Heart Failure

Pathophysiology

The common pathophysiologic state that perpetuates the progression of heart failure is extremely complex, regardless of the precipitating event. Compensatory mechanisms exist on every level of organization, from the subcellular all the way through to organ-to-organ interactions. Only when this network of adaptations becomes overwhelmed does heart failure ensue.^{[7, 8, 9, 10, 11]}

Adaptations

Most important among the adaptations are the following^[12]:

The Frank-Starling mechanism, in which an increased preload helps to sustain cardiac performance
Alterations in myocyte regeneration and death
Myocardial hypertrophy with or without cardiac chamber dilatation, in which the mass of contractile tissue is augmented
Activation of neurohumoral systems

The release of norepinephrine by adrenergic cardiac nerves augments myocardial contractility and includes activation of the renin-angiotensin-aldosterone system [RAAS], the 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.^[13]

The primary myocardial response to chronic increased wall stress is myocyte hypertrophy, death/apoptosis, and regeneration.^[14]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.^[15]

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.^[16]

The release of epinephrine and norepinephrine, along with the vasoactive substances endothelin-1 (ET-1) and vasopressin, causes vasoconstriction, which increases calcium 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 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.

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 a decreased stretch of the glomerular afferent arteriole, reduce delivery of chloride to the macula densa and increase 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, causing stimulation of the release of aldosterone. Ang II, along with ET-1, is crucial in maintaining effective intravascular homeostasis as mediated by vasoconstriction and aldosterone-induced salt and water retention.

The concept of the heart as a self-renewing organ is a relatively recent development.^[17]This paradigm for myocyte biology created an entire field of research aimed directly at augmenting myocardial regeneration. The rate of myocyte turnover has been shown to increase during times of pathologic stress.^[14]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.

Angiotensin II

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 in vitro and in vivo to increase the rate of myocyte apoptosis.^[18]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.

Myocytes and myocardial remodeling

In the failing heart, increased myocardial volume is characterized by larger myocytes approaching the end of their life cycle.^[19]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 (Frank-Starling mechanism) and decreased wall stress (Laplace law) and, later, to 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 decline occurs simultaneously with the increase in vasoconstrictor substances from the RAAS and the adrenergic system, which fosters further increases in vasoconstriction and thus preload and afterload. This results in cellular proliferation, adverse myocardial remodeling, and antinatriuresis, with total body fluid excess and worsening of heart failure symptoms.

Systolic and diastolic failure

Systolic and diastolic heart failure each result in a decrease in stroke volume.^{[20, 21]}This leads to activation of peripheral and central baroreflexes and chemoreflexes that are capable of eliciting marked increases in sympathetic nerve traffic.

Although 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.

Atrial natriuretic peptide and B-type natriuretic peptide

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. It also inhibits renin and aldosterone release and, therefore, adrenergic activation. ANP and BNP are elevated in chronic heart failure. BNP especially has potentially important diagnostic, therapeutic, and prognostic implications.

For more information, see the Medscape Drugs & Diseases article Natriuretic Peptides in Congestive Heart Failure.

Other vasoactive systems

Other vasoactive systems that play a role in the pathogenesis of heart failure include the ET receptor system, the adenosine receptor system, vasopressin, and tumor necrosis factor-alpha (TNF-alpha).^[22]ET, 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 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. Some studies suggest that local production of TNF-alpha may have toxic effects on the myocardium, thus worsening myocardial systolic and diastolic function.

In individuals with systolic dysfunction, therefore, 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.

Heart failure with preserved ejection fraction

In diastolic heart failure (heart failure with preserved ejection fraction [HFpEF]), the same pathophysiologic processes occur that lead to decreased cardiac output in systolic heart failure, but they do so in response to a different set of hemodynamic and circulatory environmental factors that depress cardiac output.^[23]

In HFpEF, 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 then leads to impaired diastolic filling of the left ventricle (LV).

Morris et al found that right venticular (RV) subendocardial systolic dysfunction and diastolic dysfunction, as detected by echocardiographic strain rate imaging, are common in patients with HFpEF. This dysfunction is potentially associated with the same fibrotic processes that affect the subendocardial layer of the LV and, to a lesser extent, with RV pressure overload. It may play a role in the symptomatology of patients with HFpEF.^[24]

LV chamber stiffness

An increase in LV chamber stiffness occurs secondary to any one, or any combination, of the following three mechanisms:

Rise in filling pressure
Shift to a steeper ventricular pressure-volume curve
Decrease in ventricular distensibility

A rise in filling pressure is the 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 results, most commonly, not only from increased ventricular mass and wall thickness (as observed in aortic stenosis and long-standing hypertension) but also from infiltrative disorders (eg, amyloidosis), endomyocardial fibrosis, and myocardial ischemia.

Parallel upward displacement of the diastolic pressure-volume curve is generally referred to as a decrease in ventricular distensibility. This is usually caused by extrinsic compression of the ventricles.

Concentric LV hypertrophy

Pressure overload that leads to concentric LV hypertrophy (LVH), as occurs in aortic stenosis, hypertension, and hypertrophic cardiomyopathy, shifts the diastolic pressure-volume curve to the left along its volume axis. As a result, ventricular diastolic pressure is abnormally elevated, although chamber stiffness may or may not be altered.

Increases in diastolic pressure lead to an 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.

Arrhythmias

Although life-threatening rhythms are more common in ischemic 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 that are common in heart failure, regardless of the underlying cause, include ventricular dilatatation, myocardial hypertrophy, and 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.

References

Etiology

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

From a clinical standpoint, classifying the causes of heart failure into the following four broad categories is useful:

Underlying causes: Underlying causes of heart failure include structural abnormalities (congenital or acquired) that affect the peripheral and coronary arterial circulation, pericardium, myocardium, or cardiac valves, thus leading to increased hemodynamic burden or myocardial or coronary insufficiency
Fundamental causes: Fundamental causes include biochemical and physiologic mechanisms, through which either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction
Precipitating causes: Overt heart failure may be precipitated by progression of the underlying heart disease (eg, further narrowing of a stenotic aortic valve or mitral valve) or various conditions (fever, anemia, infection) or medications (chemotherapy, nonsteroidal anti-inflammatory drugs [NSAIDs]) that alter the homeostasis of heart failure patients
Genetics of cardiomyopathy: Dilated, arrhythmic right ventricular and restrictive cardiomyopathies are known genetic causes of heart failure

Underlying causes

Specific underlying factors cause various forms of heart failure, such as systolic heart failure (most commonly, left vetricular [LV] systolic dysfunction), heart failure with preserved LV ejection fraction (LVEF), acute heart failure, high-output heart failure, and right heart failure.

Underlying causes of systolic heart failure include the following:

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
Drugs (either recreational, such as alcohol and cocaine, or therapeutic drugs with cardiac side effects, such as doxorubicin)
Idiopathic cardiomyopathy
Rare conditions (endocrine abnormalities, rheumatologic disease, neuromuscular conditions)

Underlying causes of diastolic heart failure include the following:

Coronary artery disease
Diabetes mellitus
Hypertension
Valvular heart disease (aortic stenosis)
Hypertrophic cardiomyopathy
Restrictive cardiomyopathy (amyloidosis, sarcoidosis)
Constrictive pericarditis

Underlying causes of acute heart failure include the following:

Acute valvular (mitral or aortic) regurgitation
Myocardial infarction (MI)
Myocarditis
Arrhythmia
Drugs (eg, cocaine, calcium channel blockers, or beta-blocker overdose)
Sepsis

Underlying causes of high-output heart failure include the following:

Anemia
Systemic arteriovenous fistulas
Hyperthyroidism
Beriberi heart disease
Paget disease of bone
Albright syndrome (fibrous dysplasia)
Multiple myeloma
Pregnancy
Glomerulonephritis
Polycythemia vera
Carcinoid syndrome

Underlying causes of right heart failure include the following:

LV failure
Coronary artery disease (ischemia)
Pulmonary hypertension
Pulmonary valve stenosis
Pulmonary embolism
Chronic pulmonary disease
Neuromuscular disease

Precipitating causes of heart failure

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 the 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. In particular, consider whether the patient has underlying coronary artery disease or valvular heart disease.

The most common cause of decompensation in a previously compensated patient with heart failure is inappropriate reduction in the intensity of treatment, such as dietary sodium restriction, physical activity reduction, or drug regimen reduction. Uncontrolled hypertension is the second most common cause of decompensation, followed closely by cardiac arrhythmias (most commonly, atrial fibrillation). Arrhythmias, particularly ventricular arrhythmias, can be life threatening. Also, 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 (LVH) may be asymptomatic until an MI develops and precipitates heart failure.

Systemic infection or the development of unrelated illness can also lead to heart failure. Systemic infection precipitates heart failure by increasing total metabolism as a consequence of fever, discomfort, and cough, increasing 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.

Cardiac infection and inflammation can also endanger the heart. 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.

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 right ventricle (RV) by further elevating RV systolic pressure, possibly causing fever, tachypnea, and tachycardia.

Intense, prolonged physical exertion or severe fatigue, such as may result from prolonged travel or emotional crisis, is a relatively common precipitant of cardiac decompensation. The same is true of exposure to severe climate change (ie, the individual comes in contact with a hot, humid environment or a bitterly cold one).

Excessive intake of water and/or salt and the administration of cardiac depressants or drugs that cause salt retention are other factors that can lead to heart failure. At the European Society of Cardiology 2017 Congress, investigators presented a study comprising more than 4630 people that indicated high daily salt intake (>13.7 g) is associated with a substantial increased risk of developing heart failure, independent of other risk factors.^{[25, 26]}

Because of increased myocardial oxygen consumption and demand beyond a critical level, the following high-output states can precipitate the clinical presentation of heart failure:

Profound anemia
Thyrotoxicosis
Myxedema
Paget disease of bone
Albright syndrome
Multiple myeloma
Glomerulonephritis
Cor pulmonale
Polycythemia vera
Obesity
Carcinoid syndrome
Pregnancy
Nutritional deficiencies (eg, thiamine deficiency, beriberi)

Longitudinal data from the Framingham Heart Study has suggested that antecedent subclinical LV systolic or diastolic dysfunction is associated with an increased incidence of heart failure, supporting the notion that heart failure is a progressive syndrome.^{[27, 28]}Another analysis of over 36,000 patients undergoing outpatient echocardiography reported that moderate or severe diastolic dysfunction, but not mild diastolic dysfunction, is an independent predictor of mortality.^[29]

Genetics of cardiomyopathy

Autosomal dominant inheritance has been demonstrated in dilated cardiomyopathy and in arrhythmic right ventricular cardiomyopathy. Restrictive cardiomyopathies are usually sporadic and associated with the gene for cardiac troponin I. Genetic tests are available at major genetic centers for cardiomyopathies.^[30]

In families with a first-degree relative who has been diagnosed with a cardiomyopathy leading to heart failure, the at-risk patient should be screened and followed.^[30]The recommended screening consists of an electrocardiogram and an echocardiogram. If the patient has an asymptomatic LV dysfunction, it should be documented and treated.^[30]

References

History

In evaluating patients with heart failure, the clinician should ask about the following comorbidities and/or risk factors:

Myopathy
Previous myocardial infarction
Valvular heart disease, familial heart disease
Alcohol use
Hypertension
Diabetes
Dyslipidemia
Coronary/peripheral vascular disease
Sleep-disordered breathing
Collagen vascular disease, rheumatic fever
Pheochromocytoma
Thyroid disease
Substance abuse (previous/current history)
History of chemotherapy/radiation to the chest

The New York Heart Association (NYHA) classification of heart failure is widely used in practice and in clinical studies to quantify clinical assessment of heart failure (see Heart Failure Criteria, Classification, and Staging). Breathlessness, a cardinal symptom of left ventricular (LV) failure, may manifest with progressively increasing severity as the following:

Exertional dyspnea
Orthopnea
Paroxysmal nocturnal dyspnea
Dyspnea at rest
Acute pulmonary edema

Other cardiac symptoms of heart failure include chest pain/pressure and palpitations. Common noncardiac signs and symptoms of heart failure include anorexia, nausea, weight loss, bloating, fatigue, weakness, oliguria, nocturia, and cerebral symptoms of varying severity, ranging from anxiety to memory impairment and confusion. Findings from the Framingham Heart Study suggested that subclinical cardiac dysfunction and noncardiac comorbidities are associated with increased incidence of heart failure, supporting the idea that heart failure is a progressive syndrome and that noncardiac factors are extremely important.^{[27, 28, 52]}

Older patients with heart failure frequently have preserved ejection fraction and an atypical and/or delayed presentation.^[53]

Exertional dyspnea

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, but 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

Orthopnea is an early symptom of heart failure and 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. In the recumbent position, decreased pooling of blood in the lower extremities and abdomen occurs. Blood is displaced from the extrathoracic compartment 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.

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, regardless of 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.

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

Paroxysmal nocturnal dyspnea usually occurs at night and is defined as the sudden awakening of the patient, after a couple of 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 a single individual.

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 may be so frightening that the patient may be afraid to resume sleeping, even after the symptoms have subsided.

Dyspnea at rest

Dyspnea at rest in heart failure is the result of the following mechanisms:

Decreased pulmonary function secondary to decreased compliance and increased airway resistance
Increased ventilatory drive secondary to hypoxemia due to increased pulmonary capillary wedge pressure (PCWP); ventilation/perfusion (V/Q) mismatching due to increased PCWP and low cardiac output; and increased carbon dioxide production
Respiratory muscle dysfunction, with decreased respiratory muscle strength, decreased endurance, and ischemia

Pulmonary edema

Acute pulmonary edema is defined as the sudden increase in PCWP (usually >25 mm Hg) as a result of acute and fulminant LV failure. It is a medical emergency and has a very dramatic clinical presentation. The patient appears extremely ill, poorly perfused, restless, sweaty, tachypneic, tachycardic, hypoxic, and coughing, with an increased work of breathing and using respiratory accessory muscles and with frothy sputum that on occasion is blood tinged.

Chest pain/pressure and palpitations

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 commonly, it is due to atrial or ventricular tachyarrhythmias.

Fatigue and weakness

Fatigue and weakness are often accompanied by a feeling of heaviness in the limbs and are generally related to poor perfusion of the skeletal muscles in patients with a lowered cardiac output. Although they are generally a constant feature of advanced heart failure, episodic fatigue and weakness are also common in earlier stages.

Nocturia and oliguria

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. Nocturia may be troublesome for patients with heart failure because it may prevent them from obtaining much-needed rest. Oliguria is a late finding in heart failure, and it is found in patients with markedly reduced cardiac output from severely reduced LV function.

