Cardiac failure
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Cardiac_failure".

Congestive heart failure (CHF), congestive cardiac failure (CCF) or just heart failure, is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with blood or pump a sufficient amount of blood through the body. It is not to be confused with "cessation of heartbeat", which is known as asystole, or with cardiac arrest, which is the cessation of normal cardiac function with subsequent hemodynamic collapse leading to death.^{citation needed} Because not all patients have volume overload at the time of initial or subsequent evaluation, the term "heart failure" (ICD-9 428.9) is preferred over the older term "congestive heart failure".^{citation needed}

Other related terms include ischemic cardiomyopathy (implying that the cause of heart failure is coronary artery disease) and dilated cardiomyopathy (which is a description of echocardiographic findings characteristic of heart failure but which does not suggest any specific etiology.)

Congestive heart failure exacerbation or decompensated heart failure (DHF) refer to episodes in which a patient with known chronic heart failure acutely develops symptoms.

Congestive heart failure also contrasts with high output heart failure. CHF denotes a pathological process intrinsic to the myocardium, whereas in high output failure, cardiac function is actually normal or even supra-normal, but the demand of end-organs and other tissues outstrips what the heart can provide, occurring in the context of severe anemia, beriberi (vitamin B₁/thiamine deficiency), thyrotoxicosis, Paget disease, arteriovenous fistulas or malformations, and inappropriate tachycardia.

Congestive heart failure is often undiagnosed due to a lack of a universally agreed definition and difficulties in diagnosis, particularly when the condition is considered "mild". Even with the best therapy, heart failure is associated with an annual mortality of 10%.^[1] It is the leading cause of hospitalization in people older than 65.^[2]

Signs and symptoms

Symptoms

Symptoms are dependent on two factors. The first is based on the side of the heart, right or left, that is involved. The second factor is based on the type of failure, either diastolic or systolic. Symptoms and presentation may be indistinguishable making diagnosis impossible based on symptoms.

Left sided failure

The most common symptoms are respiratory in nature. Failure of the left ventricle causes congestion of the pulmonary capillaries. The patient will have dyspnea (shortness of breath) on exertion (dyspnée d'effort) and in severe cases, dyspnea at rest. Easy fatigueability and exercise intolerance are also common complaints. Increasing breathlessness on reclining, called orthopnea, occurs. It is often measured in the number of pillows required to lie comfortably, and in severe cases, the patient may resort to sleeping while sitting up. Another symptoms of heart failure is paroxysmal nocturnal dyspnea, a sudden nighttime attack of severe breathlessness, usually several hours after going to sleep. If left ventricular function is extremely compromised, symptoms of poor systemic circulation become manifest, leading to dizziness, confusion and diaphoresis and cool extremities at rest.

Right sided failure

The right side of the heart pumps blood returned from the tissues to the lungs, where CO₂ is exchanged for O₂. Right ventricular failure leads to congestion of systemic capillaries. This leads to peripheral edema or anasarca and nocturia (frequent nighttime urination when the fluid from the legs is returned to the bloodstream). In more severe cases, ascites (fluid accumulation in the abdominal cavity) and hepatomegaly (painful enlargement of the liver) may develop. Hepatic congestion may actually impair liver function, and jaundice and even coagulopathy may occur.

Heart failure (suboptimal left or right ventricular function) may decompensate easily. this most commonly results from an intercurrent illness (such as pneumonia), myocardial infarction (a heart attack), arrhythmias, uncontrolled hypertension, and patient non-compliance with diet or medication.^[3] Other classic precipitating factors are anaemia and hyperthyroidism. These place additional strain on the heart muscle, which may cause symptoms to rapidly worsen. Excessive fluid or salt intake (including intravenous fluids for unrelated indications, but more commonly from dietary indiscretion), and medication that causes fluid retention (such as NSAIDs and thiazolidinediones), may also precipitate decompensation.^[4]

Signs

Left sided heart failure

Signs on physical exam indicating left ventricular failure are a laterally displaced apex beat (as the heart is enlarged) and a gallop rhythm (additional heart sounds) in case of decompensation. Heart murmurs may indicate the presence of valvular heart disease, either as a cause (e.g. aortic stenosis) or as a result (e.g. mitral regurgitation) of the heart failure.

Common respiratory signs are tachypnea and increased work of breathing (non-specific signs of respiratory distress), rales or crackles, which suggests the development of pulmonary edema, dullness of the lung fields to percussion and diminished breath sounds at the bases of the lung, which suggests the development of a pleural effusion (fluid collection in the pleural cavity) that is transudative in nature, and cyanosis which suggests hypoxemia, caused by the decreased rate of diffusion of oxygen from fluid-filled alveoli to the pulmonary capillaries.

