Heart failure is prevalent in both primary care and cardiology practices. It develops in about 1 in 5 persons during their lifetime and in about 1 in 8 of those who have not sustained a myocardial infarction (MI).1 Heart failure is also the leading cause of hospitalization in the elderly.
Although great advances have been made in diagnosis and therapy, heart failure remains a deadly disease. Large epidemiological studies show that 24% to 28% of patients die within 1 year of heart failure onset, while 45% to 59% of patients die within 5 years.2,3 These mortality rates are worse than the rates for many cancers—and are especially disheartening given the increasing number of drugs and devices that may prolong survival.
The past few years have seen dramatic changes in the diagnosis and management of heart failure. Clinical guidelines have been updated by all the major professional societies.4,5 Key revisions to the guidelines include:
•Changes in the underlying conceptualization of the heart failure syndrome.
•Recognition of the need for early and accurate detection of heart failure.
•A new standard for staging disease severity and identifying reversible causes.
•Emphasis on the need for prompt titration of lifesaving neurohormonal antagonists.
•Recognition of the potential benefits of treating underlying and comorbid diseases.
•Acknowledgment of the need for improvements in monitoring patients.
•Guidance on the appropriate use of device-based strategies.
Here I provide an overview of recent developments in the diagnosis and staging of heart failure, and I highlight what the recent guidelines recommend for everyday clinical practice, including prevention. In a coming issue, I will discuss the latest thinking on the treatment and monitoring of the disease.
CHANGES IN UNDERSTANDING AND APPROACH
Abnormal cardiac physiology. The focus of heart failure management has shifted from salvage of the decompensated state to early recognition of at-risk patients and prevention of disease progression. This change reflects a major conceptual shift. Traditionally, heart failure has been defined as the “inability of the heart to meet the body’s metabolic and physiologic everyday needs.” This definition is most prominently reflected in the decompensated state, in which clinical “congestion” is readily identified by such findings as peripheral edema, pulmonary rales, and jugular venous distention.
Recognition of the full spectrum of heart failure is needed to facilitate appropriate and timely evaluation, monitoring, and management of the condition. Some clinicians still erroneously equate heart failure with impaired left ventricular ejection fraction (LVEF). However, at least half of patients with heart failure do not have impaired systolic function (so-called heart failure with preserved left ventricular systolic function, or diastolic heart failure). These patients display all the manifestations of heart failure and require diuretics to maintain their fluid balances. Diastolic heart failure is often under-recognized in the elderly, even in the presence of imaging data, because of the assumption that an LVEF in the normal range is sufficient evidence of “normal” cardiac physiology (thus, their symptoms are considered to be noncardiac).6,7
Other patients with no overt functional limitations may exhibit an abnormal cardiac pump function as an incidental finding on a cardiac imaging study such as a stress test (so-called asymptomatic left ventricular dysfunction). In some patients, there are abnormalities of ventricular relaxation (“diastolic dysfunction”), particularly in the setting of concomitant left ventricular hypertrophy.
Myocardial remodeling. Although our understanding of the molecular underpinnings of heart failure continues to evolve, research has demonstrated that abnormalities in myocyte function, adrenergic receptors, and receptor coupling and signaling—as well as alterations in calcium fluxes—all contribute to its pathogenesis. These maladaptive processes contribute to the anatomic and morphologic changes of the heart known as myocardial remodeling.8
Myocardial remodeling encompasses hypertrophy of the cardiac myocytes, dilation and interstitial changes of the cardiac chambers, and alterations of chamber shape—which together can affect the systolic or diastolic performance of the heart. Accumulating evidence now suggests that myocardial remodeling is the altered biology in heart failure.9
Most current pharmacotherapies work by up-regulating the molecular processes that compensate for and repair myocardial remodeling. In fact, all drugs that have proved beneficial in heart failure reverse myocardial remodeling, and all ineffective or harmful drugs do not. (In addition to demonstrating an ability to improve cardiac structure and function, new drugs must be shown in large-scale clinical trials to have adverse effects of an acceptably low incidence and severity.)
Thus, myocardial remodeling has become an important gauge of disease severity and treatment response. In addition, the latest guidelines emphasize prevention of heart failure and cardiac dysfunction through strategies that help prevent ventricular remodeling (Box).
