Heart Failure (HF)

In HFrEF (also called systolic HF), global LV systolic dysfunction predominates. The LV contracts poorly and empties inadequately, leading to

• Increased diastolic volume and pressure

• Decreased ejection fraction (≤ 40%)

Many defects in energy utilization, energy supply, electrophysiologic functions, and contractile element interaction occur, with abnormalities in intracellular calcium modulation and cAMP production.

Predominant systolic dysfunction is common in heat failure due to myocardial infarction, myocarditis, and dilated cardiomyopathy. Systolic dysfunction may affect primarily the LV or the right ventricle (RV); LV failure often leads to RV failure.

In HFpEF (also called diastolic heart failure), LV filling is impaired, resulting in

• Increased LV end-diastolic pressure at rest or during exertion

• Usually, normal LV end-diastolic volume

Global contractility and hence ejection fraction remain normal (≥ 50%).

However, in some patients, marked restriction to LV filling can cause inappropriately low LV end-diastolic volume and thus cause low CO (cardiac output) and systemic symptoms. Elevated left atrial pressures can cause pulmonary hypertension and pulmonary congestion.

Diastolic dysfunction usually results from impaired ventricular relaxation (an active process), increased ventricular stiffness, valvular disease, or constrictive pericarditis. Acute myocardial ischemia is also a cause of diastolic dysfunction. Resistance to filling increases with age, reflecting both cardiomyocyte dysfunction and cardiomyocyte loss, and increased interstitial collagen deposition; thus, diastolic dysfunction is particularly common among older adults. Diastolic dysfunction predominates in hypertrophic cardiomyopathy, other disorders with ventricular hypertrophy (eg, hypertension, significant aortic stenosis), and amyloid infiltration of the myocardium. LV filling and function may also be impaired if marked increases in RV pressure shift the interventricular septum to the left.

Diastolic dysfunction has increasingly been recognized as a cause of HF. Estimates vary, but about 50% of patients with heart failure have HFpEF; the prevalence increases with age and in patients with diabetes. It is now known that HFpEF is a complex, heterogenous, multiorgan, systemic syndrome, often with multiple concomitant pathophysiologies. Current data suggest that multiple comorbidities (eg, obesity, hypertension, diabetes, chronic kidney disease) lead to systemic inflammation, widespread endothelial dysfunction, cardiac microvascular dysfunction, and, ultimately, molecular changes in the heart that cause increased myocardial fibrosis and ventricular stiffening. Thus, although HFrEF is typically associated with primary myocardial injury, HFpEF may be associated with secondary myocardial injury due to abnormalities in the periphery.

International societies have put forth the concept of HF with mildly reduced ejection fraction (HFmrEF), in which patients have an LV ejection fraction of 41 to 49%. It is unclear whether this group is a distinct population or consists of a mixture of patients with either HFpEF or HFrEF.

In heart failure that involves left ventricular dysfunction, CO decreases and pulmonary venous pressure increases. When pulmonary capillary pressure exceeds the oncotic pressure of plasma proteins (about 24 mm Hg), fluid extravasates from the capillaries into the interstitial space and alveoli, reducing pulmonary compliance and increasing the work of breathing. Lymphatic drainage increases but cannot compensate for the increase in pulmonary fluid. Marked fluid accumulation in alveoli (pulmonary edema) significantly alters ventilation-perfusion (V/Q) relationships: Deoxygenated pulmonary arterial blood passes through poorly ventilated alveoli, decreasing systemic arterial oxygenation (PaO2) and causing dyspnea. However, dyspnea may occur before V/Q abnormalities, probably because of elevated pulmonary venous pressure and increased work of breathing; the precise mechanism is unclear.

In severe or chronic LV failure, pleural effusions characteristically develop, further aggravating dyspnea. Minute ventilation increases; thus, PaCO2 decreases and blood pH increases (respiratory alkalosis). Marked interstitial edema of the small airways may interfere with ventilation, elevating PaCO2—a sign of impending respiratory failure.