Cerebral symptoms

The following may occur in elderly patients with advanced heart failure, particularly in those with cerebrovascular atherosclerosis:

Confusion
Memory impairment
Anxiety
Headaches
Insomnia
Bad dreams or nightmares
Rarely, psychosis with disorientation, delirium, or hallucinations

References

Physical Examination

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 left ventricular (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.

Patients with a recent onset of heart failure are generally well nourished, but those with chronic severe heart failure are often malnourished and sometimes even cachectic. Chronic marked elevation of the systemic venous pressure may produce exophthalmos and severe tricuspid regurgitation, and it may lead to visible pulsation of the eyes and of the neck veins. Central cyanosis, icterus, and malar flush may be evident in patients with severe heart failure.

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. 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.^[54]

Ascites occurs in patients with increased pressure in the hepatic veins and in the veins draining into the peritoneum; it usually reflects long-standing systemic venous hypertension. Fever may be present in severe decompensated heart failure because of cutaneous vasoconstriction and impairment of heat loss.

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. Diastolic arterial pressure may be slightly elevated.

Rales heard over the lung bases are characteristic of heart failure that is of at least moderate severity. With acute pulmonary edema, rales are frequently accompanied by wheezing and expectoration of frothy, blood-tinged sputum. The absence of rales does not exclude elevation of pulmonary capillary pressure due to LV failure.

Systemic venous hypertension 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. In general, elevated jugular venous pressure is the most reliable indicator of fluid volume overload in older patients, and thorough evaluation is needed.^[53]

The hepatojugular reflux is the distention of the jugular vein induced by applying manual pressure over the liver; the patient's torso should be positioned at a 45° angle. The hepatojugular reflux occurs in patients with elevated left-sided filling pressures and reflects elevated capillary wedge pressure and left-sided heart failure.

Although edema is a cardinal manifestation of heart failure, it 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. Usually, a substantial gain of extracellular fluid volume (ie, a minimum of 5 L in adults) must occur before peripheral edema develops. Edema in the absence of dyspnea or other signs of LV or right ventricular (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 is prominent in patients with chronic right-sided heart failure, but it may occur rapidly in acute heart failure. When hepatomegaly occurs acutely, the liver is usually tender. 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 right ventricle, and pulmonary hypertension (primary or secondary).

Hydrothorax is most commonly observed in patients with hypertension involving both the systemic and pulmonary circulation. It is usually bilateral, although when unilateral, it is usually confined to the right side of the chest. When hydrothorax develops, dyspnea usually intensifies because of further reductions in vital capacity.

Cardiac findings

Protodiastolic (S₃) gallop is the earliest cardiac physical finding in decompensated heart failure in the absence of severe mitral or tricuspid regurgitation or left-to-right shunts. 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.

Cardiomegaly is a nonspecific finding that nonetheless occurs in most patients with chronic heart failure. 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) occurs most commonly in heart failure due to increased resistance to LV ejection, as occurs in hypertension, aortic stenosis, coronary atherosclerosis, and dilated cardiomyopathy. Pulsus alternans is usually associated with an S₃ gallop, signifies advanced myocardial disease, and often disappears with treatment of heart failure.

Accentuation of the P₂ heart sound is a cardinal sign of increased pulmonary artery pressure; it disappears or improves after treatment of heart failure. Mitral and tricuspid regurgitation murmurs are often present in patients with decompensated heart failure because of ventricular dilatatation. These murmurs often disappear or diminish when compensation is restored. Note that the correlation is poor between the intensity of the murmur of mitral regurgitation and its significance in patients with heart failure. Severe mitral regurgitation may be accompanied by an unimpressively soft murmur.

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 occurs and, rarely, protein-losing enteropathy occurs. 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 tumor necrosis factor (TNF).

References

Approach Considerations

Medical care for heart failure includes a number of nonpharmacologic, pharmacologic, and invasive strategies to limit and reverse its manifestations.^{[3, 4, 105]} Depending on the severity of the illness, nonpharmacologic therapies include dietary sodium and fluid restriction; physical activity as appropriate; and attention to weight gain. Pharmacologic therapies include the use of diuretics, vasodilators, inotropic agents, anticoagulants, beta-blockers, and digoxin.

Invasive therapies for heart failure include electrophysiologic intervention such as cardiac resynchronization therapy (CRT), pacemakers, and implantable cardioverter-defibrillators (ICDs); revascularization procedures such as coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI); valve replacement or repair; and ventricular restoration.^{[3, 4, 56, 58, 105]}

Heart transplantation has been the criterion standard for therapy when progressive end-stage heart failure occurs despite maximal medical therapy, when the prognosis is poor, and when there is no viable therapeutic alternative.^{[3, 4, 5]} However, mechanical circulatory devices such as ventricular assist devices (VADs) and total artificial hearts (TAHs) can bridge the patient to transplantation; in addition, VADs are increasingly being used as permanent therapy.^[4]

Comorbidities to consider

Coronary artery disease

Patients with heart failure should be evaluated for coronary artery disease, which can lead to heart failure (see Etiology). Not only may this condition be the underlying cause in up to two thirds of heart failure patients with low ejection fraction, but coronary artery disease may also play a role in the progression of heart failure through mechanisms such as endothelial dysfunction, ischemia, and infarction, among others.^[3]

Patients with coronary artery disease with modestly reduced ejection fraction and angina have demonstrated symptomatic and survival improvement with coronary artery bypass grafting (CABG) in studies; however, the trials did not include individuals with heart failure or those with severely reduced ejection fractions.^[3] In patients with angina and ventricular dysfunction, evaluation with coronary angiography should not be delayed (see Catheterization and Angiography). Noninvasive cardiac testing is not recommended in patients with significant ischemic chest pain, as revascularization is advised in these patients independent of their degree of ischemia/viability.^[3]

Although there are no reports of controlled trials evaluating heart failure without angina and their outcomes with coronary revascularization, surgical revascularization is recommended in those with significant left main stenosis and in those with extensive noninfarcted but hypoperfused and hypocontractile myocardium on noninvasive testing.^[3] In patients with heart failure and reduced left ventricular (LV) ejection fraction but without angina, it has not yet been determined whether routine evaluation of possible myocardial ischemia/viability and coronary artery disease should be performed.^[3]

For patients with heart failure from LV dysfunction without chest pain and without a history of coronary artery disease, coronary angiography may be useful in young patients to exclude congenital coronary anomalies. However, because clinical outcomes have not been shown to improve in patients without angina, coronary angiography may not be as useful in older patients for evaluating the presence of coronary artery disease.^[3]Some experts nonetheless suggest excluding coronary artery disease whenever possible, particularly in the presence of diabetes or other conditions associated with silent myocardial ischemia, because LV function may show improvement with revascularization.^[3]

In general, if coronary artery disease has already been excluded as the cause of abnormalities in LV function, it is not necessary to perform repeated evaluations for ischemia (invasive or noninvasive) provided the patient’s clinical status has not changed to suggest the development of ischemic disease.^[3]

For more information, see the Medscape Drugs & Diseases articles Primary and Secondary Prevention of Coronary Artery Disease, Risk Factors for Coronary Artery Disease, and Coronary Artery Atherosclerosis.

Valvular heart disease

Valvular heart disease may be the underlying etiology or an important aggravating factor in heart failure.^{[3, 4, 5]}

Sleep apnea

Sleep apnea has an increased prevalence in patients with heart failure and is associated with increased mortality^[4]due to further neurohormonal activation, although randomized, controlled data are lacking. Patients with heart failure and suspected sleep-disordered breathing or excessive daytime sleepiness should undergo a formal sleep assessment.^[56]^[105]

Sleep apnea should be treated aggressively in heart failure patients. Guidelines recommend providing oxygen supplementation and continuous positive airway pressure (CPAP).^{[4, 56, 105]} However, the recommendations differ on the use of adaptive servo-ventilation (ASV): The 2017 focused update guideline of the 2013 American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA) guidelines indicates ASV causes harm in patients with New York Heart Association (NYHA) class II-IV heart failure with reduced ejection fraction (HFpEF) and central sleep apnea,^[56] whereas the 2016 European Society of Cardiology (ESC) indicates that ASV may be considered for treating noctural hypoxemia in those with heart failure and sleep apnea.^[4]

A long-term study involving 283 heart failure patients who had an implanted cardiac resynchronization device with cardioverter-defibrillator concluded that obstructive sleep apnea (OSA) and/or central sleep apnea (CSA) are independently associated with an increased risk for ventricular arrhythmias requiring cardioverter-defibrillator therapies.^[106]

Anemia

Anemia is also common in chronic heart failure. Whether anemia is a reflection of the severity of the heart failure or contributes to worsening heart failure is not clear. Potential etiologies of anemia in heart failure involve poor nutrition, angiotensin-converting enzyme inhibitors (ACEIs), the renin-angiotensin-aldosterone system (RAAS), inflammatory cytokines, hemodilution, and renal dysfunction. Anemia in heart failure is associated with increased mortality.^[107]

The 2010 HFSA,^[5] 2013 ACC Foundation (ACCF)/AHA,^[3]2016 ACC/AHA/HFSA,^[58]and 2016 ESC guidelines^[4] made no recommendations regarding the administration of iron to patients with heart failure, although the ACC/AHA noted that several small studies suggested a benefit in mild anemia and heart failure,^[3] and the ESC observed that intravenous (IV) ferric carboxymaltose may potentially lead to sustainable improvements in function, symptoms, and quality of life.^[4] However, the ACC/AHA's 2017 focused update to the 2013 guidelines has a class IIb recommendation for IV iron replacement for patients with NYHA class II and III heart failure and iron deficiency (ferritin < 100 ng/mL or 100-300 ng/mL if transferrin saturation < 20%).^[56] In addition, their class III recommendation is to avoid using erythropoietin-stimulating agents in patients with heart failure and anemia to improve morbidity and mortality owing to a lack of benefit.^[56]

Cardiorenal syndrome

Cardiorenal syndrome reflects advanced cardiorenal dysregulation manifested by acute heart failure, worsening renal function, and diuretic resistance. It is equally prevalent in patients with HFpEF and those with LV systolic dysfunction. Worsening renal function is one of the three predictors of increased mortality in hospitalized patients with heart failure regardless of the LVEF.

Cardiorenal syndrome can be classified into the following five types^[108]:

CR1: Rapid worsening of cardiac function leading to acute kidney injury (HFpEF, acute heart failure, cardiogenic shock, and right ventricular [RV] failure)
CR2: Worsening renal function due to progression of chronic heart failure
CR3: Abrupt and primary worsening of kidney function leading to acute cardiac dysfunction (heart failure, arrhythmia, ischemia)
CR4: Chronic kidney disease leading to progressive cardiac dysfunction, LV hypertrophy (LVH), and diastolic dysfunction
CR5: Combination of cardiac and renal dysfunction due to acute and chronic systemic conditions

The pathophysiology of CR1 and CR2 is complex and multifactorial, involving neurohormonal activation (RAAS, sympathetic nervous system, arginine vasopressin, natriuretic peptides, adenosine receptor activation), low arterial pressure, and high central venous pressure, leading to lower transglomerular perfusion pressure and decreased availability of diuretics to the proximal nephron. This results in an increased reabsorption of sodium and water and poor diuretic response—hence, diuretic resistance despite escalating doses of oral or IV diuretics.

Treatment of cardiorenal syndrome in patients with heart failure is largely empirical, but it typically involves the use of combination diuretics, vasodilators, and inotropes as indicated.^[109] Ultrafiltration is recommended for symptomatic relief by the ACC/AHA guidelines for patients with heart failure that is refractory to diuretic therapy.^{[3, 56]} The 2017 ACC/AHA focused update noted the following five criteria may be indications for renal replacement therapy in these patients^[56]:

Oliguria unresponsive to fluid resuscitation measures
Severe hyperkalaemia (potassium level >6.5 mmol/L)
Severe acidemia (pH < 7.2)
Serum urea level above 25 mmol/L (150 mg/dL)
Serum creatinine over 300 µmol/L (>3.4 mg/dL)

A sudden increase in creatinine levels can be seen after the initiation of diuretic therapy, and it is often mistakenly considered evidence of overdiuresis or intravascular depletion (even in the presence of fluid overload). A common error in this situation is to decrease the dose of ACEIs, angiotensin-receptor blockers (ARBs), and/or diuretics, or to even withdraw one of these agents. In fact, when diuresis or ultrafiltration is continued, patients demonstrate improved renal function, decreased total body fluid, and increased response to diuretics, as central venous pressure falls.

Low-dose dopamine has been used in combination with diuretic therapy, on the supposition that it can increase kidney perfusion. Data have been contradictory, however. In a randomized controlled study, Giamouzis et al found that the combination of low-dose furosemide and low-dose dopamine was equally as effective as high-dose furosemide for kidney function in patients with acute decompensated heart failure.^[110] In addition, patients who received dopamine and furosemide were less likely to have worsened renal function or hypokalemia at 24 hours.^[110]

Use of nesiritide, a synthetic natriuretic peptide, to increase diuresis in these cases has not been studied. A meta-analysis of several trials using nesiritide suggested the potential of worsening renal function, although this has not been demonstrated in prospective trials. Results of the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial suggested that, although nesiritide is safe, it does not provide additional efficacy when added to standard therapy.^[111] In another large study comprising 7141 patients with decompensated heart failure, the use of nesiritide did not have an effect on renal function, rehospitalization, and mortality, albeit there was a small but nonsignificant impact on dyspnea when used in conjunction with other therapies.^[112]

The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial showed that the addition of the vasopressin antagonist tolvaptan to diuretic therapy facilitates diuresis in acute heart failure. However, tolvaptan had no impact on mortality or hospitalizations in this setting.^[113]

Adenosine receptor antagonists have been proposed for protecting renal function in acute heart failure. However, in a double-blind, placebo-controlled trial, the adenosine A₁−receptor antagonist rolofylline demonstrated no benefit for patients hospitalized for acute heart failure with impaired renal function.^[114]

A meta-analysis performed by Badve et al suggested that treatment with beta-blockers reduced all-cause mortality in patients with chronic kidney disease and systolic heart failure (risk ratio, 0.72).^[115]

Atrial fibrillation

Many patients with heart failure also have atrial fibrillation, and the two conditions can adversely affect each other. However, in the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial, there was no difference in stroke, heart failure exacerbation, or cardiovascular mortality in patients treated with rhythm control (amiodarone) and patients treated with rate control.^[116] All of these patients require anticoagulation for stroke prevention, which can be achieved by using warfarin or a direct thrombin inhibitor (no need to follow protime).

