Heart Failure (HF)
(Congestive Heart Failure)
(See also Heart Failure in Children.)
Heart failure affects about 6.5 million people in the US; > 960,000 new cases occur each year. About 26 million people are affected worldwide.
Cardiac contractility (force and velocity of contraction), ventricular performance, and myocardial oxygen requirements are determined by
Cardiac output (CO) is the product of stroke volume and heart rate; it is also affected by venous return, peripheral vascular tone, and neurohumoral factors.
Preload is the loading condition of the heart at the end of its relaxation and filling phase (diastole) just before contraction (systole). Preload represents the degree of end-diastolic fiber stretch and end-diastolic volume, which is influenced by ventricular diastolic pressure and the composition of the myocardial wall. Typically, left ventricular (LV) end-diastolic pressure, especially if higher than normal, is a reasonable measure of preload. LV dilation, hypertrophy, and changes in myocardial distensibility (compliance) modify preload.
Afterload is the force resisting myocardial fiber contraction at the start of systole. It is determined by LV chamber pressure, radius, and wall thickness at the time the aortic valve opens. Clinically, systemic systolic blood pressure at or shortly after the aortic valve opens correlates with peak systolic wall stress and approximates afterload.
The Frank-Starling principle describes the relationship between preload and cardiac performance. It states that, normally, systolic contractile performance (represented by stroke volume or CO) is proportional to preload within the normal physiologic range (see Figure: Frank-Starling principle). Contractility is difficult to measure clinically (because it requires cardiac catheterization with pressure-volume analysis) but is reasonably reflected by the ejection fraction (EF), which is the percentage of end-diastolic volume ejected with each contraction (stroke volume/end-diastolic volume). EF can generally be adequately assessed noninvasively with echocardiography, nuclear imaging, or MRI.
The force-frequency relationship refers to the phenomenon in which repetitive stimulation of a muscle within a certain frequency range results in increased force of contraction. Normal cardiac muscle at typical heart rates exhibits a positive force-frequency relationship, so a faster rate causes stronger contraction (and corresponding greater substrate requirements). During some types of heart failure, the force-frequency relationship may become negative, so that myocardial contractility decreases as heart rate increases above a certain rate.
Cardiac reserve is the ability of the heart to increase its performance above resting levels in response to emotional or physical stress; body oxygen consumption may increase from 250 to ≥ 1500 mL/minute during maximal exertion. Mechanisms include increasing heart rate, systolic and diastolic volumes, stroke volume, and tissue extraction of oxygen (the difference between oxygen content in arterial blood and in mixed venous or pulmonary artery blood). In well-trained young adults during maximal exercise, heart rate may increase from 55 to 70 beats/minute at rest to 180 beats/minute, and CO may increase from 6 to ≥ 25 L/minute. At rest, arterial blood contains about 18 mL oxygen/dL of blood, and mixed venous or pulmonary artery blood contains about 14 mL/dL. Oxygen extraction is thus about 4 mL/dL. When demand is increased, it may increase to 12 to 14 mL/dL. This mechanism also helps compensate for reduced tissue blood flow in HF.
In heart failure, the heart may not provide tissues with adequate blood for metabolic needs, and cardiac-related elevation of pulmonary or systemic venous pressures may result in organ congestion. This condition can result from abnormalities of systolic or diastolic function or, commonly, both. Although a primary abnormality can be a change in cardiomyocyte function, there are also changes in collagen turnover of the extracellular matrix. Cardiac structural defects (eg, congenital defects, valvular disorders), rhythm abnormalities (including persistently high heart rate), and high metabolic demands (eg, due to thyrotoxicosis) also can cause HF.
In HFrEF (also called systolic HF), global LV systolic dysfunction predominates. The LV contracts poorly and empties inadequately, leading to
Many defects in energy utilization, energy supply, electrophysiologic functions, and contractile element interaction occur, with abnormalities in intracellular calcium modulation and cAMP production.
In HFpEF (also known as diastolic heart failure), LV filling is impaired, resulting in
Global contractility and hence ejection fraction remain normal (≥ 50%).
However, in some patients, marked restriction to LV filling can cause inappropriately low LV end-diastolic volume and thus cause low CO and systemic symptoms. Elevated left atrial pressures can cause pulmonary hypertension and pulmonary congestion.
Diastolic dysfunction usually results from impaired ventricular relaxation (an active process), increased ventricular stiffness, valvular disease, or constrictive pericarditis. Acute myocardial ischemia is also a cause of diastolic dysfunction. Resistance to filling increases with age, reflecting both cardiomyocyte dysfunction and cardiomyocyte loss, and increased interstitial collagen deposition; thus, diastolic dysfunction is particularly common among older adults. Diastolic dysfunction predominates in hypertrophic cardiomyopathy, other disorders with ventricular hypertrophy (eg, hypertension, significant aortic stenosis), and amyloid infiltration of the myocardium. LV filling and function may also be impaired if marked increases in RV pressure shift the interventricular septum to the left.
Diastolic dysfunction has increasingly been recognized as a cause of HF. Estimates vary, but about 50% of patients with heart failure have HFpEF; the prevalence increases with age and in patients with diabetes. It is now known that HFpEF is a complex, heterogenous, multiorgan, systemic syndrome, often with multiple concomitant pathophysiologies. Current data suggest that multiple comorbidities (eg, obesity, hypertension, diabetes, chronic kidney disease) lead to systemic inflammation, widespread endothelial dysfunction, cardiac microvascular dysfunction, and, ultimately, molecular changes in the heart that cause increased myocardial fibrosis and ventricular stiffening. Thus, although HFrEF is typically associated with primary myocardial injury, HFpEF may be associated with secondary myocardial injury due to abnormalities in the periphery.
