic function worsened in 23.4% of patients, primarily in participants aged >65 years. Diastolic dysfunction was also associated with heart failure development over an additional 6-year period, particularly in those with at least moderate diastolic dysfunction at baseline or during follow-up.)

Kannel, WB, D’Agostino, RB, Silberschatz, H, Belanger, AJ, Wilson, PW, Levy, D. “Profile for estimating risk of heart failure”. Arch Intern Med. vol. 159. 1999. pp. 1197-204. (This study provides a multivariate risk formulation to identify individuals at high risk for HF development in whom asymptomatic LV systolic dysfunction is likely to be present. Patients with high risk profiles may be appropriate candidates for additional workup, such as B-type natriuretic peptide and/or echocardiography. Covariates included in the model include age, electrocardiographic LV hypertrophy, cardiomegaly on chest X-ray film, heart rate, systolic blood pressure, vital capacity, diabetes mellitus, evidence of myocardial infarction, and clinical valvular disease.)

Patel, MR, Dehmer, GJ, Hirshfeld, JW. “ACCF/SCAI/STS/AATS/AHA/ASNC 2009 Appropriateness Criteria for Coronary Revascularization: a report by the American College of Cardiology Foundation Appropriateness Criteria Task Force, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, and the American Society of Nuclear Cardiology Endorsed by the American Society of Echocardiography, the Heart Failure Society of America, and the Society of Cardiovascular Computed Tomography”. J Am Coll Cardiol. vol. 53. 2009. pp. 530-53. (These clinical practice guidelines provide the coronary revascularization appropriateness criteria.)

Redfield, MM, Jacobsen, SJ, Burnett, JC, Mahoney, DW, Bailey, KR, Rodeheffer, RJ. “Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic”. JAMA. vol. 289. 2003. pp. 194-202. (This cross-sectional survey demonstrates that LV systolic and diastolic dysfunction both occur commonly in the community, often in the absence of symptomatic HF. Diastolic dysfunction was associated with marked increases in all-cause mortality.)

Wang, TJ, Evans, JC, Benjamin, EJ, Levy, D, LeRoy, EC, Vasan, RS. “Natural history of asymptomatic left ventricular systolic dysfunction in the community”. Circulation. vol. 108. 2003. pp. 977-82. (These authors analyzed data from the Framingham Heart Study to examine the risk of incident HF or death in patients with asymptomatic LV dysfunction (ejection fraction ≤50%). Even individuals with mild reductions in ejection fraction (40-50%) had significant increased risks of HF and death.)

C. DRG Codes and Expected Length of Stay.