case study 3 congestive heart failure

Congestive Heart Failure

Update Author Editor: Christopher Cox MD, Dalhousie University (2019)

Editor: Moises Gallegos MD MPH, Stanford Department of Emergency Medicine, 

Author: Amy Pound, MD, University Hospitals Case Medical Center, Case Western Reserve University

Last Update: September, 2019

70-year-old female with a history of coronary artery disease, and hypertension presents by ambulance to your emergency department, the morning after Thanksgiving, with progressive shortness of breath. She notes that she has had company all week and as a result she didn’t seek medical care. She has noticed shortness of breath at night and has been resting on at least two pillows. Last night she was unable to sleep and had to stay in her recliner chair until she called the paramedics this morning. She denies chest pain now or at any time this week.  She admits that she failed to follow her low salt diet and states she may have missed some of her medications this week due to the holiday.

Her vital signs are HR 105, BP160/80, RR 32, and SpO2 89% on 100% non-rebreather oxygen mask. (case study continues throughout chapter)

Upon finishing this module, the student will be able to:

• Discuss the classifications of heart failure.
• Identify the signs/symptoms for acute exacerbation of congestive heart failure.
• Describe how congestive heart failure can be diagnosed based on laboratory, chest x-ray, and Point of Care Ultrasound (PoCUS) studies.
• Prioritize and list ED treatment options for acute exacerbations of congestive heart failure.

Introduction

Congestive Heart Failure (CHF) is one of the most common illnesses treated in the Emergency Department. It affects about 2% of the US population or roughly 4.8 million Americans. In patients over the age of 65, it comprises 20% of hospitalizations, making it the most common admitting diagnosis. 

CHF arises when the ventricles fail to maintain forward blood circulation, often when the cardiac demand increases. Precipitating events include cardiac ischemia, dysrhythmias, infection, PE, physical/emotional stress, noncompliance with medication/diet, and volume overload. In this condition, the heart lacks the reserve to compensate for the increased burden within the congested circulatory system.

Classification and Terminology

NYHA CHF Classification

Class I – Ordinary activity not limited by symptoms

Class II – Ordinary activity leads to dyspnea, fatigue, etc

Class III – Marked limitation of ordinary activity

Class IV – Symptoms at rest or with any physical activity

Systolic vs Diastolic Dysfunction

Systolic dysfunction includes a dilated left ventricle with impaired contractility, often caused by ischemia, infarction cardiomyopathy, myocarditis, or dysrhythmias. In diastolic dysfunction the left ventricle remains normal in size, but has an impaired ability to relax. This limits the volume of blood in the ventricle, or preload, and causes increased pressure in the chamber which then reaches the lungs where fluid backs up. One example is infiltrative cardiomyopathy. Diastolic dysfunction has a better prognosis that systolic dysfunction.

High vs Low Output

In low output failure, there is decreased cardiac output secondary to myocardial damage, such as with ischemia, dilated cardiomyopathy, valvular disease, or chronic hypertension. In high output failure, the cardiac output is high or normal, but remains insufficient to supply oxygen demands. High output failure can be found in hyperthyroidism, pregnancy, anemia, AV fistulas, beriberi, or Paget’s disease.

Right vs Left Failure

Right sided failure, or increased pressure and fluid build up in the right ventricle, results in hepatic enlargement, increased jugular venous distention, and dependent peripheral edema of the extremities. Left sided heart failure will cause fluid build up in the left ventricle, resulting in pulmonary congestion.

Initial Actions and Primary Survey

Similar to other patients in the Emergecny Department initial actions include establishing IV access,provding supplimental O2 as needed, and vital sign monitor. These patients may require ECG and CXR

If 100% O2 by non-rebreather fails to increase O2 saturation to at least 95%, noninvasive oxygenation/ventilation (NIPPV) such as CPAP or BiPAP may assist in correcting hypoxia. If there is a failure to improve oxygenation, if the patient cannot tolerate the mask, or has a decline in mental status such that they are unable to protect their airway, then endotracheal intubation is required. The use of NIPPV used early can improve work of breathing as well as oxygenation, however caution should be taken as increased intra-thoracic pressure can reduce preload and worsen hypotension.

Hypotension can be difficult to manage in this patient population secondary to existing fluid overload. Early vasopressor support may be needed. Frequently patients with CHF exacerbation with present with significant hypertension. Nitroglycerin can be a useful medication in helping to reduce preload and reduce progression of pulmonary edema.

Presentation

Typical chief complaints, as in this case, include shortness of breath and peripheral edema.

Case Study, continued

Physical exam:

Your patient is in moderate respiratory distress, sitting forward, and speaking in only three word sentences. 

HEENT: She has no stridor. Jugular venous pressure is elevated to the mandible. (Image 1)

Chest: Her lung sounds are crackles in all lung fields without wheezing.

Cardio: She has normal S1and S2. An S3 is present. There is no murmur.

Abdomen: She has no tenderness, no hepato-splenomegaly, and no masses on exam.

Extremities: She has two plus pitting edema to the level of the tibial plateau. (Image 2)

Neuro: She is awake with no weakness, numbness, speech or vision deficits.

Skin: She is pale with central cyanosis, cool to touch, and diaphoretic.  

