Heart failure

Heart failure is a consequence of the disturbance of filling or contraction of the ventricles of the heart, which determines the decrease in the pumping function of the heart, accompanied by typical symptoms: shortness of breath and rapid fatigue. Cardiomyopathy is a general term for primary diseases of the heart muscle. There are four main types of cardiomyopathy: dilated, hypertrophic, infiltrative and restrictive. The decision has now been made to abandon the terms of secondary cardiomyopathy: hypertensive, ischemic, valvular, etc. Any of these options can lead to heart failure.

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Epidemiology

Heart failure (HF) affects approximately 5 million people in the United States, with more than 500,000 new cases occurring each year.

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Causes heart failure

Both cardiac and systemic factors can impair cardiac performance and lead to heart failure. Cardiac factors include myocardial injury (eg, acute in myocardial infarction or myocarditis, chronic in fibrosis associated with various disorders), valvular disease, arrhythmias (tachyarrhythmias or bradyarrhythmias), and a decrease in the amount of functioning myocardium (ie, ischemia). Systemic factors include any condition that increases cardiac output, such as anemia (leading to high-output heart failure), or limits output (afterload), such as systemic hypertension.

The traditional distinction between left and right ventricular failure is somewhat misleading because the heart is an integrated system, like a pump, and changes in one chamber ultimately affect the entire heart. However, these terms identify the location of the greatest damage leading to heart failure and can be useful for initial diagnosis and treatment.

Left ventricular failure usually develops in coronary artery disease (CAD), hypertension, aortic stenosis, most forms of cardiomyopathy, acquired mitral or aortic valve regurgitation, and congenital heart defects (eg, ventricular septal defect, patent ductus arteriosus with large shunt).

Right ventricular failure is usually caused by previous left ventricular failure (leading to increased pulmonary venous pressure and pulmonary arterial hypertension, i.e., right ventricular overload) or severe lung disease (then the condition is called cor pulmonale). Other causes include multiple pulmonary embolisms, pulmonary veno-occlusive disease, right ventricular infarction, primary pulmonary hypertension, tricuspid regurgitation or stenosis, mitral stenosis, and pulmonary valve or artery stenosis. Several conditions mimic right ventricular failure but may have normal cardiac function; these include volume overload and increased systemic venous pressures in polycythemia or massive transfusions, and acute renal failure with sodium and water retention leading to fluid overload. Obstruction of the vena cava may also mimic the clinical presentation of right ventricular failure.

Failure of both ventricles occurs in diseases that damage the entire myocardium (for example, viral myocarditis, amyloidosis, Chagas disease).

High-output heart failure occurs when there is a persistent demand for high CO, which may eventually lead to the inability of a normal heart to maintain adequate output. Conditions that can increase CO include severe anemia, beriberi, thyrotoxicosis, advanced Paget's disease, arteriovenous fistula, and persistent tachycardia. CO is high in various forms of cirrhosis, but most fluid retention is due to hepatic mechanisms.

Cardiomyopathy is a general term for myocardial disease, formerly used to describe an etiology (e.g., ischemic or hypertensive cardiomyopathy) resulting in secondary myocardial damage. Currently, the term is used to describe primary ventricular myocardial disease that is not caused by congenital anatomic defects, valvular, systemic, or pulmonary vascular disorders, primary diseases of the pericardium or conduction system components, or ischemic heart disease. Cardiomyopathy is often idiopathic and is classified as congestive dilated, hypertrophic, or infiltrative-restrictive cardiomyopathy.

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Pathogenesis

Cardiac contractility, ventricular function, and myocardial oxygen demand are determined by preload, afterload, nutrient availability (e.g., oxygen, fatty acids, glucose), heart rate and rhythm pattern, and viable myocardial mass. Cardiac output (CO) is proportional to heart rate per unit time and stroke volume; it is also influenced by venous return, peripheral vascular resistance, and neurohumoral factors.

Preload is the state of the heart at the end of its relaxation phase (diastole) just before contraction (systole). Preload reflects the degree of end-diastolic stretch of the myocardial fibers and the end-diastolic volume, which is influenced by ventricular diastolic pressure and the structure of the myocardial wall. As a rule, the left ventricular (LV) end-diastolic pressure, especially if it is higher than normal, serves as an acceptable indicator of preload. Dilation, hypertrophy, and changes in left ventricular compliance alter preload.

Afterload is the force of resistance to myocardial fiber contraction at the onset of systole. It is determined by intraventricular pressure, volume, and wall thickness at the time of aortic valve opening. Clinically, systemic BP at or immediately after aortic valve opening represents peak systolic wall stress and approximates afterload.

The Frank-Starling law describes the relationship between preload and cardiac performance. It states that systolic contractility (represented by stroke volume or CO) is normally proportional to preload within the normal physiological range. Contractility is difficult to measure without cardiac catheterization, but is well reflected by the ejection fraction (EF), a percentage of the end-diastolic volume ejected with each contraction (left ventricular stroke volume/end-diastolic volume).

Cardiac reserve is the ability of the heart to increase its work above resting levels in response to emotional or physical stress. During maximal exertion, the body's oxygen consumption may increase from 250 to 1500 ml/min or more. Mechanisms include increases in heart rate, systolic and diastolic volumes, stroke volume, and tissue oxygen consumption (the difference between the O ₂ content of arterial blood and mixed venous or pulmonary artery blood). In well-trained young adults, during maximal exertion, the heart rate may increase from 55-70 beats per minute (at rest) to 180 beats per minute, and CO may increase from 6 to 25 L/min or more. At rest, arterial blood contains approximately 18 ml of oxygen per dL of blood, and mixed venous or pulmonary artery blood contains about 14 ml/dL.

Thus, oxygen consumption is approximately 4.0 ml/dl, but with increasing demand it can increase to 12-14 ml/dl. These mechanisms are also involved in compensation in heart failure.

