Course preview

Heart Failure

Disclosure Statement

This course reviews the incidence, pathophysiology, categories and stages, risk factors, clinical manifestations, diagnostic testing, and treatment options for heart failure (HF).

Upon completion of this module, learners should be able to:

• describe the pathophysiologic changes that occur in HF
• explore the categories and stages of HF
• discuss the clinical manifestations of HF
• describe the risk factors and comorbidities for HF
• summarize the diagnostic and treatment algorithms for HF

Heart failure (HF) is a complex clinical syndrome of ventricular dysfunction characterized by the heart’s inability to pump blood effectively to support other organs in the body due to both functional and structural impairments. In 1997, HF was designated as an emergent epidemic due to its exponential increase in hospitalizations and remains a significant clinical and population health concern. HF affects approximately 6.7 million adults 20 years and older in the United States, or 2% of the overall population. In 2023, HF accounted for 452,572 deaths, which is 14.6% of all causes of death. It is also estimated that the financial burden of health care is approximately $30.7 billion, resulting from the costs of health care services, medications, and lost workdays. HF is more prevalent in older adults and is the primary cause of hospitalization for patients over age 65 in the United States. The management of HF is more complicated in older populations due to comorbidities and decreased cardiac, renal, and liver functioning. HF is most prevalent among non-Hispanic Black individuals (4.6 per 1,000 people), followed by Hispanic individuals (3.5 per 1,000 people) and non-Hispanic White individuals (2.4 per 1,000 people; Centers for Disease Control and Prevention, 2024; Heidenreich et al., 2022; Ignatavicius et al., 2020; Roger, 2021; Shams, Malik, et al., 2025).

Cardiac Output, Stroke Volume, and Heart Failure

A basic understanding of cardiac function is necessary to grasp how HF affects the heart and body. HF limits the heart’s ability to pump enough blood to meet the body’s metabolic demands. Cardiac output (CO) is the blood volume pumped from the heart in 1 minute. Stroke volume (SV) is the volume of blood pumped from the heart with each ventricular contraction, or the difference between end-diastolic volume (EDV) and end-systolic volume (ESV). CO is the product of heart rate and SV (Fine, 2025; Mohrman & Heller, 2018; Shams, Goyal, et al., 2025). SV and, by implication, left ventricular function are determined by three variables:

• preload (or EDV): the amount of blood in the ventricle before systole; preload can also be defined as the resting length of the myocardial muscle fibers before systole
• myocardial contractility: the force of a cardiac contraction at a given preload
• afterload: the impedance that must be overcome for blood to be pumped from the ventricles (Fine, 2025; Mohrman & Heller, 2018)

A normal heart can produce an SV large enough to supply the metabolic demands of the organs and tissues, adjusting the SV as needed to meet demand. The ventricles can expand and stretch to accommodate a large blood volume or preload. When preload increases, the myocardium responds by increasing the myocardial contraction force. However, in patients with HF, the myocardium has been damaged. This impairs the contractile ability of the myocardium, resulting in systolic dysfunction, and prevents the myocardium from stretching sufficiently to accommodate the volume of blood needed, leading to impaired diastolic filling and function. Fibrosis, hypertrophy, and other changes to the myocardium reduce the ventricles’ filling capacity; a damaged myocardium leads to systolic dysfunction and impaired pumping force. If the damage to the heart is not sudden and severe—in most cases of HF, it is not—compensatory mechanisms can compensate to maintain cardiac function. Over time, these compensations also cause injury to the heart, and in most cases, HF is a progressive disease characterized by declining cardiac function (Fine, 2025; Loscalzo et al., 2022; Shams, Malik, et al., 2025).

Classifications

There are three primary types of HF: left-sided, right-sided, and high output (discussed later in the course). Congestive heart failure (CHF) is a term that characterizes HF that leads to congestion or fluid that backs up from inefficient pumping and can be caused by left-sided (fluid accumulates in the lungs) or right-sided (fluid accumulates in the legs and ankles) HF. Left-sided HF occurs when the left ventricle of the heart is weakened and unable to effectively pump blood, leading to reduced CO and pulmonary congestion. Left-sided HF is further classified into systolic and diastolic HF based on left ventricular ejection fraction (LVEF). Systolic HF is also known as heart failure with reduced EF (HFrEF), and diastolic HF is heart failure with preserved EF (HFpEF). LVEF is determined by dividing SV by EDV and multiplying by 100. A normal LVEF for patients assigned male at birth is 52%-72%, and a normal LVEF for those assigned female is 54%-74%. HFrEF is defined as HF with an ejection fraction (EF) at or below 40%; HFpEF is defined as an EF at or above 50%. Between these two is HF, with a midrange EF (HFmrEF) characterized by an EF of 41%–49%. This stage can indicate either an improvement or a deterioration of HF based on the trend of EF results. Right-sided HF occurs with right ventricular dysfunction, leading to increased systemic venous pressure and edema that occurs primarily in dependent tissues (feet, ankles, and abdominal viscera). Although fluid can accumulate in the stomach and intestines, the liver is often the most severely affected organ with right-sided HF (Colucci, 2025; Fine, 2025; Heidenreich et al., 2022; Ignatavicius et al., 2020; Loscalzo et al., 2022; Shams, Malik, et al., 2025).

HF is also categorized based on signs, symptoms, and the functional impact of the disease using systems developed by the New York Heart Association (NYHA) and the American College of Cardiology (ACC)/American Heart Association (AHA; refer to Table 1; Heidenreich et al., 2022; Ignatavicius et al., 2020).