In heart failure that involves left ventricular dysfunction, CO decreases and pulmonary venous pressure increases. When pulmonary capillary pressure exceeds the oncotic pressure of plasma proteins (about 24 mm Hg), fluid extravasates from the capillaries into the interstitial space and alveoli, reducing pulmonary compliance and increasing the work of breathing. Lymphatic drainage increases but cannot compensate for the increase in pulmonary fluid. Marked fluid accumulation in alveoli (pulmonary edema) significantly alters ventilation-perfusion (V/Q) relationships: Deoxygenated pulmonary arterial blood passes through poorly ventilated alveoli, decreasing systemic arterial oxygenation (PaO2) and causing dyspnea. However, dyspnea may occur before V/Q abnormalities, probably because of elevated pulmonary venous pressure and increased work of breathing; the precise mechanism is unclear.
In severe or chronic LV failure, pleural effusions characteristically develop, further aggravating dyspnea. Minute ventilation increases; thus, PaCO2 decreases and blood pH increases (respiratory alkalosis). Marked interstitial edema of the small airways may interfere with ventilation, elevating PaCO2—a sign of impending respiratory failure.
In heart failure that involves right ventricular dysfunction, systemic venous pressure increases, causing fluid extravasation and consequent edema, primarily in dependent tissues (feet and ankles of ambulatory patients) and abdominal viscera. The liver is most severely affected, but the stomach and intestine also become congested; fluid accumulation in the peritoneal cavity (ascites) can occur. RV failure commonly causes moderate hepatic dysfunction, with usually modest increases in conjugated and unconjugated bilirubin, PT (prothrombin time), and hepatic enzymes (particularly alkaline phosphatase and gamma-glutamyl transpeptidase [GGT]). The impaired liver breaks down less aldosterone, further contributing to fluid accumulation. Chronic venous congestion in the viscera can cause anorexia, malabsorption of nutrients and drugs, protein-losing enteropathy (characterized by diarrhea and marked hypoalbuminemia), chronic gastrointestinal blood loss, and rarely ischemic bowel infarction.
In HFrEF, left ventricular systolic function is grossly impaired; therefore, a higher preload is required to maintain CO. As a result, the ventricles are remodeled over time: During remodelling, the LV becomes less ovoid and more spherical, dilates, and hypertrophies; the RV dilates and may hypertrophy. Initially compensatory, remodelling ultimately is associated with adverse outcomes because the changes eventually increase diastolic stiffness and wall tension (ie, diastolic dysfunction develops), compromising cardiac performance, especially during physical stress. Increased wall stress raises oxygen demand and accelerates apoptosis (programmed cell death) of myocardial cells. Dilation of the ventricles can also cause mitral or tricuspid valve regurgitation (due to annular dilation) with further increases in end-diastolic volumes. .
With reduced CO, oxygen delivery to the tissues is maintained by increasing oxygen extraction from the blood and sometimes shifting the oxyhemoglobin dissociation curve (see figure Oxyhemoglobin dissociation curve) to the right to favor oxygen release.
Reduced CO with lower systemic blood pressure activates arterial baroreflexes, increasing sympathetic tone and decreasing parasympathetic tone. As a result, heart rate and myocardial contractility increase, arterioles in selected vascular beds constrict, venoconstriction occurs, and sodium and water are retained. These changes compensate for reduced ventricular performance and help maintain hemodynamic homeostasis in the early stages of heart failure. However, these compensatory changes increase cardiac work, preload, and afterload; reduce coronary and renal perfusion; cause fluid accumulation resulting in congestion; increase potassium excretion; and may cause cardiomyocyte necrosis and arrhythmias.
As cardiac function deteriorates, renal blood flow decreases (due to low cardiac output). In addition, renal venous pressures increase, leading to renal venous congestion. These changes both result in a decrease in GFR (glomerular filtration rate), and blood flow within the kidneys is redistributed. The filtration fraction and filtered sodium decrease, but tubular resorption increases, leading to sodium and water retention. Blood flow is further redistributed away from the kidneys during exercise, but renal blood flow improves during rest.
Decreased perfusion of the kidneys (and possibly decreased arterial systolic stretch secondary to declining ventricular function) activates the renin-angiotensin-aldosterone system (RAAS), increasing sodium and water retention and renal and peripheral vascular tone. These effects are amplified by the intense sympathetic activation accompanying heart failure.
The renin-angiotensin-aldosterone- vasopressin (antidiuretic hormone [ADH]) system causes a cascade of potentially deleterious long-term effects. Angiotensin II worsens HF by causing vasoconstriction, including efferent renal vasoconstriction, and by increasing aldosterone production, which enhances sodium reabsorption in the distal nephron and also causes myocardial and vascular collagen deposition and fibrosis. Angiotensin II increases norepinephrine release, stimulates release of vasopressin, and triggers apoptosis. Angiotensin II may be involved in vascular and myocardial hypertrophy, thus contributing to the remodeling of the heart and peripheral vasculature, potentially worsening HF. Aldosterone can be synthesized in the heart and vasculature independently of angiotensin II (perhaps mediated by corticotropin, nitric oxide, free radicals, and other stimuli) and may have deleterious effects in these organs.
Heart failure that causes progressive renal dysfunction (including that renal dysfunction caused by drugs used to treat HF) contributes to worsening HF and has been termed the cardiorenal syndrome.
In conditions of stress, neurohumoral responses help increase heart function and maintain blood pressure and organ perfusion, but chronic activation of these responses is detrimental to the normal balance between myocardial-stimulating and vasoconstricting hormones and between myocardial-relaxing and vasodilating hormones.