Image 1: JVD is measured by the peak of the pressure wave in the internal jugular vein. You can see this vessel is dilated as it exits medially from under the sternocleidomastoid. See black arrow. 

By Ferencga (Own work) [CC BY-SA 3.0 ( http://creativecommons.org/licenses/by-sa/3.0 )%5D, via Wikimedia Commons. Notation added by C.Cox 4/2019.

Image 2: Pitting edema    

By James Heilman, MD (Own work) [CC BY-SA 3.0 ( http://creativecommons.org/licenses/by-sa/3.0 ) or GFDL ( http://www.gnu.org/copyleft/fdl.html )%5D, via Wikimedia Commons

Diagnostic Testing

POINT OF CARE ULTRASOUND: (POCUS)

For your patient, your attending physician shows you multiple bilateral lung views, and parasternal long axis (PSL) and apical four chamber (a4C) cardiac views, and explains their significance in making a diagnosis of CHF. (Image 3-6).

Image 3: B-lines in right lung field suggesting interstitial edema. Original contribution by author, C. Cox. CC BY-SA 3.0 ( http://creativecommons.org/licenses/by-sa/3.0 )

Image 4: B-lines in left lung field suggesting interstitial edema. Original contribution by author, C. Cox. CC BY-SA 3.0 ( http://creativecommons.org/licenses/by-sa/3.0

Image 5: PSL, Dilated Left Ventricle with poor contraction  and poor mitral valve excursion suggesting diminished Ejection Fraction (EF) Original contribution by author, C. Cox. CC BY-SA 3.0 ( http://creativecommons.org/licenses/by-sa/3.0

Image 6: a4C, Dilated Left Ventricle with poor contraction  and Mitral valve with poor excursion suggesting diminished EF Original contribution by author, C. Cox. CC BY-SA 3.0 ( http://creativecommons.org/licenses/by-sa/3.0 )

Your attending states that your patient has qualitatively diminished heart function and bilateral interstitial edema. As demonstrated at the bedside, she has B-lines in greater that 2 thoracic quadrants bilaterally which suggests a cardiac source of pulmonary edema. (Sensitivity 97%, Specificity 95%)

Common findings are cardiomegaly and effusions. Chest x-ray (CXR) findings may lag by 12 hours from onset of symptoms, and subsequently CXR findings may persist for several days despite clinical improvement. 1 out of 5 patients admitted for CHF exacerbations showed lack of any pulmonary congestion on CXR.

Cardiomegaly is defined as a cardiothoracic ratio greater than 50% diameter. Patients with diastolic failure may have normal heart size.

Image 7: By Nevit Dilmen (Own work) [GFDL]( http://www.gnu.org/copyleft/fdl.html ) or CC BY-SA 3.0 ( http://creativecommons.org/licenses/by-sa/3.0 )%5D, via Wikimedia Commons

Additional CXR findings include:

• Peribronchial cuffing – thickened bronchial walls secondary to edema. Indicated by arrow in above image.
• Perihilar congestion – large hila with indistinct margins suggest pulmonary vasculature edema. Indicated by the two arrows in the image below.

Image 8: By James Heilman, MD (Own work) [CC BY-SA 3.0 ( http://creativecommons.org/licenses/by-sa/3.0 ) or GFDL ( http://www.gnu.org/copyleft/fdl.html )%5D, via Wikimedia Commons

• Cephalization – redistribution of blood flow to upper lobes. Only seen on upright films. Circled area in the image below.

Image 9: By James Heilman, MD (Own work) [CC BY-SA 3.0 ( http://creativecommons.org/licenses/by-sa/3.0 ) or GFDL ( http://www.gnu.org/copyleft/fdl.html )%5D, via Wikimedia Commons

• Pleural effusion – meniscus at the angle of the diaphragm. Arrow in above image.
• Kerley B lines – Dilated lymphatic channels. Typically 2 cm in length and horizontal, peripherally located perpendicular to pleura. Black arrowheads in following image are kerley b lines, white arrows are septal lines

Image 10: http://www.radpod.org/2007/03/02/acute-pulmonary-oedema/ Reference: Chapman S, Nakielny R. Aids to Radiological Differential Diagnosis 4th edition. Saunders 2003 Credit: Dr Laughlin Dawes

• Alveolar edema – batwing appearance

The Breathing Not Properly study found BNP (brain natriuretic protein) to be 90% sensitive and 76% specific for the diagnosis of CHF. Release is stimulated by high ventricular filling pressures. It has a diuretic effect, and antihypertensive effect, by increasing the amount of sodium excreted in the urine.

• <100pg/ml: unlikely CHF
• 100-500pg/ml: potentially CHF, although could also be PE, pulmonary HTN, ESRD, cirrhosis, or hormone replacement therapy
• >500pg/ml: most likely CHF

BNP levels may be most useful in tracking acute disease severity when compared to previously known levels. BNP levels may not always correlate with suspicion for CHF exacerbation, however, and clinical judgment should be used to further evaluate these patients.

Other Laboratories

• CBC to check for anemia
• Electrolytes: Na, K, Mg for abnormalities due to fluid overload or renal insufficiency
• Creatinine to check for renal dysfunction
• Troponin I or T to check for acute ischemic event.