A meta-analysis found that patients with LV systolic dysfunction who underwent catheter ablation for atrial fibrillation demonstrated significant improvements in LVEF, and their risk for recurrent atrial fibrillation or atrial tachycardia after catheter ablation was similar to that in patients with normal LV function after ablation.^[117] However, patients with LV systolic dysfunction were more likely to require repeat procedures.

In contrast, MacDonald et al reported that in patients with advanced heart failure and severe LV systolic dysfunction, radiofrequency ablation for persistent atrial fibrillation resulted in long-term restoration of sinus rhythm in only 50% of cases.^[118] Radiofrequency ablation also failed to improve such secondary outcomes as walking distance or quality of life, and the rate of related serious complications was 15%.

References

Pharmacologic Therapy

Pharmacologic therapy includes^{[3, 4, 5, 58]}:

Diuretics (to reduce edema by reduction of blood volume and venous pressures) and salt restriction (to reduce fluid retention) in patients with current or previous heart failure symptoms and reduced left ventricular (LV) ejection fraction (EF) for symptomatic relief
Angiotensin-converting enzyme inhibitors (ACEIs) for neurohormonal modification, vasodilatation, improvement in LVEF, and survival benefit
Angiotensin receptor blockers (ARBs) for neurohormonal modification, vasodilatation, improvement in LVEF, and survival benefit
Hydralazine and nitrates to improve symptoms, ventricular function, exercise capacity, and survival in patients who cannot tolerate an ACEI/ARB or as an add-on therapy to ACEI/ARB and beta-blockers in the black population for survival benefit
Beta-adrenergic blockers for neurohormonal modification, improvement in symptoms and LVEF, survival benefit, arrhythmia prevention, and control of ventricular rate
Aldosterone antagonists, as an adjunct to other drugs for additive diuresis, heart failure symptom control, improved heart rate variability, decreased ventricular arrhythmias, reduction in cardiac workload, improved LVEF, and increase in survival
Digoxin, which can lead to a small increase in cardiac output, improvement in heart failure symptoms, and decreased rate of heart failure hospitalizations
Anticoagulants to decrease the risk of thromboembolism
Inotropic agents to restore organ perfusion and reduce congestion

The I(f) "funny current" inhibitor, ivabradine (Corlanor) received FDA approval in 2015 to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with an LVEF of 35% or lower, who are in sinus rhythm with a resting heart rate of 70 bpm or higher, and who are either on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use.^{[122, 123]}This drug blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker I(f) "funny" current, which regulates heart rate without any effect on ventricular repolarization or myocardial contractility.

Approval for ivabradine was based on the international, placebo-controlled SHIFT trial published in 2010, which randomized more than 6500 patients with New York Heart Association (NYHA) class II-IV heart failure and an LVEF of 35% or lower.^{[122, 123]}The trial saw a highly significant 18% drop in risk for cardiovascular death or hospitalization for worsening heart failure over an average of 23 months in patients treated with ivabradine.

The FDA approved the combination tablet sacubitril/valsartan (Entresto) in 2015 to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with NYHA class II-IV heart failure and reduced ejection fraction.^[124]The combination drug is the first approved agent in the angiotensin receptor-neprilysin inhibitor (ARNI) class and consists of the ARB valsartan affixed to the neprilysin inhibitor sacubitril. The cardiovascular and renal effects of sacubitril’s active metabolite (LBQ657) in heart failure are attributed to the increased levels of peptides that are degraded by neprilysin (eg, natriuretic peptide). Administration results in increased natriuresis, increased urine cGMP (cyclic guanosine monophosphate), and decreased plasma mid-regional proatrial natriuretic peptide (MR-proANP) and N-terminal pro-brain natriuretic peptide (NT-proBNP).

The approval was based on the Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial.^[125]PARADIGM-HF studied 8442 patients with chronic heart failure treated with either valsartan/sacubitril or enalapril. The combination significantly reduced cardiovascular death or heart-failure hospitalizations (the study's primary end point) by 20% compared with treatment with enalapril alone. All-cause mortality, a secondary end point, was also significantly reduced with the ARNI when compared with enalapril.^[125]

The Prospective Comparison of ARNI with ARB on Management of Heart Failure with Preserved Ejection Fraction (PARAMOUNT) trial compared reduction of NP-proBNP levels with sacubitril plus valsartan and valsartan alone over 12 weeks in 149 patients with LVEF of 45% or greater. Sacubitril/valsartan reduced NT-proBNP levels to a significantly greater extent (783 pg/mL at baseline and 605 pg/mL at 12 weeks) compared with valsartan alone (862 pg/mL at baseline and 835 pg/mL at 12 weeks).^[126]

Patients with heart failure and depressed LVEF are thought to have an increased risk of thrombus formation due to low cardiac output.^{[3, 4]}ref6} Anticoagulation with an international normalized ratio (INR) goal of 2-3 is indicated in the presence of LV thrombus, thromboembolic event with or without evidence of an LV thrombus, and paroxysmal or chronic atrial arrhythmias.^[5]

Routine anticoagulation with warfarin in patients with normal sinus rhythm, heart failure, and LV dysfunction has not proven to be superior to aspirin alone in decreasing death, myocardial infarction (MI), and stroke, and it was associated with an increased risk of bleeding in the warfarin arm of the WATCH (warfarin and antiplatelet therapy in chronic heart failure) trial.^[127]

The use of regularly scheduled intermittent intravenous infusions of positive inotropic drugs in a supervised outpatient setting has been proposed, but the 2013 American College of Cardiology/American Heart Association/Heart Failure Society of America (ACCF/AHA/HFSA) guidelines advise against this, given the lack of evidence to support efficacy and concerns about toxicity with an increase in mortality rate. Rather, the guidelines recommend infusion of a positive inotrope only as palliation in patients with end-stage disease who cannot be stabilized with standard medical treatment.^[3]

Nonsteroidal anti-inflammatory drugs (NSAIDs), calcium channel blockers, and most antiarrhythmic agents may exacerbate heart failure and should be avoided in most patients.^{[3, 4]} NSAIDs can cause sodium retention and peripheral vasoconstriction and can attenuate the efficacy and enhance the toxicity of diuretics and ACEIs.

Antiarrhythmic agents can have cardiodepressant effects and may promote arrhythmia; only amiodarone and dofetilide have been shown not to adversely affect survival. Calcium channel blockers can worsen heart failure and may increase the risk of cardiovascular events; only the vasoselective calcium channel blockers have been shown not to adversely affect survival.^{[3, 4]}

In a community-based cohort study of 2891 digoxin-naive adults with newly diagnosed systolic heart failure, 18% of whom initiated treatment with digoxin, incident digoxin use was associated with significantly higher rates of death (14.2 vs 11.3 per 100 person-years) during a median of 2.5 years of follow-up.^[128]Digoxin use was not associated with a significant difference in the risk of hospitalization for heart failure. Results were similar when the analyses were stratified by sex and use of beta-blockers. Digoxin currently occupies places in both US and European guidelines as no more than a second-line agent for systolic heart failure.

In a review of the safety and efficacy of digoxin in heart failure patients with a reduced EF, Konstantinou et al suggest that digoxin may still have a role in the setting of severe heart failure with evidence of congestion in patients unable to tolerate high doses of disease-modifying agents because of borderline blood pressure/renal function.^[129]The investigators indicate the goal of digoxin use should be a reduction in hospital readmissions, and that clinicians should closely monitor levels of serum digoxin, creatinine, and potassium.^[129]

References

Acute Heart Failure Treatment

Most patients who present with acute heart failure have exacerbation of chronic heart failure, with only 15-20% having acute de novo heart failure. Approximately 50% of patients with acute heart failure have a preserved left ventricular (LV) ejection fraction (EF) (>40%).^{[130, 131]}Less than 5% of patients presenting with acute heart failure are hypotensive and require inotropic therapy.^[132]Pulmonary edema is a medical emergency, but it is only one of the many presentations of acute heart failure.

A systematic and expeditious approach to management of acute heart failure is required, starting in the outpatient setting (eg, emergency department, urgent care center, office), continuing during hospitalization, and extending after discharge to the outpatient setting. The clinician’s agenda in these cases is three-fold:

Stabilize the patient's clinical condition
Establish the diagnosis, etiology, and precipitating factors
Initiate therapies to rapidly provide symptomatic relief

Administration of oxygen, if oxygen saturation is less than 90%, and noninvasive positive pressure ventilation (NIPPV) provides patients with respiratory support to avoid intubation. NIPPV has been shown to decrease the rate of intubation, hospital morality, and mechanical ventilation.^{[133, 134, 135, 136, 137]}No difference has been noted between continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP). A prospective randomized trial that compared the use of noninvasive ventilation (NIV) and standard therapy with the use of standard therapy alone suggested that although NIV may improve dyspnea and respiratory acidosis, it does not appear to improve mortality.^[138]

Medical therapy for heart failure patients, the majority who present with normal perfusion and evidence of congestion, focuses on the following goals:

Preload and afterload reduction for symptomatic relief using vasodilators (nitrates, hydralazine, nipride, nesiritide, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers [ACEI/ARB]) and diuretics
Inhibition of deleterious neurohormonal activation (renin-angiotensin-aldosterone system [RAAS] and sympathetic nervous system) using ACEIs/ARBs, beta-blockers, and aldosterone antagonists resulting in long-term survival benefit

Preload reduction results in decreased pulmonary capillary hydrostatic pressure and reduction of fluid transudation into the pulmonary interstitium and alveoli. Preload and afterload reduction provide symptomatic relief. Inhibition of the RAAS and sympathetic nervous system produces vasodilation, thereby increasing cardiac output and decreasing myocardial oxygen demand. While reducing symptoms, inhibition of the RAAS and neurohumoral factors also results in significant reductions in morbidity and mortality.^{[139, 140, 141]}Diuretics are effective in preload reduction by increasing urinary sodium excretion and decreasing fluid retention, with improvement in cardiac function, symptoms, and exercise tolerance.^{[3, 4]}

Once congestion is minimized, a combination of three types of drugs (a diuretic, an ACEI or an ARB, and a beta-blocker) is recommended in the routine management of most patients with heart failure.^{[3, 4]}This combination can accomplish all of the above goals. ACEIs/ARBs and beta-blockers are generally used together. Beta-blockers are started in the hospital once euvolemic status has been achieved.

If there is evidence of organ hypoperfusion, use of inotropic therapies and/or mechanical circulatory support (eg, intra-aortic balloon pump, extracorporeal membrane oxygenator [ECMO], left ventricular assist device [LVAD]) and continuous hemodynamic monitoring are indicated.^{[3, 4, 142]}If arrhythmia is present and if uncontrolled ventricular response is thought to contribute to the clinical scenario of acute heart failure, either pharmacologic rate control or emergent cardioversion with restoration of sinus rhythm is recommended.

A study of 85 patients with confirmed hypertensive acute heart failure found that the intravenous (IV) calcium channel blocker clevidipine (Cleviprex) was safe and more effective than standard IV drugs for rapidly reducing blood pressure and improving dyspnea.^{[143, 144]} In the 32 study patients who received clevidipine, dyspnea resolved completely in 3 hours, compared with 12 hours in the 53 patients who received usual care (mainly IV nitroglycerin or nicardipine). Target blood pressure range was achieved more often (71% vs 37% for standard care; P =.002) and reached sooner (P =.0006) in patients receiving clevidipine .^{[143, 144]}

Diuretics

Diuretics remain the cornerstone of standard therapy for acute heart failure. In such patients, IV administration of a loop diuretic (ie, furosemide, bumetanide, torsemide) is preferred initially because of potentially poor absorption of the oral form in the presence of bowel edema. In patients with hypertensive heart failure who have mild fluid retention, thiazide diuretics may be preferred because of their more persistent antihypertensive effects.^{[3, 4]}

Diuretics can be given by bolus or continuous infusion and in high or low doses. In a study of patients with acute decompensated heart failure, however, Felker et al found that there were no significant differences in effect on symptoms or renal function changes with furosemide given either by bolus or by continuous infusion; additionally, no differences were found with high versus low doses.^[145]The dose and frequency of administration depend on the diuretic response 2-4 hours after the first dose is given. If the response is inadequate, then increasing the dose and/or increasing the frequency can help enhance diuresis.

Diuretic resistance is diagnosed if there is persistent pulmonary edema despite the following^[146]:

Repeated doses of 80 mg of furosemide or
Greater than 240 mg of furosemide per day (including continuous furosemide infusion) or
Combined diuretic therapy (including loop diuretics with thiazide or an aldosterone antagonist)

Volume status, sodium levels, water intake, and hemodynamic status (for signs of poor perfusion) need to be reevaluated in case of diuretic resistance. Diuretic resistance is a known effect of long-term use of these agents. Some approaches to managing resistance to diuretics include increasing the dose and/or frequency of the drug, restricting sodium or water intake, administering the drug as an IV bolus or IV infusion, and combining diuretics.^{[3, 147]} In addition, diuretic resistance is an independent predictor of mortality in patients with chronic heart failure.^[148]Eventually, alternative strategies, such as hemodialysis or ultrafiltration,^[149]may be used to overcome it. Other agents, such as vasopressin antagonists and adenosine receptor blockers, can be used to assist diuretics.

Transition to oral diuretic therapy is made when the patient reaches a near-euvolemic state. The oral diuretic dose is usually equal to the IV dose. In most cases, 40 mg/day of furosemide is equivalent to 20 mg of torsemide and 1 mg of bumetanide. Weight, signs and symptoms, fluid balance, electrolyte levels, and renal function must be monitored carefully on a daily basis.

Vasodilators

Vasodilators (eg, nitroprusside, nitroglycerin, or nesiritide) may be considered as an addition to diuretics for patients with acute heart failure for relief of symptoms. Vasodilators decrease preload and/or afterload.

Nitrates are potent venodilators. These agents decrease preload and therefore decrease LV filling pressure and relieve dyspnea. They also selectively produce epicardial coronary artery vasodilatation and help with myocardial ischemia. Although nitrates can be used in different forms (sublingual, oral, transdermal, IV), the most common route of administration in acute heart failure is IV. However, their use is limited by tachyphylaxis and headache.

Sodium nitroprusside is a potent, primarily arterial, vasodilator that causes a very efficient afterload reduction and decrease of intracardiac filling pressures. This agent is particularly helpful for patients who present with severe pulmonary congestion in the presence of hypertension and severe mitral regurgitation. Sodium nitroprusside requires not only careful hemodynamic monitoring, often necessitating indwelling catheters, but also monitoring for cyanide toxicity, especially in the presence of renal dysfunction. Sodium nitroprusside should be titrated to off rather than abruptly stopped because of the potential for rebound hypertension.