In heart failure that involves right ventricular dysfunction, systemic venous pressure increases, causing fluid extravasation and consequent edema, primarily in dependent tissues (feet and ankles of ambulatory patients) and abdominal viscera. The liver is most severely affected, but the stomach and intestine also become congested; fluid accumulation in the peritoneal cavity (ascites) can occur. RV failure commonly causes moderate hepatic dysfunction, with usually modest increases in conjugated and unconjugated bilirubin, PT (prothrombin time), and hepatic enzymes (particularly alkaline phosphatase and gamma-glutamyl transpeptidase [GGT]). The impaired liver breaks down less aldosterone, further contributing to fluid accumulation. Chronic venous congestion in the viscera can cause anorexia, malabsorption of nutrients and drugs, protein-losing enteropathy (characterized by diarrhea and marked hypoalbuminemia), chronic gastrointestinal blood loss, and rarely ischemic bowel infarction.

In HFrEF, left ventricular systolic function is grossly impaired; therefore, a higher preload is required to maintain CO. As a result, the ventricles are remodeled over time: During remodelling, the LV becomes less ovoid and more spherical, dilates, and hypertrophies; the RV dilates and may hypertrophy. Initially compensatory, remodelling ultimately is associated with adverse outcomes because the changes eventually increase diastolic stiffness and wall tension (ie, diastolic dysfunction develops), compromising cardiac performance, especially during physical stress. Increased wall stress raises oxygen demand and accelerates apoptosis (programmed cell death) of myocardial cells. Dilation of the ventricles can also cause mitral or tricuspid valve regurgitation (due to annular dilation) with further increases in end-diastolic volumes.

With reduced CO, oxygen delivery to the tissues is maintained by increasing oxygen extraction from the blood and sometimes shifting the oxyhemoglobin dissociation curve (see figure Oxyhemoglobin dissociation curve) to the right to favor oxygen release.

Reduced CO with lower systemic blood pressure activates arterial baroreflexes, increasing sympathetic tone and decreasing parasympathetic tone. As a result, heart rate and myocardial contractility increase, arterioles in selected vascular beds constrict, venoconstriction occurs, and sodium and water are retained. These changes compensate for reduced ventricular performance and help maintain hemodynamic homeostasis in the early stages of heart failure. However, these compensatory changes increase cardiac work, preload, and afterload; reduce coronary and renal perfusion; cause fluid accumulation resulting in congestion; increase potassium excretion; and may cause cardiomyocyte necrosis and arrhythmias.

As cardiac function deteriorates, renal blood flow decreases (due to low cardiac output). In addition, renal venous pressures increase, leading to renal venous congestion. These changes both result in a decrease in GFR (glomerular filtration rate), and blood flow within the kidneys is redistributed. The filtration fraction and filtered sodium decrease, but tubular resorption increases, leading to sodium and water retention. Blood flow is further redistributed away from the kidneys during exercise, but renal blood flow improves during rest.

Decreased perfusion of the kidneys (and possibly decreased arterial systolic stretch secondary to declining ventricular function) activates the renin-angiotensin-aldosterone system (RAAS), increasing sodium and water retention and renal and peripheral vascular tone. These effects are amplified by the intense sympathetic activation accompanying heart failure.

The renin-angiotensin-aldosterone-vasopressinnorepinephrine release, stimulates release of vasopressincorticotropin, nitric oxide, free radicals, and other stimuli) and may have deleterious effects in these organs.

Heart failure that causes progressive renal dysfunction (including renal dysfunction caused by drugs used to treat HF) contributes to worsening HF and has been termed the cardiorenal syndrome.

In conditions of stress, neurohumoral responses help increase heart function and maintain blood pressure and organ perfusion, but chronic activation of these responses is detrimental to the normal balance between myocardial-stimulating and vasoconstricting hormones and between myocardial-relaxing and vasodilating hormones.

adenosine, cytokine, natriuretic peptides); the roles of all of these receptors are not yet fully defined. In patients with heart failure, beta-1 receptors (which constitute 70% of cardiac beta receptors) are downregulated, probably in response to intense sympathetic activation. The result of downregulation is impaired myocyte contractility and increased heart rate.

Plasma norepinephrine levels are increased, largely reflecting sympathetic nerve stimulation as plasma epinephrine levels are not increased. Detrimental effects include vasoconstriction with increased preload and afterload, direct myocardial damage including apoptosis, reduced renal blood flow, and activation of other neurohumoral systems, including the renin-angiotensin-aldosterone-vasopressin system.