May show underlying cardiac ischemia, dysrhythmias, LVH or heart block. A normal ECG has a high negative predictive value for systolic dysfunction.

Echocardiogram with Ejection Fraction

Normal ejection fraction is 55-75%. Patients with severe CHF may have EF less than 20%. Echocardiogram can also be used to visualize ventricular size and any wall abnormalities or valvular pathology, pericardial thickening, tamponade or constrictive pericarditis as additional contributors to CHF.

ED Treatment

In addition to initial actions noted above, treatment depends upon clinical presentation.

Normotensive patients: First give rapid acting nitrates to vasodilate and reduce afterload. These may be given sublingual, IV, or transdermal as nitroglycerin tabs/spray, push/gtt, paste/patch respectively. IV Morphine can be given for chest pain and anxiety, and may increase vasodilation. IV diuretics, such as furosemide, can increase urine output, lessening fluid overload, and may also contribute to vasodilatory effects.

Hypertensive patients: If high dose nitrates fail to control the blood pressure, some experts suggest adding Nitroprusside IV drip for severe, persistent hypertension. Nitroglycerin will have more effect as a venous dilator than arterial dilator. Nitroprusside is a more balanced venous and arterial dilator.

Hypotensive patients: Avoid nitrates, furosemide, and morphine, as they will drop the blood pressure. BiPAP may have similar adverse effect due to decreased preload as intra-thoracic pressure rises. Increased myocardial contractility with norepinephrine, dopamine, dobutamine, amrinone or milrinone may improve vital sign parameters so that some of the other therapies may be used. 

Severe or Chronic low output CHF:  Patients may be on ACE inhibitors or ARB to increase hemodynamic stability and exercise capability. If blood pressure allows, consider continuing this medication. If not already on ACEi or ARB, evidence does not support use in acute exacerbations.

Surgical Therapies

As a patient’s CHF becomes more advanced, they may need an Automatic Internal Cardiac Defibrillator (AICD), Left Ventricular Assistance Device (LVAD), or heart transplant.

AICD placement

MADIT trial showed that in patients with previous MI, EF < 35%, non-sustained ventricular tachycardia, and inducible ventricular tachycardia unresponsive to procainamide, AICD placement reduced sudden death by 54% at 2 yrs.

MADIT II trial showed that patients with history of MI and EF <30% had a 29% reduction in mortality after AICD placement.

LVAD placement

Patients may receive an LVAD as a temporizing measure until a heart transplant can be performed, or as a definitive treatment alone, if not a transplant candidate. The REMATCH study showed that patients had increased quality of life and had a 52% rate of survival at one year, compared to 25% for medical management only.

Heart transplant

Heart transplant is the only long-term definitive treatment for congestive heart failure. Patients who receive a heart transplant have a 10-year survival rate of 50%.

Pearls and Pitfalls

• Acute exacerbations of CHF can rapidly progress over hours to days, commonly due to a precipitating event, leaving the patient with no reserve to compensate for increased burden on the heart.
• The precipitating event may be an MI! Check an ECG and troponins.
• CXR findings may lag by 12 hrs. Treat clinical symptoms, and use PoCUS of the heart and lungs if available. 
• Most common CXR findings are cardiomegaly and effusions.
• Start with 100% O2 on NRB mask, but use noninvasive CPAP or BiPAP early for increased work of breathing, or intubate when necessary.
• Elevating the head of bed will reduce venous return and decrease preload and improve patient symptoms. In a small group of stable patients who are cognitively intact, placing the legs over the side of the bed may also be helpful in achieving the same physiologic outcomes mentioned previously.
• AVOID nitrates, morphine, and diuretics in hypotensive patients, and be careful with BiPAP these interventions may have a negative effect on blood pressure.
• Patients who present with new heart failure will require thorough inpatient workup to determine if it is a result of ischemic or non-ischemic disease. 

Case Study, conclusion

Your patient was started on BiPAP, received three nitro sprays sublingually, and a nitroglycerin drip was started at 4ug/min IV and was titrated to a systolic blood pressure of 130 mm Hg. She received furosemide 40mg IV and the nurses documented a diuresis of 1500 ml of urine in the next two hours. Her troponin I was normal range, as was her CBC, and CHEM 7. Her BNP was elevated to 1020 pg/ml.  She was monitored on a cardiac monitor until she was transferred to the hospital cardiac step down unit where she was weaned off of BiPAP, transitioned to oral furosemide, had her low salt diet reinstated, and was transferred to a general floor bed. She was discharged on hospital day 4 on furosemide, an ACE inhibitor, a low salt diet, and outpatient follow up with her primary care provider in one week.

