Heart Failure

Introduction
Background

Heart failure is a syndrome manifesting as the inability of the heart to fill with or eject blood due to any structural or functional cardiac conditions.1

Heart failure may be caused by myocardial failure but may also occur in the presence of near-normal cardiac function under conditions of high demand. Heart failure always causes circulatory failure, but the converse is not necessarily the case because various noncardiac conditions (eg, hypovolemic shock, septic shock) can produce circulatory failure in the presence of normal, modestly impaired, or even supranormal cardiac function.

In terms of incidence, prevalence, morbidity, and mortality, the epidemiologic magnitude of heart failure (HF) is staggering. According to the American Heart Association, heart failure is a condition that affects nearly 5.7 million Americans of all ages and is responsible for more hospitalizations than all forms of cancer combined. It is the number 1 cause for hospitalization among Medicare patients. With improvement in survival of acute myocardial infarctions and a population that continues to age, heart failure will continue to increase in prominence as a major health problem in the United States.

For additional resources, please visit Medscape’s Heart Failure Resource Center.

Pathophysiology
Regardless of the precipitating event, the common pathophysiologic state that perpetuates the progression of heart failure is extremely complex. Compensatory mechanisms exist on every level of organization from sub-cellular all the way through organ-to-organ interactions. Only when this network of adaptations becomes overwhelmed does heart failure ensue. In this section, we focus on those adaptations that represent significant therapeutic targets in the treatment of heart failure.

Most important among these adaptations are the (1) Frank-Starling mechanism, in which an increased preload helps to sustain cardiac performance; (2) alterations in myocyte regeneration and death; (3) myocardial hypertrophy with or without cardiac chamber dilatation, in which the mass of contractile tissue is augmented; and (4) activation of neurohumoral systems, especially the release of norepinephrine by adrenergic cardiac nerves, which augments myocardial contractility and includes activation of the renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system (SNS), and other neurohumoral adjustments that act to maintain arterial pressure and perfusion of vital organs. In acute heart failure, the finite adaptive mechanisms that may be adequate to maintain the overall contractile performance of the heart at relatively normal levels become maladaptive when trying to sustain adequate cardiac performance.

The primary myocardial response to chronic increased wall stress is myocyte hypertrophy, death/apoptosis, and regeneration.2 This process eventually leads to remodeling, usually the eccentric type. Eccentric remodeling further worsens the loading conditions on the remaining myocytes and perpetuates the deleterious cycle. The idea of lowering wall stress to slow the process of remodeling has long been exploited in treating heart failure patients.3

However, the concept of the heart as a self-renewing organ is a relatively recent development.4 The rate of myocyte turnover has been shown to increase during times of pathologic stress.2 In heart failure, this mechanism for replacement becomes overwhelmed by an even faster increase in the rate of myocyte loss. This imbalance of hypertrophy and death over regeneration is the final common pathway at the cellular level for the progression of remodeling and heart failure. This new paradigm for myocyte biology has created an entire field of research aimed directly at augmenting myocardial regeneration.

The reduction of cardiac output following myocardial injury sets into motion a cascade of hemodynamic and neurohormonal derangements that provoke activation of neuroendocrine systems, most notably the above-mentioned adrenergic systems and RAAS. The release of epinephrine and norepinephrine, along with the vasoactive substances endothelin-1 (ET-1) and vasopressin, causes vasoconstriction, which increases afterload, and, via an increase in cyclic adenosine monophosphate (cAMP), causes an increase in cytosolic calcium entry. The increased calcium entry into the myocytes augments myocardial contractility and impairs myocardial relaxation (lusitropy).

The calcium overload may also induce arrhythmias and lead to sudden death. The increase in afterload and myocardial contractility (known as inotropy) and the impairment in myocardial lusitropy lead to an increase in myocardial energy expenditure and a further decrease in cardiac output. The increase in myocardial energy expenditure leads to myocardial cell death/apoptosis, which results in heart failure and further reduction in cardiac output, perpetuating a cycle of further increased neurohumoral stimulation and further adverse hemodynamic and myocardial responses as described above.

In addition, the activation of the RAAS leads to salt and water retention, resulting in increased preload and further increases in myocardial energy expenditure. Increases in renin, mediated by decreased stretch of the glomerular afferent arteriole, reduced delivery of chloride to the macula densa and increased beta1-adrenergic activity as a response to decreased cardiac output. This results in an increase in angiotensin II (Ang II) levels and, in turn, aldosterone levels. This results in stimulation of the release of aldosterone. Ang II, along with ET-1, is crucial in maintaining effective intravascular homeostasis mediated by vasoconstriction and aldosterone-induced salt and water retention.