The heart contains many neurohumoral receptors (alpha-1, beta-1, beta-2, beta-3, angiotensin II type 1 [AT1] and type 2 [AT2], muscarinic, endothelin, serotonin, adenosine, cytokine, natriuretic peptides); the roles of all of these receptors are not yet fully defined. In patients with heart failure, beta-1 receptors (which constitute 70% of cardiac beta receptors) are downregulated, probably in response to intense sympathetic activation. The result of downregulation is impaired myocyte contractility and increased heart rate.
Plasma norepinephrine levels are increased, largely reflecting sympathetic nerve stimulation as plasma epinephrine levels are not increased. Detrimental effects include vasoconstriction with increased preload and afterload, direct myocardial damage including apoptosis, reduced renal blood flow, and activation of other neurohumoral systems, including the renin-angiotensin-aldosterone- vasopressin system.
Vasopressin is released in response to a fall in blood pressure via various neurohormonal stimuli. Increased vasopressin decreases renal excretion of free water, possibly contributing to hyponatremia in heart failure. Vasopressin levels in patients with HF and normal blood pressure vary.
Atrial natriuretic peptide is released in response to increased atrial volume and pressure; brain (B-type) natriuretic peptide (BNP) is released from the ventricle in response to ventricular stretching. These peptides enhance renal excretion of sodium, but in patients with HF, the effect is blunted by decreased renal perfusion pressure, receptor downregulation, and perhaps enhanced enzymatic degradation. In addition, elevated levels of natriuretic peptides exert a counter-regulatory effect on the renin-angiotensin-aldosterone system and catecholamine stimulation.
Because endothelial dysfunction occurs in HF, fewer endogenous vasodilators (eg, nitric oxide, prostaglandins) are produced, and more endogenous vasoconstrictors (eg, endothelin) are produced, thus increasing afterload.
The failing heart and other organs produce tumor necrosis factor (TNF) alpha. This cytokine increases catabolism and is possibly responsible for cardiac cachexia (loss of lean tissue ≥ 10%), which may accompany severely symptomatic HF, and for other detrimental changes. The failing heart also undergoes metabolic changes with increased free fatty acid utilization and decreased glucose utilization; these changes may become therapeutic targets.
Age-related changes in the heart and cardiovascular system lower the threshold for expression of heart failure. Interstitial collagen within the myocardium increases, the myocardium stiffens, and myocardial relaxation is prolonged. These changes lead to a significant reduction in diastolic left ventricular function, even in healthy older people. Modest decline in systolic function also occurs with aging. An age-related decrease in myocardial and vascular responsiveness to beta-adrenergic stimulation further impairs the ability of the cardiovascular system to respond to increased work demands.
As a result of these changes, peak exercise capacity decreases significantly (about 8%/decade after age 30), and CO at peak exercise decreases more modestly. This decline can be slowed by regular physical exercise. Thus, older patients are more prone than are younger ones to develop HF symptoms in response to the stress of systemic disorders or relatively modest cardiovascular insults. Stressors include infections (particularly pneumonia), hyperthyroidism, anemia, hypertension, myocardial ischemia, hypoxia, hyperthermia, renal failure, perioperative IV fluid loads, nonadherence to drug regimens or to low-salt diets, and use of certain drugs (particularly NSAIDs [nonsteroidal anti-inflammatory drugs]).
Both cardiac and systemic factors can impair cardiac performance and cause or aggravate heart failure (see table Causes of Heart Failure).
Causes of Heart Failure
Some chemotherapy drugs
Reduced substrate availability (eg, of free fatty acids or glucose)
Infiltrative or matrix disorders
Chronic fibrosis (eg, systemic sclerosis)
Disorders that increase demand for CO
Disorders that increase resistance to output (afterload)
AV = atrioventricular; CO = cardiac output.
The most common classification of HF currently in use stratifies patients into
Heart failure with reduced ejection fraction (HFrEF) is defined as heart failure with LVEF ≤ 40%. Heart failure with preserved ejection fraction (HFpEF) is defined as heart failure with LVEF ≥ 50%. Patients with LVEF between 40% and 50% are in an intermediate zone, and have recently been categorized as HF with mid-range EF (HFmrEF—1).
The traditional distinction between left and right ventricular failure is somewhat misleading because the heart is an integrated pump, and changes in one chamber ultimately affect the whole heart. However, these terms indicate the major site of pathology leading to heart failure and can be useful for initial evaluation and treatment. Other common descriptive terms for heart failure include acute or chronic; high output or low output; dilated or nondilated; and ischemic, hypertensive, or idiopathic dilated cardiomyopathy. Treatment differs based on whether the presentation is acute or chronic HF.
LV failure characteristically develops in ischemic heart disease, hypertension, mitral regurgitation, aortic regurgitation, aortic stenosis, most forms of cardiomyopathy, and congenital heart disorders (eg, ventricular septal defect, patent ductus arteriosus with large shunts).
RV failure is most commonly caused by previous LV failure (which increases pulmonary venous pressure and leads to pulmonary hypertension, thus overloading the RV) or by a severe lung disorder (in which case it is called cor pulmonale). Other causes are multiple pulmonary emboli, RV infarction, pulmonary arterial hypertension, tricuspid regurgitation, tricuspid stenosis, mitral stenosis, pulmonary artery stenosis, pulmonic valve stenosis, pulmonary venous occlusive disease, arrhythmogenic RV cardiomyopathy, or congenital disorders such as Ebstein anomaly or Eisenmenger syndrome. Some conditions mimic RV failure, except cardiac function may be normal; they include volume overload and increased systemic venous pressure in polycythemia or overtransfusion, acute kidney injury with retention of sodium and water, obstruction of either vena cava, and hypoproteinemia due to any cause resulting in low plasma oncotic pressure and peripheral edema.