Nesiritide (human brain natriuretic peptide [BNP] analogue) is a vasodilator that was initially thought to alleviate dyspnea faster than nitroglycerin when used in combination with diuretics.^{[150, 151]}This agent reduces pulmonary capillary wedge pressure (PCWP), right atrial pressure, and systemic vascular resistance but has no effect on heart contractility.

Ultrafiltration and refractory heart failure

In ultrafiltration, blood is removed from the body and run through a device that applies hydrostatic pressure across a semipermeable membrane to separate isotonic plasma water. Solutes cross the semipermeable membrane freely, so fluid can be removed without causing significant changes in the concentration of electrolytes and other solutes in serum.^[152]

Ultrafiltration was shown to be an effective alternative to IV diuretics in the Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure (UNLOAD) trial.^[153]

Indications for hospitalization

A patient whose condition is refractory to standard therapy will often require hospitalization to receive IV diuretics, vasodilators, and inotropic agents. Hospitalization is indicated for acute heart failure in the presence of the following^[5]:

Severe acute decompensated heart failure (low blood pressure, worsening renal dysfunction, altered mentation)
Dyspnea at rest
Hemodynamically significant arrhythmia
Acute coronary syndrome

Hospitalization should also be considered in the presence of the following^[5]:

Worsening congestion with or without dyspnea
Worsening signs and symptoms of systemic or pulmonary congestion, even in the absence of weight gain
Major electrolyte abnormalities
Associated comorbid conditions (eg, pneumonia, pulmonary embolism, diabetic ketoacidosis, stroke/strokelike symptoms)
Repeated implantable cardioverter-defibrillator (ICD) firings
New diagnosis of heart failure with signs of active systemic/pulmonary congestion

Most patients requiring hospitalization should be admitted to a telemetry bed or intensive care unit; a small percentage can be admitted to the floor or observation unit. The goal is to continue the diagnostic and therapeutic processes started in the office or emergency department. Treatment includes the following:

Optimization of volume and hemodynamic status using careful clinical monitoring, and optimization of the heart failure medical regimen
Consideration of surgical intervention with a ventricular device
Provision of heart failure education, behavior modification, and exercise and diet recommendations
Enrollment in heart failure disease management programs for patients with advanced and difficult-to-control heart failure

Invasive hemodynamic monitoring

Invasive hemodynamic monitoring is not indicated for stable patients with heart failure who respond appropriately to medical therapy.^{[3, 5, 104]}The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ESCAPE] trial showed no mortality or hospitalization benefit in such cases.^[104]In patients with acute decompensated heart failure, the following are indications for invasive hemodynamic monitoring^{[3, 5, 154]}:

Respiratory distress
Signs of impaired perfusion
Inability to determine intracardiac pressures on the basis of clinical examination
No improvement in clinical status despite maximal heart failure therapy

Clinical situations in which invasive hemodynamic monitoring is recommended to guide therapy include the following^{[3, 5]}:

Persistent symptomatic hypotension despite initial therapy
Worsening renal function despite initial therapy or despite adjustment of recommended therapies
Need for parenteral vasoactive agents after initial clinical improvement
Presumed cardiogenic shock requiring escalating inotrope and/or pressor therapy and consideration of mechanical support
When advanced device therapy or cardiac transplantation is under consideration

Physicians have implemented different monitoring methods in an attempt to reduce hospitalization for heart failure. The results have been equivocal, regardless of the severity of heart failure. No differences in death or hospitalization for heart failure have been found with either standard outpatient monitoring or intense telemonitoring for heart failure.^{[155, 156]}

The FDA approved the first permanently implantable wireless hemodynamic monitoring system (CardioMEMS HF System) in 2014 for patients with New York Heart Association (NYHA) class III heart failure with a history of hospitalization for heart failure within the past year.^{[157, 158]}The device measures pulmonary artery (PA) pressures (eg, systolic, diastolic, and mean) as well as heart rate, and consists of a sensor/monitor implanted permanently in the PA, a transvenous catheter to deploy the sensor within the distal PA, and an electronics system that acquires and processes the signal from the sensor/monitor and transfers PA measurements to a secure database.^{[157, 158]}This device also permits ambulatory monitoring and is designed to detect early-stage elevations in PA pressure, so that appropriate medical intervention can be provided before worsening elevation leads to congestion.^[159]

Approval for the device was based on results from 550 patients from the open-label CHAMPION study (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients), in which the device reduced hospitalizations by 30% compared with standard care.^{[158, 159]}

Discharge

The patient must be on a stable oral regimen for at least 24 hours before discharge. Patients are ready for discharge when they meet the following criteria:

Exacerbating factors have been addressed
Volume status has been optimized
Diuretic therapy has been successfully transitioned to oral medication, with discontinuation of IV vasodilator and inotropic therapy for at least 24 hours
Oral chronic heart failure therapy has been achieved with stable clinical status

Before discharge, patient and family education should be completed, and extensive postdischarge instructions and follow-up in 3-7 days should be arranged. Refractory end-stage heart failure (American College of Cardiology/American Heart Association [ACC/AHA] stage D, NYHA class IV) is often difficult to manage on an outpatient basis. Therefore, these patients may be referred to a heart failure program with expertise in management of refractory heart failure.^[3]

To ensure compliance and understanding of a complex medical regimen, a follow-up phone call can be made 3 days after discharge by a nurse with training in heart failure. Ideally, the patient should be seen in clinic 7-10 days after discharge.

References

Electrophysiologic Intervention

Devices for electrophysiologic intervention in heart failure include pacemakers, cardiac resynchronization therapy (CRT) devices, and implantable cardioverter-defibrillators (ICDs). CRT should be considered in patients with NYHA class II-IV, an LVEF of 35% or less, normal sinus rhythm and a QRS duration of 150 ms or longer, with a left bundle branch pattern.^{[3, 56]}

In April 2014, the FDA approved 10 Medtronic biventricular pacemakers, some with defibrillators and some without, for use in patients with less severe systolic heart failure and atrioventricular (AV) block.^{[162, 163]}Approval was based on a study of 691 patients with first-, second-, or third-degree AV block, New York Heart Association (NYHA) class I-III heart failure, and left ventricular ejection fraction (LVEF) below 50%, in which biventricular pacing over 3 years reduced all-cause mortality by 26%, reduced heart failure-related urgent care, and increased LV end-systolic volume index by more than 15%.^{[162, 163]}

Pacemakers

Maintaining a normal chronotropic response and AV synchrony may be particularly significant for patients with heart failure.^[4]Because right ventricular (RV) pacing may worsen heart failure due to an increase in ventricular dysynchrony, placement of a dual-chamber pacemaker in heart failure patients in the absence of symptomatic bradycardia or high-degree AV block is not recommended.

Implantable cardioverter-defibrillators

The role of implantable cardioverter-defibrillators (ICDs) has rapidly expanded. Sudden death is 5-10 times more common in patients with heart failure than in the general population. ICD placement results in remarkable reductions in sudden death from ischemic and nonischemic sustained ventricular tachyarrhythmias in heart failure patients. (See also the Medscape Reference articles Implantable Cardioverter-Defibrillators and Pacemakers and Implantable Cardioverter Defibrillators.)

In moderately symptomatic heart failure patients with an LVEF of 35% or less, primary prevention with an ICD provides no benefit in some cases but substantial benefit in others. A model based on routinely collected clinical variables can be used to predict the benefit of ICD treatment, according to a study by Levy et al.^[164]Using data from the placebo arm of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) with their risk prediction model, Levy et al showed that patients could be classified into five groups on the basis of predicted 4-year mortality. In the treatment arm, ICD implantation decreased the relative risk of sudden cardiac death by 88% in patients with the lowest baseline mortality risk but only by 24% in the highest-risk group. ICD treatment decreased relative risk of total mortality by 54% in the lowest-risk group but only by 2% in the highest-risk group.^[164]

It is important to note that use of the SCD-HeFT model has not been prospectively validated for risk stratification in the decision for ICD implantation. More trials are needed.

Cardiac resynchronization therapy/biventricular pacing

Patients with heart failure and interventricular conduction abnormalities (roughly defined as those with a QRS interval >120 ms) are potential candidates for cardiac resynchronization therapy (CRT) by means of an inserted biventricular pacemaker. CRT aims to improve cardiac performance by restoring the heart’s interventricular septal electrical and mechanical synchrony.^{[5, 165]}Thus, it reduces presystolic mitral regurgitation and optimizes diastolic function by reducing the mismatch between cardiac contractility and energy expenditure.^[166]

The combination of biventricular pacing with ICD implantation (CRT-ICD) may be beneficial for patients with NYHA class II heart failure, an LVEF of 30% or less, and a QRS duration longer than 150 ms. The Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) and Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT) investigators reported significant improvement in mortality and morbidity with CRT-ICD treatment versus ICD alone in this group of patients.^[167]

Patients with unfavorable coronary sinus anatomy often cannot have a CRT properly placed adjacent to the posterolateral wall of the LV. A study by Giraldi et al suggests that in such patients, a mini-thoracotomy allows for proper lead placement.^[168]These patients, when compared to those who had typical transvenous placement (thus not allowing for the preferred posterolateral wall lead placement), had improved outcomes in terms of improved EF and decreased end-systolic volume.^[168]

Regarding technique, three cardiac leads are placed transvenously: an atrial lead, an RV lead, and an LV lead (which is threaded through the coronary sinus and out one of its lateral wall tributaries). Surgeons have assisted difficult transvenous LV placements by epicardially inserting LV leads using a number of techniques (eg, mini-thoracotomy, thoracoscopy, robotically assisted methods).

Clinical trials of cardiac resynchronization therapy

Several prospective, randomized trials have been performed to evaluate the effectiveness of CRT. The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) study group demonstrated an improvement in NYHA functional class, quality of life, and LVEF.^[169]

As noted above, the MADIT-CRT demonstrated reduction in the risk of heart failure events in patients treated with CRT plus an ICD over that of individuals treated with ICD alone. This randomized trial included 1820 patients with an EF of 30% or less, a QRS duration of 130 ms or more, and NYHA class I or II symptoms.^[170] During an average follow-up of 2.4 years, death from any cause or a nonfatal heart failure event occurred in 17.2% of patients in the CRT-ICD group versus 25.3% of patients in the ICD-only group. In particular, there was a 41% reduction in the risk of heart failure events in patients in the CRT group, which was evident primarily in patients with a QRS duration of 150 ms or more. CRT was associated with a significant reduction in LV volume and improvement in the EF. No significant difference occurred between the two groups in the overall risk of death.^[170]

In a follow-up to MADIT-CRT, women seemed to achieve a better response result from resynchronization therapy than men, with a significant 69% reduction in death or heart failure and a 70% reduction in heart failure alone. Those benefits were associated with consistently greater echocardiographic evidence of reverse cardiac remodeling.^[171]

Additional findings from MADIT-CRT concerned the relative effects of metoprolol and carvedilol in heart failure patients with devices in place.^[172]The key variables were (a) rate of hospitalization for heart failure or death and (b) incidence of ventricular arrhythmia.

Treatment with carvedilol yielded a significantly lower rate of hospitalization for heart failure or death than treatment with metoprolol (23% vs 30%), a reduction that was especially pronounced in patients undergoing CRT with implantable cardioverter-defibrillator (CRT-D), including those with left bundle-branch block (LBBB).^[172]The incidence of ventricular arrhythmia was 26% with metoprolol and 22% with carvedilol. There was a clear dose-dependent relation for carvedilol, which was not seen for metoprolol.

In addition to augmenting functional capacity, CRT also appears to favorably affect mortality. The Cardiac Resynchronization-Heart Failure (CARE-HF) trial, which studied CRT placement in patients with NYHA class III or IV heart failure due to LV systolic dysfunction and cardiac dyssynchrony, showed a 36% reduction in death with biventricular pacing.^[173]

In the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial, biventricular pacing reduced the rate of death from any cause or hospitalization for any cause by approximately 20%. The COMPANION trial was conducted in patients with NYHA class III or IV heart failure due to ischemic or nonischemic cardiomyopathies and a QRS interval of at least 120 ms. The addition of a defibrillator to biventricular pacing incrementally increased the survival benefit, resulting in a substantial 36% reduction in the risk of death compared with optimal pharmacologic therapy.^[174]

In both the CARE-HF and the COMPANION studies, mortality was largely due to sudden death.^{[173, 174]}

Noting that high percentages of RV apical pacing could promote LV systolic dysfunction, the investigators from Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK-HF) trial found that biventricular pacing improved outcomes in patients with AV block and NYHA class I-III heart failure over that of RV pacing.^[175] A total of 691 volunteers received a pacemaker or ICD with leads in both ventricles (the LV lead was kept inactive in about half of participants). At follow-up (average, 37 months), 55.6% of the patients in the RV pacing group had died or had worsening heart failure, compared with 45.8% in the biventricular pacing group. The rate of adverse events was comparable in the two groups, and most problems occurred during the first month.^[175]

References

Valvular Surgery

Valvular heart disease may be the underlying etiology or an important aggravating factor in heart failure.^{[3, 4, 5]}

Aortic valve replacement

Diseases of the aortic valve can frequently lead to the onset and progression of heart failure. Although the natural histories of aortic stenosis and aortic regurgitation are well known, patients are often followed up conservatively after they present with clinically significant heart failure.

Heart failure is a common indication for aortic valve replacement (AVR), but one must be cautious in patients with a low left ventricular ejection fraction (LVEF) and possible aortic stenosis. Assessment of contractile reserve with dobutamine has been demonstrated as a reliable method to determine which patients with low EF and aortic stenosis may benefit from AVR.^[188]

If no contractile reserve is present (a finding that suggests some ventricular reserve), the outcome with standard AVR is poor. In this situation, transplantation might be the only option, although the use of percutaneous valves, an apical aortic conduit, or a left ventricular assist device (LVAD) may offer an intermediate solution.

Indications

Decision making regarding valve surgery should not be delayed by medical treatment. Be cautious in using vasodilators (angiotensin-converting enzyme inhibitors [ACEIs], angiotensin-receptor blockers [ARBs], and nitrates) in patients with severe aortic stenosis, as these agents may cause significant hypotension.^{[3, 4, 5, 56]}

Surgery is recommended in selected patients with symptomatic heart failure and severe aortic stenosis or severe aortic regurgitation, as well as in asymptomatic patients with severe aortic stenosis or severe aortic regurgitation and impaired LVEF (< 50%). This intervention may be considered in patients with a severely reduced valve area and LV dysfunction.