In heart failure, the heart may not deliver the amount of blood necessary for metabolism to the tissues, and the associated increase in pulmonary or systemic venous pressure can lead to plethora of peripheral organs. This condition may occur with disorders of the systolic or diastolic function of the heart (usually both).

In systolic dysfunction, the ventricle contracts weakly and empties incompletely, which initially leads to an increase in diastolic volume and pressure. Later, EF decreases. There are disturbances in energy expenditure, energy supply, electrophysiological functions, and contractility is impaired with disturbances in intracellular calcium metabolism and synthesis of cyclic adenosine monophosphate (cAMP). Predominance of systolic dysfunction is a common phenomenon in heart failure due to myocardial infarction. Systolic dysfunction can develop predominantly in the left ventricle or the right ventricle; left ventricular failure often leads to the development of right ventricular failure.

In diastolic dysfunction, ventricular filling is impaired, resulting in decreased ventricular end-diastolic volume, increased end-diastolic pressure, or both. Contractility and hence EF remain normal, and EF may even increase as the poorly filled LV contracts more effectively to maintain cardiac output. Markedly decreased left ventricular filling may result in low CO and systemic manifestations. Increased atrial pressures lead to pulmonary congestion. Diastolic dysfunction usually occurs with impaired ventricular relaxation (an active process), increased ventricular rigidity, constrictive pericarditis, or atrioventricular valve stenosis. Resistance to filling increases with age, probably reflecting decreased myocyte numbers and interstitial collagen deposition. Thus, diastolic dysfunction is quite common in older people. Diastolic dysfunction is thought to be predominant in hypertrophic cardiomyopathy, diseases that cause ventricular hypertrophy (eg, hypertension, severe aortic stenosis), and myocardial amyloid infiltration. Left ventricular filling and function may also be impaired when the interventricular septum bulges to the left as a result of a marked increase in right ventricular pressure.

In left ventricular failure, CO decreases and pulmonary venous pressure increases. Since pulmonary capillary pressure exceeds the oncotic pressure of plasma proteins (approximately 24 mm Hg), fluid in the blood leaks from the capillaries into the interstitial space and alveoli, causing peripheral edema and/or decreasing pulmonary function and increasing the respiratory rate. Lymphatic drainage increases, but cannot compensate for the increase in fluid in the lungs. The marked accumulation of fluid in the alveoli (pulmonary edema) significantly alters the ventilation/perfusion (V/Q) relationship: deoxygenated pulmonary arterial blood passes through poorly ventilated alveoli, resulting in a decrease in the partial pressure of oxygen in arterial blood (pO2) and causing dyspnea. Dyspnea may, however, occur before V/Q disorder, probably because of the increase in pulmonary venous pressure and the increase in the work of breathing; The exact mechanism of this phenomenon is unclear. In severe or chronic left ventricular failure, pleural effusion typically develops in the right half of the chest, and later on both sides, further worsening dyspnea. Minute ventilation increases, and thus pCO2 decreases and blood pH increases (respiratory alkalosis). Interstitial edema in the small airways may impede ventilation, increasing pCO2, a sign of impending respiratory failure.

In right ventricular failure, systemic venous pressure increases, causing fluid to leak into the interstitial space and progressive edema, primarily of the peripheral tissues (feet and ankles) and abdominal organs. Liver function is primarily affected, although gastric and intestinal function is impaired, and fluid may accumulate in the abdominal cavity (ascites). Right ventricular failure usually causes moderate liver dysfunction, usually with a slight increase in conjugated and free bilirubin, prothrombin time, and liver enzyme activity (eg, alkaline phosphatase, AST, ALT). The damaged liver is unable to inactivate aldosterone, and secondary aldosteronism contributes to fluid accumulation. Chronic venous congestion in viscera can cause anorexia, malabsorption syndrome, protein-losing enteropathy (characterized by diarrhea and significant hypoalbuminemia), persistent gastrointestinal blood loss, and (occasionally) ischemic bowel infarction.

Changes in cardiac function. When the pumping function of the ventricles of the heart deteriorates, an increase in preload is intended to maintain CO. As a result, over a long period of time, remodeling of the left ventricle occurs: it becomes more elliptical, expands and hypertrophies. Although initially compensatory, these changes ultimately increase diastolic rigidity and wall tension (myocardial stress), impairing cardiac function, especially during physical exertion. Increased tension of the heart wall increases the need for oxygen and accelerates apoptosis (programmed cell death) of myocardial cells.

Hemodynamic changes: When CO decreases, tissue oxygen supply is maintained by increasing O2 intake from atmospheric air, which sometimes results in a rightward shift of the oxyhemoglobin dissociation curve to improve O2 release.

Reduced CO with decreased systemic BP activates arterial baroreceptors, increasing sympathetic tone and decreasing parasympathetic tone. As a result, HR and myocardial contractility increase, arterioles in the corresponding areas of the vascular bed narrow, venoconstriction occurs, and sodium and water are retained. These changes compensate for the decrease in ventricular function and help maintain hemodynamic homeostasis in the early stages of heart failure. However, these compensatory mechanisms increase cardiac work, preload, and afterload; decrease coronary and renal blood flow; cause fluid accumulation leading to edema; increase potassium excretion, and can also cause myocyte necrosis and arrhythmia.

Changes in kidney function. As a result of deterioration of cardiac function, renal blood flow and glomerular filtration decrease, and renal blood flow is redistributed. Filtration function and sodium excretion decrease, but tubular reabsorption increases, leading to sodium and water retention. Blood flow is subsequently redistributed, decreasing in the kidneys during physical exertion but increasing during rest, which may contribute to the development of nocturia.

Reduced renal perfusion (and possibly reduced arterial systolic pressure secondary to decreased ventricular function) activates the renin-angiotensin-aldosterone system, increasing sodium and water retention and renal and peripheral vascular tone. These effects are enhanced by the intense sympathetic activation that accompanies heart failure.

