Medication Summary
The goals of pharmacotherapy for heart failure are to reduce morbidity and to prevent complications. Along with oxygen, medications assisting with symptom relief include: (1) diuretics, which reduce edema by reduction of blood volume and venous pressures; (2) vasodilators, for preload and afterload reduction; (3) digoxin, which can cause a small increase in cardiac output; (4) inotropic agents, which help to restore organ perfusion and reduce congestion; (5) anticoagulants, to decrease the risk of thromboembolism; (6) beta-blockers, for neurohormonal modification, left ventricular ejection fraction (LVEF) improvement, arrhythmia prevention, and ventricular rate control; (7) angiotensin-converting enzyme inhibitors (ACEIs), for neurohormonal modification, vasodilatation, and LVEF improvement; (8) angiotensin II receptor blockers (ARBs), also for neurohormonal modification, vasodilatation, and LVEF improvement; and (9) analgesics, for pain management.
The FDA approved vericiguat (Verquvo), a sGC stimulator, in 2021. Vericiguat stimulates sGC, the intracellular receptor for endogenous NO, which catalyzes cyclic guanosine monophosphate (cGMP) production.
Ivabradine, an I(f) inhibitor is available in the United States. It blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker I(f) "funny" current, which regulates heart rate without any effect on ventricular repolarization or myocardial contractility.
Sacubitril/valsartan (Entresto), an angiotensin receptor-neprilysin inhibitor (ARNI), was approved by the FDA in July 2015 to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with congestive heart failure (New York Heart Association [NYHA] class II-IV) and reduced ejection fraction. [135] In 2021, this indication was expanded to include heart failure in adults with preserved ejection fraction based on the PARAGON-HF (Prospective Comparison of ARNI with ARB [angiotensin-receptor blockers] Global Outcomes in HF with Preserved Ejection Fraction) study. [136]
The selective sodium-glucose cotransporter-2 (SGLT2) inhibitors empagliflozin and dapagliflozin are indicated to reduce the risk of cardiovascular death and hospitalization in patients with heart failure. These agents are also indicated to reduce the risk of hospitalization for heart failure in patients with type 2 diabetes mellitus who with either established cardiovascular disease or multiple cardiovascular risk factors. [139, 140, 141, 142]
Sotagliflozin, a dual SGLT1/SGLT2 inhibitor, was approved in 2023 and is indicated to reduce the risk of cardiovascular death, hospitalization, and urgent clinic visits for heart failure in adults with heart failure, type 2 diabetes mellitus, chronic kidney disease, or other cardiovascular risk factors. [143, 144]
Drugs that can exacerbate heart failure should be avoided, such as nonsteroidal anti-inflammatory drugs (NSAIDs), calcium channel blockers (CCBs), and most antiarrhythmic drugs (except class III). NSAIDs can cause sodium retention and peripheral vasoconstriction, and they can attenuate the efficacy and enhance the toxicity of diuretics and ACEIs. Calcium channel blockers (CCBs) can worsen heart failure and may increase the risk of cardiovascular events; only the vasoselective CCBs have been shown not to adversely affect survival. Antiarrhythmic agents can have cardiodepressant effects and may promote arrhythmia; only amiodarone and dofetilide have been shown not to adversely affect survival.
Beta-Blockers, Alpha Activity
Class Summary
Beta-blockers inhibit the sympathomimetic nervous system and block alpha1-adrenergic vasoconstrictor activity. These agents have moderate afterload reduction properties and cause slight preload reduction. In addition to decreasing mortality rates, beta-blockers also reduce hospitalizations and the risk of sudden death; improve LV function and exercise tolerance; and reduce heart failure functional class. Although other beta-blockers with similar pharmacologic properties might hypothetically be beneficial in heart failure, the target doses have not been identified in clinical trials.
Carvedilol (Coreg, Coreg CR)
Carvedilol is a nonselective beta- and alpha1-adrenergic blocker. It does not appear to have intrinsic sympathomimetic activity. Carvedilol at the target dose of 25 mg twice daily has been shown to reduce mortality in clinical trials of heart failure patients with reduced ejection fraction.
Beta-Blockers, Beta-1 Selective
Class Summary
Certain beta-1 blockers are selective in blocking beta-1 adrenoreceptors. These agents are used in heart failure to reduce heart rate and blood pressure.
Metoprolol (Lopressor, Toprol XL)
Metoprolol is a selective beta1-adrenergic blocker at lower doses. It inhibits beta2-receptors at higher doses. It does not have intrinsic sympathomimetic activity. The long-acting formulation (metoprolol succinate) at a target dose of 200 mg daily has been shown to reduce mortality in a clinical trial of patients with heart failure and low ejection fraction.
Bisoprolol (Zebeta)
Bisoprolol is a highly selective beta1-adrenergic receptor blocker that decreases the automaticity of contractions. Bisoprolol at the target dose of 10 mg daily has been shown to reduce mortality in a clinical trial of patients with heart failure and reduced ejection fraction, but is not approved for heart failure use in the US.
ACE Inhibitors
Class Summary
Angiotensin-converting enzyme inhibitors (ACEIs) prevent conversion of angiotensin I to angiotensin II, which results in lower aldosterone secretion. Use of ACEIs increases survival, improves symptoms, and decreases repeat hospitalizations.
Captopril
Captopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion. Captopril at a target dose of 25 mg three times daily has been shown to improve survival in patients with low ejection fraction after myocardial infarction.
Enalapril (Vasotec)
Enalapril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. It helps control blood pressure and proteinuria. Enalapril decreases the pulmonary-to-systemic flow ratio in the catheterization laboratory and increases systemic blood flow in patients with relatively low pulmonary vascular resistance. It has a favorable clinical effect when administered over a long period. It helps prevent potassium loss in distal tubules. The body conserves potassium; thus, less oral potassium supplementation is needed. Enalapril at a target dose of 10 mg twice daily has been shown to improve survival in patients with heart failure and reduced ejection fraction.