Patient survival

Of the three classic symptoms of aortic stenosis—syncope, angina, and dyspnea—dyspnea is the most robust risk factor for death. Only 50% of patients with dyspnea in this setting are still alive within 2 years.^[189]Angina is associated with a mortality risk of 50% within 5 years, whereas syncope confers a 50% mortality risk in 3 years.

In contrast, the age-corrected survival rate for patients undergoing AVR for aortic stenosis is similar to that for the normal population.^[190]Once patients develop severe LV dysfunction, however, the results of AVR are somewhat guarded.^[191]Because of poor LV function, these patients are unable to develop significant transvalvular gradients (ie, low-output, low-gradient aortic stenosis).

A critical aspect of the decision for or against AVR is whether the ventricular dysfunction is truly valvular or reflects other forms of cardiomyopathy, such as ischemia or restrictive processes. Valvular dysfunction improves with AVR; other forms do not.

Precise measurement of the area of the aortic valve is difficult, because the calculated area is directly proportional to cardiac output. Also, the Gorlin constant varies at lower outputs. Therefore, in this situation, valvular areas might be considered critically small when at surgery the valve is found to be only moderately diseased.

Preoperative evaluation with dobutamine testing to increase contractile reserve or with vasodilator-induced stress echocardiography by using the continuity equation rather than the Gorlin formula can be helpful in making this distinction. The results can guide the physician or surgeon in determining whether the patient is a candidate for the relatively high-risk procedure.^[192]Nevertheless, because of the possibility of ventricular recovery and lengthened patient survival, most patients with heart failure and aortic stenosis are offered valve replacement.^[193]

Surgical timing

Timing of surgical intervention for aortic insufficiency is more challenging in patients just described than in patients with aortic stenosis. However, as before, once symptoms occur and once evidence of LV structural changes become apparent, morbidity and mortality due to aortic insufficiency increase.^[194]

As with aortic stenosis, early intervention before the onset of severe LV dysfunction is crucial to improving the survival of patients with aortic insufficiency, as was shown in a retrospective review from the Mayo Clinic.^{[195, 196]}In this study, in which 450 patients who underwent AVR for aortic insufficiency were compared according to ranges of EF (< 35%, 35-50%, >50%), although the group with severe dysfunction had an operative mortality of 14%, the EF improved, and the group's 10-year survival rate was 41%.^{[195, 196]}

Mitral valve repair

Mitral valve regurgitation can either cause or result from chronic heart failure. Its presence is an independent risk factor for cardiovascular morbidity and mortality.^[197]In addition to frank rupture of the papillary muscle in association with acute myocardial infarction (MI), chronic ischemic cardiomyopathies result in migration of the papillary muscle as the ventricle dilates. This dilation causes tenting of the mitral leaflets, restricting their coaptation.

Dilated cardiomyopathies can have similar issues, as well as annular dilatation. In addition to mitral regurgitation, the alteration in LV geometry contributes to volume overload, increases LV wall tension, and leaves patients susceptible to exacerbations of heart failure.^[198]

Mitral valve surgery in patients with heart failure has gained favor because it abolishes the regurgitant lesion and decreases symptoms. The pathophysiologic rationales for repair or replacement are to reverse the cycle of excessive ventricular volume, to allow for ventricular unloading, and to promote myocardial remodeling.

Among other researchers, a group from Michigan advocated mitral repair in the population with heart failure. Bolling and colleagues demonstrated that mitral valve repair increased the EF, improved NYHA classes from 3.9 to 2.0, and decreased the number of hospitalizations, although the results were reproducible by other centers.^[199]Additional effects with repair in these patients were an increase in coronary blood flow reserve afforded by the reduction in LV volume.^[200]

Despite the potential benefits of mitral reconstruction surgery, a retrospective review showed no reduction in long-term mortality among patients with severe mitral regurgitation and significant LV dysfunction who underwent mitral valve repair.^[201]Mitral valve annuloplasty was not predictive of clinical outcomes and did not improve mortality. Factors associated with lower mortality were ACEI use, beta blockade, normal mean arterial pressures, and normal serum sodium concentrations.^[201]The results of this analysis were not overly surprising. For example, in most patients in this situation, heart failure is not due to flail leaflets but is secondary to ventricular dysfunction.

In evaluating studies of heart failure with mitral regurgitation, it is important to separate the etiology (eg, ischemic vs dilated) as well as the surgical approaches. Future trials must be designed to distinguish differences between various surgical strategies, such as annuloplasty, resuspension of the papillary muscle, secondary chordal transection, ventricular reconstruction, passive restraints, and chordal-sparing valve replacement. A paramount goal with these procedures is for the patient to have little or no residual mitral regurgitation.^[202]

Indications

Consider mitral valve surgery in patients with heart failure and severe mitral valve regurgitation whenever coronary revascularization is an option.^[4]Candidates would include the following^[4]:

Patients with severe mitral regurgitation due to an organic structural abnormality or damage to the mitral valve in whom symptoms of heart failure develop
Patients with an LVEF greater than 30%
Patients with severe ischemic mitral regurgitation and an LVEF greater than 30% when coronary artery bypass grafting (CABG) is planned

Cardiac resynchronization therapy (CRT) should be considered in eligible patients with functional mitral regurgitation, as it may improve LV geometry and papillary muscle dyssynchrony as well as potentially reduce mitral regurgitation.^[4]

Annuloplasty

Treatment of cardiomyopathy-associated mitral regurgitation most commonly involves the insertion of either a complete or a partial band attached to the annulus of the mitral valve. Thus, mitral repair deals with only one aspect of the patient's overall pathophysiologic condition. That is, annuloplasty rings may assist with tenting of the leaflet, but they do not address displacement of the papillary muscle with ventricular scarring.^[203]In many patients, the underlying problem (ie, primary myopathy) continues unabated.

In general, ischemic mitral regurgitation is a ventricular problem. Many operations allow for coaptation and no mitral regurgitation when the patient leaves the operating room. However, as the LV continues to dilate, mitral regurgitation often recurs. Therefore, it is overambitious to say that annuloplasty cures this condition. As a result, many other approaches have been attempted (eg, chordal cutting, use of restraint devices, papillary relocation). However, results have been mixed.

Mitral valve replacement

If repair is deemed improbable, mitral replacement should be performed. Traditional mitral valve replacement includes complete resection of the leaflets and the chordal attachments. This destruction of the subvalvular apparatus results in ventricular dysfunction. In patients with mitral regurgitation and heart failure, preservation of the chordal attachments to the ventricle with valve replacement might provide results similar to, or even better than, those of annuloplasty.^{[204, 205]}

Although the benefits in terms of quality of life (decreased heart failure) might not portend increased survival in these high-risk patients,^{[206, 207]}they likely keep low-EF mitral valve interventions in the armamentarium of surgeons who manage heart failure.

A relatively recent approach to functional and degenerative mitral valve regurgitation is percutaneous mitral valve repair,^{[208, 209]}using devices such as the MitraClip system. The EVEREST (Endovascular Valve Edge-to-Edge Repair Study II) randomized trial reported low rates of morbidity and mortality and reduction of acute mitral regurgitation to less than 2+ in the majority of patients, with sustained freedom from death, surgery, or recurrent mitral regurgitation in a substantial proportion of patients.^[210]

A systematic review and meta-analysis of data from 2615 patients over nine studies found that percutaneous edge-to-edge mitral valve repair with the MitraClip is likely to be a safe and effective option in patients with both functional and degenerative mitral regurgitation.^[211]Similarly, data from the German Transcatheter Mitral Valve Interventions (TRAMI) Registry found comparable MitraClip results for procedural safety of percutaneous mitral valve repair, efficacy, and clinical improvement after 1 year between patients with severely impaired LVEF (EF < 30%) and those with preserved LV function (EF >50%).^[212]Over two thirds (69.5%) of those with an EF below 30% improved by one or more NYHA functional class, a significantly higher proportion than the 56.8% of patients with preserved LV function whose NYHA class improved (P< 0.05).

References

Ventricular Assist Devices

Ventricular assist devices (VADs) are invaluable tools in the treatment of heart failure, particularly in those with advanced heart failure.^[272]A number of these devices are available to support the acutely or chronically decompensated heart (ie, American College of Cardiology/American Heart Association [ACC/AHA] stage D). Depending on the particular device used, the right ventricle (RV) and left ventricle (LV) can be assisted with a LV assist device (LVAD), a RVAD, or a biventricular assist device (BiVAD). An alternative term for a VAD is a ventricular assist system (VAS).^{[219, 220]}

In concept, LVADs, RVADs, and BiVADs are similar. Blood is removed from the failing ventricle and diverted into a pump that delivers blood to either the aorta (in the case of an LVAD) or the pulmonary artery (in the case of an RVAD). An exception is the Impella device, which is inserted percutaneously into the LV; it draws blood from the LV and expels it into the ascending aorta.

LVADs can often be placed temporarily. In patients with acute, severe myocarditis or those who have undergone cardiotomy, this approach can serve as a bridge to recovery, unloading the dysfunctional heart and perhaps allowing reverse remodeling; in patients with end-stage heart failure, it can serve as a bridge to heart transplantation,^{[3, 4, 5, 105]}allowing them to undergo rehabilitation and possibly go home before transplantation.

Long-term use (ie, destination therapy rather than bridge therapy) may be a consideration when no definitive procedure is planned.^[4]Patients with severe heart failure who are not transplant candidates and who otherwise would die without treatment are candidates for lifetime use of VADs. Destination therapy with LVADs is superior to medical therapy in terms of quantity and quality of life, according to the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial and several later studies.^{[221, 222]}

In the United States, several Food and Drug Administration (FDA)–approved options are available for bridging the patient to recovery and transplantation. These options continue to change and evolve. Some examples include the following:

Abiomed AB5000 Ventricle
AB Portable Driver
Thoratec CentriMag Blood Pump
Thoratec PVAD (Paracorporeal Ventricular Assist Device)
Thoratec IVAD (Implantable Ventricular Assist Device)
HeartMate XVE LVAD (also known as HeartMate I)
HeartMate II LVAS
TandemHeart Percutaneous LVAD
HeartAssist 5 Pediatric VAD

The HeartMate LV and HeartWare HVAD^[223]assist systems are the only LVADs that are approved by the US Food and Drug Administration (FDA) for destination therapy. Other devices are also under study in the United States for use as destination therapy (eg, Jarvik 2000 VAS^[224]).

The HeartMate XVE LVAD does not require warfarin anticoagulation, unlike another well-known first-generation pulsatile pump, the Novacor LVAD. The newer axial-flow pumps (eg, HeartMate II LVAS, Jarvik 2000, HeartAssist 5 Pediatric VAD) are relatively small and easy to insert, and they reduce morbidity; however, these devices do require anticoagulation.

Potential complications of VADs include mechanical breakdown, infection, bleeding, and thromboembolic events. Despite these potential drawbacks, however, the survival rate for patients receiving VADs is roughly 70%. This rate is impressive given the severity of illness in this cohort of patients. Furthermore, the evolving technology raises a host of clinical and physiologic questions that, when studied and answered, continue to advance the field.

Selected trials

In the REMATCH study, survival rates of medically treated and LVAD-treated patients were, respectively, 25% and 52% at 1 year and 8% and 23% at 2 years.^[225]This study offered the first prospective, randomized data of very ill, non–transplant-eligible patients with heart failure receiving optimal medical therapy versus an early-generation HeartMate LVAD. In addition to survival advantage, LVAD recipients had improvements in several measures of quality of life.

Modifications in technique and perioperative care have reduced the rates of LVAD-related morbidity and mortality observed in the REMATCH trial.^[226]Although REMATCH was a single study in very high risk patients, the data serve as proof of concept for the future development of VAD technologies.

Despite the need for an external energy source, most patients can use mechanical circulatory devices in the outpatient setting. Many patients have lived productive lives for longer than 4-6 years with their original device (depending on the device).

Starling et al used INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) data to determine that following postmarket approval by the FDA, the HeartMate II LVAS, a continuous-flow LVAD, continues to have excellent results as a bridge to heart transplantation relative to other types of LVADs in the following measures^[227]:

The 30-day operative mortality was 4% for the group receiving the HeartMate II compared with 11% for other LVADs
Ninety-one percent of the group receiving the HeartMate II reached transplantation, cardiac recovery, or ongoing LVAD support by 6 months, compared with 80% for the group receiving other LVADs
Renal function test measurements such as creatinine and blood urea nitrogen levels were lower in the HeartMate II group
For all adverse events, the rates were similar or lower for the group that received the HeartMate II, with bleeding being the most frequent adverse event for both groups
Survival for patients remaining on support at 1 year was 85% for the HeartMate II group, versus 70% for the group with other LVADs
Relative to baseline, both groups had significant improvement of quality of life at 3 months of support, which was sustained through 12 months

In another study, Ventura et al used a large national data registry to compare posttransplant outcomes between pulsatile-flow (HeartMate XVE [HeartMate I]) and continuous-flow (HeartMate II) LVADs as bridges to transplantation and found similar 1- and 3-year survival rates but less risk of early allograft rejection and sepsis with the HeartMate II device.^[228]

Patients with class IV stage D heart failure who are symptomatic despite optimal medical heart failure therapy for 45 of 60 days or who require inotropic support for 14 days or intra-aortic balloon pump (IABP) support for 7 days and have no contraindication for anticoagulation are eligible for implantation on LVAD HM II as destination therapy if they are not eligible for or do not desire cardiac transplantation. The INTERMACS registry has established a patient profile (1-7) that determines urgency to implantation and assesses risk and survival at 90 days.

Recommendations for clinical management of continuous-flow LVAD assist providers with standardized care for this patient population.^[229]Bleeding, infection, and stroke are postimplantation complications, and death may occur due to right heart failure, sepsis, or stroke. A multidisciplinary approach to LVAD implantation is needed, as destination therapy identifies patients at high risk for complications and the need to optimize these patients medically before surgery. In a report from INTERMACS, 1-year survival for destination-therapy patients was 61% for pulsatile devices and 74% for continuous-flow devices.^[230]

References

Screening and Genetic Testing

Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA) select recommendations for genetic testing for channelopathies and cardiomyopathies

Long QT syndrome (LQTS) ^[249]

Comprehensive or LQT1-3 (KCNQ1, KCNH2, and SCN5A)–targeted LQTS genetic testing is recommended for the following:

Individuals with a strong clinical index of suspicion for LQTS based on the patient's clinical history, family history, and expressed electrocardiographic (ECG) (resting 12-lead ECGs and/or provocative stress testing with exercise or catecholamine infusion) phenotype
Asymptomatic individuals with idiopathic QT prolongation on serial 12-lead ECGs defined as QTc over 480 ms (prepuberty) or longer than 500 ms (adults); may also be considered in asymptomatic individuals with idiopathic QT prolongation on serial 12-lead ECGs for QTc values over 460 ms (prepuberty) or longer than 480 ms (adults)

Mutation-specific genetic testing is recommended for family members following identification of the LQTS mutation in an index case.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) ^[249]

Comprehensive or CPVT1 and CVPT2 (RYR2 and CASQ2)–targeted CPVT genetic testing is recommended for any individual with a clinical index of suspicion for CPVT based on the patient's clinical history, family history, and expressed ECG phenotype during provocative stress testing with cycle, treadmill, or catecholamine infusion.
Mutation-specific genetic testing is recommended for family members following identification of the CPVT mutation in an index case.