The renin-angiotensin-aldosterone-vasopressin system causes a cascade of potentially deleterious effects. Angiotensin II worsens heart failure by causing vasoconstriction, including in the efferent renal arterioles, and by increasing aldosterone synthesis, which not only increases sodium reabsorption in the distal nephron but also leads to myocardial collagen deposition and fibrosis. Angiotensin II increases norepinephrine release, stimulates antidiuretic hormone (ADH) synthesis, and induces apoptosis. Angiotensin II may be involved in the development of vascular and myocardial hypertrophy, thereby contributing to cardiac and peripheral vasculature remodeling, potentially worsening heart failure. Aldosterone can be synthesized in the heart and vasculature independently of angiotensin II (possibly stimulated by corticotropin, nitric oxide, free radicals, and other stimulants) and have negative effects in these organs.

Neurohumoral response. Under stress conditions, neurohumoral activation promotes increased cardiac function, maintaining blood pressure and organ blood supply, but constant activation of these reactions leads to disruption of the normal balance between the effects that increase myocardial function and cause vasoconstriction, and the factors that cause myocardial relaxation and vasodilation.

The heart contains a large number of neurohumoral receptors (angiotensin type 1 and type 2, muscarinic, endothelin, serotonin, adenosine, cytokine). The role of these receptors has not yet been fully determined. In patients with heart failure, the receptors (which make up 70% of the cardiac receptors) are depressed, probably in response to intense sympathetic stimulation, resulting in deterioration of cardiomyocyte contractility.

Plasma norepinephrine levels are increased, largely reflecting sympathetic stimulation, while epinephrine levels are unchanged. Adverse effects include vasoconstriction with increased preload and afterload, direct myocardial injury including apoptosis, decreased renal blood flow, and activation of other neurohumoral systems including the renin-angiotensin-aldosterone-ADH cascade.

ADH is secreted in response to a decrease in blood pressure due to various neurohormonal stimulation. Increased ADH levels cause a decrease in free water excretion through the kidneys, possibly contributing to hyponatremia in heart failure. ADH levels vary in patients with heart failure and normal blood pressure.

Atrial natriuretic peptide is released in response to increased atrial volume and pressure. Brain natriuretic peptide (B-type) is released in the ventricle in response to ventricular stretch. These peptides (NUP) increase renal sodium excretion, but the effect is reduced in patients with heart failure because of decreased renal perfusion pressure, low receptor sensitivity, and possibly excessive enzymatic degradation of NUP.

Since endothelial dysfunction occurs in heart failure, the synthesis of endogenous vasodilators (eg, nitric oxide, prostaglandins) decreases and the formation of endogenous vasoconstrictors (eg, endothelin) increases.

The altered heart and other organs produce tumor necrosis factor alpha (TNF). This cytokine increases catabolism and may be responsible for cardiac cachexia (loss of more than 10% of body weight), which may worsen the manifestations of heart failure and other negative changes.

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Symptoms heart failure

Symptoms of heart failure vary depending on which ventricle is primarily affected - the right or left. The severity of clinical manifestations varies significantly and is usually determined by the New York Heart Association (NYHA) classification. Left ventricular failure leads to the development of pulmonary edema.

In left ventricular failure, the most common symptoms are dyspnea, reflecting pulmonary congestion, and fatigue as a manifestation of low CO. Dyspnea usually occurs with exercise and disappears with rest. As heart failure worsens, dyspnea may develop at rest and at night, sometimes causing a nocturnal cough. Dyspnea that begins immediately or soon after lying down and is rapidly relieved by sitting (orthopnea) is common. Paroxysmal nocturnal dyspnea (PND) awakens patients several hours after lying down and is relieved only after sitting for 15 to 20 minutes. In severe heart failure, periodic cyclic breathing (Cheyne-Stokes respiration) may occur both at night and during the day - a brief period of rapid breathing (hyperpnea) alternates with a brief period of no breathing (apnea); a sudden hyperpneic phase may awaken the patient from sleep. In contrast to paroxysmal nocturnal dyspnea, the hyperpneic phase is short, lasting a few seconds and resolving within 1 min or less. Paroxysmal nocturnal dyspnea is caused by pulmonary congestion, while Cheyne-Stokes respiration is caused by low CO. Sleep-related breathing disorders such as sleep apnea are common in heart failure and may worsen it. Severely reduced cerebral blood flow and hypoxemia can cause chronic irritability and impair mental performance.

New York Heart Association Classification of Heart Failure

NYHA class	Definition	Limit physical activity	Examples
I	Normal physical activity does not result in fatigue, shortness of breath, palpitations or angina	No	Can handle any load that requires 7 MET*: moving a 11 kg load 8 steps, lifting 36 kg, shoveling snow, digging, skiing, playing tennis, volleyball, badminton or basketball; running/walking at 8 km/h
II	Normal physical activity results in fatigue, shortness of breath, palpitations or angina	Lungs	Can handle any load that requires 5 METERS: continuous sexual intercourse, gardening, roller skating, walking on a level surface at 7 km/h
III	Feeling good at rest. A little physical activity causes fatigue, shortness of breath, palpitations or angina	Moderate	Can handle any load that requires 2 METERS: showering or dressing without resting, changing or making bedding, washing windows, playing golf, walking at 4 km/h
IV	Presence of symptoms at rest. The slightest physical activity increases discomfort	Expressed	Cannot perform or complete any of the above 2 MET activities. Cannot cope with any of the above workloads.

"MET stands for metabolic equivalent.

In right ventricular failure, the most common symptoms are swelling in the ankles and fatigue. Sometimes patients feel fullness in the abdomen or neck. Swelling of the liver can cause discomfort in the right upper quadrant of the abdomen, and swelling of the stomach and intestines can cause anorexia and bloating.

Less specific symptoms of heart failure include cold hands and feet, acrocyanosis, postural dizziness, nocturia, and decreased daytime urine output. Decreased skeletal muscle mass may occur with severe biventricular failure and reflect some nutritional depletion but also increased catabolism associated with increased cytokine synthesis. Significant weight loss (cardiac cachexia) is an ominous sign associated with high mortality.