Right sided heart failure

The exam can reveal peripheral edema, ascites, and hepatomegaly. Jugular venous pressure is frequently assessed as a marker of fluid overload, which can be accentuated by the hepatojugular reflux. Systemic venous pressure in general is elevated, and this can be seen even in veins in the hand, which are distended when dependent, but which will flatten when the force of gravity overcomes right atrial pressure. In failure, the distention may not be relieved even when the hands are held completely overhead. A parasternal heave may be present, signifying the compensatory increase in contraction strength.

Note that the most common cause of right-sided heart failure is left-sided heart failure, so that patients commonly present with both sets of signs and symptoms.

Diagnosis

Imaging

Echocardiography is commonly used to support a clinical diagnosis of heart failure. This modality uses ultrasound to determine the stroke volume (SV, the amount of blood in the heart that exits the ventricles with each beat), the end-diastolic volume (EDV, the total amount of blood at the end of diastole), and the SV in proportion to the EDV, a value known as the ejection fraction. In pediatrics, the shortening fraction is the preferred measure of systolic function. Normally, the EF should be between 50% and 70%; in systolic heart failure, it drops below 40%. Echocardiography can also identify valvular heart disease and assess the state of the pericardium (the connective tissue sac surrounding the heart). Echocardiography may also aid in deciding what treatments will help the patient, such as medication, insertion of an implantable cardioverter-defibrillator or cardiac resynchronization therapy. Echocardiography can also help determine if acute myocardial ischemia is the precipitating cause, and may manifest as regional wall motion abnormalities on echo.

Chest X-rays are frequently used to aid in the diagnosis of CHF. In the compensated patient, this may show cardiomegaly (visible enlargement of the heart), quantified as the cardiothoracic ratio (proportion of the heart size to the chest). In left ventricular failure, there may be evidence of vascular redistribution ("upper lobe blood diversion" or "cephalization"), Kerley lines, cuffing of the areas around the bronchi, and interstitial edema.

Electrophysiology

An electrocardiogram (ECG/EKG) is used to identify arrhythmias, ischemic heart disease, right and left ventricular hypertrophy, and presence of conduction delay or abnormalities (e.g. left bundle branch block). An ECG may also definitively diagnose acute myocardial ischemia (if ST elevation is present)

Blood tests

Blood tests routinely performed include electrolytes (sodium, potassium), measures of renal function, liver function tests, thyroid function tests, a complete blood count, and often C-reactive protein if infection is suspected. An elevated B-type natriuretic peptide (BNP) is a specific test indicative of heart failure. Additionally, BNP can be used to differentiate between causes of dyspnea due to heart failure from other causes of dyspnea. If myocardial infarction is suspected, various cardiac markers may be used.

According to a meta-analysis comparing BNP and N-terminal pro-BNP (NTproBNP) in the diagnosis of heart failure, BNP is a better indicator for heart failure and left ventricular systolic dysfunction. In groups of symptomatic patients, a diagnostic odds ratio of 27 for BNP compares with a sensitivity of 85% and specificity of 84% in detecting heart failure. ^[5]

Angiography

Heart failure may be the result of coronary artery disease, and its prognosis depends in part on the ability of the coronary arteries to supply blood to the myocardium (heart muscle). As a result, coronary catheterization may be used to identify possibilities for revascularisation through percutaneous coronary intervention or bypass surgery.

Monitoring

Various measures are often used to assess the progress of patients being treated for heart failure. These include fluid balance (calculation of fluid intake and excretion), monitoring body weight (which in the shorter term reflects fluid shifts).

Diagnostic criteria

No system of diagnostic criteria has been agreed as the gold standard for heart failure. Commonly used systems are the "Framingham criteria"^[6] (derived from the Framingham Heart Study), the "Boston criteria",^[7] the "Duke criteria",^[8] and (in the setting of acute myocardial infarction) the "Killip class".^[9]

Functional classification is generally done by the New York Heart Association Functional Classification.^[10] This score documents severity of symptoms, and can be used to assess response to treatment. While its use is widespread, the NYHA score is not very reproducible and doesn't reliably predict the walking distance or exercise tolerance on formal testing.^[11] The classes (I-IV) are:

• Class I: no limitation is experienced in any activities; there are no symptoms from ordinary activities.
• Class II: slight, mild limitation of activity; the patient is comfortable at rest or with mild exertion.
• Class III: marked limitation of any activity; the patient is comfortable only at rest.
• Class IV: any physical activity brings on discomfort and symptoms occur at rest.

In its 2001 guidelines, the American College of Cardiology/American Heart Association working group introduced four stages of heart failure:^[12]

• Stage A: a high risk HF in the future but no structural heart disorder;
• Stage B: a structural heart disorder but no symptoms at any stage;
• Stage C: previous or current symptoms of heart failure in the context of an underlying structural heart problem, but managed with medical treatment;
• Stage D: advanced disease requiring hospital-based support, a heart transplant or palliative care.