EARLY AND ACCURATE DETECTION OF HEART FAILURE
Clinical suspicion. Overt signs and symptoms of “congestion” (particularly, edema, orthopnea, and paroxysmal nocturnal dyspnea) are usually late phenomena in the natural history of heart failure. Many patients present with less obvious signs and symptoms, such as unexplained fatigue, early satiety, nausea and vomiting, abdominal discomfort, wheezing, cough, and insomnia. Clinical suspicion in patients at risk for heart failure is the key to early diagnosis.
A thorough history taking and physical examination remain the cornerstone of early and accurate detection. Take care to distinguish between signs and symptoms that result from abnormal cardiac function and those caused by conditions that can mimic heart failure. For example, signs and symptoms of central congestion (noticeable jugular venous distention, pulmonary rales, or an S3 gallop) are far more likely to have an underlying cardiac cause—and thus are of greater concern—than isolated peripheral edema, which can be a manifestation of other conditions (especially adverse effects of medication, renal failure, lymphedema, deep venous thrombosis, or a low albumin level) that can likely be reversed if the inciting factors are eliminated.
Imaging studies. Direct visualization of cardiac structure and performance is vital to early detection. Echocardiographic assessment of cardiac structure and function in patients with evidence of congestion or at risk for heart failure (Table 1) is used to confirm the diagnosis.
However, be aware that the ejection fraction is just one of many changes that can be associated with cardiac abnormalities. In general, any dilatation or stiffness of the cardiac chambers or valvular abnormalities can be a manifestation of heart failure, especially in settings in which the pumping function of the heart is relatively preserved. In fact, the ejection fraction may be preserved in nearly 50% of patients who show clinical evidence of congestive heart failure—and the percentage may be even higher among those with prior MI, hypertension, and diabetes. Abnormal heart rhythms may also be an early sign of heart failure.
Technological advances have made ultrasound devices more portable and affordable. However, a steep training barrier is an obstacle to the widespread use of ultrasonography in this setting, and there is concern that interpretations by inexperienced technicians and nonspecialists may result in overdiagnosis or underdiagnosis (although many studies have provided evidence that refutes the latter concern). In addition, the expense of ultrasonography has helped preclude routine screening of the general population.
Natriuretic peptides. Often referred to as “the white cell count of heart failure,” natriuretic peptide testing is a valuable tool in patients in whom acute signs and symptoms have raised suspicion of heart failure. In particular, B-type natriuretic peptide (BNP), a 32 amino-acid peptide that is primarily secreted from the ventricular walls in response to myocyte stretch or damage, has become an important tool in the diagnosis and risk stratification of heart failure. Plasma natriuretic peptide levels consistently increase with worsening heart failure symptoms (although they also increase in response to other noncardiac processes, such as worsening renal function). Several recent clinical studies have validated the diagnostic accuracy of levels of BNP10 and its counterpart, amino-terminal proBNP (NT-proBNP),11 particularly their ability to rule out heart failure in patients who present with acute dyspnea. Thus, clinical guidelines recommend that natriuretic peptide testing be used when the diagnosis is suspected.4,5
The results of BNP measurement can vary, both within a patient with stable symptoms over a period of time and between different assay types or different machines. In addition, the significance of a given level may vary depending on the clinical context (eg, values in patients with chronic stable heart failure may be below what is considered diagnostic in the acute setting, or low levels in obese patients may mask true disease severity). Nonetheless, both BNP and NT-proBNP have shown a consistent and reliable ability to predict long-term adverse events.
Moreover, plasma natriuretic peptide levels often track with changes in clinical outcomes.12 Plasma levels of NT-proBNP, despite a 5- to 10-fold difference in absolute value relative to BNP, appear to have a similar diagnostic performance in a broad range of settings. Nonetheless, the results of prospective studies are needed to determine whether serial testing of BNP or NT-proBNP can be used to help guide the management of heart failure.
Currently, studies are under way to determine whether natriuretic peptide testing can facilitate early identification of patients with underlying asymptomatic or minimally symptomatic left ventricular dysfunction in the primary care setting. However, plasma levels that reliably rule out underlying cardiac dysfunction are relatively low (as low as less than 20 mg/dL); thus, routine screening with BNP measurement is only cost-effective in at-risk patients who have significant symptoms of cardiac dysfunction and who have not yet received any neurohormonal antagonists. The precise characteristics of the population in which screening with BNP levels would be appropriate has yet to be determined. Therefore, the current guidelines do not recommend the routine use of natriuretic peptide testing for screening purposes; rather, they recommend such testing only for the evaluation of patients with ambiguous symptoms.