A general examination may reveal signs of systemic disorders that cause or worsen heart failure (eg, anemia, hyperthyroidism, alcoholism, hemochromatosis).

In left ventricular failure, tachycardia and tachypnea are possible; in patients with severe left ventricular failure, there is obvious dyspnea or cyanosis, arterial hypotension; they may experience drowsiness or agitation due to hypoxia and decreased cerebral blood supply. General cyanosis (of the entire body surface, including areas that are warm to the touch, such as the tongue and mucous membranes) reflects severe hypoxemia. Peripheral cyanosis (lips, fingers) reflects low blood flow with increased oxygen consumption. If vigorous massage improves the color of the nail bed, cyanosis can be considered peripheral; if cyanosis is central, increased local blood flow does not improve the color.

In left ventricular systolic dysfunction, the heart reveals a diffuse, increased, laterally displaced apical impulse; audible and sometimes palpable II (S2) and IV (S4) heart sounds, an accentuation of the II sound over the pulmonary artery. Pansystolic mitral regurgitation murmur may appear at the apex. Examination of the lungs reveals wheezing in the lower parts of the lungs on inspiration and, in the presence of pleural effusion, dullness on percussion and weakening of breathing in the lower parts of the lung.

Symptoms of right ventricular failure include nontense peripheral edema (visible and palpable impressions, sometimes quite deep, when pressed with a finger) in the legs; an enlarged and sometimes pulsatile liver, palpable below the right costal margin; abdominal distension, ascites, and visible jugular venous distension, increased venous pressure in the jugular veins, sometimes with high a or v waves that are visible even when the patient is sitting or standing. In severe cases, peripheral edema may extend to the thighs or even the sacrum, scrotum, lower anterior abdominal wall, and sometimes even higher. Extensive edema in many areas is called anasarca. The edema may be asymmetrical if the patient lies predominantly on one side.

In case of edema, the liver may be enlarged or hardened. When pressing on the liver, the hepatojugular reflex may be detected. When palpating the cardiac area, a bulge in the parasternal region on the left may be detected, associated with the expansion of the right ventricle, and when listening, a tricuspid regurgitation or S2 noise of the right ventricle may be detected along the left border of the sternal wall.

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Diagnostics heart failure

Clinical signs (e.g., exertional dyspnea, orthopnea, edema, tachycardia, pulmonary rales, jugular venous distension) suggestive of heart failure appear late. Similar symptoms may also occur in COPD or pneumonia, and are sometimes mistakenly attributed to old age. Heart failure should be suspected in patients with a history of myocardial infarction, arterial hypertension, or valvular disorders and the presence of additional heart sounds and murmurs. Moderate heart failure should be suspected in elderly patients or patients with diabetes mellitus.

A chest X-ray, ECG, and a test to objectively evaluate the heart's function (usually echocardiography) are needed to confirm the diagnosis. Blood tests, with the exception of B-type natriuretic peptide, are not used for diagnosis, but they are useful in determining the cause and general manifestations of heart failure.

Chest radiographic findings suggestive of heart failure include enlargement of the cardiac shadow, pleural effusion, fluid in the main interlobar fissure, and horizontal lines in the peripheral lower posterior lung fields (Kerley B lines). These findings reflect persistently elevated left atrial pressures and chronic edema-induced thickening of the interlobar septa. Upper pulmonary venous congestion and interstitial or alveolar edema may also be seen. Careful examination of the lateral cardiac shadow may reveal specific ventricular or atrial enlargement. Radiographic examination may help differentiate other disorders that cause dyspnea (eg, COPD, idiopathic pulmonary fibrosis, lung cancer).

ECG findings are not considered diagnostic, but an abnormal ECG, especially one showing previous myocardial infarction, left ventricular hypertrophy, left bundle branch block, or tachyarrhythmia (eg, rapid atrial fibrillation), increases the likelihood of heart failure and may help identify the cause.

Echocardiography can evaluate cardiac chamber size, valve function, ejection fraction, wall motion abnormalities, left ventricular hypertrophy, and pericardial effusion. Intracardiac thrombi, tumors, and calcifications around the heart valves, mitral annulus, and aortic wall abnormalities can also be detected. Localized or segmental wall motion abnormalities strongly suggest underlying coronary artery disease but may also be present in focal myocarditis. Doppler or color Doppler imaging can reliably detect valvular abnormalities and shunts. Doppler examination of mitral and pulmonary venous flow can often detect and quantify left ventricular diastolic dysfunction. Measurement of left ventricular EF can differentiate predominant diastolic dysfunction (EF > 0.40) from systolic dysfunction (EF < 0.40), which may require different treatment. Three-dimensional echocardiography has the potential to become an important diagnostic tool, but is currently only available in specialized centers.

Radioisotope scanning allows to evaluate systolic and diastolic functions, to identify previous myocardial infarction, ischemia or myocardial hibernation. Cardiac MRI allows to obtain precise images of its structures, but it is not always available and is more expensive.

Recommended blood tests include complete blood count, serum creatinine, blood urea, electrolytes (including magnesium and calcium), glucose, protein, and liver function tests. Thyroid function tests are recommended in patients with atrial fibrillation and in some, particularly elderly, patients. Serum urea is elevated in heart failure; this test may be helpful when clinical manifestations are unclear or when another diagnosis (eg, COPD) must be excluded, particularly when there is a history of both pulmonary and cardiac disease.

Cardiac catheterization and coronary angiography are indicated when coronary artery disease is suspected or when the diagnosis and etiology are uncertain.

Endocardial biopsy is usually performed only if infiltrative cardiomyopathy is suspected.