Classification

There are many different ways to categorize heart failure, including:

• the side of the heart involved, (left heart failure versus right heart failure)
• whether the abnormality is due to contraction or relaxation of the heart (systolic dysfunction vs. diastolic dysfunction)
• whether the abnormality is due to low cardiac output or high systemic vascular resistance (low-output heart failure vs. high-output heart failure)
• the degree of functional impairment conferred by the abnormality (as in the NYHA functional classification)

Causes

Causes and contributing factors to congestive heart failure include the following:^[12]

Pathophysiology

This section does not cite any references or sources. (December 2007) Please help improve this section by adding citations to reliable sources. Unverifiable material may be challenged and removed.

Heart failure is caused by any condition which reduces the efficiency of the myocardium, or heart muscle, through damage or overloading. As such, it can be caused by as diverse an array of conditions as myocardial infarction (in which the heart muscle is starved of oxygen and dies), hypertension (which increases the force of contraction needed to pump blood) and amyloidosis (in which protein is deposited in the heart muscle, causing it to stiffen). Over time these increases in workload will produce changes to the heart itself:

• Reduced contractility, or force of contraction, due to overloading of the ventricle. In health, increased filling of the ventricle results in increased contractility (by the Frank-Starling law of the heart) and thus a rise in cardiac output. In heart failure this mechanism fails, as the ventricle is loaded with blood to the point where heart muscle contraction becomes less efficient. This is due to reduced ability to cross-link actin and myosin filaments in over-stretched heart muscle.^[13]
• A reduced stroke volume, as a result of a failure of systole, diastole or both. Increased end systolic volume is usually caused by reduced contractility. Decreased end diastolic volume results from impaired ventricular filling – as occurs when the compliance of the ventricle falls (i.e. when the walls stiffen).
• Reduced spare capacity. As the heart works harder to meet normal metabolic demands, the amount cardiac output can increase in times of increased oxygen demand (e.g. exercise) is reduced. This contributes to the exercise intolerance commonly seen in heart failure.
• Increased heart rate, stimulated by increased sympathetic activity in order to maintain cardiac output. Initially, this helps compensate for heart failure by maintaining blood pressure and perfusion, but places further strain on the myocardium, increasing coronary perfusion requirements, which can lead to worsening of ischemic heart disease. Sympathetic activity may also cause potentially fatal arrhythmias.
• Hypertrophy (an increase in physical size) of the myocardium, caused by the terminally differentiated heart muscle fibres increasing in size in an attempt to improve contractility. This may contribute to the increased stiffness and decreased ability to relax during diastole.
• Enlargement of the ventricles, contributing to the enlargement and spherical shape of the failing heart. The increase in ventricular volume also causes a reduction in stroke volume due to mechanical and contractile inefficiency.^[14]

The general effect is one of reduced cardiac output and increased strain on the heart. This increases the risk of cardiac arrest (specifically due to ventricular dysrhythmias), and reduces blood supply to the rest of the body. In chronic disease the reduced cardiac output causes a number of changes in the rest of the body, some of which are physiological compensations, some of which are part of the disease process:

• Arterial blood pressure falls. This destimulates baroreceptors in the carotid body and aortic arch which link to the nucleus tractus solitarius. This center in the brain increases sympathetic activity, releasing catecholamines into the blood stream. Binding to alpha-1 receptors results in systemic arterial vasoconstriction. This helps restore blood pressure but also increases the total peripheral resistance, increasing the workload of the heart. Binding to beta-1 receptors in the myocardium increases the heart rate and make contractions more forceful, in an attempt to increase cardiac output. This also, however, increases the amount of work the heart has to perform.
• Increased sympathetic stimulation also causes the hypothalamus to secrete vasopressin (also known as antidiuretic hormone or ADH), which causes causing fluid retention at the kidneys. This increases the blood volume and blood pressure.
• Reduced perfusion (blood flow) to the kidneys stimulates the release of renin – an enzyme which catalyses the production of the potent vasopressor angiotensin. Angiotensin and its metabolites cause further vasocontriction, and stimulate increased secretion of the steroid aldosterone from the adrenal glands. This promotes salt and fluid retention at the kidneys, also increasing the blood volume.
• The chronically high levels of circulating neuroendocrine hormones such as catecholamines, renin, angiotensin, and aldosterone affects the myocardium directly, causing structural remodelling of the heart over the long term. Many of these remodelling effects seem to be mediated by transforming growth factor beta (TGF-beta), which is a common downstream target of the signal transduction cascade initiated by catecholamines^[15] and angiotensin II^[16], and also by epidermal growth factor (EGF), which is a target of the signaling pathway activated by aldosterone^[17]
• Reduced perfusion of skeletal muscle causes atrophy of the muscle fibres. This can result in weakness, increased fatigueability and decreased peak strength - all contributing to exercise intolerance.^[18]