Research indicates that local cardiac Ang II production (which decreases lusitropy, increases inotropy, and increases afterload) leads to increased myocardial energy expenditure. Ang II has also been shown both in vitro and in vivo to increase the rate of myocyte apoptosis.5 In this fashion, Ang II has similar actions to norepinephrine in heart failure.

Ang II also mediates myocardial cellular hypertrophy and may promote progressive loss of myocardial function. The neurohumoral factors above lead to myocyte hypertrophy and interstitial fibrosis, resulting in increased myocardial volume and increased myocardial mass, as well as myocyte loss. As a result, the cardiac architecture changes, which in turn leads to further increase in myocardial volume and mass.

In the failing heart, increased myocardial volume is characterized by larger myocytes approaching the end of their life cycle. As more myocytes drop out, an increased load is placed on the remaining myocardium and this unfavorable environment is transmitted to the progenitor cells responsible for replacing lost myocytes. Progenitor cells become progressively less effective as the underlying pathologic process worsens and myocardial failure accelerates. These features, namely the increased myocardial volume and mass, along with a net loss of myocytes, are the hallmark of myocardial remodeling. This remodeling process leads to early adaptive mechanisms, such as augmentation of stroke volume (Starling mechanism) and decreased wall stress (Laplace mechanism), and later, maladaptive mechanisms such as increased myocardial oxygen demand, myocardial ischemia, impaired contractility, and arrhythmogenesis.

As heart failure advances, there is a relative decline in the counterregulatory effects of endogenous vasodilators, including nitric oxide (NO), prostaglandins (PGs), bradykinin (BK), atrial natriuretic peptide (ANP), and B-type natriuretic peptide (BNP). This occurs simultaneously with the increase in vasoconstrictor substances from the RAAS and adrenergic systems. This fosters further increases in vasoconstriction and thus preload and afterload, leading to cellular proliferation, adverse myocardial remodeling, and antinatriuresis with total body fluid excess and worsening congestive heart failure symptoms.

Both systolic and diastolic heart failure result in a decrease in stroke volume. This leads to activation of peripheral and central baroreflexes and chemoreflexes that are capable of eliciting marked increases in sympathetic nerve traffic. While there are commonalities in the neurohormonal responses to decreased stroke volume, the neurohormone-mediated events that follow have been most clearly elucidated for individuals with systolic heart failure. The ensuing elevation in plasma norepinephrine directly correlates with the degree of cardiac dysfunction and has significant prognostic implications. Norepinephrine, while directly toxic to cardiac myocytes, is also responsible for a variety of signal-transduction abnormalities, such as downregulation of beta1-adrenergic receptors, uncoupling of beta2-adrenergic receptors, and increased activity of inhibitory G-protein. Changes in beta1-adrenergic receptors result in overexpression and promote myocardial hypertrophy.

ANP and BNP are endogenously generated peptides activated in response to atrial and ventricular volume/pressure expansion. ANP and BNP are released from the atria and ventricles, respectively, and both promote vasodilation and natriuresis. Their hemodynamic effects are mediated by decreases in ventricular filling pressures, owing to reductions in cardiac preload and afterload. BNP, in particular, produces selective afferent arteriolar vasodilation and inhibits sodium reabsorption in the proximal convoluted tubule. BNP inhibits renin and aldosterone release and, therefore, adrenergic activation as well. Both ANP and BNP are elevated in chronic heart failure. BNP, in particular, has potentially important diagnostic, therapeutic, and prognostic implications.

Other vasoactive systems that play a role in the pathogenesis of heart failure include the endothelin (ET) receptor system, adenosine receptor system, vasopressin, and tumor necrosis factor-alpha (TNF-alpha). Endothelin, a substance produced by the vascular endothelium, may contribute to the regulation of myocardial function, vascular tone, and peripheral resistance in heart failure. Elevated levels of endothelin-1 (ET-1) closely correlate with the severity of heart failure. ET-1 is a potent vasoconstrictor and has exaggerated vasoconstrictor effects in the renal vasculature, reducing renal plasma blood flow, glomerular filtration rate (GFR), and sodium excretion.

TNF-alpha has been implicated in response to various infectious and inflammatory conditions. Elevations in TNF-alpha levels have been consistently observed in heart failure and seem to correlate with the degree of myocardial dysfunction. Experimental studies suggest that local production of TNF-alpha may have toxic effects on the myocardium, thus worsening myocardial systolic and diastolic function.

Thus, in individuals with systolic dysfunction, the neurohormonal responses to decreased stroke volume result in temporary improvement in systolic blood pressure and tissue perfusion. However, in all circumstances, the existing data support the notion that these neurohormonal responses contribute to the progression of myocardial dysfunction in the long term.