Vasopressin is released in response to a fall in blood pressure via various neurohormonal stimuli. Increased vasopressin decreases renal excretion of free water, possibly contributing to hyponatremia in heart failure. Vasopressin levels in patients with HF and normal blood pressure vary.

Atrial natriuretic peptide is released in response to increased atrial volume and pressure; brain (B-type) natriuretic peptide (BNP) is released from the ventricle in response to ventricular stretching. These peptides enhance renal excretion of sodium, but in patients with HF, the effect is blunted by decreased renal perfusion pressure, receptor downregulation, and perhaps enhanced enzymatic degradation. In addition, elevated levels of natriuretic peptides exert a counter-regulatory effect on the renin-angiotensin-aldosterone system and catecholamine stimulation.

Because endothelial dysfunction occurs in HF, fewer endogenous vasodilators (eg, nitric oxide, prostaglandins) are produced, and more endogenous vasoconstrictors (eg, endothelin) are produced, thus increasing afterload.

The failing heart and other organs produce tumor necrosis factor (TNF) alpha. This cytokine increases catabolism and is possibly responsible for cardiac cachexia (loss of lean tissue ≥ 10%), which may accompany severely symptomatic HF, and for other detrimental changes. The failing heart also undergoes metabolic changes with increased free fatty acid utilization and decreased glucose utilization; these changes may become therapeutic targets.

Age-related changes in the heart and cardiovascular system lower the threshold for expression of heart failure. Interstitial collagen within the myocardium increases, the myocardium stiffens, and myocardial relaxation is prolonged. These changes lead to a significant reduction in diastolic left ventricular function, even in healthy older people. Modest decline in systolic function also occurs with aging. An age-related decrease in myocardial and vascular responsiveness to beta-adrenergic stimulation further impairs the ability of the cardiovascular system to respond to increased work demands.

As a result of these changes, peak exercise capacity decreases significantly (about 8%/decade after age 30), and CO at peak exercise decreases more modestly. This decline can be slowed by regular physical exercise. Thus, older patients are more prone than are younger ones to develop HF symptoms in response to the stress of systemic disorders or relatively modest cardiovascular insults. Stressors include infections (particularly pneumonia), hyperthyroidism, anemia, hypertension, myocardial ischemia, hypoxia, hyperthermia, renal failure, perioperative IV fluid loads, nonadherence to drug regimens or to low-salt diets, and use of certain drugs (particularly NSAIDs [nonsteroidal anti-inflammatory drugs]).

1. 1. Heidenreich PA, Bozkurt B, Aguilar D, et al: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 145:e876–e894, 2022, doi: 10.1161/CIR.0000000000001062

In LV failure, the most common symptoms are dyspnea and fatigue due to increased pulmonary venous pressures, and low cardiac output (CO, at rest or inability to augment CO during exertion). Dyspnea usually occurs during exertion and is relieved by rest. As HF worsens, dyspnea can occur during rest and at night, sometimes causing nocturnal cough. Dyspnea occurring immediately or soon after lying flat and relieved promptly by sitting up (orthopnea) is common as heart failure advances. In paroxysmal nocturnal dyspnea (PND), dyspnea awakens patients several hours after they lie down and is relieved only after they sit up for 15 to 20 minutes. In severe HF, periodic cycling of breathing (Cheyne-Stokes respiration—from a brief period of apnea, patients breathe progressively faster and deeper, then slower and shallower until they become apneic and repeat the cycle)—can occur during the day or night; the sudden hyperpneic phase may awaken the patient from sleep. Cheyne-Stokes breathing differs from PND in that the hyperpneic phase is short, lasting only 10 to 15 seconds, but the cycle recurs regularly, lasting 30 seconds to 2 minutes. PND is associated with pulmonary congestion, and Cheyne-Stokes respiration with low CO. Sleep-related breathing disorders, such as sleep apnea, are common in HF and may aggravate HF. Severely reduced cerebral blood flow and hypoxemia can cause chronic irritability and impair mental performance.

In RV failure, the most common symptoms are ankle swelling and fatigue. Sometimes patients feel a sensation of fullness in the abdomen or neck. Hepatic congestion can cause right upper quadrant abdominal discomfort, and stomach and intestinal congestion can cause early satiety, anorexia, and abdominal bloating.