Lisinopril (Prinivil, Zestril)
Lisinopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. Lisinopril at a target dose of 10 mg daily has been shown to reduce mortality after myocardial infarction.
Ramipril (Altace)
Ramipril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. Ramipril at a target dose of 5 mg twice daily has been shown to reduce mortality in patients with heart failure after myocardial infarction.
Quinapril (Accupril)
Quinapril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
ARBs
Class Summary
Angiotensin receptor blockers (ARBs) are reasonable first-line therapy for patients with mild to moderate heart failure symptoms and left ventricular (LV) dysfunction when patients are already taking these agents for other indications. ARBs block the renin-angiotensin-aldosterone system (RAAS) by competitive inhibition of the AT1 receptor, thereby decreasing afterload and preventing LV remodeling. The use of ARBs increases survival and decreases hospitalization rates, but these agents are not superior to angiotensin-converting enzyme inhibitors (ACEIs). ARBs can also be used as add-on therapy for patients who have refractory heart failure symptoms despite optimal heart failure therapy.
Losartan (Cozaar)
Losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II at tissue receptor sites. It may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors, and it does not affect the response to bradykinin (less likely to be associated with cough and angioedema). These agents are used in patients unable to tolerate ACE inhibitors. Losartan has not been demonstrated to improve survival in heart failure.
Valsartan (Diovan)
Valsartan is a prodrug that produces direct antagonism of angiotensin II receptors. It displaces angiotensin II from the AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses. It may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors, does not affect the response to bradykinin, and is less likely to be associated with cough and angioedema. It is used in patients unable to tolerate ACE inhibitors. Valsartan at a target dose of 160 mg twice daily has been shown to improve survival in patients with heart failure and reduced ejection fraction.
Candesartan (Atacand)
Candesartan blocks the vasoconstriction and aldosterone-secreting effects of angiotensin II. It may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors, does not affect the response to bradykinin, and is less likely to be associated with cough and angioedema. Use candesartan in patients unable to tolerate ACE inhibitors. Candesartan at a target dose of 32 mg daily has been shown to improve survival in patients with heart failure and reduced ejection fraction.
Irbesartan (Avapro)
Irbesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II at tissue receptor sites. It may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors, and it does not affect the response to bradykinin (less likely to be associated with cough and angioedema). Irbesartan has not been shown to improve survival in heart failure.
Azilsartan (Edarbi)
Azilsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II at tissue receptor sites. It may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors, and it does not affect the response to bradykinin (less likely to be associated with cough and angioedema).
Inotropic Agents
Class Summary
Inotropic agents such as milrinone, digoxin, dopamine, and dobutamine are used to increase the force of cardiac contractions. Intravenous positive inotropic agents should only be used in inpatient settings — and then only in patients who manifest signs and symptoms of low cardiac output syndrome (volume overload with evidence of organ hypoperfusion).
Milrinone
Milrinone is a type 3 phosphodiesterase inhibitor that increases inotropy, chronotropy, and lusitropy, acting via cyclic guanosine monophosphate (cGMP) to increase the intramyocardial adenosine triphosphate (ATP). It is a potent vasodilator agent, being a venous and arterial vasodilator, and it is used in patients with pulmonary hypertension. Milrinone can be used in the presence of a beta-blocker. Milrinone is thought to create less tachycardia, because it does not directly stimulate beta-receptors.
Digoxin (Lanoxin)
Digoxin is a cardiac glycoside with direct inotropic effects, in addition to indirect effects, on the cardiovascular system. It acts directly on cardiac muscle, increasing myocardial systolic contractions. Indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure. It is used to improve symptoms associated with HF by enhancing cardiac contractility. Although digoxin does not confer a survival benefit, it has reduced the number of hospitalizations that occur as a result of worsening heart failure.
Dopamine
Dopamine is a naturally occurring catecholamine that acts as a precursor to norepinephrine. It stimulates both adrenergic and dopaminergic receptors. The hemodynamic effect is dose dependent. Low-dose use is associated with dilation within renal and splanchnic vasculature, resulting in enhanced diuresis. Moderate doses enhance cardiac contractility and the heart rate. Higher doses cause increased afterload through peripheral vasoconstriction. Administer by continuous intravenous infusion. It is usually used in severe heart failure and is reserved for patients with moderate hypotension (eg, systolic blood pressure 70-90 mm Hg). Typically, moderate or higher doses are used.
Dobutamine
Dobutamine, a beta-receptor agonist, increases inotropy and chronotropy and decreases afterload, thereby improving end-organ perfusion. It produces vasodilation and increases the inotropic state. At higher dosages, it may cause increased heart rate, exacerbating myocardial ischemia. Careful hemodynamic and patient monitoring is required.
Vasodilators
Class Summary
In addition to diuretic therapy, vasodilators are recommended as first-line therapy for patients with acute heart failure in the absence of hypotension, for relief of symptoms. Vasodilators decrease preload and/or afterload as well as reduce systemic vascular resistance (SVR).
Nitroprusside sodium (Nitropress)
Nitroprusside sodium is a potent balanced arterial and venous vasodilator, resulting in a very efficient decrease of intracardiac filling pressures. It requires careful hemodynamic monitoring using indwelling catheters and monitoring for cyanide toxicity, especially in the presence of renal dysfunction. It is particularly helpful for patients who present with severe pulmonary congestion in the presence of hypertension and severe mitral regurgitation. The drug should be titrated down to cessation rather than abruptly stopped, owing to the rebound potential.
Hydralazine
Hydralazine decreases systemic resistance through direct vasodilation of arterioles. A hydralazine and nitrate combination reduces preload and afterload. Combinations of hydralazine and nitrates are recommended to improve outcomes for African Americans with moderate-to-severe symptoms of heart failure on optimal medical therapy with ACEIs/ARBs, beta-blockers, and diuretics.