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Treatment heart failure

Patients with heart failure due to certain causes (eg, acute myocardial infarction, atrial fibrillation with rapid ventricular rate, severe hypertension, acute valvular regurgitation) require emergency hospitalization, as do patients with pulmonary edema, severe manifestations, new-onset heart failure, or heart failure resistant to outpatient treatment. Patients with moderate exacerbations of established heart failure may be treated at home. The primary goal is to diagnose and eliminate or treat the pathological process that led to heart failure.

The immediate goals include reducing clinical manifestations, correcting hemodynamics, eliminating hypokalemia, renal dysfunction, symptomatic arterial hypotension, and correcting neurohumoral activation. The long-term goals include treating arterial hypertension, preventing myocardial infarction and atherosclerosis, reducing the number of hospitalizations, and improving survival and quality of life. Treatment involves changes in diet and lifestyle, drug therapy (see below), and (sometimes) surgical intervention.

Limiting dietary sodium helps reduce fluid retention. All patients should avoid adding salt to food during preparation and at the table and avoid salty foods. The most seriously ill patients should limit their sodium intake (< 1 g/day) by consuming only foods low in sodium. Monitoring body weight every morning helps to detect sodium and water retention early. If weight has increased by more than 4.4 kg, patients can adjust the dose of diuretic themselves, but if weight gain continues or other symptoms occur, they should seek medical advice. Patients with atherosclerosis or diabetes mellitus should strictly follow an appropriate diet. Obesity can cause heart failure and always worsens its symptoms; patients should aim to achieve a BMI of 21-25 kg/m ².

Regular light physical activity (eg, walking) is encouraged, depending on the severity of the disease. Activity prevents deterioration of skeletal muscle fitness (which reduces functional status); whether this recommendation affects survival is currently under investigation. Rest is necessary during exacerbations.

Treatment is based on the cause, symptoms, and response to medications, including adverse effects. Treatment of systolic and diastolic dysfunction differs somewhat, although there are some common indications. The patient and family should be involved in the choice of treatment. They should be taught the importance of adherence to medication, the signs of a severe exacerbation, and the importance of using medications that do not have a rapid effect. Close observation of the patient, especially if the patient is adherent to treatment, and the frequency of unscheduled office visits or emergency department visits and hospitalizations help determine when medical intervention is needed. Specialized nurses are essential for patient education, monitoring, and adjusting medication doses according to established protocols. Many centers (eg, tertiary care outpatient clinics) have integrated practitioners from different disciplines (eg, heart failure nurses, pharmacists, social workers, rehabilitation specialists) into multidisciplinary teams or outpatient heart failure programs. This approach can improve treatment outcomes and reduce hospitalizations and is most effective in the most severely ill patients.

If arterial hypertension, severe anemia, hemochromatosis, uncontrolled diabetes mellitus, thyrotoxicosis, beriberi, chronic alcoholism, Chagas disease, or toxoplasmosis are successfully treated, the condition of patients can improve significantly. Attempts to correct extensive ventricular infiltration (for example, in amyloidosis and other restrictive cardiomyopathies) remain unsatisfactory.

Surgical treatment of heart failure

Surgery may be indicated for certain underlying conditions of heart failure. Surgery for heart failure is usually performed in specialized centers. Therapeutic intervention may include surgical correction of congenital or acquired intracardiac shunts.

Some patients with ischemic cardiomyopathy may benefit from CABG, which can reduce the degree of ischemia. If heart failure is due to valvular disease, valve repair or replacement is considered. Better results are seen in patients with primary mitral regurgitation than in patients with mitral regurgitation due to left ventricular dilation, in whom myocardial function is unlikely to improve with surgery. Surgical correction is preferred before irreversible ventricular dilation occurs.

Heart transplantation is the treatment of choice for patients younger than 60 years with severe refractory heart failure and no other life-threatening conditions. Survival is 82% at 1 year and 75% at 3 years; however, mortality while waiting for a donor is 12-15%. Availability of human organs remains low. Left ventricular assist devices can be used until transplantation or (in some selected patients) permanently. The artificial heart is not yet a realistic alternative. Investigational surgical interventions include implantation of restrictive devices to reduce progressive chamber dilation and a modified aneurysmectomy called surgical ventricular remodeling. Dynamic cardiac myoplasty and excision of segments of dilated myocardium (Batista procedure - partial ventriculectomy) are no longer recommended.

Arrhythmias

Sinus tachycardia, a common compensatory response in heart failure, usually resolves with effective treatment of the underlying heart failure. If it does not, other causes (eg, hyperthyroidism, pulmonary embolism, fever, anemia) should be excluded. If tachycardia persists despite correction of the underlying cause, consideration should be given to administering a beta-blocker with a gradual increase in dosage.

Atrial fibrillation with uncontrolled ventricular rhythm is an indication for drug correction. Beta-blockers are the drugs of choice, but with preserved systolic function, calcium channel blockers that reduce heart rate can be used with caution. Sometimes, adding digoxin is effective. In moderate heart failure, restoring sinus rhythm may not have advantages over normalizing heart rate, but some patients with heart failure feel better with sinus rhythm. If drug therapy is ineffective in the tachystolic form of atrial fibrillation, in some cases a permanent dual-chamber pacemaker with complete or partial ablation of the AV node is implanted.

Isolated ventricular extrasystoles, characteristic of heart failure, do not require specific treatment. Persistent ventricular tachycardia that persists despite optimal treatment of heart failure may be an indication for an antiarrhythmic drug. The drugs of choice are amiodarone and beta-blockers, since other antiarrhythmic drugs can have unfavorable proarrhythmic effects in the presence of left ventricular systolic dysfunction. Since amiodarone increases digoxin levels, the digoxin dose should be halved. Since long-term use of amiodarone can be associated with adverse effects, the lowest possible dose (200-300 mg once daily) is used. Blood tests for liver function and thyroid-stimulating hormone levels are performed every 6 months and also when chest radiographs are abnormal or dyspnea worsens. Chest radiography and pulmonary function tests are performed annually to rule out the development of pulmonary fibrosis. For persistent ventricular arrhythmias, amiodarone 400 mg once daily may be required.