Less specific heart failure symptoms include cool peripheries, postural light-headedness, nocturia, and decreased daytime micturition. Skeletal muscle wasting can occur in severe biventricular failure and may reflect some disuse but also increased catabolism associated with increased cytokine production. Significant weight loss (cardiac cachexia) is an ominous sign associated with high mortality.

In older people, presenting complaints may be atypical, such as confusion, delirium, falls, sudden functional decline, nocturnal urinary incontinence, or sleep disturbance. Coexisting cognitive impairment and depression may also influence assessment and therapeutic interventions and may be worsened by the HF.

General examination may detect signs of systemic or cardiac disorders that cause or aggravate heart failure (eg, anemia, hyperthyroidism, alcohol use disorder, hemochromatosis, atrial fibrillation with rapid rate, mitral regurgitation).

In LV failure, tachycardia and tachypnea may occur. Patients with severe LV failure may appear visibly dyspneic or cyanotic, hypotensive, and confused or agitated because of hypoxia and poor cerebral perfusion. Some of these less specific symptoms (eg, confusion) are more common in older patients.

Central cyanosis (affecting all of the body, including warm areas such as the tongue and mucous membranes) reflects severe hypoxemia. Peripheral cyanosis of the lips, fingers, and toes reflects low blood flow with increased oxygen extraction. If vigorous massage improves nail bed color, cyanosis may be peripheral; increasing local blood flow does not improve color if cyanosis is central.

Cardiac findings in HFrEF include

• Diffuse, sustained, and laterally displaced apical impulse

• Audible and occasionally palpable 3rd (S3) and 4th (S4) heart sounds

• Accentuated pulmonic component (P2) of the 2nd heart sound (S2)

These abnormal heart sounds also can occur in HFpEF. A pansystolic murmur of mitral regurgitation at the apex may occur in either HFrEF or HFpEF.

Pulmonary findings include early inspiratory basilar crackles that do not clear with coughing and, if pleural effusion is present, dullness to percussion and diminished breath sounds at the lung base(s).

Signs of RV failure include

• Nontender peripheral pitting edema (digital pressure leaves visible and palpable imprints, sometimes quite deep) in the feet and ankles

• Enlarged and sometimes pulsatile liver palpable below the right costal margin

• Abdominal swelling and ascites

• Visible elevation of the jugular venous pressure, sometimes with large a or v waves that are visible even when the patient is seated or standing (see figure Normal jugular vein waves)

In severe cases of heart failure, peripheral edema can extend to the thighs or even the sacrum, scrotum, lower abdominal wall, and occasionally even higher. Severe edema in multiple areas is termed anasarca. Edema may be asymmetric if patients lie predominantly on one side.

Large V waves in the jugular veins are usually indicative of significant tricuspid regurgitation which is often present in RV failure. A paradoxical increase in the jugular venous pressure during inspiration (Kussmaul sign) is indicative of right-sided heart failure and can occur in RV failure, restrictive cardiomyopathy, constrictive pericarditis, and severe tricuspid regurgitation.

With hepatic congestion, the liver may be palpably enlarged or tender, and hepatojugular or abdominal-jugular reflux may be detected (see Approach to the Cardiac Patient). Precordial palpation may detect the left parasternal lift of RV enlargement, and auscultation may detect the murmur of tricuspid regurgitation or the RV S3 along the left sternal border; both findings are augmented upon inspiration.

Chest x-ray findings suggesting heart failure include an enlarged cardiac silhouette, pleural effusion, fluid in the major fissure, and horizontal lines in the periphery of lower posterior lung fields (Kerley B lines). These findings reflect chronic elevation of left atrial pressure and chronic thickening of the intralobular septa due to edema. Upper lobe pulmonary venous congestion and interstitial or alveolar edema may also be present. Careful examination of the cardiac silhouette on a lateral projection can identify specific ventricular and atrial chamber enlargement. The x-ray may also suggest alternative diagnoses (eg, COPD, pneumonia, idiopathic pulmonary fibrosis, lung cancer).

Imaging in Patients With Heart Failure

Chest X-Ray of a Patient with Bilateral Pleural Effusions

This patient has bilateral pleural effusions (arrows). The normally sharp costophrenic angles are obscured by fluid in ... read more

© 2017 Elliot K. Fishman, MD.