High-output HF results from a persistently high cardiac output, which may eventually result in an inability of a normal heart to maintain adequate output. Conditions that may increase CO include severe anemia, end-stage liver disease, beriberi, thyrotoxicosis, advanced Paget disease, arteriovenous fistula, and persistent tachycardia.
Cardiomyopathy is a general term indicating disease of the myocardium. Most commonly, the term refers to a primary disorder of the ventricular myocardium that is not caused by congenital anatomic defects; valvular, systemic, or pulmonary vascular disorders; isolated pericardial, nodal, or conduction system disorders; or epicardial coronary artery disease (CAD). The term is sometimes used to reflect etiology (eg, ischemic vs hypertensive cardiomyopathy). Cardiomyopathy does not always lead to symptomatic HF. It is often idiopathic and is classified as dilated, congestive, hypertrophic, infiltrative-restrictive, or apical-ballooning cardiomyopathy (also known as takotsubo or stress cardiomyopathy).
1. Yancy CW, Jessup M, Bozkurt B, et al: 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation128:e240–327, 2013.
Manifestations of heart failure differ depending on the extent to which the LV and RV are initially affected. Clinical severity varies significantly and is usually classified according to the New York Heart Association (NYHA) system (see table NYHA Classification of Heart Failure); the examples of ordinary activity may be modified for older, debilitated patients. Because HF has such a broad range of severity, some experts suggest subdividing NYHA class III into IIIA or IIIB. Class IIIB is typically reserved for those patients who recently had a heart failure exacerbation. The American College of Cardiology/American Heart Association has advocated a staging system for HF (A, B, C, or D) to highlight the need for HF prevention.
A: High risk of HF but no structural or functional cardiac abnormalities or symptoms
B: Structural or functional cardiac abnormalities but no symptoms of HF
C: Structural heart disease with symptoms of HF
D: Refractory HF requiring advanced therapies (eg, mechanical circulatory support, cardiac transplantation) or palliative care
New York Heart Association (NYHA) Classification of Heart Failure
In LV failure, the most common symptoms are dyspnea and fatigue due to increased pulmonary venous pressures, and low CO (at rest or inability to augment CO during exertion). Dyspnea usually occurs during exertion and is relieved by rest. As HF worsens, dyspnea can occur during rest and at night, sometimes causing nocturnal cough. Dyspnea occurring immediately or soon after lying flat and relieved promptly by sitting up (orthopnea) is common as HF advances. In paroxysmal nocturnal dyspnea (PND), dyspnea awakens patients several hours after they lie down and is relieved only after they sit up for 15 to 20 minutes. In severe HF, periodic cycling of breathing (Cheyne-Stokes respiration—from a brief period of apnea, patients breathe progressively faster and deeper, then slower and shallower until they become apneic and repeat the cycle)—can occur during the day or night; the sudden hyperpneic phase may awaken the patient from sleep. Cheyne-Stokes breathing differs from PND in that the hyperpneic phase is short, lasting only 10 to 15 seconds, but the cycle recurs regularly, lasting 30 seconds to 2 minutes. PND is associated with pulmonary congestion, and Cheyne-Stokes respiration with low CO. Sleep-related breathing disorders, such as sleep apnea, are common in HF and may aggravate HF. Severely reduced cerebral blood flow and hypoxemia can cause chronic irritability and impair mental performance.
In RV failure, the most common symptoms are ankle swelling and fatigue. Sometimes patients feel a sensation of fullness in the abdomen or neck. Hepatic congestion can cause right upper quadrant abdominal discomfort, and stomach and intestinal congestion can cause early satiety, anorexia, and abdominal bloating.
Less specific heart failure symptoms include cool peripheries, postural light-headedness, nocturia, and decreased daytime micturition. Skeletal muscle wasting can occur in severe biventricular failure and may reflect some disuse but also increased catabolism associated with increased cytokine production. Significant weight loss (cardiac cachexia) is an ominous sign associated with high mortality.
In older people, presenting complaints may be atypical, such as confusion, delirium, falls, sudden functional decline, nocturnal urinary incontinence, or sleep disturbance. Coexisting cognitive impairment and depression may also influence assessment and therapeutic interventions and may be worsened by the HF.
General examination may detect signs of systemic or cardiac disorders that cause or aggravate heart failure (eg, anemia, hyperthyroidism, alcoholism, hemochromatosis, atrial fibrillation with rapid rate, mitral regurgitation).
In LV failure, tachycardia and tachypnea may occur. Patients with severe LV failure may appear visibly dyspneic or cyanotic, hypotensive, and confused or agitated because of hypoxia and poor cerebral perfusion. Some of these less specific symptoms (eg, confusion) are more common in older patients.
Central cyanosis (affecting all of the body, including warm areas such as the tongue and mucous membranes) reflects severe hypoxemia. Peripheral cyanosis of the lips, fingers, and toes reflects low blood flow with increased oxygen extraction. If vigorous massage improves nail bed color, cyanosis may be peripheral; increasing local blood flow does not improve color if cyanosis is central.
Cardiac findings in HFrEF include
These abnormal heart sounds also can occur in HFpEF. A pansystolic murmur of mitral regurgitation at the apex may occur in either HFrEF or HFpEF.
Pulmonary findings include early inspiratory basilar crackles that do not clear with coughing and, if pleural effusion is present, dullness to percussion and diminished breath sounds at the lung base(s).
Signs of RV failure include
Nontender peripheral pitting edema (digital pressure leaves visible and palpable imprints, sometimes quite deep) in the feet and ankles
Enlarged and sometimes pulsatile liver palpable below the right costal margin
Abdominal swelling and ascites
Visible elevation of the jugular venous pressure, sometimes with large a or v waves that are visible even when the patient is seated or standing (see figure Normal jugular vein waves)
In severe cases of HF, peripheral edema can extend to the thighs or even the sacrum, scrotum, lower abdominal wall, and occasionally even higher. Severe edema in multiple areas is termed anasarca. Edema may be asymmetric if patients lie predominantly on one side.