• American Heart Association. Classes of heart failure. Available at:  http://www.heart.org/HEARTORG/Conditions/HeartFailure/AboutHeartFailure/Classes-of-Heart-Failure_UCM_306328_Article.jsp . Accessed: Mar 16, 2016.
• Collins, S.P., Storrow, A.B. Chapter 53: Acute Heart Failure. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e. Online@ Access Medicine. McGraw-Hill Medical
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• PMID: 18614781, Gray, A, Goodacre, S, et al. Noninvasive ventilationin acute cardiogenic pulmonary edema. N Engl J Med 2008; 359: 142-151. 
• PMID: 8960472, Moss AJ, Hall WJ, Cannom DS, et: Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996; 335:1933.
• PMID: 11794191, Rose EA, Gelijns AC, Moskowitz AJ, et al: Long-Term Use of a Left Ventricular Assist Device for End-Stage Heart Failure. N Engl J Med 2001; 345:1435-1443.
• PMID: 16387212, Collins SP, Lindsell CJ, Storrow AB et al: Prevalence of negative chest radiography results in the emergency department patient with decompensated heart failure. Ann Emerg Med. Jan 2006;47(1):13-8.
• PMID: 11911755, Publication Committee for the VMAC Investigators : Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: A randomized controlled trial. JAMA 2002; 287:1531.
• PMID: 18403664, Lichtenstein,D. Meziere, G. Relevance of Lung Ultrasound in the diagnosis of respiratory failure. Chest, 134 (1) (2008), pp. 117-125.
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• PMID: 30266198, Long B, Koyfman A, Gottlieb M. Management of Heart Failure in the Emergency Department Setting: An Evidence-Based Review of the Literature. J Emerg Med, 55(5), 2018, 635-646.Congestive Heart Failure (CHF) 

Heart Failure (CHF): Nursing Diagnoses, Care Plans, Assessment & Interventions

Heart failure (HF) , sometimes referred to as Congestive Heart Failure (CHF) , occurs when the heart can’t supply blood effectively to the rest of the body . The left ventricle of the heart is larger and is responsible for most of the pumping action. In left-sided HF , the left ventricle either loses its contractility, so it can’t pump normally, or the ventricle becomes stiff and cannot relax and fill with blood properly between each beat.

Left-sided HF often leads to right-sided heart failure. In right-sided HF , if the right ventricle can’t pump properly, blood backs up in the veins, which leads to congestive heart failure (CHF). If the heart isn’t pumping blood effectively to the body, all organ systems will suffer.

In this article:

• Nursing Process
• Review of Health History
• Physical Assessment
• Diagnostic Procedures
• Nursing Interventions
• Activity Intolerance
• Decreased Cardiac Output
• Decreased Cardiac Tissue Perfusion
• Excess Fluid Volume
• Impaired Gas Exchange
• Ineffective Health Maintenance
• Risk for Unstable Blood Pressure

Nurses play a pivotal role not only in treating patients with heart failure but educating them on lifestyle modifications to prevent disease progression or complications.

The nurse must understand the mechanism of the heart and the pathophysiology of HF in order to effectively treat patients, monitor for impending changes, and prevent worsening effects on other body systems.

Nursing Assessment

The first step of nursing care is the nursing assessment, during which the nurse will gather physical, psychosocial, emotional, and diagnostic data. In this section we will cover subjective and objective data related to heart failure.

1. Assess the patient’s general symptoms. Record the patient’s complaints and general symptoms, such as:

• Dyspnea on exertion  
• Orthopnea  
• Fatigue /weakness 
• Edema in lower extremities  
• Tachycardia   
• Irregular heartbeat  
• Exercise intolerance 
• Persistent cough  
• Wheezing  
• Abdominal swelling 
• Rapid weight gain  
• Lack of appetite  
• Decreased alertness  

2. Investigate the underlying cause. Heart failure typically occurs due to something else (i.e., another condition/disease or possibly a medication) causing damage to the heart muscle. Conditions that could potentially damage the heart and lead to heart failure include: 

• Coronary artery disease
• Myocardial infarction
• Hypertension
• Heart valve disease
• Myocarditis
• Congenital heart defects
• Cardiac arrhythmias
• Other long-term, chronic conditions that are poorly managed (such as diabetes mellitus , HIV , hyperthyroidism, or hypothyroidism )

3. Identify the stage of heart failure. Heart failure classification is used to denote the severity of symptoms.

Stages of Heart Failure:

• Class I: No limitation to physical activity.
• Class II: Activities of daily living can be completed without difficulty; however, exertion causes shortness of breath and some fatigue.
• Class III: Difficulty completing activities of daily living without fatigue, palpitations, or dyspnea.
• Class IV: Shortness of breath occurs at rest.

4. Know the patient’s risk.

Non-modifiable risk factors:

• Age: The heart can become stiff and frail with advanced age. The risk of heart failure is increased in people over 65. Elderly patients are also more prone to various health issues that cause heart failure.
• Gender: Heart failure is twice as likely to occur in men.
• Family history of ischemic heart disease: There is a high risk if a close female relative (mother or sister) had heart disease before age 65 or if a close male relative (father or brother) had it before age 55.
• Race/ethnicity: Heart failure is more common in African-Americans and Latinos than in Caucasian people.