Kerley B Lines

Kerley B lines (arrows) are horizontal lines in the lung periphery that extend to the pleural surface. They denote thic... read more

© 2017 Elliot K. Fishman, MD.

Chest X-Ray of a Patient with Cardiomegaly and Cephalization

This patient has cardiomegaly (width of cardiac silhouette is > 50% of thoracic cage on a posterior-anterior chest x-ra... read more

© 2017 Elliot K. Fishman, MD.

Chest X-Ray of a Patient with Fluid in Minor and Major Fissures

Lateral chest x-ray in a patient with fluid in major (1) and minor (2) fissures as well as a loculated effusion (3) see... read more

© 2017 Elliot K. Fishman, MD.

Chest X-Ray of a Patient with Bilateral Pleural Effusions

This patient has bilateral pleural effusions (arrows). The normally sharp costophrenic angles are obscured by fluid in ... read more

© 2017 Elliot K. Fishman, MD.

Kerley B Lines

Kerley B lines (arrows) are horizontal lines in the lung periphery that extend to the pleural surface. They denote thic... read more

© 2017 Elliot K. Fishman, MD.

Chest X-Ray of a Patient with Cardiomegaly and Cephalization

This patient has cardiomegaly (width of cardiac silhouette is > 50% of thoracic cage on a posterior-anterior chest x-ra... read more

© 2017 Elliot K. Fishman, MD.

Chest X-Ray of a Patient with Fluid in Minor and Major Fissures

Lateral chest x-ray in a patient with fluid in major (1) and minor (2) fissures as well as a loculated effusion (3) see... read more

© 2017 Elliot K. Fishman, MD.

ECG findings are not diagnostic, but an abnormal ECG, especially showing previous myocardial infarction, left ventricular hypertrophy, left bundle branch block, or tachyarrhythmia (eg, rapid atrial fibrillation), increases suspicion for HF and may help identify the cause. An entirely normal ECG is uncommon in chronic HF.

Echocardiography can help evaluate chamber dimensions, valve function, LVEF, wall motion abnormalities, LV hypertrophy, diastolic function, pulmonary artery pressure, LV and RV filling pressures, RV function, and pericardial effusion. Intracardiac thrombi, tumors, and calcifications within the heart valves, mitral annulus, and aortic wall abnormalities can be detected. Localized or segmental wall motion abnormalities strongly suggest underlying coronary artery disease but can also be present with patchy myocarditis. Doppler or color Doppler echocardiography accurately detects valvular disorders and shunts. The combination of Doppler evaluation of mitral inflow with tissue Doppler imaging of the mitral annulus can help identify and quantify LV diastolic dysfunction and LV filling pressures. Measuring LVEF can distinguish between predominant HFpEF (EF ≥ 50%) and HFrEF (EF ≤ 40%). It is important to re-emphasize that heart failure can occur with a normal LVEF. Speckle-tracking echocardiography (which is useful in detecting subclinical systolic dysfunction and specific patterns of myocardial dysfunction) may become important but currently is routinely reported only in specialized centers.

Radionuclide imaging also can help assess systolic and diastolic function, previous MI (myocardial infarction), and inducible ischemia or myocardial hibernation. It is used most commonly to assess the presence and/or severity of ischemic heart disease and can also be used to quantify left ventricular ejection fraction.

Cardiac MRI provides accurate images of cardiac structures and is becoming more widely available. Cardiac MRI using late gadolinium enhancement imaging (LGE, also called fibrosis or scar imaging) is useful to evaluate the cause of myocardial disease and to detect focal and diffuse myocardial fibrosis. Cardiac amyloidosis, sarcoidosis, hemachromatosis, and myocarditis are causes of HF that can be detected with or suspected by cardiac MRI findings.

Serum BNP levels are often high in heart failure; this finding may help when clinical findings are unclear or other diagnoses (eg, COPD) need to be excluded. It may be particularly useful for patients with a history of both pulmonary and cardiac disorders. NT-pro-BNP, an inactive moiety created when pro-BNP is cleaved, can be used similarly to BNP. However, a normal BNP level does not exclude the diagnosis of heart failure, particularly in patients with HFpEF and/or obesity. In HFpEF, BNP levels tend to be about 50% of those associated with HFrEF (at similar degree of symptoms), and up to 30% of patients with acute HFpEF have a BNP level below the commonly used threshold of 100 pg/mL (100 ng/L). Obesity, which is becoming an increasingly common comorbidity in HF, is associated with reduced BNP production and increased BNP clearance, resulting in lower levels.