Large V waves in the jugular veins are usually indicative of significant tricuspid regurgitation which is often present in RV failure. A paradoxical increase in the jugular venous pressure during inspiration (Kussmaul sign) is indicative of right-sided heart failure and can occur in RV failure, restrictive cardiomyopathy, constrictive pericarditis, and severe tricuspid regurgitation.
With hepatic congestion, the liver may be palpably enlarged or tender, and hepatojugular or abdominal-jugular reflux may be detected (see Neck veins). Precordial palpation may detect the left parasternal lift of RV enlargement, and auscultation may detect the murmur of tricuspid regurgitation or the RV S3 along the left sternal border; both findings are augmented upon inspiration.
Clinical findings (eg, exertional dyspnea or fatigue, orthopnea, edema, tachycardia, pulmonary crackles, S3, jugular venous distention) suggest heart failure but are usually not apparent early. Similar symptoms may result from COPD (chronic obstructive pulmonary disease) or recurrent pneumonia or may be erroneously attributed to obesity or old age. Suspicion for heart failure should be high in patients with a history of myocardial infarction, hypertension, or valvular disorders or murmurs and should be moderate in any patient who is older or has diabetes.
Chest x-ray, ECG, and an objective test of cardiac function, typically echocardiography, should be done (see figure Diagnosis of heart failure of acute onset). Blood tests, except for BNP levels, are not used for diagnosis but are useful for identifying cause and systemic effects (1–4).
Diagnosis of heart failure of acute onset
Chest x-ray findings suggesting heart failure include an enlarged cardiac silhouette, pleural effusion, fluid in the major fissure, and horizontal lines in the periphery of lower posterior lung fields (Kerley B lines). These findings reflect chronic elevation of left atrial pressure and chronic thickening of the intralobular septa due to edema. Upper lobe pulmonary venous congestion and interstitial or alveolar edema may also be present. Careful examination of the cardiac silhouette on a lateral projection can identify specific ventricular and atrial chamber enlargement. The x-ray may also suggest alternative diagnoses (eg, COPD, pneumonia, idiopathic pulmonary fibrosis, lung cancer).
ECG findings are not diagnostic, but an abnormal ECG, especially showing previous myocardial infarction, left ventricular hypertrophy, left bundle branch block, or tachyarrhythmia (eg, rapid atrial fibrillation), increases suspicion for HF and may help identify the cause. An entirely normal ECG is uncommon in chronic HF.
Echocardiography can help evaluate chamber dimensions, valve function, LVEF, wall motion abnormalities, LV hypertrophy, diastolic function, pulmonary artery pressure, LV and RV filling pressures, RV function, and pericardial effusion. Intracardiac thrombi, tumors, and calcifications within the heart valves, mitral annulus, and aortic wall abnormalities can be detected. Localized or segmental wall motion abnormalities strongly suggest underlying coronary artery disease but can also be present with patchy myocarditis. Doppler or color Doppler echocardiography accurately detects valvular disorders and shunts. The combination of Doppler evaluation of mitral inflow with tissue Doppler imaging of the mitral annulus can help identify and quantify LV diastolic dysfunction and LV filling pressures. Measuring LVEF can distinguish between predominant HFpEF (EF ≥ 50%) and HFrEF (EF ≤ 40%). It is important to re-emphasize that heart failure can occur with a normal LVEF. Speckle-tracking echocardiography (which is useful in detecting subclinical systolic function and specific patterns of myocardial dysfunction) may become important but currently is routinely reported only in specialized centers.
Radionuclide imaging also can help assess systolic and diastolic function, previous MI, and inducible ischemia or myocardial hibernation.
Cardiac MRI provides accurate images of cardiac structures and is becoming more widely available. Cardiac MRI is useful to evaluate the cause of myocardial disease and to detect focal and diffuse myocardial fibrosis. Cardiac amyloidosis, sarcoidosis, hemachromatosis, and myocarditis are causes of HF that can be detected with or suspected by cardiac MRI findings.
Serum BNP levels are often high in heart failure; this finding may help when clinical findings are unclear or other diagnoses (eg, COPD) need to be excluded. It may be particularly useful for patients with a history of both pulmonary and cardiac disorders. NT-pro-BNP, an inactive moiety created when pro-BNP is cleaved, can be used similarly to BNP. However, a normal BNP level does not exclude the diagnosis of heart failure, particularly in patients with HFpEF and/or obesity. In HFpEF, BNP levels tend to be about 50% of those associated with HFrEF (at similar degree of symptoms), and up to 30% of patients with acute HFpEF have a BNP level below the commonly used threshold of 100 pg/mL (100 ng/L). Obesity, which is becoming an increasingly common comorbidity in HF, is associated with reduced BNP production and increased BNP clearance, resulting in lower levels.
Besides BNP, recommended blood tests include complete blood count, creatinine, BUN (blood urea nitrogen), electrolytes (including magnesium and calcium), glucose, albumin, ferritin, and liver tests. Thyroid function tests are recommended for patients with atrial fibrillation and for selected, especially older, patients.
Thoracic ultrasonography is a noninvasive method of detecting pulmonary congestion in patients with heart failure. Sonographic "comet tail artifact" on thoracic ultrasonography corresponds to the x-ray finding of Kerley B lines.
Coronary angiography or CT coronary angiography is indicated when coronary artery disease is suspected or the etiology of HF is uncertain.