The increased peripheral resistance and greater blood volume place further strain on the heart and accelerates the process of damage to the myocardium. Vasoconstriction and fluid retention produce an increased hydrostatic pressure in the capillaries. This shifts of the balance of forces in favour of interstitial fluid formation as the increased pressure forces additional fluid out of the blood, into the tissue. This results in oedema (fluid build-up) in the tissues. In right-sided heart failure this commonly starts in the ankles where venous pressure is high due to the effects of gravity (although if the patient is bed-ridden, fluid accumulation may begin in the sacral region.) It may also occur in the abdominal cavity, where the fluid build-up is called ascites. In left-sided heart failure oedema can occur in the lungs - this is called cardiogenic pulmonary oedema. This reduces spare capacity for ventilation, causes stiffening of the lungs and reduces the efficiency of gas exchange by increasing the distance between the air and the blood. The consequences of this are shortness of breath, orthopnoea and paroxysmal nocturnal dyspnea.

The symptoms of heart failure are largely determined by which side of the heart fails. The left side pumps blood into the systemic circulation, whilst the right side pumps blood into the pulmonary circulation. Whilst left-sided heart failure will reduce cardiac output to the systemic circultion, the initial symptoms often manifest due to effects on the pulmonary circulation. In systolic dysfunction, the ejection fraction is decreased, leaving an abnormally elevated volume of blood in the left ventricle. In diastolic dysfunction, end-diastolic ventricular pressure will be high. This increase in volume or pressure backs up to the left atrium and then to the pulmonary veins. Increased volume or pressure in the pulmonary veins impairs the normal drainage of the alveoli and favors the flow of fluid from the capillaries to the lung parenchyma, causing pulmonary edema. This impairs gas exchange. Thus, left-sided heart failure often presents with respiratory symptoms: shortness of breath, orthopnea and paroxysmal nocturnal dyspnea.

In severe cardiomyopathy, the effects of decreased cardiac output and poor perfusion become more apparent, and patients will manifest with cold and clammy extremities, cyanosis, claudication, generalized weakness, dizziness, and syncope

The resultant hypoxia caused by pulmonary edema causes vasoconstriction in the pulmonary circulation, which results in pulmonary hypertension. Since the right ventricle generates far lower pressures than the left ventricle (approximately 20 mmHg versus around 120 mmHg, respectively, in the healthy individual) but nonetheless generates cardiac output exactly equal to the left ventricle, this means that a small increase in pulmonary vascular resistance causes a large increase in amount of work the right ventricle must perform. However, the main mechanism by which left-sided heart failure causes right-sided heart failure is actually not well understood. Some theories invoke mechanisms that are mediated by neurohormonal activation. Mechanical effects may also contribute. As the left ventricle distends, the intraventricular septum bows into the right ventricle, decreasing the capacity of the right ventricle.

Systolic dysfunction

Heart failure caused by systolic dysfunction is more readily recognized. It can be simplistically described as failure of the pump function of the heart. It is characterized by a decreased ejection fraction (less than 45%). The strength of ventricular contraction is attenuated and inadequate for creating an adequate stroke volume, resulting in inadequate cardiac output. In general, this is caused by dysfunction or destruction of cardiac myocytes or their molecular components. In congenital diseases such as Duchenne muscular dystrophy, the molecular structure of individual myocytes is affected. Myocytes and their components can be damaged by inflammation (such as in myocarditis) or by infiltration (such as in amyloidosis). Toxins and pharmacological agents (such as ethanol, cocaine, and amphetamines) cause intracellular damage and oxidative stress. The most common mechanism of damage is ischemia causing infarction and scar formation. After myocardial infarction, dead myocytes are replaced by scar tissue, deleteriously affecting the function of the myocardium. On echocardiogram, this is manifest by abnormal or absent wall motion.

Because the ventricle is inadequately emptied, ventricular end-diastolic pressure and volumes increase. This is transmitted to the atrium. On the left side of the heart, the increased pressure is transmitted to the pulmonary vasculature, and the resultant hydrostatic pressure favors extravassation of fluid into the lung parenchyma, causing pulmonary edema. On the right side of the heart, the increased pressure is transmitted to the systemic venous circulation and systemic capillary beds, favoring extravassation of fluid into the tissues of target organs and extremities, resulting in dependent peripheral edema.

Diastolic dysfunction

Heart failure caused by diastolic dysfunction is generally described as the failure of the ventricle to adequately relax and typically denotes a stiffer ventricular wall. This causes inadequate filling of the ventricle, and therefore results in an inadequate stroke volume. The failure of ventricular relaxation also results in elevated end-diastolic pressures, and the end result is identical to the case of systolic dysfunction (pulmonary edema in left heart failure, peripheral edema in right heart failure.)

Diastolic dysfunction can be caused by processes similar to those that cause systolic dysfunction, particularly causes that affect cardiac remodeling.