Nitrates
Class Summary
Nitrates improve hemodynamic effects in heart failure by decreasing left ventricular filling pressure and systemic vascular resistance. These agents also result in a slight improvement on cardiac output.
Nitroglycerin (Nitrostat, Nitro-Dur, Nitrolingual, Nitro-Time, NitroMist, Minitran)
Nitroglycerin is first-line therapy for patients who are not hypotensive. It provides excellent and reliable preload reduction. Higher doses provide mild afterload reduction. It has rapid onset and offset (both within minutes), allowing rapid clinical effects and rapid discontinuation of effects in adverse clinical situations. It produces vasodilation and increases inotropic activity of the heart. At higher dosages, it may exacerbate myocardial ischemia by increasing the heart rate.
Isosorbide dinitrate (Dilatrate-SR, Isordil Titradose)
Isosorbide dinitrate relaxes vascular smooth muscle by stimulating intracellular cyclic GMP. It decreases left ventricular pressure (preload) and arterial resistance (afterload). By decreasing left ventricular pressure and dilating arteries, it reduces cardiac oxygen demand. Chronic use of isosorbide dinitrate as a sole vasodilating agent is not recommended.
Isosorbide dinitrate and Hydralazine (BiDil)
This is a fixed-dose combination of isosorbide dinitrate (20 mg/tab), a vasodilator with effects on both arteries and veins, and hydralazine (37.5 mg/tab), a predominantly arterial vasodilator. It is indicated for heart failure in black patients, based in part on results from the African American Heart Failure Trial. Two previous trials in the general population of patients with severe heart failure found no benefit but suggested a benefit in black patients. Black patients showed a 43% reduction in mortality rate, a 39% decrease in hospitalization rate, and a decrease in symptoms from heart failure.
Isosorbide mononitrate (Monoket)
Isosorbide mononitrate causes relaxation of vascular smooth muscle and consequent dilatation of peripheral arteries and veins. Dilation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure (afterload).
B-type Natriuretic Peptides
Class Summary
Human B-type natriuretic peptides (hBNPs) such as nesiritide are used in patients with acutely decompensated heart failure. These agents reduce pulmonary capillary wedge pressure and improve dyspnea.
Nesiritide (Natrecor)
Nesiritide is a recombinant DNA form of hBNP that dilates veins and arteries. hBNP binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial cells. Binding to the receptor causes an increase in cGMP, which serves as a second messenger to dilate veins and arteries. It reduces PCWP and improves dyspnea in patients with acutely decompensated HF.
I(f) Inhibitors
Class Summary
The I(f) inhibitor ivabradine is used to lower heart rate and has been shown to reduce the risk for hospitalization.
Ivabradine (Corlanor)
Ivabradine blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker I(f) ‘funny' current, which regulates heart rate without any effect on ventricular repolarization or myocardial contractility. It is indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with LVEF ≤35%, who are in sinus rhythm with resting heart rate ≥70 bpm and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use.
Angiotensin Receptor-Neprilysin Inhibitors (ARNi)
Class Summary
Angiotensin receptor-neprilysin inhibitor (ARNI) combinations have been shown to significantly reduce cardiovascular death and hospitalization in patients with chronic heart failure.
Sacubitril/valsartan (Entresto)
An angiotensin receptor-neprilysin inhibitor (ARNI). The cardiovascular and renal effects of sacubitril’s active metabolite (LBQ657) in heart failure are attributed to the increased levels of peptides that are degraded by neprilysin (eg, natriuretic peptide). Administration results in increased natriuresis, increased urine cGMP, and decreased plasma MR-proANP (mid-regional proatrial natriuretic peptide) and NT-proBNP (N-terminal pro B-type natriuretic peptide). It is indicated to reduce the risk of cardiovascular death and hospitalization in chronic heart failure. Benefits for this indication are most clearly evident in patients with LVEF below normal. The combination drug is also indicated for symptomatic HF with systemic left ventricular systolic dysfunction in children aged 1 year and older.
Diuretics, Loop
Class Summary
Diuretics remain the mainstay of therapy and the current standard of care for acute heart failure. First-line diuretic therapy is a loop diuretic (furosemide, bumetanide, torsemide) in the lowest effective dose, either once or twice a day — although it can be used up to 3-4 times a day — depending on the individual response and renal function. Response to diuretic therapy often depends on bioavailability of the drug (better on an empty stomach) and nutritional level (loop diuretics are bound to proteins for renal delivery).
Furosemide (Lasix)
Furosemide increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. The dose must be individualized to the patient. Depending on the response, administer furosemide at small dose increments (20-200 mg) until desired diuresis occurs.
Torsemide (Demadex)
Torsemide acts from within the lumen of the thick ascending portion of the loop of Henle, where it inhibits the sodium, potassium, and chloride carrier system. It increases urinary excretion of sodium, chloride, and water, but does not significantly alter the glomerular filtration rate, renal plasma flow, or acid-base balance. Torsemide is roughly twice as potent as furosemide on a milligram basis. Depending on the response, administer furosemide at small dose increments (10-100 mg) until desired diuresis occurs.
Bumetanide
Bumetanide increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium, potassium, and chloride reabsorption in the ascending loop of Henle. These effects increase urinary excretion of sodium, chloride, and water, resulting in profound diuresis. Renal vasodilation occurs following administration, renal vascular resistance decreases, and renal blood flow is enhanced. Bumetanide is roughly four times as potent as furosemide on a milligram basis. Depending on the response, administer bumetanide at small dose increments (0.5-5 mg) until desired diuresis occurs.