Brugada syndrome (BrS) ^[249]

Consider comprehensive or BrS1 (SCN5A)–targeted BrS genetic testing for individuals with a clinical index of suspicion for BrS based on the patient's clinical history, family history, and expressed ECG (resting 12-lead ECGs and/or provocative drug challenge testing) phenotype.
Mutation-specific genetic testing is recommended for family members following identification of the BrS mutation in an index case.
Genetic testing is not indicated in individuals with an isolated type 2 or type 3 Brugada ECG pattern.

Cardiac conduction disease (CCD) ^[249]

Consider genetic testing as part of the diagnostic evaluation for individuals with either isolated CCD or CCD with concomitant congenital heart disease, particularly in cases of a documented positive family history of CCD.
Mutation-specific genetic testing is recommended for family members following identification of the CCD mutation in an index case.

Short QT syndrome (SQTS) ^[249]

Consider comprehensive or SQT1-3 (KCNH2, KCNQ1, and KCNJ2)–targeted SQTS genetic testing for individuals with a clinical index of suspicion for SQTS based on the patient's clinical history, family history, and ECG phenotype.
Mutation-specific genetic testing is recommended for family members following identification of the SQTS mutation in an index case.

Hypertrophic cardiomyopathy (HCM) ^[249]

Comprehensive or targeted (MYBPC3, MYH7, TNNI3, TNNT2, TPM1) HCM genetic testing is recommended for individuals with a clinical diagnosis of HCM based on the patient's clinical history, family history, and ECG/echocardiographic phenotype.
Mutation-specific genetic testing is recommended for family members following identification of the HCM mutation in an index case.

Arrhythmogenic cardiomyopathy (ACM) / arrhythmogenic right ventricular cardiomyopathy (ARVC) ^[249]

Comprehensive or targeted (DSC2, DSG2, DSP, JUP, PKP2, and TMEM43) ACM/ARVC genetic testing can be useful for individuals who fulfill the task force diagnostic criteria for ACM/ARVC.
Consider genetic testing for patients with possible ACM/ARVC (1 major or 2 minor criteria) based on the 2010 task force criteria.^[243]
Mutation-specific genetic testing is recommended for family members following identification of the ACM/ARVC mutation in an index case.
Genetic testing is not recommended for patients with only a single minor criterion according to the 2010 task force criteria.^[243]

Dilated cardiomyopathy (DCM) ^[249]

Comprehensive or targeted (LMNA and SCN5A) DCM genetic testing is recommended for individuals with DCM and significant cardiac conduction disease (ie, first-, second-, or third-degree heart block) and/or a family history of premature unexpected sudden death.
Mutation-specific genetic testing is recommended for family members following identification of the DCM mutation in an index case.
Genetic testing can be useful for individuals with familial DCM to confirm the diagnosis, identify those at highest risk of arrhythmia/syndromic features, facilitate cascade screening among family members, and aid in family planning.

Left ventricular noncompaction (LVNC) ^[249]

Genetic testing may be useful for individuals with a clinical diagnosis of LVNC based on the patient's clinical history, family history, and ECG/echocardiographic phenotype
Mutation-specific genetic testing is recommended for family members following identification of the LVNC mutation in an index case.

Restrictive cardiomyopathy (RCM) ^[249]

Consider genetic testing for individuals with a suspected clinical diagnosis of RCM based on the patient's clinical history, family history, and ECG/echocardiographic phenotype.
Mutation-specific genetic testing is recommended for family members following identification of the RCM mutation in an index case.

2013 ACCF/AHA guidelines for screening and genetic testing for DCM

Familial DCM (DCM with 2 close relatives who meet the criteria for idiopathic DCM)^[3]

First-degree relatives not known to be affected should undergo periodic, serial echocardiographic screening with assessment of LV function and size.
Although the screening frequency is uncertain, every 3-5 years is reasonable.
Consider genetic testing in conjunction with genetic counseling.

Idiopathic DCM ^[3]

Inform first-degree relatives of index diagnosis.
Relatives should discuss with their clinicians whether they should undergo echocardiographic screening.
Although the value of genetic testing is unclear in this setting, it is potentially valuable in patients with significant cardiac conduction disease and/or a family history of premature sudden cardiac death.

Heart Failure Society of America (HFSA) recommendations for genetic evaluation of cardiomyopathy

Note the following^[5]:

For all patients with cardiomyopathy, obtain a detailed family history for at least 3 generations (HCM, DCM, arrhythmic right ventricular dysplasia [ARVD], LVNC, RCM, and cardiomyopathies associated with extracardiac manifestations)
Carefully assess the patient's medical history as well as that of asymptomatic first-degree relatives, with special focus on heart failure symptoms, arrhythmias, presyncope, and syncope.
Screen asymptomatic first-degree relatives for cardiomyopathy (HCM, DCM, ARVD, LVNC, RCM, and cardiomyopathies associated with extracardiac manifestations)
Screen for cardiomyopathy at intervals in asymptomatic at-risk relatives who are known to carry the disease-causing mutation(s) (For details, see Recommendations 17.2e and 17.2f in HFSA Guideline Approach to Medical Evidence for Genetic Evaluation of Cardiomyopathy^[5])
Screen for cardiomyopathy in asymptomatic at-risk first-degree relatives who have not undergone genetic testing or in whom a disease-causing mutation has not been identified.

Note: Due to the complexity of genetic evaluation, testing, and counseling of patients with cardiomyopathy, it is recommended that patients be referred to centers with expertise in these matters and in family-based management.^[5]

References

Diagnostic Procedures

Guidelines for the diagnosis and management of heart failure have been issued by the following organizations:

American College of Cardiology Foundation/American Heart Association (ACCF/AHA)^[3]
Heart Failure Society of America (HFSA)^[5]
European Society of Caridiology (ESC)^[4]

The 2013 ACCF/AHA guidelines and its 2017 ACC/AHA/HFSA focused update,^{[3, 56]} 2010 HFSA guidelines,^[5] and 2016 ESC guidelines ^[4] all recommend the following basic laboratory tests and studies in the initial evaluation of patients with suspected heart failure:

Complete blood count (CBC), which may indicate anemia or infection as potential causes of heart failure
Urinalysis (UA), which may reveal proteinuria, which is associated with cardiovascular disease
Serum electrolyte levels, which may be abnormal owing to causes such as fluid retention or renal dysfunction
Blood urea nitrogen (BUN) and creatinine levels, which may indicate decreased renal blood flow
Fasting blood glucose levels, because elevated levels indicate a significantly increased risk for heart failure (diabetic and nondiabetic patients
Liver function tests (LFTs), which may show elevated liver enzyme levels and indicate liver dysfunction due to heart failure
Electrocardiography (ECG) (12-lead), which may reveal arrhythmias, ischemia/infarction, and coronary artery disease as possible causes of heart failure

In addition, these guidelines recommend measuring B-type natriuretic peptide (BNP) and N-terminal pro-B-type (NT-proBNP) natriuretic peptide levels, which are increased in heart failure.^{[3, 4, 5, 56]}Baseline measurements correlate closely with the New York Heart Association (NYHA) heart failure functional classification and can be useful for prognosis in acutely decompensated patients.^[56]The ACCF/AHA, HFSA, and ESC also indicate obtaining BNP or NT-proBNP levels in the workup of heart failure particularly when the diagnosis is unclear.^{[3, 4, 5]}The HFSA recommends this test in all cases of suspected heart failure, particularly in ambiguous cases.^[5]

The ACC/AHA recommendations also include obtaining a lipid profile and thyroid stimulating hormone (TSH) level.^[3] These tests reveal potential cardiovascular or thyroid disease as causes of heart failure. If the clinical presentation also suggests an acute coronary syndrome, the ESC recommends obtaining levels of troponin I or T^[4]; increased troponin levels indicate injury to the myocytes and the severity of heart failure.

The ACC/AHA, HFSA, and ESC also recommend the following imaging studies and procedures^{[3, 4, 5]}:

Chest radiography (posterior-anterior, lateral), which may show pulmonary congestion, an enlarged cardiac silhouette, or other potential causes of the patient's symptoms
Two-dimesional echocardiographic and Doppler flow ultrasonographic studies, which may reveal ventricular dysfunction and/or valvular abnormalities
Coronary arteriography in patients with a history of exertional angina or suspected ischemic left ventricular (LV) dysfunction, which may reveal coronary artery disease (CAD)
Maximal exercise testing with/without respiratory gas exchange and/or blood oxygen saturation, which assesses cardiac and pulmonary function with activity, the inability to walk more than short distances, and a decreased peak oxygen consumption reflect more severe disease

Other studies may be indicated in selected patients,^[3] such as the following:

Screening for hemochromatosis, in which iron overload affects cardiac function
Screening for sleep-disturbed breathing, which affects neurohormonal activation
Screening for human immunodeficiency virus (HIV), which may result in heart failure from possible direct infectious effects, from disease treatment effects causing CAD, or from other causes
Testing for rheumatologic diseases, amyloidosis, or pheochromocytoma, all of which may cause cardiomyopathy
Serum and urine electrophoresis for light-chain disease
Genetic testing for at-risk patients with a first-degree relative who has been diagnosed with a cardiomyopathy leading to heart failure, which may aid in detecting early disease onset and guide treatment^[30]
Holter monitoring, which may reveal arrhythmias or abnormal electrical activity (eg, in patients with heart failure and a history of myocardial infarction (MI) who are being considered for electrophysiologic study to document ventricular tachycardia [VT] inducibility)^{[4, 5]}

Catheterization and angiography

According to the ACCF/AHA, HFSA, and ESC cardiac catheterization and coronary angiography should be considered for patients with heart failure in the following situations^{[3, 4, 5]}:

When symptoms worsen without a clear cause in patients with heart failure, no angina, and known coronary artery disease
In heart failure caused by systolic dysfunction in association with angina or regional wall-motion abnormalities and/or scintigraphic evidence of reversible myocardial ischemia when revascularization is being considered
When the pretest probability of the underlying ischemic cardiomyopathy is high and surgical coronary procedures are being considered
Before cardiac transplantation or LV assist device placement
In cases of heart failure secondary to postinfarction ventricular aneurysm or other mechanical complications of MI

Endomyocardial biopsy

According to the ACCF/AHA guidelines, routine endomyocardial biopsy (EMB) is not recommended in all cases of HF given the risk of complications. However, it may be considered in the following situations^[3]:

In rapidly progressive heart failure or worsening ventricular dysfunction that persists despite appropriate medical therapy
In suspected cases of acute cardiac rejection status after heart transplantation or myocardial infiltrative processes
In rapidly progressive and unexplained cardiomyopathy for which active myocarditis, especially giant cell myocarditis, is being considered
When a specific diagnosis is suspected and EMB would influence therapy

The 2016 ESC guidelines recommend considering EMB in rapidly progressive HF despite appropriate medical therapy when there is a probability of a specific diagnosis that can be confirmed only in mycardial samples and there is an effective specfic therapy available.^[4]

The HFSA suggests that EMB be considered in patients with rapidly progressive clinical heart failure or ventricular dysfunction, despite appropriate medical therapy, as well as in patients suspected of having myocardial infiltrative processes (eg, sarcoidosis, amyloidosis) or in patients with malignant arrhythmias out of proportion to their LV dysfunction (eg, sarcoidosis, giant cell myocarditis).^[5]

Assessment of functional capacity

The ACCF/AHA indicates the 6-minute walk test may be indicated in patients with heart failure whose adequacy of rate control is in question^[3]; the HFSA indicates it is a good indicator of functional status and prognosis in patients with heart failure.^[5]

The ACCF/AHA and HFSA do not recommend routine maximal exercise stress testing.^{[3, 5]} HFSA guidelines indicate it may be useful in situations such as the following with measurement of gas exchange^[5]:

To assess the disparity between symptomatic limitation and objective indicators of disease severity
To distinguish non HF-related causes of functional limitation, specifically cardiac versus pulmonary
To consider whether patients are candidates for cardiac transplantation or mechanical circulatory support
To determine the prescription for cardiac rehabilitation

ACCF/AHA and ESC guidelines note that values of peak oxygen consumption of less than 50% of predicted or less than 14 mL/kg/min reflect poor cardiac performance and a likelihood of 1-year survival less than 50%, facilitating referral for cardiac transplantation or mechanical circulatory device placement.^{[3, 4]}

