Heart failure (HF) is the inability of the heart to pump an adequate supply of blood to meet the demands of the body. It is an epidemic and is associated with significant morbidity, mortality, and healthcare expenditure. Heart failure has an estimated prevalence of 5.8 million in the United States, and affects over 23 million people worldwide.1 The cost of HF in the United States was around $30 billion in 2012, a number that is projected to increase to around $70 billion by the year 2030.2 Acute decompensated HF (ADHF) is the clinical syndrome of new onset or worsening HF symptoms and signs requiring urgent treatment.3 In the United States, ADHF exacerbations result in about 1 million hospitalizations yearly and contribute largely to the overall HF healthcare expenditure.2 Hospitalization for ADHF serves as a poor prognostic indicator with an approximate 30% and 50% readmission rate at 1 month and 6 months, respectively, and a 1-year all-cause mortality as high as 30%.4,5
TYPES, PATHOPHYSIOLOGY, AND CLINICAL MANIFESTATIONS
Patients with HF can either present to the hospital with symptoms for the first time or present with ADHF in the setting of having a diagnosis of chronic HF. Heart failure is classified based on the left ventricular ejection fraction (LVEF), as usually determined by echocardiography, into HF with reduced ejection fraction (EF) (HFrEF) with an LVEF less than 40%, or HF with preserved EF (HFpEF) with an LVEF 50% or greater.6 An EF between 40% and 49% is considered a gray zone. Epidemiological data indicates that HFpEF and HFrEF contribute equally to the total HF population.6 Patients with HFpEF have a similar postdischarge mortality risk and equally high rates of rehospitalization as patients with HFrEF.7 The pathophysiology of HF is complex and involves intricate interactions between neurohormonal systems and hemodynamic abnormalities, resulting in abnormal myocardial remodeling and progressive myocardial, endothelial, valvular, and vascular dysfunction.8
Heart failure with reduced EF results from systolic dysfunction, which limits the ability of the contracting myocardium to effectively eject the preload of the failing myocardium. This results in backward failure, elevated end-diastolic pressure, and an inability to produce an adequate cardiac output. Heart failure with preserved EF results from abnormal or impaired myocardial diastolic relaxation, which causes elevated end-diastolic pressures and prevents an appropriate increase in the ejection fraction under conditions of stress. Regardless of the type of HF, symptoms of acute decompensation are from elevated left ventricular end-diastolic pressure (filling pressure) with resultant alveolar and interstitial edema causing pulmonary congestion and dyspnea. The backward transmission of elevated filling pressures and subsequent pulmonary venous hypertension increase pulmonary arterial and right heart pressures, causing systemic congestive symptoms.
Irrespective of the type of HF, the symptoms and signs of HF are due to either congestion or decreased cardiac output and tissue perfusion. The spectrum of presentation in ADHF ranges from dyspnea to overt cardiogenic shock with end-organ damage. Hospitalization for HF is more commonly for congestive symptoms than for low cardiac output states.3 At presentation, approximately 25% patients are hypertensive (systolic blood pressure [SBP] > 160 mmHg), around 50% are normotensive, and less than 10% are hypotensive (SBP < 90 mmHg).3
CLASSIFICATION AND STAGING
The New York Heart Association (NYHA) functional classification of HF is based primarily on symptoms (Table 7-1). In this classification, functional class is dynamic and can suddenly worsen if the patient is in acute decompensation, or it can improve with treatment. The American College of Cardiology (ACC)/American Heart Association (AHA) staging system of HF recognizes the progressive nature of HF and emphasizes the fact that established risk factors and structural abnormalities are necessary for the development of HF (Table 7-2).8 The Killip-Kimball system, which classifies decompensated HF in the post–acute myocardial infarction state, is highly predictive of 30-day mortality (Table 7-3).9
|At risk for development of heart failure but no apparent structural abnormality of the heart
|Structural abnormality of the heart without any previous or current symptoms
|Structural heart disease with current or previous symptom of heart failure
|End-stage symptoms of heart failure refractory to standard treatment
|No clinical signs of heart failure
|Rales in the lungs, third heart sound (S3), and elevated jugular venous pressure
|Acute pulmonary edema
|Cardiogenic shock or arterial hypotension (measured as systolic blood pressure < 90 mmHg), and evidence of peripheral vasoconstriction (oliguria, cyanosis, and diaphoresis)
INITIAL EVALUATION AND DIAGNOSTIC CONSIDERATIONS
The initial evaluation of HF should focus on identifying the potential cause of new onset HF or the precipitants of ADHF in patients with chronic HF (Table 7-4). Etiologies of HF are manifold, with ischemic dilated cardiomyopathy being the most common cause of HFrEF, and hypertension being more commonly associated with HFpEF. Many cases of HFrEF are idiopathic. Other etiologies of HF include hypertrophic cardiomyopathy, restrictive cardiomyopathy, stress (Takotsubo cardiomyopathy), infection, inflammation, valvular heart disease and endocarditis, metabolic-nutritional, alcohol and toxins, chemotherapy-induced cardiomyopathy, connective tissue diseases including lupus, peripartum cardiomyopathy, and hereditary muscular dystrophies.