Diastolic dysfunction may not manifest itself except in physiologic extremes if systolic function is preserved. The patient may be completely asymptomatic at rest. However, they are exquisitely sensitive to increases in heart rate, and sudden bouts of tachycardia (which can be caused simply by physiological responses to exertion, fever, or dehydration, or by pathological tachyarrhythmias such as atrial fibrillation with rapid ventricular response) may result in flash pulmonary edema. Adequate rate control (usually with a pharmacological agent that slows down AV conduction such as a calcium channel blocker or a beta-blocker) is therefore key to preventing decompensation.

Left ventricular diastolic function can be determined through echocardiography by measurement of various parameters such as the E/A ratio (early-to-atrial left ventricular filling ratio), the E (early left ventricular filling) deceleration time, and the isovolumic relaxation time.

Treatment

The treatment of CHF focuses on treating the symptoms and signs of CHF and preventing the progression of disease. If there is a reversible cause of the heart failure (e.g. infection, alcohol ingestion, anemia, thyrotoxicosis, arrhythmia, or hypertension), that should be addressed as well. Treatments include exercise, eating healthy foods, reduction in salty foods, and abstinence from smoking and drinking alcohol.

Modalities

Diet and lifestyle measures

Patients with CHF are educated to undertake various non-pharmacological measures to improve symptoms and prognosis. Such measures include:^[19]

• Moderate physical activity, when symptoms are mild or moderate; or bed rest when symptoms are severe.
• Weight reduction – through physical activity and dietary modification, as obesity is a risk factor for heart failure and left ventricular hypertrophy.
• Monitor weight - this is a parameter that can easily be measured at home. Rapid weight increase is generally due to fluid retention. Weight gain of more than 2 pounds is associated with admission to the hospital for heart failure^[20]
• Sodium restriction – excessive sodium intake may precipitate or exacerbate heart failure, thus a "no added salt" diet (60–100 mmol total daily intake) is recommended for patients with CHF. More severe restrictions may be required in severe CHF.
• Fluid restriction – patients with CHF have a diminished ability to excrete free water load. Hyponatremia frequently develops in decompensated heart failure due to the effects of excess circulating neuroendocrine hormones. While the activation of the renin-angiotensin-aldosterone axis due to decreased renal perfusion promotes both sodium and water retention, the activation of atrial natriuretic peptide due to atrial stretch favors sodium excretion, and the activation of antidiuretic hormone due to peripheral baroreceptors that sense hypotension as well as due to the activation of the sympathetic nervous system favors water retention alone, leading to disproportionately more water retention than sodium retention. The severity of the hyponatremia during an episode of decompensated heart failure can be predictive of mortality. Generally water intake should be limited to 1.5 L daily or less in patients with hyponatremia, though fluid restriction may be beneficial regardless in symptomatic reduction.

Pharmacological management

There is a significant evidence–practice gap in the treatment of CHF; particularly the underuse of ACE inhibitors and β-blockers and aldosterone antagonists which have been shown to provide mortality benefit.^[21] Treatment of CHF aims to relieve symptoms, maintain a euvolemic state (normal fluid level in the circulatory system), and to improve prognosis by delaying progression of heart failure and reducing cardiovascular risk. Drugs used include: diuretic agents, vasodilator agents, positive inotropes, ACE inhibitors, beta blockers, and aldosterone antagonists (e.g. spironolactone). It should be noted that while intuitive, increasing heart function with some drugs, such as the positive inotrope Milrinone, leads to increased mortality.^[22][23]

Angiotensin-modulating agents

ACE inhibitor (ACE) therapy is recommended for all patients with systolic heart failure, irrespective of symptomatic severity or blood pressure.^[24][12][25] ACE inhibitors improve symptoms, decrease mortality and reduce ventricular hypertrophy. Angiotensin II receptor antagonist therapy (also referred to as AT₁-antagonists or angiotensin receptor blockers), particularly using candesartan, is an acceptable alternative if the patient is unable to tolerate ACEI therapy.^[26][27] ACEIs and ARBs decrease afterload by antagonizing the vasopressor effect of angiotensin, thereby decreasing the amount of work the heart must perform. It is also believed that angiotensin directly affects cardiac remodeling, and blocking its activity can thereby slow the deterioration of cardiac function.

Diuretics

Diuretic therapy is indicated for relief of congestive symptoms. Several classes are used, with combinations reserved for severe heart failure:^[19]

• Loop diuretics (e.g. furosemide, bumetanide) – most commonly used class in CHF, usually for moderate CHF.
• Thiazide diuretics (e.g. hydrochlorothiazide, chlorthalidone, chlorthiazide) – may be useful for mild CHF, but typically used in severe CHF in combination with loop diuretics, resulting in a synergistic effect.
• Potassium-sparing diuretics (e.g. amiloride) – used first-line use to correct hypokalaemia.
  • Spironolactone is used as add-on therapy to ACEI plus loop diuretic in severe CHF.
  • Eplerenone is specifically indicated for post-MI reduction of cardiovascular risk.