STAGING DISEASE SEVERITY
The main purpose of the new American College of Cardiology/American Heart Association staging scheme is to emphasize the natural history of disease progression rather than symptom progression. In this, it is very different from the commonly used New York Heart Association (NYHA) functional classification, which focuses mainly on exercise capacity and symptomatology in patients with overt heart failure (Table 2). Thus, the new system includes 2 stages of asymptomatic disease that have no counterpart in the NYHA classification:
•Stage A: patients who have no structural heart disease but who are at high risk for heart failure.
•Stage B: patients with structural heart disease but no signs or symptoms of heart failure.
The latest guidelines recommend close monitoring and appropriate treatment for patients classed as Stage A or B, even though they have no significant heart failure signs and symptoms. The new staging system is based on graded risk; it promotes the therapeutic goal of prevention and limitation of disease progression.
Note that with the new classification system, the staging of heart failure, like cancer staging, can advance in only one direction and cannot be reversed; that is, even when a patient becomes asymptomatic as a result of medical therapy, he or she will remain in Stage C. With the old staging system, a patient with symptomatic NYHA class III heart failure who became asymptomatic or minimally symptomatic following appropriate therapy would have been reclassified as NYHA class I or II—or no class at all.
IDENTIFYING REVERSIBLE CAUSES AND EXACERBATING FACTORS
Although many cases of heart failure are associated with common, definable index events (such as MI or chemotherapy), most develop from underlying, usually reversible risk factors or comorbidities. These include a precedent viral syndrome, coronary artery disease and myocardial ischemia, poorly controlled hypertension, uncorrected valvular disorders, rhythm abnormalities, thyroid problems, and excessive alcohol intake. One of the most important aspects of the evaluation of a patient with new-onset heart failure is determining whether any of the observed cardiac abnormalities are attributable to reversible causes.
Recently released guidelines also discuss the importance of identifying barriers to adherence and compliance, and of educating patients about the need to avoid exacerbation factors (eg, NSAIDs) and to be vaccinated against pneumococcal pneumonia and influenza.5
Reliable and prompt diagnosis of heart failure remains an important challenge, especially in busy clinical practices. The biggest advance in the past decade in the field of heart failure has been the introduction of a new staging system and tools that permit better diagnosis of the disease. Prevention may be the most effective treatment strategy: early identification of at-risk patients can lead to prompt treatment with lifesaving medications, which, in turn, can prevent or reverse disease progression.
1. Lloyd-Jones DM, Larson MG, Leip EP, et al. Lifetime risk for developing congestive heart failure: the Framingham Heart Study. Circulation. 2002;106:3068-3072.
2. Levy D, Kenchaiah S, Larson MG, et al. Long-term trends in the incidence of and survival with heart failure. N Engl J Med. 2002;347:1397-1402.
3. Roger VL, Weston SA, Redfield MM, et al. Trends in heart failure incidence and survival in a community-based population. JAMA. 2004;292:344-350.
4. Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2005;112:e154-e235.
5. Heart Failure Society of America. Executive summary: HFSA 2006 Comprehensive Heart Failure Practice Guideline. J Card Fail. 2006;12:10-38. Available at: www.heartfailureguidelines.org
6. Redfield MM, Jacobsen SJ, Burnett JC Jr, et al. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003;289:194-202.
7. Vasan RS, Benjamin EJ, Levy D. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol. 1995;26:1565-1574.
8. Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol. 2000;35:569-582.
9. Cohn JN. New therapeutic strategies for heart failure: left ventricular remodeling as a target. J Card Fail. 2004;10(6 suppl):S200-S201.
10. Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347:161-167.
11. Januzzi JL Jr, Camargo CA, Anwaruddin S, et al. The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol. 2005;95:948-954.
12. Morrow DA, de Lemos JA, Blazing MA, et al. Prognostic value of serial B-type natriuretic peptide testing during follow-up of patients with unstable coronary artery disease. JAMA. 2005;294:2866-2871.