Table 1

ACC/AHA HF Categories Compared to NYHA Functional Classification of Cardiovascular Disability

(Colucci, 2025; Heidenreich et al., 2022; Ignatavicius et al., 2020; Shams, Malik, et al., 2025)

Pathophysiology of Heart Failure

Heart Failure With Reduced Ejection Fraction

The primary pathophysiology underlying HFrEF is acute or chronic damage to the myocardium and impaired systolic function with insufficient contractile force to produce an adequate SV. The most common causes of HFrEF are described further on; however, the majority of cases of HFrEF are attributed to ischemic heart disease or hypertension. For approximately 20%-30% of patients, the cause remains unidentified; these cases are referred to as nonischemic or idiopathic cardiomyopathy (Colucci, 2025; Fine, 2025; Golla et al., 2024; Loscalzo et al., 2022).

HFrEF is a complex disorder characterized by three basic steps: the initiation of the disease or event, the development of compensatory mechanisms, and the progression of the disease leading to the development of clinical manifestations. Patients with HFrEF are initially asymptomatic or minimally symptomatic and may remain so for many years due to multiple compensatory mechanisms that can restore ventricular function and CO. These compensatory mechanisms improve the CO, SV, vascular tone, and pump function. Although these mechanisms are discussed separately (refer to Table 2), they overlap and influence each other (Colucci, 2025; Fine, 2025; Golla et al., 2024; Loscalzo et al., 2022).

Table 2

Compensatory Mechanisms

(Colucci, 2025; Fine, 2025; Golla et al., 2024; Loscalzo et al., 2022; Schwinger, 2021)

These compensatory mechanisms are effective. However, renin-angiotensin-aldosterone system (RAAS) activation, increased sympathetic activation and tone, and other HF adaptations can cause myocardial damage and dysfunction (i.e., apoptosis and necrosis of myocardial cells, dilated ventricles, an abnormal response to adrenergic stimulation, and abnormal myocardial metabolism). The compensatory mechanisms are initially beneficial but weaken the heart over time, and the patient develops symptomatic HF (Colucci, 2025; Fine, 2025; Golla et al., 2024; Loscalzo et al., 2022; Schwinger, 2021).

Heart Failure With Preserved Ejection Fraction

The primary cause of HFpEF is the inability of the ventricles to fill sufficiently with blood. The underlying dysfunction of the ventricles in HFpEF is complex. It may include myocardial stiffness and elevated diastolic pressure, resulting in congestion, pulmonary hypertension, and a decreased ability to produce enough CO to meet metabolic demands. Systemic inflammation that damages the myocardial blood vessels—initiated by chronic kidney disease (CKD), diabetes, hypertension, and obesity—is a common and important mechanism of injury found with HFpEF. However, normal aging and myocardial ischemia from coronary artery disease (CAD) are also contributing factors. In addition, although HFpEF is characterized primarily by left ventricular stiffness and impaired left ventricular relaxation, other forms of myocardial dysfunction can result from HFpEF (Colucci, 2025; Fine, 2025; Golla & Shams, 2024; Schwinger, 2021).

High-Output Heart Failure

High-output HF is similar to HFrEF and HFpEF, but there is usually no intrinsic heart damage, the EF is normal, and the CO is high yet insufficient to meet metabolic demands. Decreased systemic vascular resistance with poor tissue perfusion, increased metabolic demands, myocardial dysfunction, or a combination of these factors characterizes high-output HF. In certain conditions like cirrhosis, chronic obstructive pulmonary disease (COPD), and severe obesity (BMI greater than 30 kg/m²), HF is relatively common. It can involve changes in the vascular bed, damage to the myocardium, and increased metabolic demand. By contrast, in patients with anemia, arteriovenous fistulas, pregnancy, and other conditions, high-output HF develops only if there is structural heart disease or a particularly severe form of the disease (e.g., thyroid storm; Givertz, 2023; Loscalzo et al., 2022; Singh & Sharma, 2023).

Risk Factors

General risk factors for HF include advanced age, hypertension, COPD, CAD, cardiomyopathy, diabetes, BMI greater than 30 kg/m², and smoking. These risk factors likely impact the development of HF due to systemic inflammation, a process implicated in the development of HF. The lifetime risk for HF in people with an average blood pressure above 160/90 mmHg is almost doubled. The most significant benefit of lowering blood pressure in patients with hypertension is a reduced risk of HF. As blood pressure increases, the heart must work harder to pump blood throughout the body. Without intervention, sustained increased pressure and work affect the heart’s ability to relax and fill completely. With CAD, the arteries narrow due to plaque buildup from increased serum cholesterol. This narrowing reduces blood flow and increases pressure. When the plaques deposit in the circulatory system, oxygen deprivation or ischemia of the muscle can occur; a total blockage of cardiac vessels can lead to myocardial infarction (Colucci, 2025; Givertz, 2023; Loscalzo et al., 2022; Shams, Malik, et al., 2025).