If a heart failure patient exhibits a resistance to or poor response to diuretic therapy, ultrafiltration or aquapheresis may be needed to achieve adequate control of fluid retention and congestion. The use of such mechanical methods of fluid removal can produce meaningful clinical benefits in patients with diuretic-resistant heart failure and may restore responsiveness to conventional doses of diuretics.⁹

Beta blockers

Until recently (within the last 20 years), β-blockers were contraindicated in CHF, owing to their negative inotropic effect and ability to produce bradycardia – effects which worsen heart failure. However, current guidelines recommend β-blocker therapy for patients with systolic heart failure due to left ventricular systolic dysfunction after stabilization with diuretic and ACEI therapy, irrespective of symptomatic severity or blood pressure.^[25] As with ACEI therapy, the addition of a β-blocker can decrease mortality and improve left ventricular function. Several β-blockers are specifically indicated for CHF including: bisoprolol, carvedilol, and extended-release metoprolol. The antagonism of β₁ inotropic and chronotropic effects decreases the amount of work the heart must perform. It is also thought that catecholamines and other sympathomimetics have an effect on cardiac remodeling, and blocking their activity can slow the deterioration of cardiac function.

Positive inotropes

Digoxin (a mildly positive inotrope and negative chronotrope), once used as first-line therapy, is now reserved for control of ventricular rhythm in patients with atrial fibrillation; or where adequate control is not achieved with an ACEI, a beta blocker and a loop diuretic.^[25] There is no evidence that digoxin reduces mortality in CHF, although some studies suggest a decreased rate in hospital admissions.^[28] It is contraindicated in cardiac tamponade and restrictive cardiomyopathy.

The inotropic agent dobutamine is advised only in the short-term use of acutely decompensated heart failure, and has no other uses.^[25]

Phosphodiesterase inhibitors such as milrinone are sometimes utilized in severe cardiomyopathy. The mechanism of action is through the antagonism of adenosine receptors, resulting in inotropic effects and modest diuretic effects.

Alternative vasodilators

The combination of isosorbide dinitrate/hydralazine is the only vasodilator regimen, other than ACE inhibitors or angiotensin II receptor antagonists, with proven survival benefits. This combination appears to be particularly beneficial in CHF patients with an African American background, who respond less effectively to ACEI therapy.^[29][30]

Aldosterone receptor antagonists

The RALES trial^[31] showed that the addition of spironolactone can improve mortality, particularly in severe cardiomyopathy (ejection fraction less than 25%.) The related drug eplerenone was shown in the EPHESUS trial^[32] to have a similar effect, and it is specifically labelled for use in decompesated heart failure complicating acute myocardial infarction. While the antagonism of aldosterone will decrease the effects of sodium and water retention, it is thought that the main mechanism of action is by antagonizing the deleterious effects of aldosterone on cardiac remodeling.

Recombinant neuroendocrine hormones

Nesiritide, a recombinant form of B-natriuretic peptide, is indicated for use in patients with acute decompensated heart failure who have dyspnea at rest. Nesiritide promotes diuresis and natriuresis, thereby ameliorating volume overload. It is thought that, while BNP is elevated in heart failure, the peptide that is produced is actually dysfunctional or non-functional and thereby ineffective.

Vasopressin receptor antagonists

Tolvaptan and conivaptan antagonize the effects of antidiuretic hormone (vasopressin), thereby promoting the specific excretion of free water, directly ameliorating the volume overloaded state, and counteracting the hyponatremia that occurs due to the release of neuroendocrine hormones in an attempt to counteract the effects of heart failure. The EVEREST trial, which utilized tolvaptan, showed that when used in combination with conventional therapy, many symptoms of acute decompensated heart failure were significantly improved compared to conventional therapy alone^[33] although they found no difference in mortality and morbidity when compared to conventional therapy.^[34].

Devices

Patients with NYHA class III or IV, left ventricular ejection fraction (LVEF) of 35% or less and a QRS interval of 120 ms or more may benefit from cardiac resynchronization therapy (CRT; pacing both the left and right ventricles), through implantation of a bi-ventricular pacemaker, or surgical remodeling of the heart. These treatment modalities may make the patient symptomatically better, improving quality of life and in some trials have been proven to reduce mortality.

The COMPANION trial demonstrated that CRT improved survival in individuals with NYHA class III or IV heart failure with a widened QRS complex on an electrocardiogram.^[35] The CARE-HF trial showed that patients receiving CRT and optimal medical therapy benefited from a 36% reduction in all cause mortality, and a reduction in cardiovascular-related hospitalization.^[36]

Patients with NYHA class II, III or IV, and LVEF of 35% (without a QRS requirement) may also benefit from an implantable cardioverter-defibrillator (ICD), a device that is proven to reduce all cause mortality by 23% compared to placebo. This mortality benefit was observed in patients who were already optimally-managed on drug therapy.^[37] Patients with severe cardiomyopathy are at high risk for sudden cardiac death due to ventricular dysrhythmias.