An implantable cardioverter-defibrillator (ICD) is recommended for patients with a good life expectancy if they have symptomatic sustained ventricular tachycardia (especially leading to syncope), ventricular fibrillation, or LVEF < 0.30 after myocardial infarction.

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Refractory heart failure

Symptoms of heart failure may persist after treatment. This may be due to persistence of the underlying disorder (eg, hypertension, ischemia, valvular regurgitation), inadequate treatment of heart failure, noncompliance with medications, excessive dietary sodium or alcohol intake, undetected thyroid disease, anemia, or arrhythmia (eg, high-efficiency atrial fibrillation, nonsustained ventricular tachycardia). In addition, drugs used to treat other disorders may interact adversely with drugs used to treat heart failure. NSAIDs, antidiabetics, and short-acting dihydropyridine and nondihydropyridine calcium channel blockers may worsen heart failure and are therefore not generally used. Biventricular pacemakers reduce the severity of clinical manifestations in patients with heart failure, severe systolic dysfunction and widened QRS complex.

Medicines for heart failure

Drugs that reduce the manifestations of heart failure include diuretics, nitrates, and digoxin. ACE inhibitors, beta-blockers, aldosterone receptor blockers, and angiotensin II receptor blockers are effective in the long term and improve survival. Different strategies are used to treat systolic and diastolic dysfunction. In patients with severe diastolic dysfunction, diuretics and nitrates should be given in lower doses because these patients do not tolerate reductions in blood pressure or plasma volume. In patients with hypertrophic cardiomyopathy, digoxin is ineffective and may even be harmful.

Diuretics

Diuretics are prescribed to all patients with systolic dysfunction accompanied by symptoms of heart failure. The dose is selected starting with the minimum, capable of stabilizing the patient's body weight and reducing the clinical manifestations of heart failure. Preference is given to loop diuretics. Furosemide is used most often, starting with 20-40 mg once a day with an increase in the dose to 120 mg once a day (or 60 mg 2 times a day) if necessary, taking into account the effectiveness of treatment and kidney function. Bumetanide and especially torasemide are alternatives. Torasemide has better absorption and can be used orally for a longer period (the dose ratio with furosemide is 1:4). In addition, due to the antialdosterone effects, the use of torasemide leads to a smaller electrolyte imbalance. In refractory cases, furosemide 40-160 mg intravenously, ethacrynic acid 50-100 mg intravenously, bumetanide 0.5-2.0 mg orally or 0.5-1.0 mg intravenously can be prescribed. Loop diuretics (especially when used with thiazides) can cause hypovolemia with arterial hypotension, hyponatremia, hypomagnesemia, and severe hypokalemia.

Serum electrolytes are monitored daily at the beginning of treatment (if intravenous diuretics are prescribed), then as needed, especially after increasing the dose. Potassium-sparing diuretics - spironolactone or eplerenone (which are aldosterone receptor blockers) - can be added to prevent potassium loss when high doses of loop diuretics are prescribed. Hyperkalemia may develop, especially with concomitant use of ACE inhibitors or angiotensin II receptor blockers, so electrolyte composition should be monitored regularly. Thiazide diuretics are usually used in concomitant arterial hypertension.

Some patients are taught to increase the dose of diuretics on an outpatient basis if weight gain or peripheral edema occurs. If weight gain persists, these patients should seek immediate medical attention.

Experimental drugs from the ADH blocker group increase water excretion and serum sodium concentrations and are less likely to cause hypokalemia and renal dysfunction. These agents may be a useful adjunct to chronic diuretic therapy.

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Angiotensin converting enzyme inhibitors

All patients with systolic dysfunction, in the absence of contraindications (eg, plasma creatinine > 250 μmol/L, bilateral renal artery stenosis, renal artery stenosis to a solitary kidney, or angioedema due to a history of ACE inhibitor use), are prescribed oral ACE inhibitors.

ACE inhibitors reduce the synthesis of angiotensin II and the breakdown of bradykinin, mediators that affect the sympathetic nervous system, endothelial function, vascular tone, and myocardial function. Hemodynamic effects include dilation of arteries and veins, a significant decrease in left ventricular filling pressure at rest and during exercise, a decrease in systemic vascular resistance, and a beneficial effect on ventricular remodeling. ACE inhibitors increase survival and reduce the number of hospitalizations for heart failure. In patients with atherosclerosis and vascular pathology, these drugs can reduce the risk of myocardial infarction and stroke. In patients with diabetes mellitus, they delay the development of nephropathy. Thus, ACE inhibitors can be prescribed to patients with diastolic dysfunction in combination with any of these diseases.

The starting dose should be low (1/4 - 1/2 of the target dose depending on blood pressure and renal function). The dose is gradually increased over 2-4 weeks until the maximum tolerated dose is reached, then long-term treatment is administered. The usual target doses of existing drugs are as follows:

• enalapril - 10-20 mg 2 times a day;
• lisinopril - 20-30 mg once a day;
• ramipril 5 mg 2 times a day;
• captopril 50 mg 2 times a day.

If the hypotensive effect (more often seen in patients with hyponatremia or decreased circulating volume) is poorly tolerated, the dose of diuretics can be reduced. ACE inhibitors often cause mild reversible renal failure due to dilation of glomerular efferent arterioles. An initial increase in creatinine of 20-30% is not considered an indication for discontinuing the drug, but a slower increase in dose, a decrease in the dose of the diuretic, or discontinuation of NSAIDs is necessary. Potassium retention may occur due to a decrease in the effect of aldosterone, especially in patients receiving additional potassium preparations. Cough occurs in 5-15% of patients, probably due to accumulation of bradykinin, but other possible causes of cough should be considered. Rashes or dysgeusia sometimes occur. Angioedema is rare but can be life-threatening and is considered a contraindication to this class of drugs. Angiotensin II receptor blockers may be used as an alternative, but cross-reactivity has occasionally been reported. Both groups of drugs are contraindicated in pregnancy.