Cardiomyopathy also increases the risk of HF. Cardiomyopathy results from the heart not pumping or relaxing normally, but the cause is not related to hypertension or CAD. Cardiomyopathy often results from an autoimmune disease, a genetic condition (e.g., muscular dystrophy), an infection, or from an unknown cause. Valvular disease can also lead to HF. The valves within the heart can become narrow or stenosed, inhibiting blood flow through the valve and leading to increased pressure, or can become leaky, causing the blood to flow backward. Hyperglycemia, insulin resistance, and diabetes independently increase the risk for HF, and the prevalence among patients with diabetes is four times that of the general population. The lifetime risk for HF among people with a BMI of 30 kg/m² or more is double that of people who have a BMI of less than 25 kg/m² (Colucci, 2025; Givertz, 2023; Loscalzo et al., 2022; Shams, Malik, et al., 2025). In addition to the foregoing risk factors, there are additional risk factors specific to certain types of HF:

• risk factors for HFrEF include:
  • alcohol misuse
  • cardiac rate or rhythm disorders
  • untreated Chagas disease (caused by infection with the parasite Trypanosoma cruzi)
  • chronic lung disease
  • drug- or toxin-induced myocardial damage
  • viral infection
• risk factors for HFpEF include:
  • cardiomyopathy
  • pericardial disease
  • valvular disease
• risk factors for high-output HF include:
  • anemia
  • arteriovenous fistula
  • beriberi (thiamin [vitamin B1] deficiency)
  • cirrhosis
  • hyperthyroidism
  • severe obesity
  • pregnancy
  • renal disease
  • sepsis (Colucci, 2025; Givertz, 2023; Loscalzo et al., 2022; Shams, Malik, et al., 2025)

Signs and Symptoms

Left-Sided Heart Failure

Left-sided HF is associated with decreased CO and increased pulmonary pressure. This can limit blood flow throughout the body, leading to dysfunction in various body systems (Colucci & Borlaug, 2025; Fine, 2025; Ignatavicius et al., 2020). Symptoms that accompany left-sided HF include:

• weakness
• fatigue
• dizziness
• acute confusion
• pulmonary congestion (e.g., a hacking cough, dyspnea, crackles and wheezes on auscultation, frothy pink-tinged sputum, tachypnea, S3/S4 summation gallop)
• oliguria (decreased urine output) during the day and nocturia at night
• angina
• dizziness
• tachycardia or palpitations
• weak peripheral pulses
• cool extremities (Colucci & Borlaug, 2025; Fine, 2025; Ignatavicius et al., 2020)

Right-Sided Heart Failure

Right-sided HF leads to increased systemic venous pressure and congestion due to dysfunction of the right atrium and ventricle (Colucci & Dunlay, 2024; Fine, 2025; Ignatavicius et al., 2020). This congestion and pressure result in the following symptoms:

• jugular vein distention (JVD)
• hepatomegaly (liver enlargement) and splenomegaly (spleen enlargement)
• anorexia and nausea as a result of pressure from the accumulation of intra-abdominal fluid; without intervention, this can lead to malnutrition
• dependent edema in the legs and ankles when ambulatory and in the sacrum when bed-bound
• distended abdomen/ascites; intra-abdominal fluid volume can reach levels greater than 10 L
• swollen hands and fingers
• nighttime polyuria
• weight gain
• clubbing (the angle of the nail increases to 180˚, and the nail bed becomes spongy)
• hypertension from increased fluid volume or hypotension due to HF (Colucci & Dunlay, 2024; Fine, 2025; Ignatavicius et al., 2020)
• 
  

Diagnosis

HF is a clinical diagnosis and a diagnosis of exclusion based on the clinician’s assessment of the patient’s risk factors and reported signs and symptoms. Laboratory studies, imaging, and other diagnostic tests can confirm the diagnosis, determine the cause, and assess the degree of impairment. The first step in the diagnostic algorithm for HF is patient assessment. The healthcare provider (HCP) will obtain a clinical history, perform a physical examination, and order an electrocardiogram (ECG) and serum laboratory tests (Colucci & Borlaug, 2025; Fine, 2025; Heidenreich et al., 2022; Loscalzo et al., 2022).

Laboratory Testing

Laboratory testing should be completed as part of a standard diagnostic assessment. Recommended laboratory studies include a complete blood count (CBC), urinalysis, electrolytes (sodium, potassium, calcium, and magnesium), blood urea nitrogen (BUN), serum creatinine, blood glucose, lipid profile (fasting), liver function tests, iron studies, and thyroid-stimulating hormone (TSH). These laboratory tests help clinicians eliminate other causes of the patient’s symptoms. Measurement of the natriuretic peptides—B-type natriuretic peptide (BNP) and n-terminal pro-BNP (NT-proBNP)—is recommended by the ACC, the AHA, and the Heart Failure Society of America (HFSA) as a way to confirm or exclude the presence of HF, determine the severity of the disease, and establish a prognosis. BNP is a hormone, and NT-proBNP is a prohormone. They are released from the ventricles (and, to a lesser degree, from the atria) when fluid volume overload and myocardial stretching are present. Per the HF guidelines, an abnormal NT-proBNP result is above 125 pg/mL, and an abnormal BNP result is above 35 pg/mL. Other cardiac causes of elevated natriuretic hormones include atrial fibrillation, left ventricular hypertrophy, and pericardial disease. In addition, many conditions and diseases can cause elevated BNP and NT-proBNP levels, including (but not limited to) advanced age, anemia, the use of an angiotensin receptor-neprilysin inhibitor (ARNI), obstructive sleep apnea (OSA), and renal impairment. Those assigned female at birth tend to have a higher BNP and NT-proBNP. Elevated BMI (over 30 kg/m²) can cause falsely low levels due to the increased leptin released by adipose cells. Leptin and BNP have opposite effects; therefore, when leptin levels increase, BNP levels decrease. Cardiac troponin T or I is recommended for patients with acute decompensated HF or suspected acute coronary syndrome. In addition to evaluating laboratory values at the time of diagnosis, providers should follow the 2022 HF treatment guidelines from the ACC/AHA/HFSA, which recommend that laboratory studies should be repeated with any change in condition or medication regimen (Colucci & Borlaug, 2025; Heidenreich et al., 2022; Loscalzo et al., 2022).