Diuretics, Thiazide
Class Summary
If patients with heart failure do not have a response to treatment with loop diuretics, a thiazide diuretic such as hydrochlorothiazide or metolazone can be added 30 minutes before adminstration of the loop diuretic to enhance the response. Thiazide diuretics inhibit reabsorption of sodium and chloride in the cortical thick ascending limb of the loop of Henle and the distal tubules. They also increase potassium and bicarbonate excretion as well as decrease calcium excretion and uric acid retention. Combination diuretic therapy should be monitored closely for development of hypovolemia, hypokalemia, hypomagnesemia, and hyponatremia.
Hydrochlorothiazide (Microzide)
Hydrochlorothiazide inhibits reabsorption of sodium in the distal tubules, causing increased excretion of sodium, water, potassium, and hydrogen ions.
Indapamide
Indapamide has a diuretic effect that is localized at the proximal segment of the distal tubule of the nephron. Similar to other diuretics it may enhance sodium, chloride and water excretion.
Chlorthalidone (Thalitone)
Chlorthalidone inhibits the reabsorption of sodium in distal tubules, causing increased excretion of sodium and water, as well as potassium and hydrogen ions.
Chlorothiazide (Diuril)
Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. It increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate
Diuretics, Other
Class Summary
Metolazone is a diuretic of the quinazoline class and has thiazidelike properties. This agent interferes with the renal tubular mechanism of electrolyte reabsorption.
Metolazone (Zaroxolyn)
Metolazone increases excretion of sodium, water, potassium, and hydrogen ions by inhibiting reabsorption of sodium in the distal tubules. Metolazone may be more effective in patients with impaired renal function.
Diuretics, Potassium-Sparing
Class Summary
The potassium-sparing diuretics interfere with sodium reabsorption at the distal tubules, resulting in decreased potassium secretion. These agents have a weak diuretic and antihypertensive effect when used alone. The potassium-sparing diuretics spironolactone or triamterene are usually used in addition to the loop diuretics. Note that careful monitoring of renal function and potassium is necessary for all diuretics.
Spironolactone (Aldactone)
Spironolactone is used for the management of edema resulting from excessive aldosterone excretion. It competes with aldosterone for receptor sites in the distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions. Spironolactone at a target dose of 25 mg has been shown to improve survival in patients with heart failure and reduced ejection fraction.
Amiloride (Midamor)
Amiloride is unrelated chemically to other known antikaliuretic or diuretic agents. It is a potassium-conserving (antikaliuretic) drug that, compared with thiazide diuretics, possesses weak natriuretic, diuretic, and antihypertensive activity.
Triamterene (Dyrenium)
Triamterene is a potassium-sparing diuretic with relatively weak natriuretic properties. It exerts its diuretic effect on the distal renal tubules by inhibiting the reabsorption of sodium in exchange for potassium and hydrogen. It increases sodium excretion and reduces excessive loss of potassium and hydrogen associated with hydrochlorothiazide.
Aldosterone Antagonists, Selective
Class Summary
Aldosterone antagonists are weak diuretics that reduce mortality and the risk of sudden death by blocking the effects of aldosterone, thereby decreasing myocardial and vascular inflammation and collagen production. This, in turn, prevents apoptosis, decreases stimulation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS), and acts as a membrane stabilizer, thus preventing arrhythmia. Aldosterone antagonists are recommended for patients who have moderately severe and severe heart failure and reduced left ventricular (LV) systolic function (Randomized Aldactone Evaluation Study [RALES]) who can be carefully monitored for preserved renal function and normal potassium concentration.
Eplerenone (Inspra)
Eplerenone selectively blocks aldosterone at the mineralocorticoid receptors in epithelial (eg, kidney) and nonepithelial (eg, heart, blood vessels, and brain) tissues; thus, it decreases blood pressure and sodium reabsorption. It is indicated to improve survival for heart failure or left LV dysfunction following acute MI. Compared with placebo, a significant risk reduction (15%) has been observed. The EMPHASIS-HF trial has shown that patients with systolic heart failure with mild symptoms treated with eplerenone have a significant reduction in cardiovascular death or heart failure hospitalization when compared with placebo.
SGLT2 Inhibitors
Class Summary
Empagliflozin and dapagliflozin are inhibitors of the sodium-glucose cotransporter 2 (SGLT2), the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. This action increases urinary glucose excretion.
SGLT2 inhibitors also reduce sodium reabsorption and increase the delivery of sodium to the distal tubule. This may influence several physiologic functions, such as lowering both preload and afterload of the heart and downregulating sympathetic activity.
Empagliflozin (Jardiance)
In addition to improving glycemic control in adults with type 2 diabetes mellitus (T2DM), empagliflozin is indicated to reduce the risk of cardiovascular (CV) death and hospitalization for heart failure (HF) in adults with HF (either HF with reduced ejection fraction [HFrEF] or HF with preserved EF [HFpEF]).
It is also indicated to reduce the risk of CV death in adults with T2DM and CV disease.
Dapagliflozin (Farxiga)
Dapagliflozin is indicated to reduce hospitalization risk for heart failure in adults with T2DM and established cardiovascular disease (CVD) or multiple CV risk factors. It is also indicated to reduce the risk of CV death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction (HFrEF) or heart failure with preserved EF (HFpEF).
Additionally, dapagliflozin is indicated to reduce the risk of sustained eGFR decline, ESRD, CV death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression.
Dual SGLT1/2 Inhibitors
Class Summary
Inhibiting SGLT1 reduces intestinal absorption of glucose and sodium.
Inhibiting SGLT2 reduces renal reabsorption of glucose and sodium, which may influence several physiologic functions, such as lowering both pre- and afterload of the heart and downregulating sympathetic activity.
Sotagliflozin (Inpefa)
Sotagliflozin is ndicated to reduce the risk of cardiovascular (CV) death, hospitalization for heart failure (HF), and urgent visits for HF in adults with HF or type 2 diabetes, chronic kidney disease, or other CV risk factors.