A focused history and physical examination is required to diagnose the syndrome of HF and identify probable etiologic/precipitating factors. Data from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) registry showed that precipitating factors were independently associated with in-hospital and postdischarge outcomes.10 Routine diagnostic investigations as recommended by the ACC/AHA, the Heart Failure Society of America (HFSA), and the European Society of Cardiology (ESC) supplement the history and physical exam to identify the cause of HF, and also provide valuable information about various prognostic markers.11-13 These diagnostic investigations include the following:
The electrocardiogram (ECG) is a critical component in the initial diagnostic evaluation of HF. It can be used to rapidly identify the causes of ADHF, like myocardial ischemia/infarction and tachyarrhythmias. Prolonged QRS duration suggests ventricular dyssynchrony. The ECG can reveal conduction disease, evidence of prior myocardial infarction (MI), and left ventricular hypertrophy.
Several different laboratory tests are available to help in the diagnosis and management of ADHF. Initial laboratory testing should include a complete blood count, urinalysis, and a comprehensive metabolic panel. Anemia can precipitate HF in patients with advanced HF or underlying coronary artery disease. Severe anemia can cause high-output HF. In patients with NYHA class II and III HF and iron deficiency (ferritin < 100 ng/mL or 100–300 ng/mL if transferrin saturation is < 20%), intravenous (IV) iron replacement is reasonable for improving functional status and quality of life (Class of Recommendation [COR] IIb, Level of Evidence [LOE] B-R).14 Leukocytosis can suggest an underlying infection. An elevated blood glucose level at presentation is associated with increased 30-day mortality independent of the patient’s diabetic status.15 Hyponatremia in HF is associated with a poorer prognosis.16 Hypo- or hyperkalemia can be present if the patient was on diuretics or renin-angiotensin-aldosterone system inhibitors. Cardiorenal syndrome is an important consideration when acute kidney injury is present in the setting of HF. A variety of factors contribute to the reduction in glomerular filtration rate in setting of HF including neurohumoral adaptations. These adaptations include: (1) reduced stroke volume and cardiac output; (2) activation of sympathetic nervous system and renin-angiotensin system; (3) systemic vasoconstriction, salt and water retention; (4) increased reabsorption of urea; (5) reduced renal perfusion due to systemic vasoconstriction; (6) increased renal venous pressure; (7) and right ventricular dysfunction. A cholestatic pattern (disproportionate elevation in the serum alkaline phosphatase compared with the serum aminotransferases) and congestive hepatopathy (elevated liver biochemical tests due to passive hepatic congestion in setting of right-sided heart failure) can be seen. Ischemic hepatitis, also known as shock liver, also can be seen due to acute liver hypoperfusion from cardiogenic shock, leading to marked serum aminotransferase elevation. The frequency of monitoring the above laboratory tests should depend on the initial values and response to therapy. Hemoglobin AIC and a lipid panel can identify patients with metabolic syndrome. Other laboratory tests like thyroid function, iron studies with ferritin (for hemochromatosis), serum-free light chains (κ and λ, for amyloid light chain disease), antinuclear antibody (ANA), and rheumatoid factor (for autoimmune heart dysfunction) should be obtained based on clinical suspicion. Serum myocardium-specific troponin levels can be elevated in acute HF patients secondary to cardiac myocyte injury from decompensation or from infiltrative diseases. An elevated troponin level in patients with ADHF is a poor prognostic marker and mildly elevated levels are often seen in ADHF.17 A significantly elevated troponin level should also raise a suspicion of acute coronary syndrome precipitating HF.