Modifiable risk factors:

• Hypertension: Uncontrolled high blood pressure can result in stiffening and rigid arteries. Coronary artery constriction may impair blood flow.
• Hyperlipidemia/hypercholesterolemia/coronary artery disease: Increased levels of low-density lipoprotein (LDL) or decreasing levels of high-density lipoprotein (HDL) in the blood can increase the risk of atherosclerosis, narrowing the blood vessels.
• Diabetes or insulin resistance: Hardening of the blood arteries and accumulating fatty plaque are effects of diabetes or insulin resistance.
• Heart valve disease: If the heart valves are impaired, the heart must work harder to pump blood throughout the body, which can lead to heart failure.
• Tobacco use: Smoking accelerates the buildup of plaque in blood vessels. Smokers experience heart failure at a rate twice that of non-smokers.
• Obesity: Obesity increases the risk of high blood pressure, raised blood cholesterol, and diabetes. All are risk factors for heart failure.
• Physical inactivity: Those who are physically inactive are almost two times more likely to acquire heart disease than those who are active.
• Diet: A diet high in fatty, processed foods, high-sodium, or sugary foods increases the risk of obesity and chronic diseases that can lead to heart failure.  
• Stress: Blood vessels constrict as inflammatory levels rise under stress. Excessive stress hormones secreted can lead to heart failure.
• Alcohol use: Alcohol impairs the heart muscle and alters blood clot formation, resulting in the occlusion of blood vessels.
• Lack of sleep: Stress levels rise with insufficient sleep and cause blood vessels to constrict.
• Urinary tract infections
• Endocarditis

5. Review the patient’s treatment record. Medications and past vascular surgery compromise artery integrity. These medications include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Diabetes medications rosiglitazone (Avandia) and pioglitazone (Actos) 
• Antihypertensive medications
• Blood disorders
• Irregular or abnormal heartbeats
• Nervous system disorders
• Mental health issues
• Lung and urinary issues
• Inflammatory diseases

1. Assess the vital signs. Vital indicators, particularly pulse rate and blood pressure, are anticipated to rise or change due to the heart’s reduced oxygenated blood supply. Monitor Spo2 for changes in oxygen saturation that signal deteriorating perfusion.

2. Systemic assessment approach:

• Neck: distended jugular veins 
• CNS: decreased alertness
• Cardiovascular: tachycardia, chest pain, abnormal heart sounds (pathological S3) upon auscultation, arrhythmias
• Circulatory: decreased peripheral pulses, narrow pulse pressure (less than 25 mmHg caused by reduced cardiac output)
• Respiratory: dyspnea on exertion or at rest, tachypnea, orthopnea, persistent or nocturnal cough, crackles or rhonchi in the lung bases upon auscultation
• Gastrointestinal: nausea and vomiting, lack of appetite, abdominal swelling from hepatic congestion and ascites
• Lymphatic: edema in the lower extremities
• Musculoskeletal: neck, arm, back, jaw, and upper body pain, fatigue, muscle weakness, activity intolerance, rapid weight gain from fluid
• Integumentary: cyanotic and pale skin and excessive sweating

1. Obtain ECG. ECG findings in heart failure are characterized by P wave changes resulting in left atrial hypertrophy (enlargement).

2. Analyze BNP lab results. As heart failure occurs, the heart releases B-type natriuretic peptide (BNP) in the blood, causing an elevation in the blood test. 

3. Investigate other blood tests.

• Complete blood count with differential indicates the presence of infection (WBC), blood coagulation (platelets), and anemia (low RBC levels).
• Cholesterol levels show a risk for coronary artery disease (a risk factor for heart failure).
• Thyroid levels reflect disturbed thyroid hormones that can cause arrhythmias.

4. Review chest X-ray results. Chest X-ray shows any changes in the size of the heart. It also reflects fluid accumulation around the heart and lungs.

5. Prepare the patient for an echocardiogram. An echocardiogram assesses the heart’s structure. This test is used to identify ejection fraction (EF) , a percentage that measures how well the ventricles pump blood. 

• An EF of 55-70% is normal
• 40-54% is slightly below normal and may not produce symptoms
• 35-39% is considered mild heart failure
• EF less than 35% is moderate to severe heart failure

6. Investigate further.

• Exercise treadmill test benefits a patient who is physically capable of exercising and has a normal resting ECG.
• Nuclear stress test shows images of blood flow to the heart muscle using an IV radioactive tracer dye. This is combined with exercise or medication to stimulate the heart rate.
• Stress imaging is for patients who had revascularization, with challenging ECGs to read, or are physically unable to exercise.
• Cardiac CT scan displays calcium deposits and cardiac artery blockages.
• Cardiac catheterization reveals any obstructed cardiac arteries or the presence of coronary artery disease.
• CT coronary angiogram is comparable to a cardiac CT scan but creates a more detailed image using dye (contrast).
• Myocardial biopsy investigates other heart diseases that can cause heart failure.

Nursing interventions and care are essential for the patients recovery. In the following section you’ll learn more about possible nursing interventions for a patient with heart failure.

Promote Perfusion

1. Relax the blood vessels. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) improve blood flow by relaxing the blood vessels. It also lowers blood pressure and cardiac muscle strain.

2. Lower the heart rate and pressure. Administer beta-blockers to reduce the heart rate and blood pressure, which can improve heart function.

3. Induce diuresis. Diuretics cause an increase in urination to remove excess fluid from the body.

4. Consider potassium-sparing diuretics. Aldosterone antagonists are potassium-sparing diuretics that help treat systolic heart failure. It removes the excess fluid in the heart and body.

5. Strengthen the heart contraction.

• Inotropes are typically given IV while hospitalized. These are designed to increase the effectiveness of the heart pumping and maintain blood pressure.
• Digoxin increases the strength of the heart’s contractions. Monitor closely for digoxin toxicity through lab testing.