Soluble Guanylate Cyclase Stimulators
Class Summary
Heart failure is associated with impaired nitric oxide (NO) synthesis and decreased soluble guanylate cyclase (sGC) activity, which may contribute to myocardial and vascular dysfunction.
By directly stimulating sGC, independently of and synergistically with NO, vericiguat augments levels of intracellular cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation and vasodilation.
Vericiguat (Verquvo)
Vericiguat stimulates sGC, the intracellular receptor for endogenous NO, which catalyzes cGMP production. It is indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization in adults following a hospitalization for HF or a need for outpatient IV diuretics, who have symptomatic chronic HF and an ejection fraction < 45%.
Alpha/Beta Adrenergic Agonists
Class Summary
In the presence of significant hypotension, adrenergic agonists are used to improve cardiac output and organ perfusion.
Epinephrine (Adrenaclick, Adrenalin, EpiPen, EpiPen Jr.)
Epinephrine is an alpha-agonist and its effects include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Beta2-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.
Norepinephrine (Levophed)
Norepinephrine is a naturally occurring catecholamine with potent alpha-receptor and mild beta-receptor activity. It stimulates beta1- and alpha-adrenergic receptors, resulting in increased cardiac muscle contractility, heart rate, and vasoconstriction. It increases blood pressure and afterload. Increased afterload may result in decreased cardiac output, increased myocardial oxygen demand, and cardiac ischemia. It is generally reserved for use in patients with severe hypotension (eg, systolic blood pressure < 70 mm Hg) or hypotension that is unresponsive to other medications.
Calcium Channel Blockers
Class Summary
Generally, calcium channel blockers (CCBs) should be avoided. CCBs do not play a direct role in the management of heart failure; however, these agents may be used to treat other conditions, such as hypertension or angina in heart failure patients.
CCBs may be used in heart failure with normal left ventricular ejection fraction. These drugs may also improve exercise tolerance via their vasodilatory properties.
Amlodipine (Norvasc)
Amlodipine has antianginal and antihypertensive effects. It blocks the post-excitation release of calcium ions into cardiac and vascular smooth muscle, thereby inhibiting the activation of ATPase on myofibril contraction. The overall effect is reduced intracellular calcium levels in cardiac and smooth muscle cells of the coronary and peripheral vasculature, resulting in dilatation of the coronary and peripheral arteries. It also increases myocardial oxygen delivery in patients with vasospastic angina.
Nifedipine (Adalat CC, Afeditab CR, Nifediac CC, Nifedical XL, Procardia, Procardia XL)
Nifedipine relaxes coronary smooth muscle and produces coronary vasodilation, which in turn, improves myocardial oxygen delivery. Sublingual administration is generally safe, despite theoretical concerns.
Felodipine (Cabren, Cardioplen XL, Felendil XL)
Felodipine is a dihydropyridine calcium channel blocker. It inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes. The resultant decrease in intracellular calcium inhibits the contractile processes of the smooth muscle cells, resulting in dilation of coronary and systemic arteries.
Anticoagulants, Cardiovascular
Class Summary
Patients with heart failure and depressed left ventricular (LV) ejection fraction are thought to have an increased risk of thrombus formation due to low cardiac output. Hospitalized patients with heart failure are at a high risk for venous thromboembolism and should receive prophylaxis. Anticoagulation with an international normalized ratio (INR) goal of 2-3 is indicated in the presence of: (1) an LV thrombus, (2) a thromboembolic event with or without evidence of an LV thrombus, and (3) paroxysmal or chronic atrial arrhythmias.
Warfarin (Coumadin, Jantoven)
Warfarin interferes with hepatic vitamin K–dependent carboxylation. It is used for the prophylaxis and treatment of thromboembolic disorders.
Dabigatran (Pradaxa)
Competitive, direct thrombin inhibitor. Thrombin enables fibrinogen conversion to fibrin during the coagulation cascade, thereby preventing thrombus development. Inhibits both free and clot-bound thrombin and thrombin-induced platelet aggregation.
Opioid Analgesics
Class Summary
Opioid analgesics such as morphine sulfate may help to relieve patients’ anxiety, distress, and dyspnea.
Morphine sulfate (Astramorph, Avinza, DepoDur, Duramorph, Infumorph 200, Infumorph 500, Kadian, MS Contin, Oramorph SR, Roxanol)
Morphine is the drug of choice for narcotic analgesia because of its reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Morphine sulfate administered intravenously may be dosed in a number of ways and commonly is titrated until the desired effect is obtained. Morphine sulfate also decreases preload in heart failure and relieves dyspnea.
-
Heart Failure. This chest radiograph shows an enlarged cardiac silhouette and edema at the lung bases, signs of acute heart failure.
-
Heart Failure. Cardiac cirrhosis. Congestive hepatopathy with large renal vein.
-
Heart Failure. Cardiac cirrhosis. Congestive hepatopathy with large inferior vena cava.
-
Heart Failure. This electrocardiogram (ECG) is from a 32-year-old female with recent-onset congestive heart failure and syncope. The ECG demonstrates a tachycardia with a 1:1 atrial:ventricular relationship. It is not clear from this tracing whether the atria are driving the ventricles (sinus tachycardia) or the ventricles are driving the atria (ventricular tachycardia [VT]). At first glance, sinus tachycardia in this ECG might be considered with severe conduction disease manifesting as marked first-degree atrioventricular block with left bundle branch block. On closer examination, the ECG morphology gives clues to the actual diagnosis of VT. These clues include the absence of RS complexes in the precordial leads, a QS pattern in V6, and an R wave in aVR. The patient proved to have an incessant VT associated with dilated cardiomyopathy.