Both B-type natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP) are very useful in addition to clinical criteria in the diagnosis of ADHF18,19 (COR I, LOE A). proBNP cleavage produces biologically active BNP and NT-proBNP. B-type natriuretic peptide is a natriuretic hormone that is primarily released from the heart (mostly from the ventricles). Release of BNP is increased in HF due to ventricular wall stretching in response to high filling pressures. These hormones have a very high negative predictive value and can be used to rule out cardiac causes of dyspnea when they are in the normal range. The diagnostic levels of BNP and NT-proBNP for ADHF are shown in Table 7-5.18,19 In patients taking LCZ696, an NT-proBNP level should be checked instead of BNP, as the sacubitril (neprilysin inhibitor) component of LCZ696 can elevate circulating BNP levels. Levels of BNP can be either normal or only mildly elevated in HFpEF patients and in morbidly obese patients.7,20 The levels of these hormones can be elevated with increasing age and renal dysfunction.20 Natriuretic peptide level–guided management of ADHF is controversial. An elevated BNP is a significant predictor of in-hospital mortality in ADHF patients with either HFrEF or HFpEF.21 Patients whose natriuretic peptide concentrations fall during admission have lower cardiovascular mortality and readmission rates at 6 months.13 In patients without HF, BNP can be elevated in the presence of MI, arrhythmias, sepsis, cirrhosis, renal failure, hyperthyroidism, and pulmonary disease. Serial BNP measurements alone have not proven to be useful in guiding management of acute HF patients and should be used in conjunction with the clinical scenario. Atrial natriuretic peptide (ANP) is another hormone released from the atria in response to atrial stretching (volume expansion) in HF. Although higher levels of ANP are seen in HF, ANP assays are still under investigation to prove clinical utility and not widely used or available commercially.
Chest radiography must be obtained in suspected HF and is useful in evaluating the pulmonary parenchyma for the presence of vascular congestion and edema, possible infectious processes, and pleural effusions. Additionally, heart size can be evaluated.
Echocardiography provides the most useful information regarding the etiology and type of HF. It is a simple, noninvasive tool that provides both structural and functional assessment of the heart. It is essential in distinguishing between HFrEF and HFpEF, as it can estimate LVEF. Regional wall-motion abnormalities suggest an ischemic etiology of cardiomyopathy but can also be seen in cardiac sarcoidosis, nonischemic dilated cardiomyopathy (NICM), Chagas cardiomyopathy, focal myocarditis, and Takotsubo cardiomyopathy (typically hyperdynamic basal LV function with apical akinesis). Sepsis can cause myocardial depression and resultant global hypokinesis. Left ventricle end-diastolic dimensions inform on the chronicity of the disease process, with a greater level of dilation of the heart being consistent with chronic HF and LV remodeling. Valvular etiology of HF, pericardial effusion, tamponade physiology, and pulmonary arterial pressure estimates can be assessed with echocardiography. Patterns of LV hypertrophy can suggest hypertrophic cardiomyopathy, restrictive cardiomyopathy (such as amyloidosis), or hypertensive LV hypertrophy, which is common in HFpEF.
Coronary angiography in indicated (a) in patients with ADHF and known coronary artery disease (CAD) without a clear precipitant, especially if the troponin is elevated; (b) with a high pretest probability of underlying ischemic cardiomyopathy in patients who are candidates for percutaneous or surgical revascularization; (c) before heart transplant or left ventricular assist device (LVAD) placement; (d) in HF secondary to postinfarction ventricular aneurysm or other mechanical complications of MI; or (e) in HFrEF in association with angina or regional wall-motion abnormalities and/or scintigraphic evidence of reversible myocardial ischemia when revascularization is being considered.11-13
Right heart catheterization (RHC) provides important information regarding filling pressures, cardiac output, and pulmonary vascular resistance. The routine use of invasive hemodynamic monitoring for managing ADHF did not decrease overall mortality or hospitalizations, and is not recommended in routine practice.22 However, RHC can guide therapy in patients with refractory HF, unclear volume status, hemodynamic instability and hypotension, worsening renal function, or cardiogenic shock, or when evaluating patients for heart transplantation or mechanical circulatory support devices.11,13
Cardiac magnetic resonance (CMR) imaging is reasonable to assess left ventricular dimensions and EF when echocardiography is inadequate. Additional information about myocardial perfusion, tissue injury (inflammation in myocarditis or necrosis), viability, and fibrosis from CMR imaging can help identify HF etiology and assess prognosis. Cardiac magnetic resonance provides very high anatomical resolution and is very useful in assessing suspected congenital heart disease, myocardial infiltrative processes (such as hemochromatosis and amyloidosis), or scar burden.11 It is also useful in the evaluation of rarer diseases such as sarcoidosis, arrhythmogenic right ventricular cardiomyopathy, and Chagas disease.
Endomyocardial biopsy can be considered in patients with rapidly progressive HF despite appropriate medical treatment, in patients with suspected infiltrative diseases (amyloidosis, sarcoidosis, hemochromatosis), or in patients with malignant arrhythmias rising a suspicion for giant cell myocarditis.12,13
|NT-proBNP, age < 50 y (ng/mL)
|NT-proBNP, age 50–75 y (ng/mL)
|NT-proBNP, age > 75 y (ng/mL)