Thoracic ultrasonography is a noninvasive method of detecting pulmonary congestion in patients with heart failure. Sonographic "comet tail artifact" on thoracic ultrasonography corresponds to the x-ray finding of Kerley B lines.

Comet Tail Artifact

Image

© 2017 Elliot K. Fishman, MD.

Coronary angiography or CT coronary angiography is indicated when coronary artery disease is suspected or the etiology of HF is uncertain.

Endocardial biopsy is sometimes done when an infiltrative cardiomyopathy, or acute giant cell myocarditis is strongly suspected but cannot be confirmed with noninvasive imaging (eg, cardiac MRI).

1. 1. McDonagh TA, Metra M, Adamo M, et al: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 42(36):3599-3726, 2021. doi: 10.1093/eurheartj/ehab368

2. 2. Heidenreich PA, Bozkurt B, Aguilar D, et al: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 145:e876–e894, 2022, doi: 10.1161/CIR.0000000000001062

All patients and family members should be taught about disease progression and the risk of sudden cardiac death. For some patients, improving quality of life is as important as increasing quantity of life. Thus, it is important to determine patients’ wishes about resuscitation (eg, endotracheal intubation, CPR [cardiopulmonary respiration]) if their condition deteriorates, especially when HF is already severe.

All patients should be reassured that symptoms will be relieved, and they should be encouraged to seek medical attention early if their symptoms change significantly. Involvement of pharmacists, nurses, social workers, and clergy (when desired), who may be part of an interdisciplinary team or disease management program already in place, is particularly important in end-of-life care.

General measures, especially patient and caregiver education and diet and lifestyle modifications, are important for all patients with heart failure.

• Education

• Sodium restriction

• Appropriate weight and fitness levels

• Correction of underlying conditions

Patient and caregiver education are critical to long-term success. The patient and family should be involved in treatment choices. They should be taught the importance of drug adherence, warning signs of an exacerbation, and how to link cause with effect (eg, increased salt in the diet with weight gain or symptoms).

Many centers (eg, specialized outpatient clinics) have integrated health care practitioners from different disciplines (eg, HF nurses, pharmacists, social workers, rehabilitation specialists) into multidisciplinary teams or outpatient heart failure management programs. These approaches can improve outcomes and reduce hospitalizations and are most effective in the sickest patients.

Dietary sodium restriction helps limit fluid retention. All patients should eliminate salt in cooking and at the table and avoid salted foods; the most severely ill should limit sodium to < 2 g/day by consuming only low-sodium foods.

Monitoring daily morning weight helps detect sodium and water accumulation early. If weight increases > 2 kg over a few days, patients may be able to adjust their diuretic dose themselves, but if weight gain continues or symptoms occur, patients should seek medical attention.

Intensive case management, particularly by monitoring drug adherence and frequency of unscheduled visits to the physician or emergency department and hospitalizations, can identify when intervention is needed. Specialized HF nurses are valuable in education, follow-up, and dosage adjustment according to predefined protocols.

Patients with atherosclerosis or diabetes should strictly follow a diet appropriate for their disorder. Obesity may cause and always aggravates the symptoms of HF; patients should attain a body mass index (BMI) ≤ 30 kg/m² (ideally 21 to 25 kg/m²).

Regular light activity (eg, walking), tailored to symptoms, is generally encouraged. Activity prevents skeletal muscle deconditioning, which worsens functional status; however, activity does not appear to improve survival or decrease hospitalizations. Rest is appropriate during acute exacerbations. Formal exercise cardiac rehabilitation is useful for chronic HFrEF and is likely helpful for patients with HFpEF.

Patients should have annual influenza vaccination because influenza can precipitate HF exacerbations, particularly in institutionalized or older patients. Patients should be vaccinated against SARS-CoV-2.