-
Heart Failure. This is a posteroanterior view of a right ventricular endocardial activation map during ventricular tachycardia in a patient with a previous septal myocardial infarction. The earliest activation is recorded in red; late activation displays as blue to magenta. Fragmented low-amplitude diastolic local electrocardiograms were recorded adjacent to the earliest (red) breakout area, and local ablation in this scarred zone (red dots) resulted in termination and noninducibility of this previously incessant arrhythmia.
-
Heart Failure. A 28-year-old woman presented with acute heart failure secondary to chronic hypertension. The enlarged cardiac silhouette on this anteroposterior (AP) radiograph is caused by acute heart failure due to the effects of chronic high blood pressure on the left ventricle. The heart then becomes enlarged, and fluid accumulates in the lungs (ie, pulmonary congestion).
-
Heart Failure. Epsilon wave on an electrocardiogram in a patient with arrhythmogenic right ventricular dysplasia (ARVD). ARVD is a congenital cardiomyopathy that is characterized by infiltration of adipose and fibrous tissue into the RV wall and loss of myocardial cells. Primary injuries usually are at the free wall of the RV and right atria, resulting in ventricular and supraventricular arrhythmias. The most significant of all rhythms associated with heart failure are the life-threatening ventricular arrhythmias.
-
Heart Failure. Electrocardiogram depicting ventricular fibrillation in a patient with a left ventricular assist device (LVAD). Ventricular fibrillation is often due to ischemic heart disease and can lead to myocardial infarction and/or sudden death.
-
Heart Failure. The rhythm on this electrocardiogram (ECG) is sinus with borderline PR prolongation. There is evidence of an acute/evolving anterior ischemia/myocardial infarction (MI) superimposed on the left bundle branch block (LBBB)–like pattern. Note the primary T-wave inversions in leads V2-V4, rather than the expected discordant (upright) T waves in the leads with a negative QRS. Although this finding is not particularly sensitive for ischemia/MI with LBBB, such primary T-wave changes are relatively specific. The prominent voltage with left atrial abnormality and leftward axis in concert with the left ventricular intraventricular conduction delay (IVCD) are consistent with underlying left ventricular hypertrophy. This ECG is an example of "bundle branch block plus." Image courtesy of http://ecg.bidmc.harvard.edu.
-
Heart Failure. This electrocardiogram (ECG) shows evidence of severe left ventricular hypertrophy (LVH) with prominent precordial voltage, left atrial abnormality, lateral ST-T abnormalities, and a somewhat leftward QRS axis (–15º). The patient had malignant hypertension with acute heart failure, accounting also for the sinus tachycardia (blood pressure initially 280/180 mmHg). The ST-T changes seen here are nonspecific and could be due to, for example, LVH alone or coronary artery disease. However, the ECG is not consistent with extensive inferolateral myocardial infarction. Image courtesy of http://ecg.bidmc.harvard.edu.
-
Heart Failure. The rhythm on this electrocardiogram is atrial tachycardia (rate, 154 beats/min) with a 2:1 atrioventricular (AV) block. Note the partially hidden, nonconducted P waves on the ST segments (eg, leads I and aVL). The QRS is very wide with an atypical intraventricular conduction defect (IVCD) pattern. The rSR' type complex in the lateral leads (I, aVL) is not due to a right bundle branch block (RBBB) but to an atypical left ventricular conduction defect. These unexpected rSR' complexes in the lateral leads (El-Sherif sign) correlate with underlying extensive myocardial infarction (MI) and, occasionally, ventricular aneurysm. (El-Sherif. Br Heart J. 1970;32:440-8.) The notching on the upstroke of the S waves in lead V4 with a left bundle branch block-type pattern also suggests underlying MI (Cabrera sign). This patient had severe cardiomyopathy secondary to coronary artery disease, with extensive left ventricular wall motion abnormalities. Image courtesy of http://ecg.bidmc.harvard.edu.
-
Heart Failure. On this electrocardiogram, baseline artifact is present, simulating atrial fibrillation. Such artifact may be caused by a variety of factors, including poor electrode contact, muscle tremor, and electrical interference. A single premature ventricular complex (PVC) is present with a compensatory pause such that the RR interval surrounding the PVC is twice as long as the preceding sinus RR interval. Evidence of a previous anterior myocardial infarction is present with pathologic Q waves in leads V1-V3. Borderline-low precordial voltage is a nonspecific finding. Cardiac catheterization showed a 90% stenosis in the patient's proximal portion the left anterior descending coronary artery, which was treated with angioplasty and stenting. Broad P waves in lead V1 with a prominent negative component is consistent with a left atrial abnormality. Image courtesy of http://ecg.bidmc.harvard.edu.
-
Heart Failure. This electrocardiogram (ECG) is from a patient who underwent urgent cardiac catheterization, which revealed diffuse severe coronary spasm (most marked in the left circumflex system) without any fixed obstructive lesions. Severe left ventricular wall motion abnormalities were present, involving the anterior and inferior segments. A question of so-called takotsubo cardiomyopathy (left ventricular apical ballooning syndrome) is also raised (see Bybee et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Int Med 2004:141:858-65). The latter is most often reported in postmenopausal, middle-aged to elderly women in the context of acute emotional stress and may cause ST elevations acutely with subsequent T-wave inversions. A cocaine-induced cardiomyopathy (possibly related to coronary vasospasm) is a consideration but was excluded here. Myocarditis may also be associated with this type of ECG and the cardiomyopathic findings shown here. No fixed obstructive epicardial coronary lesions were detected by coronary arteriography. The findings in this ECG include low-amplitude QRS complexes in the limb leads (with an indeterminate QRS axis), loss of normal precordial R-wave progression (leads V1-V3), and prominent anterior/lateral T-wave inversions. Image courtesy of http://ecg.bidmc.harvard.edu.