In diastolic heart failure (heart failure with normal ejection fraction [HFNEF]), the same pathophysiologic processes leading to decreased cardiac output that occur in systolic heart failure also occur, but they do so in response to a different set of hemodynamic and circulatory environmental factors that depress cardiac output.

In HFNEF, altered relaxation and increased stiffness of the ventricle (due to delayed calcium uptake by the myocyte sarcoplasmic reticulum and delayed calcium efflux from the myocyte) occur in response to an increase in ventricular afterload (pressure overload). The impaired relaxation of the ventricle leads to impaired diastolic filling of the left ventricle (LV).

An increase in LV chamber stiffness occurs secondary to any one of the following 3 mechanisms or to a combination thereof:

* A rise in filling pressure (ie, movement of the ventricle up along its pressure-volume curve to a steeper portion, as may occur in conditions such as volume overload secondary to acute valvular regurgitation or acute LV failure due to myocarditis)
* A shift to a steeper ventricular pressure-volume curve, occurring most commonly as a result of not only increased ventricular mass and wall thickness, as observed in aortic stenosis and long-standing hypertension, but also due to infiltrative disorders (such as amyloidosis), endomyocardial fibrosis, and myocardial ischemia
* A parallel upward displacement of the diastolic pressure-volume curve, generally referred to as a decrease in ventricular distensibility, usually caused by extrinsic compression of the ventricles.

Whereas volume overload, as observed in chronic aortic and/or mitral valvular regurgitant disease, shifts the entire diastolic pressure-volume curve to the right, indicating increased chamber stiffness, pressure overload that leads to concentric LV hypertrophy (as occurs in aortic stenosis, hypertension, and hypertrophic cardiomyopathy) shifts the diastolic pressure-volume curve to the left along its volume axis so that at any diastolic volume ventricular diastolic pressure is abnormally elevated, although chamber stiffness may or may not be altered. Increases in diastolic pressure lead to increased myocardial energy expenditure, remodeling of the ventricle, increased myocardial oxygen demand, myocardial ischemia, and eventual progression of the maladaptive mechanisms of the heart that lead to decompensated heart failure.

Another clinically important process in the development of heart failure is the generation of arrhythmias. While life-threatening rhythms are more common in ischemic versus nonischemic cardiomyopathy, arrhythmia imparts a significant burden in all forms of heart failure. In fact, some arrhythmias even perpetuate heart failure. The most significant of all rhythms associated with heart failure are the life-threatening ventricular arrhythmias. Structural substrates for ventricular arrhythmias common in heart failure, regardless of the underlying cause include (1) ventricular dilatation, (2) myocardial hypertrophy, and (3) myocardial fibrosis. At the cellular level, myocytes may be exposed to increased stretch, wall tension, catecholamines, ischemia, and electrolyte imbalance. The combination of these factors contributes to an increased incidence of arrhythmogenic sudden cardiac death in patients with heart failure.
Frequency
United States

* Heart failure is the fastest-growing clinical cardiac disease entity in the United States, affecting 2% of the population.
* In 2006, 1.1 million patients were admitted to the hospital for acute decompensated heart failure in the United States, almost double the number seen 15 years ago. In addition, 3.4 million visits for heart failure were outpatient.
* 550,000 new cases of heart failure are diagnosed and 300,000 deaths are caused by heart failure each year.
* The rehospitalization rates6 during the 6 months following discharge are as much as 50%.
* Nearly 2% of all hospital admissions in the United States are for decompensated heart failure, and heart failure is the most frequent cause of hospitalization in patients older than 65 years with an annual incidence of 10 per 1,000.
* The average duration of hospitalization is about 6 days.
* In 2008, the estimated total cost of heart failure in the United States was $37.2 billion. This represents 1-2% of all healthcare expenditures.
* For updated statistics and epidemiology please see the American Heart Association and National Institutes of Health official Web sites or published summaries.7

International

Heart failure is a worldwide problem, but little accurate financial data are available. As discussed elsewhere, the most common cause of heart failure in industrialized countries is ischemic cardiomyopathy. Other causes, including Chagas disease and valvular cardiomyopathy, assume a more important role in underdeveloped countries than in the United States. However, as underdeveloped countries urbanize and become more affluent, the rate of heart failure increases in concordance with rates of diabetes, hypertension, a more processed diet, and a more sedentary lifestyle. This was illustrated in a population study in Soweto, South Africa. As the community transformed into a more urban and westernized city, an increase in diabetes and hypertension was met with an increased rate of heart failure.8

In terms of treatment, a 2006 study of European nations showed few important international differences in uptake of key therapies amongst European countries with widely differing cultures and economic status for patients with heart failure. In contrast, studies of sub-Saharan Africa, where health care resources are more limited, have shown poor outcomes in certain populations.9 For instance, hypertensive heart failure carries a 25% one-year mortality in some countries and HIV-associated cardiomyopathy generally progresses to death within 100 days of diagnosis in patients who are not treated with antiretroviral drugs.