Cardiac catheterization with intracardiac pressure measurements (invasive hemodynamics) may be helpful in the diagnosis of restrictive cardiomyopathies and constrictive pericarditis. Invasive hemodynamic measurements are also very helpful when the diagnosis of HF is equivocal, particularly in patients with HFpEF. In addition, perturbing the cardiovascular system (eg, exercise testing, volume challenge, drug challenges [eg, nitroglycerin, nitroprusside]) can be very helpful during invasive hemodynamic testing to help diagnose HF.
Endocardial biopsy is sometimes done when an infiltrative cardiomyopathy, or acute giant cell myocarditis is strongly suspected but cannot be confirmed with noninvasive imaging (eg, cardiac MRI).
1. Ezekowitz JA, O'Meara E, McDonald MA, et al: 2017 Comprehensive Update of the Canadian Cardiovascular Society Guidelines for the Management of Heart Failure. Can J Cardiol 33:1342–1433, 2017. doi: https://doi.org/10.1016/j.cjca.2017.08.022
2. Ponikowski P, Voors A, Anker SD, et al: 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37 (27):2129–2200, 2016. doi: 10.1093/eurheartj/ehw128
3. Yancy CW, Jessup M, Bozkurt B, et al: 2013 ACCF/AHA Guideline for the Management of Heart FailureA Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 128:e240–e327, 2013. doi: 10.1161/CIR.0b013e31829e8776
4. Yancy CW, Jessup M, Bozkurt B, et al: 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 136:e137–e161, 2017. doi: 10.1161/CIR.0000000000000509
Generally, patients with heart failure have a poor prognosis unless the cause is correctable. Five-year survival after an initial hospitalization for heart failure is about 35% regardless of the patient's EF. In overt chronic HF, mortality depends on severity of symptoms and ventricular dysfunction and can range from 10 to 40%/year.
Specific factors that suggest a poor prognosis include hypotension, low ejection fraction, presence of coronary artery disease, troponin release, elevation of BUN, reduced GFR, hyponatremia, and poor functional capacity (eg, as tested by a 6-minute walk test).
BNP, NTproBNP, and risk scores such as the MAGGIC Risk Score and the Seattle Heart Failure model, are helpful to predict prognosis in HF patients as an overall group, although there is significant variation in survival among individual patients.
HF usually involves gradual deterioration, interrupted by bouts of severe decompensation, and ultimately death, although the time course is being lengthened with modern therapies. However, death can also be sudden and unexpected, without prior worsening of symptoms.
All patients and family members should be taught about disease progression and the risk of sudden cardiac death. For some patients, improving quality of life is as important as increasing quantity of life. Thus, it is important to determine patients’ wishes about resuscitation (eg, endotracheal intubation, CPR [cardiopulmonary respiration]) if their condition deteriorates, especially when HF is already severe.
All patients should be reassured that symptoms will be relieved, and they should be encouraged to seek medical attention early if their symptoms change significantly. Involvement of pharmacists, nurses, social workers, and clergy (when desired), who may be part of an interdisciplinary team or disease management program already in place, is particularly important in end-of-life care.
Immediate inpatient treatment is required for patients with acute or worsening heart failure due to certain disorders (eg, acute myocardial infarction, atrial fibrillation with a very rapid ventricular rate, severe hypertension, acute valvular regurgitation), as well as for patients with pulmonary edema, severe symptoms, new-onset HF, or HF unresponsive to outpatient treatment. Patients with mild exacerbations of previously diagnosed HF can be treated at home.
The primary goal is to diagnose and to correct or treat the disorder that led to heart failure.
Short-term goals include relieving symptoms and improving hemodynamics; avoiding hypokalemia, renal dysfunction, and symptomatic hypotension; and correcting neurohumoral activation.
Long-term goals include correcting hypertension, preventing myocardial infarction and atherosclerosis, improving cardiac function, reducing hospitalizations, and improving survival and quality of life.
Treatment involves dietary and lifestyle changes, drugs, devices, and sometimes percutaneous coronary interventions or surgery.
Treatment is tailored to the patient, considering causes, symptoms, and response to drugs, including adverse effects. There are currently several evidence-based therapies for chronic HFrEF (1). There are fewer evidence-based treatments for chronic HFpEF, acute HF syndromes, and RV failure (2).
General measures, especially patient and caregiver education and diet and lifestyle modifications, are important for all patients with heart failure.
Patient and caregiver education are critical to long-term success. The patient and family should be involved in treatment choices. They should be taught the importance of drug adherence, warning signs of an exacerbation, and how to link cause with effect (eg, increased salt in the diet with weight gain or symptoms).
Many centers (eg, specialized outpatient clinics) have integrated health care practitioners from different disciplines (eg, HF nurses, pharmacists, social workers, rehabilitation specialists) into multidisciplinary teams or outpatient HF management programs. These approaches can improve outcomes and reduce hospitalizations and are most effective in the sickest patients.
Dietary sodium restriction helps limit fluid retention. All patients should eliminate salt in cooking and at the table and avoid salted foods; the most severely ill should limit sodium to < 2 g/day by consuming only low-sodium foods.
Monitoring daily morning weight helps detect sodium and water accumulation early. If weight increases > 2 kg over a few days, patients may be able to adjust their diuretic dose themselves, but if weight gain continues or symptoms occur, patients should seek medical attention.
Intensive case management, particularly by monitoring drug adherence and frequency of unscheduled visits to the physician or emergency department and hospitalizations, can identify when intervention is needed. Specialized HF nurses are valuable in education, follow-up, and dosage adjustment according to predefined protocols.
Patients with atherosclerosis or diabetes should strictly follow a diet appropriate for their disorder. Obesity may cause and always aggravates the symptoms of HF; patients should attain a body mass index (BMI) ≤ 30 kg/m2 (ideally 21 to 25 kg/m2).