Another current treatment involves the use of left ventricular assist devices (LVADs). LVADs are battery-operated mechanical pump-type devices that are surgically implanted on the upper part of the abdomen. They take blood from the left ventricle and pump it through the aorta. LVADs are becoming more common and are often used by patients who have to wait for heart transplants.

Surgery

The final option, if other measures have failed, is heart transplantation or (temporary or prolonged) implantation of an artificial heart. These remain the recommended surgical treatment options. However, the limited number of hearts available for transplantation in a growing group of candidates, has led to the development of alternative surgical approaches to heart failure. These commonly involve surgical left ventricular remodeling. The aim of the procedures is to reduce the ventricle diameter (targeting Laplace's law and the disease mechanism of heart failure), improve its shape and/or remove non-viable tissue.^[38] These procedures can be performed together with coronary artery bypass surgery or mitral valve repair.

If heart failure ensues after a myocardial infarction due to scarring and aneurysm formation, reconstructive surgery may be an option. These aneurysms bulge with every contraction, making it inefficient. Cooley and coworkers reported the first surgical treatment of a left ventricular aneurysm in 1958.^[39] The used a linear closure after their excision. In the 1980s, Vincent Dor developed a method using an circular patch stitched to the inside of the ventricle (the endoventricular circular patch plasty or Dor procedure) to close the defect after excision.^[40] His approach has been modified by others. Today, this is the preferred method for surgical treatment of incorrectly contracting (dyskinetic) left ventricle tissue, although a linear closure technique combined with septoplasty might be equally effective.^[41][42] The multicenter RESTORE trial of 1198 participants demonstrated an increase in ejection fraction from about 30% to 40% with a concomitant shift in NYHA classes, with an early mortality of 5% and a 5-year survival of 70%.^[43] As of yet, it remains unknown if surgery is superior to optimal medical therapy. The STICH trial (Surgical Treatment for IschemiC Heart Failure) will examine the role of medical treatment, coronary artery bypass surgery and left ventricle remodeling surgery in heart failure patients. Results are expected to be published in 2009 and 2011.^[44]

The Batista procedure was invented by Brazilian doctor Randas Batista in 1994 for use in patients with non-ischemic dilated cardiomyopathy. It involves removal of a portion of viable tissue from the left ventricle to reduce its size (partial left ventriculectomy), with or without repair or replacement of the mitral valve.^[45]. Although several studies showed benefits from this surgery, studies at the Cleveland Clinic concluded that this procedure was associated with a high early and late failure rate. At 3 years only 26 percent were event-free and survival rate was only 60 percent.^[46] Most hospitals have abandoned this operation and it is no longer included in heart failure guidelines.^[38]

Newer procedures under examination are based on the observation that the spherical configuration of the dilated heart reduces ejection fraction compared to the elliptical form. Mesh-like constraint devices such as the Acorn CorCap aim to improve contraction efficacy and prevent further remodeling. Clinical trials are underway.^[47] Another technique which aims to divide the spherical ventricle into two elliptical halves is used with the Myosplint device.^[48]

Approach

Acute decompensation

In acute decompensated heart failure, the immediate goal is to re-establish adequate perfusion and oxygen delivery to end organs. This entails ensuring that airway, breathing, and circulation are secure. Supplemental oxygen should be administered immediately to correct hypoxemia. Acute decompensation may be complicated by respiratory failure, which will require treatment with endotracheal intubation and mechanical ventilation. While heart failure is associated with a volume overloaded state, volume status should be adequately evaluated. Since heart failure patients are generally on chronic diuretics, overdiuresis can occur. In the case of diastolic dysfunction without systolic dysfunction, fluid resuscitation may in fact improve circulation by decreasing heart rate, which will allow the ventricles more time to fill. Even if the patient is edematous, fluid resuscitation may be the first line of treatment if the patient is hypotensive. The patient may in fact be intravascularly volume depleted, although if the hypotension is due to cardiogenic shock, additional fluid may make the situation worse. If the patient's circulatory volume is adequate but there is persistent evidence of inadequate end-organ perfusion, inotropes may be administered. In certain circumstances, a left-ventricle assist device (LVAD) may be necessary.

Certain scenarios will require emergent consultation with cardiothoracic surgery. Heart failure due to acute aortic regurgitation is a surgical emergency associated with high mortality. Heart failure may occur after rupture of ventricular aneurysm. These can form after myocardial infarction. If it ruptures on the free wall, it will cause cardiac tamponade. If it ruptures on the intraventricular septum, it can create a ventricular septal defect. Other causes of cardiac tamponade may also require surgical intervention, although emergent treatment at bedside may be adequate. It should also be determined whether the patient had a history of a repaired congenital heart disease as they often have complex cardiac anatomy with artificial grafts and shunts that may sustain damage, leading to acute decompensated heart failure.