-
Heart Failure. This electrocardiogram shows an extensive acute/evolving anterolateral myocardial infarction pattern, with ST-T changes most apparent in leads V2-V6, I, and aVL. Slow R-wave progression is also present in leads V1-V3. The rhythm is borderline sinus tachycardia with a single premature atrial complex (PAC) (fourth beat). Note also the low limb-lead voltage and probable left atrial abnormality. Left ventriculography showed diffuse hypokinesis as well as akinesis of the anterolateral and apical walls, with an ejection fraction estimated at 33%. Image courtesy of http://ecg.bidmc.harvard.edu.
-
Heart Failure. This electrocardiogram shows a patient is having an evolving anteroseptal myocardial infarction secondary to cocaine. There are Q waves in leads V2-V3 with ST-segment elevation in leads V2-V5 associated with T-wave inversion. Also noted are biphasic T waves in the inferior leads. These multiple abnormalities suggest occlusion of a large left anterior descending artery that wraps around the apex of the heart (or multivessel coronary artery disease). Image courtesy of http://ecg.bidmc.harvard.edu.
-
Heart Failure. A color-enhanced angiogram of the left heart shows a plaque-induced obstruction (top center) in a major artery, which can lead to myocardial infarction (MI). MIs can precipitate heart failure.
-
Heart Failure. Emphysema is included in the differential diagnosis of heart failure. In this radiograph, emphysema bubbles are noted in the left lung; these can severely impede breathing capacity.
-
Heart Failure. Cervicocephalic fibromuscular dysplasia (FMD) can lead to complications such as hypertension and chronic kidney failure, which can lead to heart failure. In this color Doppler and spectral Doppler ultrasonographic examination of the left internal carotid artery (ICA) in a patient with cervicocephalic FMD, stenoses of about 70% is seen in the ICA.
-
Heart Failure. Cervicocephalic fibromuscular dysplasia (FMD) can lead to complications such as hypertension and chronic kidney failure, which, in turn, can lead to heart failure. Nodularity in an artery is known as the "string-of-beads sign," and it can be seen this color Doppler ultrasonographic image from a 51-year-old patient with low-grade stenosing FMD of the internal carotid artery (ICA).
-
Heart Failure. Electrocardiogram from a 46-year-old man with long-standing hypertension. Note the left atrial abnormality and left ventricular hypertrophy with strain.
-
Heart Failure. Electrocardiogram from a 46-year-old man with long-standing hypertension. Left atrial abnormality and left ventricular hypertrophy with strain is revealed.
-
Heart Failure. Apical four-chamber echocardiogram in a 37-year-old man with arrhythmogenic right ventricular dysplasia (ARVD), a congenital cardiomyopathy. Note the prominent trabeculae and abnormal wall motion of the dilated RV. ARVD can result in ventricular and supraventricular arrhythmias. The most significant of all rhythms associated with heart failure are the life-threatening ventricular arrhythmias.
-
Heart Failure. Cardiac magnetic resonance image (CMRI), short-axis view. This image shows right ventricular (RV) dilatation, trabucular derangement, aneurysm formation, and dyskinetic free wall in a patient with arrhythmogenic RV dysplasia.
-
Heart Failure. This transthoracic echocardiogram demonstrates severe mitral regurgitation with a heavily calcified mitral valve and prolapse of the posterior leaflet into the left atrium.
-
Heart Failure. Echocardiogram of a patient with severe pulmonic stenosis. This image shows a parasternal short-axis view of a thickened pulmonary valve. Pulmonic stenosis can lead to pulmonary hypertension, which can result in hepatic congestion and in right-sided heart failure.
-
Heart Failure. Echocardiogram of a patient with severe pulmonic stenosis. This image shows a Doppler scan of the peak velocity (5.2 m/s) and gradients (peak 109 mmHg, mean 65 mmHg) across the valve.
-
Heart Failure. Echocardiogram of a patient with severe pulmonic stenosis. This image shows moderately severe pulmonary insufficiency (orange color flow) is also present.
-
Heart Failure. This video is an echocardiogram of a patient with severe pulmonic stenosis. The first segment shows the parasternal short-axis view of the thickened pulmonary valve. The second segment shows the presence of moderate pulmonary insufficiency (orange color flow). AV = aortic valve, PA = pulmonary artery, PI = pulmonary insufficiency, PV = pulmonary valve.
-
Heart Failure. Transesophageal echocardiogram with continuous wave Doppler interrogation across the mitral valve. An increased mean gradient of 16 mmHg is revealed, consistent with severe mitral stenosis.