While data in developing countries is not as robust as in Western society, a few clear trends are apparent: (1) Causes tend to be largely nonischemic, (2) patients tend to present at a younger age, (3) outcomes are largely worse where health care resources are limited, and (4) isolated right heart failure tends to be more prominent with a variety of postulated causes from tuberculous pericardial disease to lung disease and pollution.

Mortality/Morbidity

In unselected samples from the community, rates of improvement in mortality have been about 20% in both short- and long-term followup between 1985 and 1995.10 This translated to a 6-month increase in survival. However, despite recent advances in the management of patients with heart failure, morbidity and mortality rates remain high, with an estimated 5-year mortality rate of 50%.

* Assigning figures for inpatient mortality rates is difficult because the causes and the severity of heart failure vary considerably. The most recent estimates of inpatient mortality rates indicate that death occurs in up to 5-20% of patients.
* Hypoxemia that occurs in decompensated heart failure, which may be severe, can result in diffuse end-organ damage including myocardial ischemia or myocardial infarction and hypoxic brain injury.
* Respiratory failure with hypercapnic respiratory acidosis may occur in severe decompensated heart failure, requiring mechanical ventilation if medical therapy is delayed or unsuccessful. Endotracheal intubation and mechanical ventilation are associated with their own risks, including aspiration (during the intubation process), mucosal trauma (more common with nasotracheal intubation than orotracheal intubation), and barotrauma.
* In patients with heart failure, the risk of cardiac sudden death from ventricular tachycardia (VT) or ventricular fibrillation (VF) is considerable, and the degree of risk is correlated with the degree of decompensation and the degree of LV dysfunction. Recognition of the role of ventricular arrhythmias and advances in their treatment have resulted in decreased mortality rates in individuals with heart failure.
* Progressive renal insufficiency is common in patients with long-standing heart failure as well as acutely decompensated heart failure. Furthermore, renal function is at least as powerful an adverse prognostic factor as most clinical variables, including ejection fraction and New York Heart Association (NYHA) function class. Although renal dysfunction predicts all-cause mortality, it is most predictive of death from progressive heart failure, which suggests that it is a manifestation of and/or exacerbating factor for left ventricular dysfunction.11
* Liver dysfunction due to passive hepatic congestion is particularly common in patients with right-sided heart failure with elevated right ventricular (RV) pressure that is transmitted back into the portal vein.
o Mild jaundice, mild abnormalities in coagulation, and derangements in liver metabolism of medications, some of which are used in the treatment of heart failure, may result from this liver dysfunction.
o Toxic levels of medications such as warfarin, theophylline, phenytoin, and digoxin can result from delayed liver metabolic clearance of these drugs in the presence of decompensated heart failure, thereby leading to potentially fatal bleeding, cardiac dysrhythmias, and neurologic abnormalities.
* Patients with heart failure have high rates of depression compared with the general population; in addition, depression may confer a negative prognostic impact when present in patients with heart failure, with an increased risk of both rehospitalization and mortality. Reported prevalence rates have ranged from 11-25% for outpatients and 35-70% for inpatients. Even more so than in the general population, depression in heart failure patients goes largely untreated with published rates of around 7% of patients with heart failure who are clinically depressed receiving antidepressant medication.12

Race

The incidence and prevalence of heart failure are higher in African Americans, Hispanics, Native Americans, and recent immigrants from nonindustrialized nations, Russia, and the former Soviet republics.

* The higher prevalence of heart failure in African Americans, Hispanics, and Native Americans is directly related to the higher incidence and prevalence of hypertension and diabetes. This problem is particularly exacerbated by a lack of access to health care and to substandard preventive health care of the most indigent of these and other groups; many persons within these groups are without adequate health insurance coverage.
* The higher incidence and prevalence of heart failure among recent immigrants from nonindustrialized nations is largely due to a lack of prior preventive health care and to a lack of treatment or to substandard treatment for common conditions such as hypertension, diabetes, rheumatic fever, and ischemic heart disease.

Sex

Men and women have equivalent incidence and prevalence of heart failure. However, many differences between men and women are observed.

* Women tend to develop heart failure later in life.
* Women are more likely to have preserved systolic function.
* Women develop depression more commonly than men.
* Women have similar, but more pronounced, signs and symptoms.
* Women survive longer with heart failure than men do.