If causes such as hypertension, persistent tachyarrhythmia, severe anemia, hemochromatosis, uncontrolled diabetes, thyrotoxicosis, beriberi, alcohol use disorder, or toxoplasmosis are successfully treated, patients may dramatically improve. Significant myocardial ischemia should be treated aggressively; treatment may include revascularization by percutaneous coronary intervention or bypass surgery. Management of extensive ventricular infiltration (eg, in amyloidosis) has improved considerably. Newer treatments for amyloidosis have markedly improved prognosis for many of these patients.

Because arrhythmias can worsen heart failure, it is important to identify and treat the cause of any arrhythmia.

• Electrolytes are normalized.

• Atrial and ventricular rates are controlled.

• Sometimes antiarrhythmic drugs are given.

Sinus tachycardia, a common compensatory change in heart failure, usually subsides when HF treatment is effective. If it does not, associated causes (eg, hyperthyroidism, pulmonary emboli, fever, anemia, pain) should be sought. If sinus tachycardia persists despite correction of causes, a beta-blocker, given in gradually increasing doses, may help selected patients. However, lowering heart rate with a beta-blocker can be detrimental to patients with advanced HFpEF (eg, restrictive cardiomyopathy), in whom stroke volume is fixed because of severe diastolic dysfunction. In these patients, CO is heart rate–dependent, and lowering heart rate can thus lower CO at rest and/or with exertion.

Atrial fibrillation with an uncontrolled ventricular rate must be treated; the target resting ventricular rate is typically <atrial fibrillation ablation procedures, may be considered in selected patients to restore a sinus or regular rhythm.

Isolated ventricular premature beats, which are common in HF, do not require specific treatment, although rarely very frequent ventricular premature beats (> 15,000/day) have been shown to precipitate heart failure (that reverses with suppression). However, optimization of HF treatments and correction of electrolyte abnormalities (especially potassium and magnesium) reduce the risk of ventricular arrhythmias.

Sustained ventricular tachycardia that persists despite correction of cause (eg, low potassium or magnesium, ischemia) and optimal medical treatment of HF may require an antiarrhythmic drug

Use of an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy (CRT) is appropriate for some patients.

An ICD is recommended for patients with an otherwise good life expectancy if they have symptomatic sustained ventricular tachycardia or ventricular fibrillation or if they remain symptomatic and have an LVEF persistently < 35% while receiving guideline-directed medical therapy. The data for ICD use in HFrEF are stronger for ischemic cardiomyopathy than in nonischemic cardiomyopathy. A clinical trial that included HFrEF patients with nonischemic cardiomyopathy demonstrated no mortality benefit from prophylactic (primary prevention) ICD placement (4).

CRT is a mode of pacing that synchronizes contraction of the left ventricle by simultaneously pacing its opposing wall, thereby improving stroke volume. CRT may relieve symptoms and reduce heart failure hospitalizations for patients who have HF, LVEF < 35%, and a widened QRS complex with a left bundle branch block pattern (> 0.15 second—the wider the QRS, the greater potential benefit). CRT devices are effective but expensive, and patients should be appropriately selected. Many CRT devices also incorporate an ICD in their mechanism.

An implantable device that remotely monitors invasive hemodynamics (eg, pulmonary artery pressure) may help guide heart failure management in highly selected patients. For example, drug (eg, diuretic) titration based on readings from one of these devices was associated with a marked reduction in HF hospitalization in one clinical trial that included patients with both HFrEF and HFpEF. The device uses the pulmonary artery diastolic pressure as a surrogate for pulmonary capillary wedge pressure (and hence left atrial pressure) in HF patients. However, it has been evaluated only in NYHA (New York Heart Association) class III patients who had recurrent HF exacerbations. Further evidence will help guide how this technology should be implemented.

Ultrafiltration (venovenous filtration) can be useful in selected hospitalized patients with severe cardiorenal syndrome and volume overload refractory to diuretics. However, ultrafiltration should not be used routinely because clinical trials do not show long-term clinical benefit.

An intra-aortic counterpulsation balloon pump (IABP) is helpful in selected patients with acute HF who have a good chance of recovery (eg, acute HF following myocardial infarction) or in those who need a bridge to a more permanent solution such as cardiac surgery (eg, to fix severe valvular disease or to revascularize multivessel coronary artery disease), an LV assist device, or heart transplantation. Other forms of temporary mechanical circulatory support for patients with acute HF and cardiogenic shock include surgically placed devices such as extracorporeal membrane oxygenation (ECMO, typically venoarterial cannulation) and centrifugal flow ventricular assist devices that can support either the LV, the RV, or both and can also be combined with an oxygenator to provide full cardiopulmonary support. Percutaneously placed devices such as intravascular microaxial ventricular assist devices are available for both LV and RV support. Selection of temporary mechanical circulatory support devices is based mainly on availability and local medical center experience.