Imaging

A chest radiograph can be beneficial in diagnosing left-ventricular HF. Chest radiographs can show the presence of cardiomegaly resulting from hypertrophy and dilation, pulmonary venous congestion, and interstitial edema. Chest radiographs can also help determine whether another cause, such as pulmonary disease, is causing the symptoms of dyspnea. A transthoracic echocardiogram (echo or TTE) is considered the gold standard for the diagnosis of HF. The test is noninvasive and can be used to measure EF. It can also display the size of the heart chambers and identify any abnormalities in the heart wall, valvular function, and markers of diastolic function (Colucci & Borlaug, 2025; Fine, 2025; Heidenreich et al., 2022; Ignatavicius et al., 2020; McDonagh et al., 2021).

Electrocardiogram

An ECG is part of the routine evaluation of patients with HF. An ECG provides information on electrical activity within the heart, including heart rate and rhythm. This information can help determine the cause and prognosis of HF. Although not diagnostic, an abnormal ECG can show previous MI, left ventricular hypertrophy, and arrhythmias, which increase the suspicion for HF. An ECG is repeated whenever there is a clinical indication, including a suspected arrhythmia, presence of ischemia, myocardial injury, or conduction abnormalities. A normal ECG makes a diagnosis of HF unlikely (Colucci & Borlaug, 2025; Fine, 2025; McDonagh et al., 2021).

Treatment

Dietary and Lifestyle Changes

Dietary and lifestyle changes are recommended for patients and can be implemented alone or in combination with pharmacologic treatment to prevent, slow the progression of, or improve HF (AHA, 2025c; Borlaug & Colucci, 2025; Fine, 2025). The following are the most common dietary and lifestyle changes recommended (AHA, 2025c; Borlaug & Colucci, 2025; Fine, 2025):

• Monitor weight daily to detect fluid accumulation and facilitate early intervention, resulting in improved outcomes. Daily weights should be taken in the morning after urination, using the same scale in the same place on the floor, wearing a similar amount of clothing. A weight change of 2 lb (1 kg) in a day or 4 lb (2 kg) in a week should be reported to the provider to determine whether intervention is needed.
• Maintain a healthy weight. Being overweight increases the strain on the heart, and losing weight can decrease this strain; losing too much weight rapidly without trying can signify the development of cardiac cachexia, which can occur with severe HF; cardiac cachexia indicates increased morbidity and mortality independent of other variables, with a life expectancy below 18 months in 50% of patients affected.
• Decrease salt and fluid intake. A high-salt diet can lead to fluid retention, increasing strain on the heart; the amount of salt restriction recommended depends on the patient’s condition and comorbidities. Fluid restriction is also recommended to decrease excess fluid volume, reducing strain on the heart. Most patients are instructed to limit fluid intake to less than 2 L (66 oz) per day.
• Stop smoking. Cigarette smoking can double the risk of HF due to adverse effects on the cardiovascular system and increased cholesterol, leading to plaque deposits in the arteries.
• Limit alcohol intake. If the HF is alcohol-induced, patients should abstain entirely from alcohol; individuals with HF due to another cause should limit alcohol consumption to no more than one serving per day (e.g., 12 oz beer, 5 oz wine, 1.5 oz distilled spirits).
• Engage in regular exercise if tolerated. Regular exercise, 5 days per week, is recommended to improve cardiovascular health and alleviate symptoms; some patients may be referred to a cardiac rehabilitation program for further improvement under medical supervision.

Pharmacologic Treatment

Guideline-Directed Medical Therapy

Guideline-directed medical therapy (GDMT) is the standard medical therapy for HFrEF. Early use of GDMT reduces mortality, prevents readmissions, and improves quality of life for patients with HF. The classes of drugs included in the GDMT include angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs)/ARNIs, beta-blockers, mineralocorticoid or aldosterone receptor antagonists (MRAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors. The benefits of GDMT are most significant when medications from all four drug classes are used in conjunction. Despite evidence from high-quality randomized controlled trials, GDMT remains underutilized due to a lack of awareness of how to safely initiate and titrate these medications (Gottlieb, 2021; Patel et al., 2023).

ACE Inhibitors/ARBs/ARNIs. ACE inhibitors prevent the production of angiotensin II, resulting in vasodilation and a decrease in blood pressure. ACE inhibitors used as part of GDMT include ramipril (Altace), captopril (Capoten), enalapril (Vasotec), and lisinopril (Prinivil, Zestril). Common side effects of ACE inhibitors include a dry, nagging cough; hyperkalemia; fatigue; dizziness; headaches; and loss of taste. In rare cases, ACE inhibitors may cause angioedema (swelling of the lips, tongue, or face), requiring discontinuation. ACE inhibitors are contraindicated in patients with hyperkalemia, renal artery stenosis, or a history of angioedema. Concomitant use of an ARNI and an ACE inhibitor is contraindicated (Maddox et al., 2024; Meyer, 2025; Vallerand & Sanoski, 2020).