Age

The prevalence of heart failure increases with age. The prevalence is 1-2% of the population younger than 55 years and increases dramatically to a rate of 10% of those older than 75 years. Nonetheless, heart failure can occur at any age, depending on the cause.
Clinical
History

The NYHA classification of heart failure (see Staging), which varies slightly from the above categorization of heart failure symptoms, is widely used in practice and in clinical studies to quantify clinical assessment of heart failure. Breathlessness, a cardinal symptom of LV failure, may manifest with progressively increasing severity as (1) exertional dyspnea, (2) orthopnea, (3) paroxysmal nocturnal dyspnea, (4) dyspnea at rest, and (5) acute pulmonary edema. Other cardiac symptoms of heart failure include chest pain/pressure and palpitations. Patients often manifest noncardiac symptoms of heart failure like anorexia, nausea, weight loss, bloating, fatigue, weakness, oliguria, nocturia, and cerebral symptoms of different severity ranging from anxiety to memory impairment and confusion.

* Exertional dyspnea
o The principal difference between exertional dyspnea in patients who are healthy and exertional dyspnea in patients with heart failure is the degree of activity necessary to induce the symptom. As heart failure first develops, exertional dyspnea may simply appear to be an aggravation of the breathlessness that occurs in healthy persons during activity.
o As LV failure advances, the intensity of exercise resulting in breathlessness progressively declines; however, subjective exercise capacity and objective measures of LV performance at rest in patients with heart failure are not closely correlated. Exertional dyspnea, in fact, may be absent in sedentary patients.
* Orthopnea
o This early symptom of heart failure may be defined as dyspnea that develops in the recumbent position and is relieved with elevation of the head with pillows. As in the case of exertional dyspnea, the change in the number of pillows required is important.
o In the recumbent position, decreased pooling of blood in the lower extremities and abdomen occurs. Blood is displaced from the extrathoracic to the thoracic compartment. The failing LV, operating on the flat portion of the Frank-Starling curve, cannot accept and pump out the extra volume of blood delivered to it without dilating. As a result, pulmonary venous and capillary pressures rise further, causing interstitial pulmonary edema, reduced pulmonary compliance, increased airway resistance, and dyspnea.
o Orthopnea occurs rapidly, often within a minute or two of recumbency, and develops when the patient is awake. Orthopnea may occur in any condition in which the vital capacity is low. Marked ascites, whatever its etiology, is an important cause of orthopnea. In advanced LV failure, orthopnea may be so severe that the patient cannot lie down and must sleep sitting up in a chair or slumped over a table.
o Cough, particularly during recumbency, may be an "orthopnea equivalent." This nonproductive cough may be caused by pulmonary congestion and is relieved by the treatment of heart failure.
* Paroxysmal nocturnal dyspnea
o Paroxysmal nocturnal dyspnea usually occurs at night and is defined as the sudden awakening of the patient, after a couple hours of sleep, with a feeling of severe anxiety, breathlessness, and suffocation. The patient may bolt upright in bed and gasp for breath. Bronchospasm increases ventilatory difficulty and the work of breathing and is a common complicating factor of paroxysmal nocturnal dyspnea. On chest auscultation, the bronchospasm associated with a heart failure exacerbation can be difficult to distinguish from an acute asthma exacerbation, although other clues from the cardiovascular examination should lead the examiner to the correct diagnosis. Both types of bronchospasm can be present in the same individual.
o In contrast to orthopnea, which may be relieved by immediately sitting up in bed, paroxysmal nocturnal dyspnea may require 30 minutes or longer in this position for relief. Episodes of this may be so frightening that the patient may be afraid to resume sleeping, even after the symptoms have abated.
* Dyspnea at rest is the result of the following mechanisms:
o Decreased pulmonary function
+ Decreased compliance
+ Increased airway resistance
o Increased ventilatory drive
+ Hypoxemia due to increased pulmonary capillary wedge pressure (PCWP)
+ Ventilation/perfusion (V/Q) mismatching due to increased PCWP and cardiac output
+ Increased carbon dioxide production
o Respiratory muscle dysfunction
+ Decreased respiratory muscle strength
+ Decreased endurance
+ Ischemia
* Acute pulmonary edema is defined as the sudden increase in pulmonary capillary pressure (usually more than 25 mm Hg) as a result of acute and fulminant left ventricular failure. It is a medical emergency and has a very dramatic clinical presentation. Patient appears extremely ill, poorly perfused, restless, sweaty, with an increased work of breathing and using respiratory accessory muscles, tachypneic, tachycardic, hypoxic and coughing with frothy sputum that on occasion is blood tinged.
* Chest pain/pressure may occur as a result of either primary myocardial ischemia from coronary disease or secondary myocardial ischemia from increased filling pressure, poor cardiac output and therefore poor coronary diastolic filling, or hypotension and hypoxemia.
* Palpitations are the sensation a patient has when the heart is racing. It can be secondary to sinus tachycardia due to decompensated heart failure, or more common due to atrial or ventricular tachyarrhythmias.
* Fatigue and weakness
o These symptoms are often accompanied by a feeling of heaviness in the limbs.
o Fatigue and weakness are generally related to poor perfusion of the skeletal muscles in patients with a lowered cardiac output. Although generally a constant feature of advanced heart failure, episodic fatigue and weakness are common in earlier stages.
* Nocturia
o Nocturia may occur relatively early in the course of heart failure. Recumbency reduces the deficit in cardiac output in relation to oxygen demand; renal vasoconstriction diminishes and urine formation increases. This may be troublesome for the patient with heart failure because it may prevent the patient from obtaining much-needed rest.
o Oliguria is a late finding in heart failure and is found in patients with markedly reduced cardiac output from severely reduced LV function.
* Cerebral symptoms: Confusion, memory impairment, anxiety, headaches, insomnia, bad dreams or nightmares, and, rarely, psychosis with disorientation, delirium, or hallucinations may occur in elderly patients with advanced heart failure, particularly in those with cerebrovascular atherosclerosis.
* Predominant right-sided heart failure
o Ascites, congestive hepatomegaly, and anasarca due to elevated right-sided heart pressures transmitted backward into the portal vein circulation may result in increased abdominal girth and epigastric and right upper quadrant (RUQ) abdominal pain. Other gastrointestinal symptoms, caused by congestion of the hepatic and gastrointestinal venous circulation, include anorexia, bloating, nausea, and constipation. In preterminal heart failure, inadequate bowel perfusion can cause abdominal pain, distention, and bloody stools. Distinguishing right-sided heart failure from hepatic failure is often clinically difficult.
o Dyspnea, prominent in LV failure, becomes less prominent in isolated right-sided heart failure because of the absence of pulmonary congestion. On the other hand, when cardiac output becomes markedly reduced in patients with terminal right-sided heart failure (as may occur in isolated RV infarction and in the late stages of primary pulmonary hypertension and pulmonary thromboembolic disease), severe dyspnea may occur as a consequence of the reduced cardiac output, poor perfusion of respiratory muscles, hypoxemia, and metabolic acidosis.