Regular light activity (eg, walking), tailored to symptoms, is generally encouraged. Activity prevents skeletal muscle deconditioning, which worsens functional status; however, activity does not appear to improve survival or decrease hospitalizations. Rest is appropriate during acute exacerbations. Formal exercise cardiac rehabilitation is useful for chronic HFrEF and is likely helpful for patients with HFpEF.
Patients should have annual influenza vaccination because influenza can precipitate HF exacerbations, particularly in institutionalized or older patients
If causes such as hypertension, persistent tachyarrhythmia, severe anemia, hemochromatosis, uncontrolled diabetes, thyrotoxicosis, beriberi, alcohol use disorder, Chagas disease, or toxoplasmosis are successfully treated, patients may dramatically improve. Significant myocardial ischemia should be treated aggressively; treatment may include revascularization by percutaneous coronary intervention or bypass surgery. Management of extensive ventricular infiltration (eg, in amyloidosis) has improved considerably. Newer treatments for amyloidosis have markedly improved prognosis for many of these patients.
Drug treatment of heart failure involves
(For details on the specific drugs and classes, see Drugs for Heart Failure.)
In HFrEF, all these drug classes have been studied and have shown benefit for long-term management. Recently, addition of a sodium-glucose co-transporter 2 inhibitor, dapagliflozin, has been shown to reduce morbidity and mortality when added to standard care in patients with elevated natriuretic peptide levels; benefit was similar in patients with and without diabetes.
In HFpEF, fewer drugs have been adequately studied. However, ACE inhibitors, ARBs, or aldosterone antagonists (mineralocorticoid receptor antagonists) are generally used to treat HFpEF. ARNIs may reduce hospitalizations for heart failure but do not improve other outcomes. Randomized, controlled trials suggest aldosterone antagonists are beneficial, but nitrates probably are not. Beta blockers should be used only when there is another existing indication (eg, control of heart rate during atrial fibrillation, angina, following myocardial infarction). In patients with severe HFpEF (in contrast to HFrEF), lowering the heart rate (eg, with a beta-blocker) can exacerbate symptoms because these patients have a relatively fixed stroke volume due to severe diastolic dysfunction. In these patients, CO is heart rate dependent and lowering heart rate can thus lower CO at rest and/or with exertion.
In HFmrEF, there may be a specific benefit from ARNIs, although this possibility requires further prospective confirmation.
In patients with infiltrative, restrictive, or hypertrophic cardiomyopathy, digoxin is not effective and may be harmful. In addition, vasodilator therapy may also be poorly tolerated and has not shown benefit in these patients.
All patients should be given clear and explicit information about their drugs, including the importance of timely prescription renewal and adherence to therapy, how to recognize adverse effects, and when to contact their physician.
It is important to identify and treat the cause of an arrhythmia.
Sinus tachycardia, a common compensatory change in heart failure, usually subsides when HF treatment is effective. If it does not, associated causes (eg, hyperthyroidism, pulmonary emboli, fever, anemia, pain) should be sought. If sinus tachycardia persists despite correction of causes, a beta-blocker, given in gradually increasing doses, may help selected patients. However, lowering heart rate with a beta-blocker can be detrimental to patients with advanced HFpEF (eg, restrictive cardiomyopathy), in whom stroke volume is fixed because of severe diastolic dysfunction. In these patients, CO is heart rate–dependent, and lowering heart rate can thus lower CO at rest and/or with exertion.
Atrial fibrillation with an uncontrolled ventricular rate must be treated; the target resting ventricular rate is typically < 80 beats/minute. Beta-blockers are the treatment of choice, although rate-limiting calcium channel blockers may be used cautiously if systolic function is preserved. Adding digoxin, low-dose amiodarone, or other rhythm and/or rate controlling drugs may help some patients. Routine conversion to and maintenance of sinus rhythm has not been shown to be superior to rate control alone in large clinical trials. However, it is best to make this determination on a case-by-case basis because some patients improve significantly with restoration of normal sinus rhythm. If rapid atrial fibrillation does not respond to drugs, permanent pacemaker insertion with complete or partial ablation of the atrioventricular node, or other atrial fibrillation ablation procedures, may be considered in selected patients to restore a sinus or regular rhythm.
Isolated ventricular premature beats, which are common in HF, do not require specific treatment, although rarely very frequent ventricular premature beats (> 15,000/day) have been shown to precipitate heart failure (that reverses with suppression). However, optimization of HF treatments and correction of electrolyte abnormalities (especially potassium and magnesium) reduce the risk of ventricular arrhythmias.
Sustained ventricular tachycardia that persists despite correction of cause (eg, low potassium or magnesium, ischemia) and optimal medical treatment of HF may require an antiarrhythmic drug. Amiodarone, beta-blockers, and dofetilide are the drugs of choice because other antiarrhythmics have adverse proarrhythmic effects when LV systolic dysfunction is present. Because amiodarone increases digoxin and warfarin levels, digoxin and/or warfarin doses should be decreased by half or stopped. Serum digoxin level and INR (international normalized ratio) level should be routinely monitored. However, drug toxicity can occur even at therapeutic levels. Because long-term use of amiodarone can cause adverse effects, a low dose (200 mg orally once a day) is used when possible; blood tests for liver function and thyroid-stimulating hormone are done every 6 months. If chest x-ray is abnormal or dyspnea worsens significantly, chest x-ray and pulmonary function tests are done yearly to check for pulmonary fibrosis. For sustained ventricular arrhythmias, amiodarone may be required; to reduce risk of sudden death, a loading dose of 400 to 800 mg orally twice a day is given for 1 to 3 weeks until rhythm control is adequate, then dose is decreased over 1 month to a maintenance dose of 200 mg orally once a day.