Switching to an ARB may be beneficial for patients who report a cough while using ACE inhibitors. ARBs used as part of GDMT include valsartan (Diovan), losartan (Cozaar), and candesartan (Atacand). ARBs decrease blood pressure through competitive antagonist activity at angiotensin II receptor sites. Side effects include dizziness, headaches, hyperkalemia, angioedema, nausea, vomiting, severe diarrhea, and weight loss. ARBs are contraindicated in patients with a life-threatening reaction to ARBs, SBP less than 80 mmHg, hyperkalemia, or renal artery stenosis. All ARBs are dosed once daily; however, if a patient’s BP is not controlled, losartan (Cozaar) may be dosed twice daily (Maddox et al., 2024; Meyer, 2025; Vallerand & Sanoski, 2020).

ARNIs are a new pharmacologic class that combines sacubitril with valsartan under the trade name Entresto. ARNIs lower blood pressure, change the neurohormonal response to HF, and promote diuresis. Sacubitril/valsartan (Entresto) is recommended as a replacement for ACE inhibitors and ARBs for individuals with HFrEF and is more effective than some ACE inhibitors at treating HFrEF. Side effects include a cough, dizziness, hyperkalemia, hypotension, renal failure, and angioedema. The risk of angioedema with an ARNI is comparable to that of an ACE inhibitor. For this reason, ARNIs are contraindicated in patients with a history of ACE inhibitor–related angioedema. Sacubitril/valsartan (Entresto) can cause death to a developing fetus and is, therefore, contraindicated for use in pregnancy. It is also contraindicated in patients with a GFR below 60 mL/min/1.73 m² (Maddox et al., 2024; Meyer, 2025; Vallerand & Sanoski, 2020). Sacubitril/valsartan (Entresto) is approved for use in pediatric patients aged 1 year and older. The pediatric dose is administered orally twice daily and increased at 2-week intervals as tolerated until the maintenance dose is reached (US Food and Drug Administration [FDA], 2024).

Beta-Adrenergic Blockers. Beta-adrenergic blockers block beta-1 and/or beta-2 receptors. Some are specific to beta 1 receptors located in the cardiac muscle. Beta-adrenergic blockers help improve the long-term adverse effects of the compensatory adrenergic stimulation that occurs in chronic HF. In combination with an ACE inhibitor or an ARB, beta-adrenergic blockers reduce the risk of mortality and hospitalization in patients with HFrEF. Bisoprolol (Zebeta), carvedilol (Coreg), and metoprolol succinate (Toprol XL) are preferred as these drugs have the strongest evidence for efficacy. Unfortunately, they can cause bradycardia, dizziness, dyspnea, and fatigue at therapeutic doses. Other symptoms experienced by patients include erectile dysfunction and central nervous system (CNS) disturbances (i.e., hallucinations, memory loss, nightmares). These adverse effects can make it difficult to use the target dose. Beta-adrenergic blockers can be safely used in patients with COPD and diabetes. For patients with diabetes, using beta-adrenergic blockers may mask the symptoms of palpitations, tachycardia, and tremor associated with hypoglycemia. These medications should be discontinued in a gradual taper over several weeks. Abrupt discontinuation may cause MI or ventricular arrhythmias (Maddox et al., 2024; Meyer, 2025; Woods, 2024).

Mineralocorticoid or Aldosterone Receptor Antagonists. The MRAs eplerenone (Inspra) and spironolactone (Aldactone) have been shown to reduce mortality and hospitalizations in patients with HFrEF. MRAs block the effects of aldosterone, resulting in a decreased amount of water and sodium retained by the renal system. Since MRAs are potassium-sparing diuretics, there is a decreased risk of hypokalemia and arrhythmias. Hyperkalemia has been reported in 5%–17.5% of HF patients taking an MRA (Ignatavicius et al., 2020; Maddox et al., 2024; Meyer, 2025).

Sodium-Glucose Cotransporter 2 Inhibitors. Adding an SGLT2 inhibitor to the HF treatment regimen is a new recommendation. For patients with HFrEF, adding an SGLT2 inhibitor can decrease hospitalizations and deaths, even among patients without diabetes. The exact mechanism of action of these medications in HFrEF is not entirely known; however, their use can promote osmotic diuresis and decrease arterial pressure and stiffness. SGLT2 inhibitors are indicated for patients with HFrEF and NYHA Classes II–IV. Side effects include hypovolemia, hypotension (including orthostatic), constipation, nausea, polyuria (excessive urination), urinary tract infection, and hypoglycemia. Using these medications in combination with a loop diuretic can increase the risk of hypotension (Borlaug & Colucci, 2025; Maddox et al., 2024; Meyer, 2025; Woods, 2024).

Other Medications

Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Blockers. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers reduce heart rate by acting on the channels that maintain the cardiac pacemaker (SA node). Ivabradine (Corlanor) is the only HCN channel blocker approved for use in HF and has been available since 2015. According to AHA guidelines, the use of ivabradine (Corlanor) is indicated for patients with symptomatic NYHA Class II or III HFrEF with an EF of less than 35% who are already receiving a beta-adrenergic blocker at the maximum tolerated dose or who are unable to take beta-adrenergic blockers due to a contraindication, are in sinus rhythm on ECG, and have a regular heart rate above 70 bpm at rest. For these patients, ivabradine (Corlanor) can be beneficial in reducing HF-related hospitalizations and mortality. Side effects include bradycardia, conduction dysfunction, atrial fibrillation, and hypertension. Ivabradine (Corlanor) should be used cautiously in patients with first- or second-degree atrioventricular (AV) block, with sinus node dysfunction, and in conjunction with negative chronotropes (e.g., digoxin [Digitek] or amiodarone [Pacerone]). This medication should not be used in patients with an on-demand pacemaker set to a heart rate above 60 bpm (Heidenreich et al., 2022; Maddox et al., 2024; Meyer, 2025; Woods, 2024).