Physical

* General appearance
o Patients with mild heart failure appear to be in no distress after a few minutes of rest, but they may be obviously dyspneic during and immediately after moderate activity. Patients with LV failure may be dyspneic when lying flat without elevation of the head for more than a few minutes. Those with severe heart failure appear anxious and may exhibit signs of air hunger in this position.
o Patients with recent onset of heart failure are generally well nourished, but those with chronic severe heart failure are often malnourished and sometimes even cachectic.
o Chronic marked elevation of systemic venous pressure may produce exophthalmos and severe tricuspid regurgitation and may lead to visible pulsation of the eyes and of the neck veins.
o Central cyanosis, icterus, and malar flush may be evident in patients with severe heart failure.
o In mild or moderate heart failure, stroke volume is normal at rest; in severe heart failure, it is reduced, as reflected by a diminished pulse pressure and a dusky discoloration of the skin.
o With very severe heart failure, particularly if cardiac output has declined acutely, systolic arterial pressure may be reduced. The pulse may be weak, rapid, and thready; the proportional pulse pressure (pulse pressure/systolic pressure) may be markedly reduced. The proportional pulse pressure correlates reasonably well with cardiac output. In one study, when pulse pressure was less than 25%, it usually reflected a cardiac index of less than 2.2 L/min/m2.
* Evidence of increased adrenergic activity
o Increased adrenergic activity is manifested by tachycardia, diaphoresis, pallor, peripheral cyanosis with pallor and coldness of the extremities, and obvious distention of the peripheral veins secondary to venoconstriction.
o Diastolic arterial pressure may be slightly elevated.
* Pulmonary rales
o Rales heard over the lung bases are characteristic of heart failure of at least moderate severity. With acute pulmonary edema, rales are frequently accompanied by wheezing and expectoration of frothy, blood-tinged sputum.
o The absence of rales certainly does not exclude elevation of pulmonary capillary pressure due to LV failure.
* Systemic venous hypertension: This is manifested by jugular venous distention. Normally, jugular venous pressure declines with respiration; however, it increases in patients with heart failure, a finding known as the Kussmaul sign (also found in constrictive pericarditis). This reflects an increase in right atrial pressure and therefore right-sided heart failure.
* Hepatojugular reflux: This represents distension of the jugular vein induced by applying manual pressure over the liver. The patient's body should be positioned at a 45 º angle. This is found in patients with elevated left-sided filling pressures and reflects elevated capillary wedge pressure and left-sided heart failure.
* Edema
o Although a cardinal manifestation of heart failure, edema does not correlate well with the level of systemic venous pressure. In patients with chronic LV failure and low cardiac output, extracellular fluid volume may be sufficiently expanded to cause edema in the presence of only slight elevations in systemic venous pressure.
o Usually, a substantial gain of extracellular fluid volume (ie, a minimum of 5 L in adults) must occur before peripheral edema is manifested.
o Edema, in the absence of dyspnea or other signs of LV or RV failure, is not solely indicative of heart failure and can be observed in many other conditions, including chronic venous insufficiency, nephrotic syndrome, or other syndromes of hypoproteinemia or osmotic imbalance.
* Hepatomegaly
o Hepatomegaly is prominent in patients with chronic right-sided heart failure, but it may occur rapidly in acute heart failure.
o When occurring acutely, the liver is usually tender.
o In patients with considerable tricuspid regurgitation, a prominent systolic pulsation of the liver, attributable to an enlarged right atrial V wave, is often noted. A presystolic pulsation of the liver, attributable to an enlarged right atrial A wave, can occur in tricuspid stenosis, constrictive pericarditis, restrictive cardiomyopathy involving the RV, and pulmonary hypertension (primary or secondary).