References

What is heart failure?What are the signs and symptoms of heart failure?What are the Framingham diagnostic criteria for heart failure?What are the Framingham major diagnostic criteria for heart failure?What are the Framingham minor diagnostic criteria for heart failure?How does the New York Heart Association (NYHA) classification system categorize heart failure?What is the American College of Cardiology/American Heart Association (ACC/AHA) staging system?Which tests may be performed in the initial evaluation for suspected heart failure?What are the nonsurgical treatment options for heart failure?What are the surgical treatment options for heart failure?What is heart failure?What causes heart failure?What are the signs and symptoms of heart failure?How is heart failure classified?What are the stages of heart failure defined by the American College of Cardiology/American Heart Association (ACC/AHA) staging system?What is the role of lab studies in the diagnosis of heart failure?What is included in patient care for acute heart failure?What are the goals of drug treatment for heart failure?How is heart failure progression pathophysiologically perpetuated?Which pathophysiological adaptations prevent heart failure?What is the role of norepinephrine in the pathogenesis of heart failure?What is the pathophysiology of acute heart failure?What is the role of chronic increased wall stress in the pathogenesis of heart failure?What can trigger hemodynamic and neurohormonal derangements in the pathogenesis of heart failure?What is the role of epinephrine in the pathogenesis of heart failure?What is the role of calcium overload in the pathophysiology of heart failure?What is the role of the renin-angiotensin-aldosterone system (RAAS) in the pathophysiology of heart failure?What is the paradigm of myocyte biology and heart failure?What is the role of angiotensin II in the pathogenesis of heart failure?What is the role of myocardial volume in the pathogenesis of heart failure?What are the features of myocardial remodeling in the pathogenesis of heart failure?What is the pathophysiology of advanced heart failure?What is the pathophysiology of systolic and diastolic heart failure?What is the role of neuro-hormone mediated events in the pathogenesis of heart failure?What is the role of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in the pathophysiology of heart failure?Which vasoactive systems have a role in the pathogenesis of heart failure?What is the role of tumor necrosis factor (TNF)-alpha in the pathogenesis of heart failure?What is systolic heart failure?What is diastolic heart failure?What is the pathophysiology of heart failure with preserved ejection fraction (HFpEF)?What causes increase in left ventricle (LV) chamber stiffness in the pathophysiology of heart failure?How does the rise in filling pressure affect the pathogenesis of heart failure?What is the role of ventricular pressure-volume curve in the pathophysiology of heart 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decomposition causing heart failure?How does salt retention cause heart failure?What are the high-output states that can precipitate heart failure?What does longitudinal data from the Framingham Heart Study reveal about the etiology of heart failure?What is the role of genetics in the etiology of heart failure?Which patients at high-risk of heart failure should be screened and followed?What is the prevalence of heart failure in the US?What is the incidence of heart failure in the US?What is the mortality rate for heart failure?What are the AHA statistics for heart failure in the US?What are the racial predilections of heart failure in the US?What has caused an increase in incidence of heart failure in the US among recent immigrants from developing countries?How does the presentation of heart failure in the US vary by sex?How does the prevalence of heart failure vary by age in the US?What are the common causes for the increased prevalence of heart failure in industrialized countries?How does the mortality rate for heart failure vary between industrialized and developing countries?What are the trends for heart failure in developing nations?What is the mortality rate for heart failure?What is the mortality rate for systolic heart failure?What variables are used as prognostic factors in heart failure?How does the prognosis of heart failure compare to that of coronary artery disease?How does pulmonary artery systolic pressure (PASP) affect the prognosis of heart failure?Which factors worsen the prognosis of heart failure?How can recurrence of heart failure be prevented?What information about heart failure should patients receive?What should be the focus of clinical history during the evaluation of heart failure?What are common cardiac signs and symptoms of heart failure?What are non-cardiac symptoms of heart failure?What is a common presentation of heart failure in the elderly?How is exertional dyspnea characterized in patients with heart failure?How is orthopnea characterized in patients with heart failure?How is paroxysmal nocturnal dyspnea characterized in patients with heart failure?What causes dyspnea at rest in heart failure?How is acute pulmonary edema characterized in heart failure?What causes chest pain or chest pressure in heart failure?What causes palpitations in heart failure?How are fatigue and weakness characterized in heart failure?What causes nocturia and oliguria in heart failure?Which symptoms of heart failure in the elderly are caused by cerebrovascular atherosclerosis?How do the presentations of mild and severe heart failure differ?What are the clinical presentations of recently onset heart failure?What are the clinical presentations of mild or moderate heart failure?What causes ascites in patients with heart failure?What are the signs and symptoms of increased adrenergic activity in patients with heart failure?What is the significance of rales in patients with heart failure?How is systemic venous hypertension manifested during heart failure?What causes hepatojugular reflux in heart failure?What is the significance of edema in heart failure?What causes hepatomegaly in heart failure?What causes hydrothorax in heart failure?What is protodiastolic gallop in heart failure?What is the significance of cardiomegaly in heart failure?What is the significance of pulsus alternans in heart failure?What are the common heart sounds in patients with heart failure?What is the significance of cardiac cachexia in heart failure?What are the clinical manifestations of predominant right-sided heart failure?What are the clinical manifestations of heart failure in children?What are the characteristics of right-sided venous congestion in heart failure?What are the characteristics of left-sided venous congestion in heart failure?What is required for the diagnosis of heart failure using the Framingham system?What is the basis for the New York Heart Association (NYHA) functional classification of heart failure?How does the American College of Cardiology/American Heart Association (ACC/AHA) classify heart failure?What are the prevention measures for ACC/AHA stage A heart failure?What screening should patients with a family history of dilated cardiomyopathy receive?What are the clinical characteristics of ACC/AHA stage B heart failure?What are the clinical characteristics of ACC/AHA stage C heart failure?What are the clinical characteristics of ACC/AHA stage D heart failure?What are the cardiac and noncardiac causes of heart failure?What is the most common form of heart failure in the US?How is heart failure differentiated from pulmonary edema?Which features may differentiate cardiogenic from noncardiogenic pulmonary edema in heart failure?What are the clinical features of noncardiogenic pulmonary edema in heart failure?How is right-sided heart failure presented?How is heart failure diagnosed in elderly patients?What are the differential diagnoses for Heart Failure?What is included in a careful workup of suspected heart failure?When is endomyocardial biopsy indicated in the workup of suspected heart failure?Which lab studies are performed in the diagnosis of heart failure?Should iron levels be measured in the workup of heart failure?What is the role of serum electrolyte values in the diagnosis of heart failure?What is the role of potassium levels in the diagnosis of heart failure?What is the role of pulmonary function testing (PFT) in the diagnosis of heart failure?What is the role of renal function tests in the diagnosis of heart failure?What is the role of liver function tests in the diagnosis of heart failure?How is acute hepatic venous congestion identified in heart failure?What is the role of rapid measurement of B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) in the diagnosis of heart failure?What are the limitations of B-type natriuretic peptide (BNP) measurements for the diagnosis of heart failure?When is measurement of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) indicated for the diagnosis of heart failure?What is the specificity and sensitivity of B-type natriuretic peptide (BNP) testing for diagnosis of heart failure?What are the cutoff values of B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) for the diagnosis of heart failure?In which patient groups do BNP and NT-proBNP levels vary from the norm for the diagnosis of heart failure?When is the measurement of B-type natriuretic peptide (BNP) contraindicated in the diagnosis of heart failure?What are the levels of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in patients with advanced heart failure?What is the role of genetic testing in the diagnosis of heart failure?Where can one go for specific genetic testing information related to the diagnosis of heart failure?Which types of cardiomyopathy have the highest yield of genetic testing for heart failure?How is genetic testing used to diagnose dilated cardiomyopathy and heart failure?How is genetic testing used to diagnose hypertrophic cardiomyopathy and heart failure?How is autosomal dominant arrhythmogenic right ventricular dysplasia/cardiomyopathy diagnosed in heart failure?When should genetic testing be considered for the diagnosis of heart failure?When is the measurement of arterial blood gas (ABG) indicated for the diagnosis of heart failure?What is the significance of a finding of hypoxemia in the evaluation of heart failure?What is assessed with arterial blood gas (ABG) measurement in the evaluation of heart failure?What is the role of mixed venous oxygen saturation in the diagnosis of heart failure?How is pulse oximetry used for the diagnosis of heart failure?What is the significance of oxygen saturation in the diagnosis of heart failure?When is a screening electrocardiogram (ECG) indicated in the evaluation of heart failure?What are the possible presentations of heart failure on electrocardiography?What is the role of chest radiographs in the diagnosis of heart failure?How is transesophageal echocardiography (TEE) used for the diagnosis of heart failure?How is stress echocardiography used for the diagnosis of heart failure?What is the role of two-dimensional (2-D) echocardiography in the diagnosis of heart failure?What is the role of Doppler echocardiography in the diagnosis of heart failure?What is the appearance of arrhythmogenic right ventricular dysplasia (ARVD) on echocardiogram for the diagnosis of heart failure?How are CT scanning and MRI used in the diagnosis of heart failure?What are the benefits of MRI in the diagnosis of heart failure?How is radionuclide multiple-gated acquisition (MUGA) scan used for the diagnosis of heart failure?What is the role of ECG-gated SPECT imaging in the diagnosis of heart failure?What is the benefit of combining interpretations of perfusion and function on electrocardiogram (ECG)-gated SPECT images for the diagnosis of heart failure?Why is ECG-gated SPECT considered state of the art for radionuclide myocardial perfusion imaging in heart failure?Which issues need to be addressed in the evaluation of presumed ischemic dysfunction in heart failure?How is equilibrium radionuclide angiocardiography (ERNA) used for the diagnosis of heart failure?How is the analysis from radionuclide angiocardiography (ERNA) obtained for the diagnosis of heart failure?How is radionuclide ventriculography used for the diagnosis of heart failure?How is the scintigraphic imaging agent iobenguane I 123 injection (AdreView) used in the diagnosis of heart failure?What is the role of coronary angiography in the diagnosis of heart failure?When is angiography indicated in the evaluation of heart failure?What is the role of right heart catheterization in the diagnosis of heart failure?What are normal right-sided hemodynamics in the evaluation of heart failure?How is pulmonary capillary wedge pressure (PCWP) measured for the diagnosis of heart failure?When are left-sided heart catheterization and coronary angiography indicated for the diagnosis of heart failure?How is cardiopulmonary stress testing used in the evaluation of heart failure?What is the prognostic relationship between sleep apnea and heart failure?What is the relationship between anemia and heart failure?What is included in the medical care of heart failure?Which invasive therapies are used in the treatment of heart failure?What is the role of heart transplantation in the treatment of heart failure?Why is it important to evaluate patients with heart failure for coronary artery disease?What is the benefit of coronary artery bypass grafting (CABG) in patients with heart failure?When is surgical revascularization recommended for the treatment of heart failure?When is coronary angiography useful in the management of heart failure?When are repeated evaluations for ischemia indicated in the management of heart failure?What is the relationship between valvular heart disease and heart failure?What are the treatment approaches to sleep apnea in patients with heart failure?What risks are increased in patients with comorbid sleep apnea and heart failure?What are the treatment approaches for anemia in patients with heart failure?What is the relationship between cardiorenal syndrome and heart failure?What are the classifications of cardiorenal syndrome in patients with heart failure?What is the pathophysiology of CR1 and CR2 of cardiorenal syndrome in heart failure?What are the indications for renal replacement therapy in heart failure?What is the significance of an increase in creatine levels in heart failure?How is dopamine used in the treatment of heart failure?What is the role of nesiritide in the treatment of heart failure?What is the role of tolvaptan in the treatment of heart failure?What is the role of adenosine receptor antagonists in the treatment of heart failure?What is the role of beta-blockers in the treatment of heart failure?What is the relationship between atrial fibrillation and heart failure?What is the role of catheter ablation in the treatment of heart failure?What is the role of radiofrequency ablation in the treatment of heart failure?What are the nonpharmacologic therapy options for heart failure?What are the benefits of aerobic exercise in the treatment of heart failure?Which measures improve treatment adherence in heart failure?What are the dietary restrictions for patients with heart failure?What is the significance of plasma eicosapentaenoic acid (EPA) concentrations in the prognosis of heart failure?What is the benefit of polyunsaturated fatty acids (PUFA) in the treatment of heart failure?Which pharmacologic therapies are used in the treatment of heart failure?What is the role of ivabradine (Corlanor) in the treatment of heart failure?What is the role of combination therapies for the treatment of heart failure?What is the role of anticoagulation therapy in the treatment of heart failure?When is infusion of positive inotropic drugs indicated in the treatment of heart failure?Which drugs should be avoided during the treatment of heart failure?What is the role of digoxin in the treatment of heart failure?What are the clinical characteristics of acute heart failure?How is acute heart failure managed?What are the treatment options to increase ventilation in patients with acute heart failure?What are the goals of medical therapy for acute heart failure?How is preload reduction achieved in the treatment of acute heart failure?Which 3 drugs are used in combination to manage acute heart failure following preload reduction?How is hypoperfusion treated in acute heart failure?What is the role of calcium channel blockers in the treatment of acute heart failure?What is the role of diuretics in the treatment of acute heart failure?How are diuretics administered for the treatment of heart failure?How is diuretic resistance diagnosed in acute heart failure?How is diuretic resistance managed in the treatment of acute heart failure?When is the transition to oral diuretic therapy made in the treatment of acute heart failure?What is the role of vasodilators in the treatment of acute heart failure?What is the role of nitrates in the treatment of acute heart failure?What is the role of sodium nitroprusside in the treatment of acute heart failure?What is the role of nesiritide in the treatment of acute heart failure?What is the role of ultrafiltration in the treatment of acute heart failure?When is inpatient treatment required for acute heart failure?When should hospitalization be considered for the treatment of acute heart failure?What is included in inpatient treatment of acute heart failure?What is the role of invasive hemodynamic monitoring in the treatment of acute heart failure?When is invasive hemodynamic monitoring used to guide therapy for acute heart failure?What is the role of monitoring in the management of acute heart failure?Which implantable wireless hemodynamic monitoring system are FDA approved for acute heart failure?What are the discharge criteria following treatment of acute heart failure?What are the predischarge requirements for patients with acute heart failure?What further care is required following treatment for acute heart failure?What are the goals of treatment for heart failure with preserved left ventricular ejection fraction (HFpEF)?What are the ACC/AHA/HFSA treatment guidelines for stage C of left ventricular ejection fraction (HFpEF) heart failure?What are lifestyle modifications for the treatment of left ventricular ejection fraction (HFpEF) heart failure?What is the role of diuretic therapy in the treatment of left ventricular ejection fraction (HFpEF) heart failure?What is the role of ACEIs and ARBs in the treatment of left ventricular ejection fraction (HFpEF) heart failure?When are beta-blockers indicated for the treatment of left ventricular ejection fraction (HFpEF) heart failure?When are aldosterone receptor and calcium channel blockers indicated for the treatment of left ventricular ejection fraction (HFpEF) heart failure?When should restoration of sinus rhythm be considered for the treatment of left ventricular ejection fraction (HFpEF) heart failure?What is the treatment approach for right ventricular (RV) heart failure?What are the general measures for the management of right ventricular (RV) heart failure?What are the precipitating factors for right ventricular (RV) heart failure?What is the role of ACEI/ARB therapy in the treatment of right ventricular (RV) heart failure?What is the role of inotropic therapy in the treatment of right ventricular (RV) heart failure?When are anticoagulants indicated for the treatment of right ventricular (RV) heart failure?When is atrial septostomy considered for the treatment of right ventricular (RV) heart failure?What is the prognosis of right ventricular (RV) heart failure?What are the electrophysiological interventions used to treat heart failure?What is the role of biventricular pacemakers in the treatment of heart failure?When are dual chamber pacemakers contraindicated in the management of heart failure?What is the role of implantable cardioverter-defibrillators (ICDs) in the treatment of heart failure?What are the benefits of using implantable cardioverter-defibrillators (ICDs) for the primary prevention of heart failure?How is cardiac resynchronization therapy (CRT) used in the treatment of heart failure?What are the benefits of combined CRT-ICD for the treatment of heart failure?When is cardiac resynchronization therapy (CRT) contraindicated in the treatment of heart failure?What is the CRT techniques used in the treatment of heart failure?What improvements have been seen following cardiac resynchronization therapy (CRT) for the treatment of heart failure?What is the efficacy of combined CRT-ICD treatment for heart failure?What is the difference in outcomes between men and women treated with combined CRT-ICD for heart failure?Which medications were evaluated in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) for the treatment of heart failure?What is the role of carvedilol in the treatment of heart failure?How does CRT affect mortality in patients with heart failure?What decrease in mortality was seen from biventricular pacing in the treatment of heart failure?What is a common cause of mortality in patients with heart failure?What is the efficacy of biventricular pacing for the treatment of heart failure?What factors are used to determine choice of revascularization procedure in the treatment of heart failure?How is the need for angiography determined in patients with heart failure at low risk for coronary artery disease (CAD)?What are the prognostic comparisons between medical and surgical therapy for coronary artery disease (CAD) in heart failure?What is the efficacy of surgical revascularization for the treatment of heart failure?What are the benefits of surgical revascularization in ischemic heart failure?What is the role of coronary artery bypass grafting (CABG) in the treatment of coronary artery disease (CAD) and heart failure?What is the prognosis of coronary artery diseases (CAD) and heart failure following coronary artery bypass grafting (CABG)?What is the efficacy of combined medical therapy and CABG for the treatment of heart failure?In which patient groups is medical therapy alone effective for the treatment of heart failure?How do mortality rates compare between combined CABG with medical therapy and medical therapy alone for the treatment of heart failure?Which surgical techniques and preventive strategies are used in the treatment of high-risk patients with heart failure?What is the relationship between valvular heart disease and heart failure?What is the relationship between diseases of the aortic valve and heart failure?When is aortic valve replacement indicated in the treatment of heart failure?What precautions should be taken when treating heart failure in patients with aortic valve disease?In which patient group is valvular surgery recommended for the treatment of heart failure?Which common symptom of aortic stenosis is a strong indicator of mortality from heart failure?What is the age-corrected survival rate for heart failure following aortic valve replacement (AVR)?How does the etiology of ventricular dysfunction affect the efficacy of aortic valve replacement (AVR) for treatment of heart failure?Why is precise measurement of the aortic valve difficult in patients with heart failure?What is the role of dobutamine testing in the preoperative evaluation of patients with heart failure?How does surgical timing affect the survival in heart failure?What the relationship between mitral valve regurgitation and heart failure?What are the goals of mitral valve surgery in patients with heart failure?What are the benefits of mitral valve repair for the treatment of heart failure?What are the limitations of mitral valve repair in patients with heart failure?What is the role of mitral regurgitation etiology in treatment selection for heart failure?In which patients should mitral valve surgery be considered for the treatment of heart failure?What is the role of cardiac resynchronization therapy (CRT) in the treatment of heart failure with mitral valve regurgitation?What is the role of annuloplasty in the treatment of heart failure?What are the limitations of annuloplasty in the treatment of heart failure?How is mitral valve replacement performed in the treatment of heart failure?What is the role of percutaneous mitral valve repair in the treatment of heart failure?What is the efficacy of percutaneous mitral valve repair in the treatment of heart failure?What is the ventricular response to heart failure?What is the goal of ventricular restoration following heart failure?What is the role of the Batista procedure in the treatment of heart failure?What is the focus of ventricular restoration following heart failure?What are the benefits from ventricular restoration in the treatment of heart failure?What is the efficacy of ventricular restoration in the treatment of heart failure?What is the role of extracorporeal membrane oxygenation (ECMO) in the treatment of heart failure?What are the indications for extracorporeal membrane oxygenation (ECMO) in the treatment of heart failure?What is the role of ventricular assist devices in the treatment of heart failure?How are ventricular assistive devices used in the treatment of heart failure?What are the options for bridging patient with heart failure to recovery and transplantation?Which left ventricular assist devices (LVADs) are FDA approved for heart failure destination therapy?What are the potential complications of left ventricular assist devices (LVADs) for the treatment of heart failure?What is efficacy of left ventricular assist devices (LVADs) in the treatment of heart failure?What modifications have reduced the mortality rates of left ventricular assist devices (LVADs) for the treatment of heart failure?Which types of ventricular assist devices (VADs) can be used by outpatients with heart failure?What is the postmarket approval efficacy of left ventricular assist devices (LVADs) for the treatment of heart failure?What are the advantages of continuous-flow left ventricular (LV) assist devices (LVADs) in the bridge treatment of heart failure?How is class IV stage D heart failure treated?What are the possible complications of continuous-flow left ventricular assist devices (LVADs) in severe heart failure?What is the role of heart transplantation in the treatment of heart failure?In which patient groups is heart transplantation the criterion standard for therapy for heart failure?What are the benefits of heart transplantation for heart failure?Which factors are critical for a good outcome following heart transplantation for heart failure?What are the absolute indications for heart transplantation for treatment of heart failure?What are the relative indications for heart transplantation for treatment of heart failure?Which indications in isolation are not sufficient for heart transplantation to treat heart failure?When is heart transplantation contraindicated for the treatment of heart failure?Which treatments are not recommended by the HFSA for the treatment of heart failure?How does coronary graft atherosclerosis affect the outcome of heart transplantation for heart failure?How often is heart transplantation performed in the US?What is the role of the total artificial heart (TAH) in the treatment of heart failure?What are the advantages of the total artificial heart (TAH) in the treatment of heart failure?Which artificial hearts (TAHs) are commercially available for the treatment of heart failure?What is the SynCardia TAH for the treatment of heart failure?What is the AbioCor TAH for the treatment of heart failure?What are the limitations of the AbioCor TAH for the treatment of heart failure?What surgery is required prior to implementation of TAHs for the treatment of heart failure?How is the CARMAT TAH used in the treatment of heart failure?What are the clinical applications of artificial-heart technology in the treatment of heart failure?Who is the contributor for heart failure guidelines?What is the Framingham classification of heart failure?What are the major diagnostic criteria for heart failure?What are the minor diagnostic criteria for heart failure?What are the New York Heart Association (NYHA) functional classifications of heart failure?What is the ACCF/AHA staging system for heart failure?What are the HRS-EHRA guidelines for targeted LQTS genetic testing in individuals at high risk for heart failure?What are the HRS-EHRA guidelines for LQTS mutation specific genetic testing in individuals at high risk for heart failure?What are the HRS-EHRA guidelines for targeted CPVT genetic testing in individuals at high risk for heart failure?What are the HRS-EHRA guidelines for targeted BrS genetic testing in individuals at high risk for heart failure?What are the HRS-EHRA guidelines for genetic testing for cardiac conduction disease (CCD) in individuals at high risk for heart failure?What are the HRS-EHRA guidelines for targeted SQTS genetic testing in individuals at high risk for heart failure?What are the HRS-EHRA guidelines for targeted HCM genetic testing in individuals at high risk for heart failure?What are the HRS-EHRA guidelines for targeted ACM/ARVC genetic testing in individuals at high risk for heart failure?What are the HRS-EHRA guidelines for targeted DCM genetic testing in individuals at high risk for heart failure?What are the HRS-EHRA guidelines for genetic testing for left ventricular noncompaction (LVNC) in individuals at high risk for heart failure?What are the HRS-EHRA guidelines for genetic testing for restrictive cardiomyopathy (RCM) in individuals at high risk for heart failure?What are the HRS-EHRA guidelines for genetic testing for familial DCM in individuals at high risk for heart failure?What are the HRS-EHRA guidelines for genetic testing for idiopathic DCM in individuals at high risk for heart failure?What are HFSA recommendations for genetic evaluation of cardiomyopathy in individuals at high risk for heart failure?Which organizations have issued guidelines for the diagnosis and management of heart failure?Which basic lab tests are recommended for the initial evaluation of suspected heart failure?What are the guidelines for measurement of BNP and NT-proBNP levels in the evaluation of suspected heart failure?What are the guidelines for use of imaging studies in evaluation of suspected heart failure?According to guidelines, which studies may be indicated in selected patients with heart failure?What are the guidelines for use of cardiac catheterization and coronary angiography in the evaluation of suspected heart failure?According to the ACCF/AHA guidelines, when is routine endomyocardial biopsy (EMB) indicated to diagnose heart failure?When does the ESC recommend considering endomyocardial biopsy (EMB) in the diagnosis of heart failure?When does the ACCF/AHA recommend a 6-minute walk test in the diagnosis of heart failure?In which situations does HFSA guidelines suggest routine maximal exercise stress testing in the diagnosis of heart failure?Which values of peak oxygen consumption reflect poor cardiac performance in the evaluation of heart failure?What are the guidelines for nonpharmacologic therapy of heart failure?What are the treatment guidelines for chronic heart failure?What is the purpose of patient education in the management of heart failure?What are the dietary treatment guidelines for heart failure?Which agents should be avoided by patients with heart failure?When are angiotensin receptor blockers (ARBs) recommended in patients with chronic heart failure?Which organizations have aligned their guidelines for pharmacologic therapy of heart failure?What are the class I recommendations for pharmacologic therapy of chronic heart failure with reduced ejection fraction (HFrEF)?When are ACE inhibitors recommended in patients with chronic heart failure?When are angiotensin receptor–neprilysin inhibitors (ARNIs) recommended in patients with chronic heart failure?When is ivabradine recommended in the treatment of chronic heart failure?When should angiotensin receptor–neprilysin inhibitors (ARNIs) contraindicated in the treatment of chronic heart failure?What is the role of device therapy for heart failure?What are the HFSA recommendations for the use of pacemakers in patients with heart failure?What are the ACC/AHA guidelines for consideration of cardiac resynchronization therapy (CRT) to treat heart failure?What are the ACCF/AHA and ESC guidelines for implantable cardioverter-defibrillator (ICD) placement in patients with heart failure?What are the ACCF/AHA guidelines for patient selection for cardiac resynchronization therapy (CRT) in heart failure?What are European Society of Cardiology (ESC) guidelines class I recommendations for the use of cardiac resynchronization therapy (CRT) in patients with heart failure?For which groups should cardiac resynchronization therapy (CRT) be considered for the treatment of heart failure?For which groups should cardiac resynchronization therapy (CRT) be considered for the treatment of heart failure?When is cardiac resynchronization therapy (CRT) contraindicated in the treatment of heart failure?What are the guidelines for use of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) revascularization procedures in patients with heart failure?For which patients with heart failure is revascularization recommended?In which patients with heart failure is the benefit-risk balance of revascularization uncertain?When is aortic valve replacement (AVR) recommended by the ACCF/AHA for the treatment of heart failure?What is the HFSA guideline for mitral valve repair or replacement in patients with heart failure?What are the ESC recommendations for valvular surgery in heart failure?Which organizations have release guidelines for the use of mechanical circulatory support (MCS) in patients with heart failure?Which mechanical circulatory support (MCS) devices are available for the treatment of heart failure?What are the SCAI/ACC/HFSA/STS recommendation for the use of mechanical circulatory support (MCS) devices in heart failure?What is the recommendation for routine use of mechanical circulatory support (MCS) devices for heart failure?What are the ISHLT guidelines for mechanical circulatory support (MCS) devices in the treatment of patients in acute cardiogenic shock?What are the ISHLT guidelines for heart failure therapy via mechanical circulatory support (MCS) devices?What are the AHA guidelines for mechanical circulatory support (MCS) in the treatment of heart failure?What are the ACCF/AHA and HFSA guidelines for consideration of heart transplantation in the treatment of heart failure?What are the ESC guidelines for consideration of heart transplantation in the treatment of heart failure?What do the ESC guidelines consider contraindications for heart transplantation in patients with heart failure?What are the HFSA recommended treatment goals for acute decompensated heart failure (ADHF)?What are the HFSA guidelines indications for hospital admission in acute decompensated heart failure (ADHF)?What are the ACCF/AHA guidelines for adjustment of maintenance medications in acute decompensated heart failure (ADHF)?What is the aim of diuretic therapy for heart failure?What are the recommended doses of diuretics for the treatment of heart failure?When is beta-blocker therapy initiated in hospitalized patients with heart failure?What are the recommendations for adjuvant treatment in heart failure?What are the HFSA guidelines for invasive hemodynamic monitoring in patients with heart failure?What are the HFSA recommendations for routine administration of supplemental oxygen in the treatment of heart failure?What are the goals of drug treatment for the treatment of heart failure?What is the role of ivabradine (Corlanor) in the treatment of heart failure?What is the role of combination sacubitril/valsartan (Entresto) therapy for the treatment of heart failure?Which drugs should be avoided by patients with heart failure?Which medications in the drug class Opioid Analgesics are used in the treatment of Heart Failure?Which medications in the drug class Anticoagulants, Cardiovascular are used in the treatment of Heart Failure?Which medications in the drug class Calcium Channel Blockers are used in the treatment of Heart Failure?Which medications in the drug class Alpha/Beta Adrenergic Agonists are used in the treatment of Heart Failure?Which medications in the drug class Aldosterone Antagonists, Selective are used in the treatment of Heart Failure?Which medications in the drug class Diuretics, Potassium-Sparing are used in the treatment of Heart Failure?Which medications in the drug class Diuretics, Other are used in the treatment of Heart Failure?Which medications in the drug class Diuretics, Thiazide are used in the treatment of Heart Failure?Which medications in the drug class Diuretics, Loop are used in the treatment of Heart Failure?Which medications in the drug class ARNIs are used in the treatment of Heart Failure?Which medications in the drug class I(f) Inhibitors are used in the treatment of Heart Failure?Which medications in the drug class B-type Natriuretic Peptides are used in the treatment of Heart Failure?Which medications in the drug class Nitrates are used in the treatment of Heart Failure?Which medications in the drug class Vasodilators are used in the treatment of Heart Failure?Which medications in the drug class Inotropic Agents are used in the treatment of Heart Failure?Which medications in the drug class ARBs are used in the treatment of Heart Failure?Which medications in the drug class ACE Inhibitors are used in the treatment of Heart Failure?Which medications in the drug class Beta-Blockers, Beta-1 Selective are used in the treatment of Heart Failure?Which medications in the drug class Beta-Blockers, Alpha Activity are used in the treatment of Heart Failure?

References

Author

Ioana Dumitru, MD, Associate Professor of Medicine, Division of Cardiology, Founder and Medical Director, Heart Failure and Cardiac Transplant Program, University of Nebraska Medical Center; Associate Professor of Medicine, Division of Cardiology, Veterans Affairs Medical Center