Tables
- Table 1. Framingham Diagnostic Criteria for Heart Failure
- Table 2. Evidence-Based BNP and NT-proBNP Cutoff Values for Diagnosing HF
- Table 3. 2013 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Heart Failure Staging System
- Table 4. 2022 ACC/AHA/Heart Failure Society of America (HFSA) Heart Failure Staging System
- Table 5. 2022 ACC/AHA/HFSA Classification of Heart Failure (HF) by Left Ventricular Ejection Fraction (LVEF)
Major Criteria |
Minor Criteria |
Paroxysmal nocturnal dyspnea |
Nocturnal cough |
Weight loss of 4.5 kg in 5 days in response to treatment |
Dyspnea on ordinary exertion |
Neck vein distention |
A decrease in vital capacity by one third the maximal value recorded |
Rales |
Pleural effusion |
Acute pulmonary edema |
Tachycardia (rate of 120 bpm) |
Hepatojugular reflux |
Hepatomegaly |
S3 gallop |
Bilateral ankle edema |
Central venous pressure >16 cm water |
|
Circulation time of ≥25 seconds |
|
Radiographic cardiomegaly |
|
Pulmonary edema, visceral congestion, or cardiomegaly at autopsy |
|
Source: Ho KK, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol. |
|
Criterion |
BNP, pg/mL |
NT-proBNP, pg/mL |
|||
HF Unlikely (LR-Negative) |
HF Likely (LR-Positive) |
HF Unlikely (LR-Negative) |
HF Likely (LR-Positive) |
||
Age, y |
>17 |
< 100 (0.13)* |
>500 (8.1)* |
- |
- |
>21 |
- |
- |
< 300 (0.02)† |
- |
|
21-50 |
- |
- |
- |
>450 (14)† |
|
50-75 |
- |
- |
- |
>900 (5.0)† |
|
>75 |
- |
- |
- |
>1800 (3.1)† |
|
Estimated GFR, < 60 mL/min |
< 200 (0.13)‡ |
>500 (9.3)‡ |
- |
- |
|
BNP = B-type natriuretic peptide; GRF = glomerular filtration rate; HF = heart failure; LR = likelihood ratio; NPV = negative predictive value; NT-pro-BNP = N-terminal proBNP; PPV = positive predictive value; – = not specifically defined. * Derived from Breathing Not Properly data (1586 emergency department [ED] patients, prevalence of HF = 47%). [65] † Derived from PRIDE data (1256 ED patients, prevalence of HF = 57%). [66, 75] ‡ Derived from subset of Breathing Not Properly data (452 ED patients, prevalence of HF = 49%). [74] |
|||||
Stage |
Description |
Examples |
Notes |
A |
At high risk for heart failure but without structural heart disease or symptoms of heart failure |
Patients with coronary artery disease, hypertension, or diabetes mellitus without impaired left ventricular (LV) function, LV hypertrophy (LVH), or geometric chamber distortion |
Patients with predisposing risk factors for developing heart failure No corresponding New York Heart Association (NYHA) functional classification |
B |
Structural heart disease but without signs/symptoms of heart failure |
Patients who are asymptomatic but who have LVH and/or impaired LV function |
Corresponds with patients with NYHA class I |
C |
Structural heart disease with current or past symptoms of heart failure |
Patients with known structural heart disease and shortness of breath and fatigue, as well as reduced exercise tolerance |
The majority of patients with heart failure are in this stage Corresponds with NYHA classes I, II, III and IV |
D |
Refractory heart failure requiring specialized interventions |
Patients who have marked symptoms at rest despite maximal medical therapy |
Patients in this stage may be eligible to receive mechanical circulatory support, receive continuous inotropic infusions, undergo procedures to facilitate fluid removal, or undergo heart transplantation or other procedures Corresponds with patients with NYHA class IV |
Proposed Terminology |
Stage |
Definition and Criteria |
At risk for HF |
A |
At risk of HF; asymptomatic, no structural heart disease nor cardiac biomarkers of stretch injury (eg, patients with hypertension, atherosclerotic cardiovascular disease, diabetes, metabolic syndrome and obesity, exposure to cardiotoxic agents, genetic variant for cardiomyopathy, or positive family history of cardiomyopathy) |
Pre-HF |
B |
No signs/symptoms of HF and evidence of one of the following: Structural heart disease
Evidence for raised filling pressures by invasive hemodynamic measurements or by noninvasive imaging that suggests elevated filling pressures (eg, Doppler echocardiography) Patients with risk factors and raised levels of B-type natriuretic peptides or persistently elevated cardiac troponin in the absence of competing diagnoses that result in such biomarker elevations (eg, acute coronary syndrome, chronic kidney disease, pulmonary embolus, or myopericarditis) |
Symptomatic HF |
C |
Structural heart disease with current or previous symptoms of HF |
Advanced HF |
D |
Marked HF symptoms that interfere with daily life and with repeated hospitalizations despite attempts to optimize guideline-directed medical therapy |
HF = heart failure |
||
HF Type by LVEF |
Criteria |
HF with reduced EF (HFrEF) |
LVEF ≤40% |
HF with improved EF (HFimpEF) |
Previous LVEF ≤40% and a followup LVEF >40% |
HF with mildly reduced EF (HFmrEF) |
LVEF of 41%-49% Evidence of spontaneous/provokable increased LV filling pressures (eg, elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement) |
HF with preserved EF (HFpEF) |
LVEF ≥50% Evidence of spontaneous/provokable increased LV filling pressures (eg, elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement) |
What would you like to print?
- Overview
- Presentation
- DDx
- Workup
- Treatment
- Approach Considerations
- Nonpharmacologic Therapy
- Pharmacologic Therapy
- Acute Heart Failure Treatment
- Treatment of Heart Failure with Preserved LVEF
- Treatment of Right Ventricular Heart Failure
- Electrophysiologic Intervention
- Revascularization Procedures
- Valvular Surgery
- Ventricular Restoration
- Extracorporeal Membrane Oxygenation
- Ventricular Assist Devices
- Heart Transplantation
- Total Artificial Heart
- Show All
- Guidelines
- Guidelines Summary
- Screening and Genetic Testing
- Diagnostic Procedures
- Nonpharmacologic Therapy
- Pharmacologic Therapy
- Electrophysiologic Intervention
- Revascularization Procedures
- Valvular Surgery
- Mechanical Circulatory Support Devices
- Heart Transplantation
- Management of Acute Decompensated Heart Failure (ADHF)
- Show All
- Medication
- Medication Summary
- Beta-Blockers, Alpha Activity
- Beta-Blockers, Beta-1 Selective
- ACE Inhibitors
- ARBs
- Inotropic Agents
- Vasodilators
- Nitrates
- B-type Natriuretic Peptides
- I(f) Inhibitors
- Angiotensin Receptor-Neprilysin Inhibitors (ARNi)
- Diuretics, Loop
- Diuretics, Thiazide
- Diuretics, Other
- Diuretics, Potassium-Sparing
- Aldosterone Antagonists, Selective
- SGLT2 Inhibitors
- Dual SGLT1/2 Inhibitors
- Soluble Guanylate Cyclase Stimulators
- Alpha/Beta Adrenergic Agonists
- Calcium Channel Blockers
- Anticoagulants, Cardiovascular
- Opioid Analgesics
- Show All
- Questions & Answers
- Media Gallery
- Tables
- References