6. Treat the underlying condition.

• Coronary artery bypass graft surgery (CABG) builds an additional pathway for blood in the heart. The blocked or constricted coronary artery is bypassed using an artery from another part of the body, such as the leg.
• Heart valve repair or replacement fixes or replaces the defective heart valve causing heart failure. 
• Cardiac resynchronization therapy (CRT) uses a biventricular pacemaker to correct electrical signals in the heart that causes arrhythmias.
• Ventricular assist devices (VADs) are mechanical pumps that improve heart contraction and pumping in heart failure.
• Heart transplant is recommended for patients with severe heart failure when treatments are no longer effective.

Cardiac Rehabilitation

1. Collaborate with the team. Patients will work with cardiologists, cardiac rehab nurse specialists, dieticians, social workers, and physical and occupational therapists to meet their health needs.

2. Improve activity tolerance. Following surgery or a procedure for heart failure, recovery will take time. Cardiac rehab will slowly introduce exercises to strengthen the heart.

3. Strengthen the patient’s health. Cardiac rehab enhances the patient’s health and quality of life by supporting the patient in restoring strength and preventing HF recurrence and complications.

Reduce the Risk of Complications

1. Regulate the heart rhythm. Implantable cardioverter-defibrillators (ICDs) are devices that prevent heart failure complications. ICD tracks the heart rhythm and keeps the heart rate regular if an arrhythmia occurs.

2. Repeat the importance of lifestyle modifications.  Adopting lifestyle adjustments can reduce heart failure symptoms and keep the condition from getting worse.

• Regular exercise
• Heart-healthy diets
• Smoking cessation
• Avoiding secondhand smoke
• Stress management
• Vaccinations
• Limiting alcohol consumption
• Restful sleep

3. Advise on activity.  Aerobic exercise regularly improves heart function in persons with heart disease. Physical activity may be difficult or impossible for patients with severe HF. Advise the patient to go for five to ten minutes at a moderate pace and aim to add one or two minutes daily as they can. 

4. Keep a healthy weight. Being overweight can cause fatty deposits to build up in the arteries. Advise the patient to limit saturated or trans fat. Blood pressure, cholesterol, and metabolic activity all improve with weight loss. 

5. Promote patient adherence to treatment. Treatment adherence promotes continuity of care and patient-centered care. Increased patient adherence leads to more efficient HF treatment and prevention of complications.

6. Decrease stress. Stress raises blood pressure and heart rate. Because the inflammatory response is activated, blood vessels constrict, increasing the risk of HF. Guided imagery, yoga, deep breathing exercises, muscle relaxation, meditation, and getting adequate sleep are examples of stress reduction techniques.

7. Prevent fluid accumulation. Monitor for any swelling in the lower extremities, which may indicate the presence of edema or fluid accumulation. Instruct on contacting their healthcare team if weight gain of more than 2.5 lbs overnight or 5 lbs in a week is observed. Also, limit sodium (salt) intake to prevent water retention. Fluid accumulation can increase the heart’s workload. 

8. Teach the patient when to seek medical attention. HF signs and symptoms that are a cause for concern are:

• Sudden weight gain
• Fainting (syncope)
• Sudden productive cough with white or pink, foamy secretions

9. Follow up with the cardiologist. Visits to a cardiologist and regular examinations, such as blood tests and echocardiograms, will aid in monitoring the disease process. Patients with HF are advised to visit their cardiologist every three-six months or as recommended.

10. Emphasize the use of medical identification. The emergency responders can be alerted about the patient’s history of HF by a medical identity bracelet, necklace, or ID tag. This can be helpful, especially for patients who are living alone.

Nursing Care Plans

Once the nurse identifies nursing diagnoses for heart failure, nursing care plans help prioritize assessments and interventions for both short and long-term goals of care. In the following section you will find nursing care plan examples for heart failure.

Activity intolerance is a common manifestation and nursing diagnosis related to HF that can lead to worsening health conditions and physical deconditioning.

Nursing Diagnosis: Activity Intolerance

Related to:

• Imbalance between oxygen supply and demand 
• Weakness/deconditioning 
• Sedentary lifestyle 

As evidenced by:

• Fatigue 
• Dyspnea 
• Immobility  
• Vital sign changes in response to activity 
• Chest pain on exertion 
• Diaphoresis 

Expected outcomes:

• Patient will perform activities within their limitations so as not to stress cardiac workload.
• Patient will alternate between work and rest periods to complete ADLs.
• Patient will demonstrate vital signs and heart rhythm within normal limits during activity.

Assessment:

1. Observe cardiopulmonary response to activity. The nurse can monitor the patient’s heart rate, oxygen saturation, and cardiac rhythm during activity. A rise or drop in blood pressure, tachycardia, or EKG changes can signify overexertion and help plan appropriate interventions.

2. Assess the patient’s perspective. Assess the patient’s understanding of their condition and their perceived activity limitations. The goal is to ensure the patient is not overexerting themselves but also feels motivated to make progress with their activity tolerance and maintain independence.

3. Assess the degree of debility. Interventions can be tailored to the severity of the patient’s symptoms. Assess the level of fatigue, weakness, and dyspnea in relation to activity and length of exertion. The nurse may need to assist with ADLs or adjust the activities the patient can undertake for their safety .