Diuretics. Fluid retention and hypervolemia—along with the resulting dyspnea, peripheral edema, and decreased activity tolerance—are common in patients with HF. Loop diuretics are the initial treatment for patients with persistent edema and congestion. Bumetanide (Bumex), furosemide (Lasix), and torsemide (Demadex) are most often used for patients needing diuresis to relieve the symptoms of hypervolemia. There is no conclusive evidence that one loop diuretic is superior to another. Initial dosing is dependent on kidney function and any history of previous treatment with a diuretic. Titration of the dosage needed to relieve symptoms should occur over several weeks. If the maximum dose of the initial loop diuretic is reached without remission of symptoms, a change of loop diuretic or the initiation of a thiazide diuretic is indicated. Fluid and electrolyte losses are common adverse effects of loop diuretics. For this reason, close monitoring of body weight and serum electrolytes is required in patients taking these medications. Hypokalemia is a common side effect in patients treated with loop diuretics. In view of this risk, potassium chloride (Klor-Con) is often used concurrently to prevent hypokalemia and the associated adverse effects, including cardiac arrhythmias such as torsades de pointes, ventricular fibrillation, and polymorphic ventricular tachycardia. Diuretic resistance, defined as fluid retention and failure to decongest despite the use of a diuretic, is a common side effect of long-term use of these medications, occurring in approximately 25%–30% of all HF patients (Colucci & Sterns, 2025; Heidenreich et al., 2022; Woods, 2024).

Thiazide diuretics should be added to the treatment regimen for patients who do not respond to treatment with loop diuretics despite dosage increases. Chlorthalidone (Thalitone) or hydrochlorothiazide (HCTZ; HydroDiuril) should be used in patients with hypertension and HF with mild hypervolemia. Metolazone (Zaroxolyn) or HCTZ (HydroDiuril) may be added to the treatment regimen with a loop diuretic or used as an alternative to a loop diuretic if a patient has refractory edema that has not responded to loop diuretics despite changes in medication and titration. Thiazide diuretics may cause potassium depletion, hypercholesterolemia, hypercalcemia, hyperglycemia, hypomagnesemia, hyponatremia, and photosensitivity. These medications should be used cautiously in patients with decreased renal and liver function (Colucci & Sterns, 2025; Heidenreich et al., 2022; Woods, 2024).

Vasodilators. Vasodilators, such as hydralazine (Apresoline) and isosorbide dinitrate (Dilatrate), should be initiated if an adequate response has not been achieved with an ACE inhibitor, an ARB, and a beta-adrenergic blocker. Hydralazine (Apresoline) is a direct vasodilator of the arterioles. Isosorbide dinitrate (Dilatrate) is a nitrate that dilates the peripheral veins and, to a lesser degree, the peripheral arteries. These medications can be taken together in a combined formulation, known as BiDil. This combination has been established as an effective treatment for HFrEF. Side effects of isosorbide dinitrate/hydralazine (BiDil) are dizziness, lightheadedness, weakness, nausea, vomiting, ventricular tachycardia, flushing, and headaches. Unfortunately, these drugs must be taken 3–4 times a day, whether in combination or individually (Heidenreich et al., 2022; Woods, 2024).

ACE inhibitors and ARBs are less effective at reducing blood pressure in Black individuals, perhaps due to differences in the RAAS or drug metabolism. ACE inhibitors are specifically less effective in Black individuals who have HFrEF. In contrast, research has shown that hydralazine (Apresoline) and nitrates decrease the mortality and hospitalization rate for Black individuals with HFrEF. Their use for individuals with HFrEF is a Class I recommendation in current guidelines. Hydralazine (Apresoline) and nitrates are less effective than ACE inhibitors for non-Black patients who have HFrEF, and this combination is often used only when these patients cannot tolerate an ACE inhibitor or an ARB (Al-Mohammad, 2019; Heidenreich et al., 2022; Woods, 2024).

Nonsurgical Interventions

Continuous Positive Airway Pressure

Continuous positive airway pressure (CPAP) is a respiratory treatment commonly used for patients with OSA. Sleep-disordered breathing (SDB) is a common and underdiagnosed condition in patients with HF. SDB in patients with HF can occur in two forms: OSA and central sleep apnea. Management of SDB should focus on optimizing HF and treating abnormal breathing patterns. CPAP can be used for patients with HF to increase oxygen supply and improve CO and EF by decreasing preload, afterload, and blood pressure (Ignatavicius et al., 2020; Malhotra & Fang, 2024).

Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT), also known as biventricular pacing, involves the implantation of a pacemaker alone or in combination with a defibrillator. The electrical stimulation that CRT provides can improve CO and EF. This treatment is indicated for patients with Class II or IV HF with an EF of less than 35% who also have a left bundle branch block. Utilizing CRT in these patients has dramatically increased their ability to complete activities of daily living independently and improved their quality of life (Adelstein & Saba, 2024; AHA, 2025a; Ignatavicius et al., 2020).

CardioMems

CardioMems is a monitoring system implanted into the pulmonary artery during a right heart cardiac catheterization. It is approximately the size of a quarter and is considered a permanent implant. The patient should check the device daily, or as instructed by their provider, to monitor their pulmonary artery pressure. Checking the device requires the patient to lie face down on a specialized pouch containing an electronic monitoring unit. The device advises the patient if their positioning needs to be changed. The readings from the device can then be sent electronically to the HCP, allowing for rapid medication titration or adjustments even before symptoms emerge, which leads to more outpatient treatment and fewer hospitalizations. CardioMems has significantly reduced HF-related hospitalizations and improved quality of life by facilitating early intervention before clinical symptoms (Ignatavicius et al., 2020; Tolu-Akinnawo et al., 2025).