* Hydrothorax (pleural effusion)
o Hydrothorax is most commonly observed in patients with hypertension involving both systemic and pulmonary systems. Hydrothorax is usually bilateral, although when unilateral, it is usually confined to the right side of the chest.
o When hydrothorax develops, dyspnea usually intensifies because of further reductions in vital capacity.
* Ascites
o This finding occurs in patients with increased pressure in the hepatic veins and in the veins draining into the peritoneum.
o Ascites usually reflects long-standing systemic venous hypertension.
* Protodiastolic (S3) gallop: This is the earliest cardiac physical finding in decompensated heart failure in the absence of severe mitral or tricuspid regurgitation or left-to-right shunts.
* Cardiomegaly
o A nonspecific finding, cardiomegaly nonetheless occurs in most patients with chronic heart failure.
o Notable exceptions include heart failure from acute myocardial infarction, constrictive pericarditis, restrictive cardiomyopathy, valve or chordae tendineae rupture, or heart failure due to tachyarrhythmias or bradyarrhythmias.
* Pulsus alternans (during pulse palpation, this is the alternation of one strong and one weak beat without a change in the cycle length)
* Pulsus alternans occurs most commonly in heart failure due to increased resistance to LV ejection, as occurs in hypertension, aortic stenosis, coronary atherosclerosis, and dilated cardiomyopathy.
o It is usually associated with an S3 gallop, signifies advanced myocardial disease, and often disappears with treatment of heart failure.
* Accentuation of P2 heart sound, S3 gallop, and systolic murmurs
o This accentuation is a cardinal sign of increased pulmonary artery pressure. It disappears or improves after treatment of heart failure.
o Mitral and tricuspid regurgitation murmurs are often present in patients with decompensated heart failure because of ventricular dilatation. These murmurs often disappear or diminish when compensation is restored. Note that correlation between the intensity of the murmur of mitral regurgitation and its significance in patients with heart failure is poor. Severe mitral regurgitation may be accompanied by an unimpressively soft murmur.
o The presence of an S3 gallop in adults is important, pathologic, and often the most apparent finding on cardiac auscultation in patients with significant heart failure.
* Cardiac cachexia
o Cardiac cachexia is found in long-standing heart failure, particularly of the RV, because of anorexia from hepatic and intestinal congestion and sometimes because of digitalis toxicity. Occasionally, impaired intestinal absorption of fat and (rarely) protein-losing enteropathy occur.
o Patients with heart failure may also exhibit increased total metabolism secondary to augmentation of myocardial oxygen consumption, excessive work of breathing, low-grade fever, and elevated levels of circulating TNF.
* Fever: Fever may be present in severe decompensated heart failure because of cutaneous vasoconstriction and impairment of heat loss.

Causes

From a clinical standpoint, classifying the causes of heart failure into 3 broad categories is useful: (1) underlying causes, comprising structural abnormalities (congenital or acquired) that affect the peripheral and coronary arterial circulation, pericardium, myocardium, or cardiac valves, thus leading to the increased hemodynamic burden or myocardial or coronary insufficiency responsible for heart failure; (2) fundamental causes, comprising the biochemical and physiological mechanisms, through which either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction; and (3) precipitating causes.

Note that most patients who present with significant heart failure do so because of an inability to provide adequate cardiac output in that setting. This is often a combination of the causes listed above in the setting of an abnormal myocardium. The list of causes responsible for presentation of a patient with a congestive heart failure exacerbation is very long, and searching for the proximate cause to optimize therapeutic interventions is important.