Interventions:

1. Provide a calm environment. Dyspnea from HF can result in anxiety and restlessness. Provide the patient with a cool, dimly lit space free from clutter and stimulation. Assist the patient in taking slow, controlled breaths and provide emotional support so they feel in control.

2. Encourage participation. Even a patient with chronic HF and severe activity intolerance can assist with care to some extent. Provide toiletries at the bedside so the patient can brush their teeth or comb their hair. Have the patient assist with turning themselves in bed. A patient who becomes immobile from a sedentary lifestyle is at an increased risk for other complications such as skin breakdown, deep vein thrombosis (DVT) , and pneumonia.

3. Teach methods to conserve energy. Group tasks together, sit when possible when performing ADLs, plan rest periods, promote restful sleep, do not rush activities, and avoid activities in hot or cold temperatures.

4. Recommend cardiac rehabilitation. This is a medically supervised outpatient program that teaches a patient with a cardiac history how to reduce their risk of heart problems through exercise, heart-healthy diets, stress reduction , and management of chronic conditions. This is a team-based approach working with providers, nurses who specialize in cardiac care, PT and OT, and dieticians.

A decline in stroke volume from a loss of cardiac contractility or muscle compliance results in reduced filling or ejection of the ventricles. This reduced output decreases blood flow to other organs.

Nursing Diagnosis: Decreased Cardiac Output

• Altered heart rate/rhythm 
• Altered contractility 
• Structural changes (aneurysm, rupture) 
• Increased heart rate (palpitations) 
• Dysrhythmias 
• Shortness of breath 
• Anxiety  
• Orthopnea 
• Jugular vein distention; edema 
• Central venous pressure changes 
• Murmurs 
• Decreased peripheral pulses 
• Decreased urine output 
• Skin pallor, mottling, or cyanosis 
• Patient will display hemodynamic stability with vital signs, cardiac output, and renal perfusion within normal limits.
• Patient will participate in activities that reduce the workload of the heart.
• Patient will report an absence of chest pain or shortness of breath.

1. Assess vital signs, cardiac rhythm, and hemodynamic measurements. HF patients benefit from continuous cardiac monitoring via telemetry. The nurse can then act quickly if a dysrhythmia is observed. Blood pressure, pulse rate, and oxygen saturation should also be assessed regularly for changes. Unstable patients may need hemodynamic monitoring to maintain adequate perfusion.

2. Monitor skin and pulses. Poor cardiac output will result in decreased tissue perfusion . The nurse may observe skin mottling, pallor, or cyanosis. The skin may also feel cool or clammy. Along with these outward changes, peripheral pulses may be weak or irregular due to the lack of circulating blood volume.

3. Monitor mental status changes. HF can have long-term mental effects on the brain leading to poor memory and impaired cognition. The nurse can monitor for subtle changes or a decline in baseline presentation such as acute confusion or altered alertness.

1. Apply oxygen. Patients with low oxygen saturation may need supplemental oxygen due to the heart’s inability to pump oxygen-rich blood to the body. Patients with chronic HF may require oxygen therapy at home.

2. Administer medications. Vasodilators open arteries and veins to allow for decreased vascular resistance, increasing cardiac output and reducing ventricular workload. Morphine and anti-anxiety medications help with relaxing and calming the patient which can reduce cardiac workload. Angiotensin receptor blockers (ARBs) lower blood pressure and make pumping blood easier for the heart.

3. Instruct on ways to reduce the workload of the heart. Depending on the severity of the patient’s HF, they may need to modify daily activities. They may need assistance with ADLs, plenty of rest periods, and reduced exercise regimens.

4. Educate on risk factors and lifestyle modifications. Patients who are not yet diagnosed with HF or only have mild HF should be educated on prevention. Educate patients on risk factors such as hypertension, diabetes, atherosclerosis, and myocardial infarction that increase the risk of developing heart failure. Modifiable risk factors like smoking, obesity , sedentary lifestyle, and diets high in fat also increase the risk.

Decreased cardiac tissue perfusion associated with heart failure can be caused by insufficient blood flow resulting from impaired cardiac function.

Nursing Diagnosis: Decreased Cardiac Tissue Perfusion

• Structural impairment of the heart
• Malfunctions of the heart structures
• Difficulty of the heart muscle to pump
• Increased exertion in workload
• Inadequate blood supply to the heart
• Inability to contract and relax effectively
• Erratic signals causing chaotic or irregular heart contraction
• Decreased cardiac output
• Decreased blood pressure (hypotension)
• Decreased peripheral pulses
• Increased central venous pressure (CVP)
• Increased pulmonary artery pressure (PAP)
• Tachycardia
• Dysrhythmias
• Ejection fraction less than 40%
• Decreased oxygen saturation
• Presence of abnormal S3 and S4 heart sounds upon auscultation
• Patient will manifest pulse rate and rhythm within normal limits.
• Patient will demonstrate ejection fraction >40%.
• Patient will maintain palpable peripheral pulses.

1. Auscultate the apex of the heart. Determine if an abnormal heart sound S3 or S4 can be detected by auscultating the left lower sternal border. Children and athletes may naturally produce an S3 heart sound, but it is an abnormal finding in older adults and those with heart failure. Blood ejecting into a rigid ventricle causes the S4 heart sound.