Surgical Intervention

Typically, once patients reach end-stage HF with a significant loss of quality of life, they are referred to hospice care for symptom management and end-of-life care. However, some patients can undergo surgery to have a ventricular assist device (VAD) placed. This surgically implanted pump works in conjunction with the patient’s heart to enhance its pumping ability and perfusion. VADs are specific to right or left HF. Patients with end-stage renal disease, severe lung disease, clotting disorders, or an infection resistant to antibiotic therapy are not candidates for this procedure. There can be postoperative complications, including bleeding, infective endocarditis, development of ventricular dysrhythmias, or stroke. VADs can be utilized on a short-term basis by patients awaiting a donor heart for transplantation. Often, a VAD will keep a patient alive long enough to undergo transplantation. VADs can also be used long-term as a last treatment option (Birks & Mancini, 2023; Ignatavicius et al., 2020).

Nonadherence to Treatment

Nonadherence to treatment often results in poor patient outcomes. There are several reasons why patients may struggle to adhere to their prescribed treatment regimen or dietary and lifestyle changes (Maddox et al., 2024). Common reasons that patients do not adhere to treatment, along with strategies to address these barriers, are outlined in Table 3.

Table 3

Reasons for Nonadherence

(Maddox et al., 2024)

Heart Failure Core Measure Set

The HF core measure set seeks to ensure that HF patients receive proper outpatient treatment and disease management education to reduce rehospitalizations. These standards are established and monitored by the Joint Commission (TJC) for hospital accreditation (AHA, 2022, 2025b; Ignatavicius et al., 2020). Some of the key core measures include:

• thorough discharge instructions (diet, activity, meds, weight monitoring, planning for worsening symptoms)
• evaluation of left ventricular systolic function
• an ACE inhibitor or ARB for left ventricular systolic dysfunction was prescribed at discharge, or documentation as to why these medications are contraindicated
• evidence-based beta-blocker prescribed at discharge
• ARNI is prescribed at discharge
• SGLT2 inhibitor prescribed at discharge for HFrEF
• MRA is prescribed at discharge for patients with HfrEF (LVEF ≤ 40)
• smoking cessation advice and counseling
• outpatient appointment with an HCP within 7 days of discharge (AHA, 2022, 2025b; Ignatavicius et al., 2020)

References

Adelstein, E., & Saba, S. (2024). Cardiac resynchronization therapy in systolic heart failure: Indications and choice of system. UpToDate. Retrieved July 22, 2025, from https://www.uptodate.com/contents/cardiac-resynchronization-therapy-in-systolic-heart-failure-indications-and-choice-of-system

Al-Mohammad, A. (2019). Hydralazine and nitrates in the treatment of heart failure with reduced ejection fraction. ESC Heart Failure, 6(4), 878–883. https://doi.org/10.1002/ehf2.12459

American Heart Association. (2022). Get with the guidelines—Heart failure recognition criteria. https://www.heart.org/en/professional/quality-improvement/get-with-the-guidelines/get-with-the-guidelines-heart-failure/get-with-the-guidelines-heart-failure-recognition-criteria

American Heart Association. (2025a). Cardiac resynchronization therapy (CRT). https://www.heart.org/en/health-topics/heart-failure/treatment-options-for-heart-failure/cardiac-resynchronization-therapy-crt

American Heart Association. (2025b). Get with the guidelines: Heart failure. https://www.heart.org/en/-/media/Files/Professional/Quality-Improvement/Get-With-the-Guidelines/GWTG-Award-Criteria/2025-Recognition-Documents/HFRecognition2025112023.pdf

American Heart Association. (2025c). Lifestyle changes for heart failure. https://www.heart.org/en/health-topics/heart-failure/treatment-options-for-heart-failure/lifestyle-changes-for-heart-failure

Birks, E. J., & Mancini, D. (2023). Treatment of advanced heart failure with a durable mechanical circulatory support device. UpToDate. Retrieved July 22, 2025, from https://www.uptodate.com/contents/treatment-of-advanced-heart-failure-with-a-durable-mechanical-circulatory-support-device

Borlaug, B. A., & Colucci, W. S. (2025). Treatment and prognosis of heart failure with preserved ejection fraction. UpToDate. Retrieved July 21, 2025, from https://www.uptodate.com/contents/treatment-and-prognosis-of-heart-failure-with-preserved-ejection-fraction

Centers for Disease Control and Prevention. (2024). About heart failure. https://www.cdc.gov/heart-disease/about/heart-failure.html

Colucci, W. S. (2025). Determining the etiology and severity of heart failure or cardiomyopathy. UpToDate. Retrieved July 18, 2025, from https://www.uptodate.com/contents/determining-the-etiology-and-severity-of-heart-failure-or-cardiomyopathy

Colucci, W. S., & Borlaug, B. A. (2025). Heart failure: Clinical manifestations and diagnosis in adults. UpToDate. Retrieved July 20, 2025, from https://www.uptodate.com/contents/heart-failure-clinical-manifestations-and-diagnosis-in-adults

Colucci, W. S., & Dunlay, S. M. (2024). Clinical manifestations and diagnosis of advanced heart failure. UpToDate. Retrieved July 20, 2025, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-advanced-heart-failure