Before prescribing ACE inhibitors, it is necessary to study the electrolyte composition of blood plasma and renal function, then 1 month after the start of treatment and then after each significant increase in the dose or change in the clinical condition of the patient. If dehydration develops as a result of any acute disease or renal function deteriorates, the ACE inhibitor can be temporarily discontinued.

[ 61 ], [ 62 ], [ 63 ], [ 64 ], [ 65 ]

Angiotensin II receptor blockers

Angiotensin II receptor blockers (ARBs) do not have significant advantages over ACE inhibitors, but they cause cough and Quincke's edema less often. They can be used when these adverse effects do not allow the use of ACE inhibitors. It is still unclear whether ACE inhibitors and ARBs are equally effective in chronic heart failure; the choice of the optimal dose is also under study. The usual target doses for oral administration for valsartan are 160 mg twice daily, candesartan - 32 mg once daily, losartan - 50-100 mg once daily. Starting doses, the scheme of their increase and monitoring when taking ARBs and ACE inhibitors are similar. Like ACE inhibitors, ARBs can cause reversible renal dysfunction. If dehydration develops or renal function worsens due to any acute illness, temporary cancellation of ARBs is possible. The addition of ARBs to ACE inhibitors, beta-blockers, and diuretics is considered in patients with persistent heart failure and frequent rehospitalizations. Such combination therapy requires targeted monitoring of blood pressure, plasma electrolyte levels, and renal function.

[ 66 ], [ 67 ], [ 68 ], [ 69 ], [ 70 ], [ 71 ], [ 72 ]

Aldosterone receptor blockers

Since aldosterone can be synthesized independently of the renin-angiotensin system, its adverse effects are not completely eliminated even with the maximum use of ACE inhibitors and ARBs. Thus, aldosterone receptor blockers, spironolactone and eplerenone, can reduce mortality, including sudden death. In most cases, spironolactone is prescribed at a dose of 25-50 mg once daily to patients with severe chronic heart failure, and eplerenone at a dose of 10 mg once daily to patients with acute heart failure and LVEF < 30% after myocardial infarction. Additional potassium administration is discontinued. Serum potassium and creatinine concentrations should be monitored every 1-2 weeks during the first 4-6 weeks of treatment and after dose changes, with the dose being reduced if potassium concentrations are between 5.5 and 6.0 mEq/L and the drug discontinued if values are > 6.0 mEq/L, creatinine increases to more than 220 μmol/L, or if ECG changes suggestive of hyperkalemia occur.

[ 73 ], [ 74 ], [ 75 ], [ 76 ], [ 77 ], [ 78 ]

Beta-blockers

Beta-blockers are an important adjunct to ACE inhibitors in chronic systolic dysfunction in most patients, including the elderly, patients with diastolic dysfunction due to hypertension, and hypertrophic cardiomyopathy. BBs should be withdrawn only in the presence of clear contraindications (grade II or III asthma, atrioventricular block, or previous intolerance). Some of these drugs improve LVEF, survival, and other key cardiovascular parameters in patients with chronic systolic dysfunction, including severe disease. Beta-blockers are particularly effective in diastolic dysfunction because they reduce heart rate, prolonging diastolic filling time, and possibly improving ventricular relaxation.

In acute decompensation of CHF, beta-blockers should be used with caution. They should be prescribed only when the patient's condition is completely stabilized, excluding even minor fluid retention; in patients already taking a beta-blocker, it is temporarily discontinued or the dose is reduced.

The starting dose should be low (1/8 to 1/4 of the target daily dose), with gradual titration over 6 to 8 weeks (based on tolerability). Typical target oral doses are 25 mg twice daily for carvedilol (50 mg twice daily for patients weighing more than 85 kg), 10 mg once daily for bisoprolol, and 200 mg once daily for metoprolol (extended-release metoprolol succinate). Carvedilol, a third-generation nonselective beta-blocker, also serves as a vasodilator with antioxidant and alpha-blocker effects. It is the drug of choice, but in many countries it is more expensive than other beta-blockers. Some beta-blockers (eg, bucindolol, xamoterol) have been shown to be ineffective and may even be harmful.

After the start of treatment, the heart rate and myocardial oxygen demand change, while the stroke volume and filling pressure remain the same. At a lower heart rate, diastolic function improves. The type of ventricular filling normalizes (increases in early diastole), becoming less restrictive. Improvement of myocardial function is noted in many patients after 6-12 months of treatment, EF and CO increase, and LV filling pressure decreases. Exercise tolerance increases.

After initiation of treatment, beta-blocker therapy may require a temporary increase in the diuretic dose if the acute negative inotropic effects of beta-blockade cause a decrease in heart rate and fluid retention. In such cases, a slow gradual increase in the beta-blocker dose is advisable.

[ 79 ], [ 80 ], [ 81 ], [ 82 ]

Vasodilators

Hydralazine in combination with isosorbide dinitrate can be used only for the treatment of patients who do not tolerate ACE inhibitors or ARBs (usually due to severe renal dysfunction), although long-term results of using this combination do not show a pronounced positive effect. As vasodilators, these drugs improve hemodynamics, reduce valvular regurgitation, and increase exercise tolerance without significantly changing renal function. Hydralazine is prescribed starting at a dose of 25 mg 4 times a day and increasing it every 3-5 days to a target dose of 300 mg per day, although many patients do not tolerate this drug at a dose higher than 200 mg per day due to arterial hypotension. Isosorbide dinitrate is started at a dose of 20 mg 3 times a day (with a 12-hour interval without using nitrate) and increased to 40-50 mg 3 times a day. It is not yet known whether lower doses (often used in clinical practice) provide a long-term effect. In general, vasodilators have been replaced by ACE inhibitors: these drugs are easier to use, are usually better tolerated by patients, and have a greater proven effect.