Durable or ambulatory LV assist devices (LVADs) are longer-term implantable pumps that augment LV output. They are commonly used to maintain patients with severe HF who are awaiting transplantation and are also used as "destination therapy" (ie, as a long-term or permanent solution) in some patients who are not transplant candidates.

Surgery may be appropriate when certain underlying disorders are present. Surgery in patients with advanced HF should be done in a specialized center.

Surgical closure of congenital or acquired intracardiac shunts can be curative.

Coronary artery bypass grafting (CABG) for patients with LV systolic dysfunction secondary to coronary artery disease and evidence of myocardial viability may be beneficial; however, those patients with prior myocardial infarction and non-viable myocardium are less likely to benefit from CABG. Thus, the decision to revascularize a HF patient with multivessel coronary artery disease should be made on a case-by-case basis.

If HF is primarily due to a valvular disorder, valve repair or replacement should be considered. Patients with primary mitral regurgitation are more likely to benefit than patients with mitral regurgitation secondary to LV dilation, in whom poor myocardial function is likely to continue postoperatively. Surgery is preferably done before myocardial dilation and damage become irreversible. More recently, percutaneous mitral valve repair procedure (also called transcatheter end-to-end repair [TEER]), in which a clip is applied to approximate the anterior and posterior mitral leaflets, has been shown to reduce death and HF hospitalization in carefully selected patients with symptomatic HF despite optimal medical management and moderate to severe or severe mitral regurgitation with preserved LV size (end-systolic dimension ≤ 70 mm—5).

Heart transplantation is the treatment of choice for patients < 60 who have severe, refractory HF and no other life-threatening conditions and who are highly adherent to management recommendations. Some older patients (about 60 to 70 years) with otherwise good health are also typically considered if they meet other criteria for transplantation. Survival is 85 to 90% at 1 year, and annual mortality thereafter is about 4%/year; however, mortality rate while waiting for a donor is 12 to 15%. Human organ donation remains low.

Anemia is common among patients with chronic heart failure and is frequently multifactorial. Anemia is associated with worse symptoms and outcomes in HF and so reversible causes should be sought and treated. Iron deficiency is among the most common causes of anemia in HF, and iron replacement therapy should be considered once treatable causes such as blood loss (gastrointestinal or other) have been excluded. Oral iron replacement is often less effective due to poor absorption and other reasons, thus intravenous iron replacement is preferred.

After treatment, symptoms often persist. Reasons include

• Persistence of the underlying disorder (eg, hypertension, ischemia/infarction, valvular disease) despite treatment

• Suboptimal treatment of heart failure

• Drug nonadherence

• Excess intake of dietary sodium or alcohol

• Presence of an undiagnosed thyroid disorder, anemia, or supervening arrhythmia (eg, atrial fibrillation with rapid ventricular response, intermittent ventricular tachycardia)

1. 1. McDonagh TA, Metra M, Adamo M, et al: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 42(36):3599-3726, 2021. doi: 10.1093/eurheartj/ehab368

2. 2. Heidenreich PA, Bozkurt B, Aguilar D, et al: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 145:e876–e894, 2022, doi: 10.1161/CIR.0000000000001062

3. 3. Shah SJ, Kitzman D, Borlaug B, et al: Phenotype-specific treatment of heart failure with preserved ejection fraction: A multiorgan roadmap. Circulation 134(1):73–90, 2016. doi: 10.1161/CIRCULATIONAHA.116.021884

4. 4. Kober L, Thune JJ, Nielsen JC, et al: Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med 375(13):1221–2130, 2016. doi: 10.1056/NEJMoa1608029

5. 5. Stone GW, Lindenfield J, Abraham WT, et al: Transcatheter mitral-valve repair in patients with heart failure. N Engl J Med 379(24):2307–2318, 2018. doi: 10.1056/NEJMoa1806640