Colucci, W. S., & Sterns, R. H. (2025). Use of diuretics in patients with heart failure. UpToDate. Retrieved July 21, 2025, from https://www.uptodate.com/contents/use-of-diuretics-in-patients-with-heart-failure

Fine, N. M. (2025). Heart failure (HF). https://www.merckmanuals.com/professional/cardiovascular-disorders/heart-failure/heart-failure-hf

Givertz, M. M. (2023). Causes and pathophysiology of high-output heart failure. UpToDate. Retrieved July 19, 2025, from https://www.uptodate.com/contents/causes-and-pathophysiology-of-high-output-heart-failure

Golla, M. S. G., Hajouli, S., & Ludhwani, D. (2024). Heart failure and ejection fraction. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK553115

Golla, M. S. G., & Shams, P. (2024). Heart failure with preserved ejection fraction (HfpEF). StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK599960

Gottlieb, S. H. (2021). Heart failure with reduced ejection fraction: "Guideline-directed medical therapy (GDMT)" versus "the art of medicine." Journal of the American College of Cardiology, 78(20), 2013–2016. https://www.jacc.org/doi/10.1016/j.jacc.2021.09.015

Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., Deswal, A., Drazner, M. H., Dunlay, S. M., Evers, L. R., Fang, J. C., Fedson, S. E., Fonarow, G. C., Hayek, S. S., Hernandez, A. F., Khazanie, P., Kittleson, M. M., Lee, C. S., Link, M. S., . . . Yancy, C. W. (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, e895–e1032. https://doi.org/10.1161/CIR.0000000000001063

Ignatavicius, D. D., Workman, M. L., Rebar, C. R., & Heimgartner, N. M. (2020). Medical-surgical nursing: Concepts for interprofessional collaborative care (10th ed.). Elsevier.

Loscalzo, J., Fauci, A. S., Kasper, D. L., Hauser, S., Longo, D., & Jameson, J. L. (2022). Harrison's principles of internal medicine (21st ed.). McGraw-Hill Education.

Maddox, T. M., Januzzi, J. L., Jr., Allen, L. A., Breathett, K., Brouse, S., Butler, J., Davis, L. L., Fonarow, G. C., Ibrahim, N. E., Lindenfeld, J., Masoudi, F. A., Motiwala, S. R., Oliveros, E., Walsh, M. N., Wasserman, A., Yancy, C. W., & Youmans, Q. R. (2024). 2024 ACC expert consensus decision pathway for treatment of heart failure with reduced ejection fraction: A report of the American College of Cardiology Solution Set Overwight Committee. Journal of the American College of Cardiology, 83(15), 1444–1488. https://doi.org/10.1016/j.jacc.2023.12.024

Malhotra, A., & Fang, J. C. (2024). Sleep-disordered breathing in heart failure. UpToDate. Retrieved July 22, 2025, from https://www.uptodate.com/contents/sleep-disordered-breathing-in-heart-failure

McDonagh, T. A., Metra, M., Adamo, M., Gardner, R. S., Baumbach, A., Bohm, M., Burri, H., Butler, J., Celutkiene, J., Chioncel, O., Cleland, J. G. F., Coats, A. J. S., Crespo-Leiro, M. G., Farmakis, D., Gilard, M., & Heymans, S. (2021). 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal, 42, 3599–3726. https://doi.org/10.1093/eurheartj/ehab368

Meyer, T. E. (2025). Primary pharmacologic therapy for heart failure with reduced ejection fraction. UpToDate. Retrieved July 21, 2025, from https://www.uptodate.com/contents/primary-pharmacologic-therapy-for-heart-failure-with-reduced-ejection-fraction

Mohrman, D. E., & Heller, L. J. (2018). Cardiovascular physiology (9th ed.). McGraw-Hill Education.

Patel, J., Rassekh, N., Fonarow, G. C., Deedwania, P., Sheikh, F. H., Ahmed, A., & Lam, P. H. (2023). Guideline-directed medical therapy for the treatment of heart failure with reduced ejection fraction. Drugs, 83(9), 747–759. https://doi.org/10.1007/s40265-023-01887-4

Roger, V. L. (2021). Epidemiology of heart failure: A contemporary perspective. Circulation Research, 128(10), 1421–1434. https://doi.org/10.1161/CIRCRESAHA.121.318172

Schwinger, R. H. G. (2021). Pathophysiology of heart failure. Cardiovascular Diagnosis & Therapy, 11(1), 263–276. https://doi.org/10.21037/cdt-20-302

Shams, P., Malik, A., & Chhabra, L. (2025). Heart failure (congestive heart failure). StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK430873

Shams, P., Goyal, A., & Makaryus, A. N. (2025). Left ventricular ejection fraction. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK459131

Singh, S., & Sharma, S. (2023). High-output cardiac failure. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK513337

Tolu-Akinnawo, O., Akhtar, N., Zalavadia, N., & Guglin, M. (2025). CardioMEMS heart failure system: An up-to-date review. Cureus, 17(1), e77816. https://doi.org/10.7759/cureus.77816

US Food and Drug Administration. (2024). Highlights of prescribing information: Entresto. https://www.novartis.com/us-en/sites/novartis_us/files/entresto.pdf

Vallerand, A., & Sanoski, C. (2020). Davis's drug guide for nurses (17th ed.). F. A. Davis Company.

Woods, A. D. (2024). Nursing 2025–2026 drug handbook. Wolters Kluwer.

Powered by Froala Editor