Overt heart failure may be precipitated by progression of the underlying heart disease. A previously stable compensated patient may develop heart failure that is clinically apparent for the first time when the intrinsic process has advanced to a critical point, such as with further narrowing of a stenotic aortic valve or mitral valve. Alternatively, decompensation may occur as a result of failure or exhaustion of the compensatory mechanisms but without any change in the load on the heart in patients with persistent severe pressure or volume overload.

* Precipitating causes of heart failure
o Inappropriate reduction of therapy: The most common cause of decompensation in a previously compensated patient with heart failure is inappropriate reduction in the intensity of treatment, whether dietary sodium restriction, physical activity reduction, drug regimen reduction, or, most commonly, a combination of these measures.
o Arrhythmias
+ Tachyarrhythmias, most commonly atrial fibrillation
+ Marked bradycardia
+ Atrioventricular dissociation
+ Abnormal intraventricular conduction
o Systemic infection or development of unrelated illness
+ Systemic infection precipitates heart failure by increasing total metabolism as a consequence of fever, discomfort, and cough, which increases the hemodynamic burden on the heart.
+ Septic shock, in particular, can precipitate heart failure by the release of endotoxin-induced factors that can depress myocardial contractility.
o Pulmonary embolism: Patients with heart failure, particularly when confined to bed, are at high risk of developing pulmonary emboli, which can increase the hemodynamic burden on the RV by further elevating RV systolic pressure, possibly causing fever, tachypnea, and tachycardia.
o Physical, environmental, and emotional excesses: Intense, prolonged physical exertion or severe fatigue, such as may result from prolonged travel or emotional crises, or severe climate changes, either to a hot, humid environment or to a bitterly cold environment, are relatively common precipitants of cardiac decompensation.
o Cardiac infection and inflammation
+ Myocarditis or infective endocarditis may directly impair myocardial function and exacerbate existing heart disease. The anemia, fever, and tachycardia that frequently accompany these processes are also deleterious.
+ In the case of infective endocarditis, the additional valvular damage that ensues may precipitate cardiac decompensation.
o Excessive intake of water and/or sodium
o Administration of cardiac depressants or drugs that cause salt retention
o High-output states: Profound anemia, thyrotoxicosis, myxedema, Paget disease of bone, Albright syndrome, multiple myeloma, glomerulonephritis, cor pulmonale, polycythemia vera, obesity, carcinoid syndrome, pregnancy, or nutritional deficiencies (eg, thiamine deficiency, beriberi) can precipitate the clinical presentation of heart failure because of increased myocardial oxygen consumption and demand beyond a critical level (ie, beyond the ability of the underlying myocardial oxygen supply to meet these demands). In particular, consider whether the patient has underlying coronary artery disease or valvular heart disease.
o Development of a second form of heart disease
+ Patients with one form of underlying heart disease that may be well compensated can develop heart failure when a second form of heart disease ensues.
+ For example, a patient with chronic hypertension and asymptomatic LV hypertrophy may be asymptomatic until a myocardial infarction develops and precipitates heart failure.
* Underlying causes
o Systolic heart failure
+ Coronary artery disease
+ Diabetes mellitus
+ Hypertension
+ Valvular heart disease (stenosis or regurgitant lesions)
+ Arrhythmia (supraventricular or ventricular)
+ Infections and inflammation (myocarditis)
+ Peripartum cardiomyopathy
+ Congenital heart disease
+ Drug induced (either recreational like alcohol and cocaine, or therapeutic drugs with cardiac side effects like doxorubicin)
+ Idiopathic cardiomyopathy
+ Rare conditions (endocrine abnormalities, rheumatologic disease, neuromuscular conditions)
o Diastolic heart failure
+ Coronary artery disease
+ Diabetes mellitus
+ Hypertension
+ Valvular disease (aortic stenosis)
+ Hypertrophic cardiomyopathy
+ Restrictive cardiomyopathy (amyloidosis)
+ Constrictive pericarditis
o Acute heart failure
+ Acute valvular (mitral or aortic) regurgitation
+ Myocardial infarction
+ Myocarditis
+ Arrhythmia
+ Drug induced (eg, cocaine, calcium channel blocker or beta-blocker overdose)
+ Sepsis
o High-output heart failure
+ Anemia
+ Systemic arteriovenous fistulas
+ Hyperthyroidism
+ Beriberi heart disease
+ Paget disease of bone
+ Albright syndrome (fibrous dysplasia)
+ Multiple myeloma
+ Pregnancy
+ Glomerulonephritis
+ Polycythemia vera
+ Carcinoid syndrome
o Right heart failure
+ Left ventricular failure
+ Coronary artery disease (ischemia)
+ Pulmonary hypertension
+ Pulmonary valve stenosis
+ Pulmonary embolism
+ Chronic pulmonary disease
+ Neuromuscular disease

http://emedicine.medscape.com/article/163062-overview