An ICD is recommended for patients with an otherwise good life expectancy if they have symptomatic sustained ventricular tachycardia or ventricular fibrillation or if they remain symptomatic and have an LVEF persistently < 0.30 while receiving guideline-directed medical therapy. The data for ICD use in HFrEF are stronger for ischemic cardiomyopathy than in nonischemic cardiomyopathy.
CRT may relieve symptoms and reduce heart failure hospitalizations for patients who have HF, LVEF < 35%, and a widened QRS complex with a left bundle branch block pattern (> 0.15 second—the wider the QRS, the greater potential benefit). CRT devices are effective but expensive, and patients should be appropriately selected. Many CRT devices also incorporate an ICD in their mechanism.
An implantable device that remotely monitors invasive hemodynamics (eg, pulmonary artery pressure) may help guide HF management in highly selected patients. For example, drug (eg, diuretic) titration based on readings from one of these devices was associated with a marked reduction in HF hospitalization in one clinical trial that included patients with both HFrEF and HFpEF. The device uses the pulmonary artery diastolic pressure as a surrogate for pulmonary capillary wedge pressure (and hence left atrial pressure) in HF patients. However, it has been evaluated only in NYHA class III patients who had recurrent HF exacerbations. Further evidence will help guide how this technology should be implemented.
Ultrafiltration (venovenous filtration) can be useful in selected hospitalized patients with severe cardiorenal syndrome and volume overload refractory to diuretics. However, ultrafiltration should not be used routinely because clinical trials do not show long-term clinical benefit.
An intra-aortic counterpulsation balloon pump is helpful in selected patients with acute HF who have a good chance of recovery (eg, acute HF following myocardial infarction) or in those who need a bridge to a more permanent solution such as cardiac surgery (eg, to fix severe valvular disease or to revascularize multivessel coronary artery disease), an LV assist device, or heart transplantation.
LV assist devices are implantable pumps that augment LV output. They are commonly used to maintain patients with severe HF who are awaiting transplantation and are also used as "destination therapy" (ie, as a long-term solution) in some patients who are not transplant candidates.
Surgery may be appropriate when certain underlying disorders are present. Surgery in patients with advanced HF should be done in a specialized center.
Surgical closure of congenital or acquired intracardiac shunts can be curative.
Coronary artery bypass grafting (CABG) to reduce ischemia did not improve overall 5-year survival in a large clinical trial of HF patients with ischemic LV systolic dysfunction; however, CABG was associated with reduced overall 10-year mortality and with reduced 10-year mortality and hospitalizations due to cardiovascular causes. Thus, the decision to revascularize a HF patient with multivessel CAD should be made on a case-by-case basis.
If HF is primarily due to a valvular disorder, valve repair or replacement should be considered. Patients with primary mitral regurgitation are more likely to benefit than patients with mitral regurgitation secondary to LV dilation, in whom poor myocardial function is likely to continue postoperatively. Surgery is preferably done before myocardial dilation and damage become irreversible. More recently, percutaneous mitral valve procedures, in which a clip is applied to approximate the anterior and posterior mitral leaflets, has been shown to possibly reduce death and hospitalization in carefully selected patients with severe mitral regurgitation (effective regurgitant orifice > 0.30 cm2) and mild or moderately enlarged LV volumes (LV end-diastolic volume < 200 mL).
Heart transplantation is the treatment of choice for patients < 60 who have severe, refractory HF and no other life-threatening conditions and who are highly adherent to management recommendations. Some older patients (about 60 to 70 years) with otherwise good health are also typically considered if they meet other criteria for transplantation. Survival is 85 to 90% at 1 year, and annual mortality thereafter is about 4%/year; however, mortality rate while waiting for a donor is 12 to 15%. Human organ donation remains low.
After treatment, symptoms often persist. Reasons include
Persistence of the underlying disorder (eg, hypertension, ischemia/infarction, valvular disease) despite treatment
Suboptimal treatment of heart failure
Excess intake of dietary sodium or alcohol
Presence of an undiagnosed thyroid disorder, anemia, or supervening arrhythmia (eg, atrial fibrillation with rapid ventricular response, intermittent ventricular tachycardia)
Also, drugs used to treat other disorders may interfere with HF treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs), thiazolidinediones (eg, pioglitazone) for diabetes, and short-acting dihydropyridine or nondihydropyridine calcium channel blockers can worsen heart failure and should be avoided unless no alternative exists; patients who must take such drugs should be followed closely.
1. Yancy CW, Jessup M, Bozkurt B, et al: 2016 ACC/AHA/HFSA Focused update on new pharmacological therapy for heart failure: An update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 134(13):e282–293, 2016.
2. Shah SJ, Kitzman D, Borlaug B, et al: Phenotype-specific treatment of heart failure With preserved ejection fraction: A multiorgan roadmap. Circulation134(1):73–90, 2016.
Heart failure (HF) involves ventricular dysfunction that ultimately leads to the heart not providing tissues with adequate blood for metabolic needs.
In heart failure with reduced ejection fraction (HFrEF), the ventricle contracts poorly and empties inadequately; EF is low.
In heart failure with preserved ejection fraction (HFpEF), ventricular filling is impaired, resulting in increased end-diastolic pressure at rest and/or during exercise; EF is normal.
Consider HF in patients with exertional dyspnea or fatigue, orthopnea, and/or edema, particularly in those with a history of myocardial infarction, hypertension, or valvular disorders or murmurs.
Do chest x-ray, ECG, BNP levels, and an objective test of cardiac function, typically echocardiography.
Unless adequately treated, HF tends to progress and has a poor prognosis.
Treatment includes education and lifestyle changes, control of underlying disorders, a variety of drugs, and sometimes implantable devices (CRT, ICDs).
Drugs Mentioned In This Article
|Drug Name||Select Trade|