Acute myocardial infarction can precipitate acute decompensated heart failure and will necessitate emergent revascularization with thrombolytics, percutaneous coronary intervention, or coronary artery bypass graft.

Once the patient is stabilized, attention can be turned to treating pulmonary edema to improve oxygenation. Intravenous furosemide is generally the first line. However, patients on long-standing diuretic regimens can become tolerant, and dosages must be progressively increased. If high doses of furosemide are inadequate, boluses or continuous infusions of bumetanide may be preferred. These loop diuretics may be combined with thiazide diuretics such as oral metolazone or intravenous chlorthiazide for a synergistic effect. Intravenous preparations are preferred because of more predictable absorption. When a patient is extremely fluid overloaded, they can develop intestinal edema as well, which can affect enteral absorption of medications.

Another option is nesiritide, although it should only be considered if conventional therapy has been ineffective and the patient is extremely symptomatic.

Provided that the patient has an adequate blood pressure and is not bradycardia, a β₁ selective beta-blocker such as metoprolol should be started. In cases of more severe cardiomyopathy, a beta blocker with alpha antagonist effects such as carvedilol or labetalol may be preferred. An ACE inhibitor or angiotensin receptor blockers should be started as well. If the ejection fraction is poor, an aldosterone receptor antagonist should be started as well.

The criteria for successful treatment of acute decompensated heart failure is the re-establishment of adequate oxygenation off of supplemental oxygen, adequate perfusion of end-organs, and return to baseline symptomatology. A parameter frequently used is return to "dry" weight. As the test is becoming more easily available, return to baseline BNP can also serve as a measure of adequate treatment.

Chronic management

The goal is to prevent the development of acute decompensated heart failure, to counteract the deleterious effects of cardiac remodeling, and to minimize the symptoms that the patient suffers. In addition to pharmacologic agents (oral loop diuretics, beta-blockers, ACE inhibitors or angiotensin receptor blockers, vasodilators, and in severe cardiomyopathy aldosterone receptor antagonists), behavioral modification should be pursued, specifically with regards to dietary guidelines regarding salt and fluid intake. Exercise should be encouraged as tolerated, as sufficient conditioning can significantly improve quality-of-life.

In patients with severe cardiomyopathy, implantation of an automatic implantable cardioverter defibrillator(AICD) should be considered. A select population will also probably benefit from ventricular resynchronization.

In select cases, cardiac transplantation can be considered. While this may resolve the problems associated with heart failure, the patient generally must remain on an immunosuppressive regimen to prevent rejection, which has its own significant downsides.

Palliative care and hospice

Without transplantation, heart failure caused by ischemic heart disease is not reversible, and cardiac function typically deteriorates with time. (In particular, diastolic function worsens as a function of age even in individuals without ischemic heart disease.) The growing number of patients with Stage D heart failure (intractable symptoms of fatigue, shortness of breath or chest pain at rest despite optimal medical therapy) should be considered for palliative care or hospice, according to American College of Cardiology/American Heart Association guidelines.

Prognosis

Prognosis in heart failure can be assessed in multiple ways including clinical prediction rules and cardiopulmonary exercise testing. Clinical prediction rules use a composite of clinical factors such as lab tests and blood pressure to estimate prognosis. Among several clinical prediction rules for prognosing acute heart failure, the 'EFFECT rule' slightly outperformed other rules in stratifying patients and identifying those at low risk of death during hospitalization or within 30 days.^[49] Easy methods for identifying low risk patients are:

• ADHERE Tree rule indicates that patients with blood urea nitrogen < 43 mg/dl and systolic blood pressure at least 115 mm Hg have less than 10% chance of inpatient death or complications.
• BWH rule indicates that patients with systolic blood pressure over 90 mm Hg, respiratory rate of 30 or less breaths per minute, serum sodium over 135 mmol/L, no new ST-T wave changes have less than 10% chance of inpatient death or complications.

A very important method for assessing prognosis in advanced heart failure patients is cardiopulmonary exercise testing (CPX testing). CPX testing is usually required prior to heart transplantation as an indicator of prognosis. Cardiopulmonary exercise testing involves measurement of exhaled oxygen and carbon dioxide during exercise. The peak oxygen consumption (VO2 max) is used as an indicator of prognosis. As a general rule, a VO2 max less than 12-14 cc/kg/min indicates a poorer survival and suggests that the patient may be a candidate for a heart transplant. Patients with a VO2 max<10 cc/kg/min have clearly poorer prognosis. The most recent International Society for Heart and Lung Transplantation (ISHLT) guidelines (http://www.jhltonline.org/article/PIIS1053249806004608/fulltext#sec1) also suggest two other parameters that can be used for evaluation of prognosis in advanced heart failure, the heart failure survival score and the use of a criteria of VE/VCO2 slope>35 from the CPX test. The heart failure survival score is a score calculated using a combination of clinical predictors and the VO2 max from the cardiopulmonary exercise test.

References