As monotherapy, nitrates can reduce the symptoms of heart failure. Patients should be trained in the use of nitroglycerin spray (as needed for acute symptoms) and patches (for nocturnal dyspnea). In patients with heart failure and angina, nitrates are safe, effective, and well tolerated.

Other vasodilators, such as calcium channel blockers, are not used to treat systolic dysfunction. Short-acting dihydropyridines (eg, nifedipine) and non-dihydropyridine drugs (eg, diltiazem, verapamil) may worsen the condition. However, amlodipine and felodipine are well tolerated and may have a beneficial effect in patients with heart failure associated with angina or hypertension. Both drugs may cause peripheral edema, with amlodipine occasionally causing pulmonary edema. Felodipine should not be taken with grapefruit juice, which significantly increases felodipine plasma levels and its side effects due to inhibition of cytochrome P450 metabolism. In patients with diastolic dysfunction, calcium channel blockers may be prescribed as needed for the treatment of hypertension or ischemia or for rate control in atrial fibrillation. Verapamil is used for hypertrophic cardiomyopathy.

Digitalis preparations

These drugs inhibit Na,K-ATPase. As a result, they cause a weak positive inotropic effect, reduce sympathetic activity, block the atrioventricular node (slowing the ventricular rate in atrial fibrillation or prolonging the PR interval in sinus rhythm), reduce vasoconstriction and improve renal blood flow. The most commonly prescribed digitalis drug is digoxin. It is excreted by the kidneys, the half-life is 36-40 hours in patients with normal renal function. Digoxin is largely excreted in the bile. It serves as an alternative for patients with poor renal function, but is rarely prescribed.

Digoxin has no proven survival benefit but may reduce clinical manifestations when used with a diuretic and an ACE inhibitor. Digoxin is most effective in patients with large LV end-diastolic volumes and S3 _. Abrupt withdrawal of digoxin may increase hospitalizations and worsen heart failure. Toxicity is troublesome, especially in patients with renal impairment and predominantly in women. Such patients may require a lower oral dose, as do the elderly, low-weight patients, and patients taking amiodarone concomitantly. Patients weighing more than 80 kg may require a higher dose. In general, lower doses are used now than in the past, and mean blood levels (8–12 h after administration) of 1–1.2 ng/mL are considered acceptable. The method of dosing digoxin varies considerably among different specialists and in different countries.

In patients with normal renal function, when digoxin is administered (0.125-0.25 mg orally once a day depending on age, sex and body weight), complete digitalization is achieved in approximately 1 week (5 half-lives). Faster digitalization is not currently recommended.

Digoxin (and all digitalis glycosides) has a narrow therapeutic window. The most severe toxic effects are life-threatening arrhythmias (eg, ventricular fibrillation, ventricular tachycardia, complete atrioventricular block). Bidirectional ventricular tachycardia, nonparoxysmal junctional tachycardia with atrial fibrillation, and hyperkalemia are serious signs of digitalis toxicity. Nausea, vomiting, anorexia, diarrhea, confusion, amblyopia, and (rarely) xerophthalmia may also occur. In hypokalemia or hypomagnesemia (often due to diuretic therapy), lower doses may cause toxic effects. Electrolyte levels should be monitored frequently in patients taking diuretics and digoxin to prevent adverse effects. It is advisable to prescribe potassium-sparing diuretics.

If toxic effects of digitalis occur, the drug is discontinued and electrolyte deficiency is corrected (intravenously in case of severe disorders and acute manifestations of toxicity). Patients with severe symptoms of intoxication are hospitalized in the observation department and prescribed Fab fragment of antibodies to digoxin (fragments of sheep antibodies to digoxin) in the presence of arrhythmias or if the overdose is accompanied by a serum potassium concentration above 5 mmol/l. This drug is also effective in glycoside intoxication due to an overdose of plant glycosides. The dose is selected depending on the plasma concentration of digoxin or the total oral dose. Ventricular arrhythmias are treated with lidocaine or phenytoin. Atrioventricular block with a slow ventricular rhythm may require placement of a temporary pacemaker; Isoproterenol is contraindicated because it increases the risk of ventricular arrhythmia.

[ 83 ], [ 84 ], [ 85 ], [ 86 ], [ 87 ], [ 88 ], [ 89 ]

Other drugs

Various drugs with positive inotropic effects have been studied in patients with heart failure, but all except digoxin increase mortality. Routine intravenous administration of inotropic drugs (eg, dobutamine) to outpatients increases mortality and is not currently recommended.

Forecast

In general, patients with heart failure have a pessimistic prognosis if the cause of its development cannot be corrected. Mortality within 1 year after the first hospitalization for heart failure is approximately 30%. In chronic heart failure, mortality depends on the severity of symptoms and ventricular dysfunction, it can vary within 10-40% per year.

Heart failure usually involves progressive deterioration with episodes of severe decompensation and ultimately death. However, death may also be sudden and unexpected without prior worsening of symptoms.

Further care of the sick

All patients and their families should be advised of disease progression. For some patients, improving quality of life is as important as increasing life expectancy. Therefore, patients' concerns (e.g., need for endotracheal intubation, mechanical ventilation) should be taken into account if their condition worsens, especially in severe heart failure. All patients should be reassured that symptoms will improve and should seek early medical attention if their condition changes significantly. Involvement of pharmacists, nurses, social workers, and clergy, who may be part of the multidisciplinary team implementing the patient's home care plan, is especially important in end-of-life care.

Heart failure is a consequence of ventricular dysfunction. Left ventricular failure leads to shortness of breath and rapid fatigue, right ventricular failure - to peripheral edema and fluid accumulation in the abdominal cavity. Usually both ventricles are involved to some extent. The diagnosis is established clinically, confirmed by chest X-ray and echocardiography. Treatment includes diuretics, ACE inhibitors, beta-blockers and therapy for the underlying disease that caused heart failure.

[ 90 ], [ 91 ], [ 92 ], [ 93 ], [ 94 ], [ 95 ]