2. Assist in myocardial perfusion test. Myocardial perfusion imaging (nuclear stress test) demonstrates how efficiently blood flows through the heart muscle. Additionally, it displays how efficiently the heart is pumping.

3. Check the BNP or NT-proBNP. B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) diagnoses heart failure (HF). It also supports the diagnosis of acutely decompensated HF in hospitalized patients or those treated in emergency rooms.

4. Obtain EKG. EKG can help rule out HF with a high sensitivity but low specificity. It can reveal the cause (such as a history of previous MI) and offer therapeutic indications (such as anticoagulation for atrial fibrillation).

5. Assist in TEE. Transthoracic echocardiography (TEE) can be useful in determining ejection fraction, left-atrial pressure, and cardiac output.

6. Prepare for a left heart catheterization or coronary angiography. Left-heart catheterization or coronary angiography is done to identify blockages or abnormalities with blood vessels in the heart to guide interventions.

1. Set the goal with the patient. Therapy aims to increase survival and symptoms, shorten hospital stays and avoid HF readmission, minimize morbidity, prevent HF-related organ damage, and suppress symptoms in patients with asymptomatic heart failure.

2. Administer medications as ordered. The following medications are included in the pharmacologic treatment of HF:

• Angiotensin system blockers (ACE inhibitors, ARBs, or ARNIs)
• Hydralazine with nitrate as an alternative if angiotensin system blockers are not tolerable
• Beta-blockers

3. Instruct on lifestyle modifications. Behavioral and lifestyle modifications include the following:

• Dietary and nutritional consultation
• Limit sodium to 2 to 3 g/day
• Fluid restriction to 2 L/day 
• Weight monitoring
• Aerobic exercise training 
• Control of existing risk factors (such as DM and lipid disorders)
• Smoking/alcohol/ illicit drug use cessation

4. Consider device therapy. Device therapies include cardiac resynchronization treatment (CRT) and implanted cardioverter-defibrillators (ICD). Patients should receive ACE inhibitors/ARB plus beta-blockers for at least three months prior to surgery. 

5. Anticipate the possibility of surgery. Heart transplantation, heart valve replacement, catheter ablation, and more are procedures to remodel, repair, or replace all or part of the heart’s function in treating HF. Surgery is often considered when medications aren’t effective.

Heart failure results in poor perfusion of the kidneys. If the kidneys cannot excrete sodium, water retention will occur and accumulate in tissues leading to fluid overload.

Nursing Diagnosis: Excess Fluid Volume

• Fluid intake or sodium intake 
• Reduced glomerular filtration rate  
• Increased secretion of antidiuretic hormone 
• Weight gain 
• Edema in extremities 
• Jugular vein distention 
• Adventitious breath sounds (crackles, rales) 
• High blood pressure 
• Oliguria 
• Tachycardia 
• Pulmonary congestion 
• Cough 
• S3 heart sound 
• Patient will demonstrate stable fluid volume through balanced intake and output, normal baseline weight, and no peripheral edema.
• Patient will verbalize signs and symptoms of fluid overload and when to seek help.
• Patient will verbalize dietary recommendations and fluid restrictions to maintain.

1. Assess for peripheral edema, anasarca, and JVD. Signs of fluid retention include edema in the lower legs and feet which is often pitting or generalized edema to the entire body known as anasarca. The most reliable sign indicating fluid overload is jugular vein distention (JVD).

2. Monitor breath and heart sounds. Patients with congestive heart failure (CHF) will present with shortness of breath and may have a cough with blood-tinged sputum due to pulmonary congestion. Upon assessment, the nurse will likely hear “wet” breath sounds (crackles). An S3 gallop signifies significant heart failure.

3. Monitor urine output and strict I&Os. Strict documentation of intake and output is required to monitor hydration and prevent worsening fluid overload. The nurse should record intake from oral and IV sources, maintain adherence to fluid restrictions, and assess urine output and characteristics. This is especially important if the patient is on diuretic therapy.

1. Maintain upright position. Semi-Fowlers or Fowler’s positioning will help the patient breathe easier and maintain comfort. They may require extra pillows or need to sleep in a reclining chair at home.

2. Administer diuretics. Diuretics are often prescribed as they rid the body of excess fluid which will decrease edema and dyspnea. Diuretics can be given by mouth or IV and must be monitored closely as they increase urination, decrease blood pressure, and decrease potassium.

3. Instruct on sodium and fluid restrictions. Diet education may include decreasing sodium and restricting fluids and will be directed by a provider. Patients should not use table salt or add salt to foods and should be aware of sodium contents in frozen or canned food. If a fluid restriction is ordered, the patient can track this by using a large pitcher that is their daily amount of fluid and drinking from it throughout the day. Ensure the patient understands their restriction includes all sources of fluid: soups, jello, and ice cream.

4. Teach how to monitor for fluid volume overload. Educate patients at discharge on signs of fluid retention. They should weigh themselves daily, using the same scale and at the same time each day. If a weight gain of 2 lbs in 24 hours or 5 lbs in a week is observed, they should call their doctor. Observed swelling to ankles or feet as well as an increase in dyspnea also requires assessment.

Inadequate blood flow results in decreased oxygenation and perfusion to tissues and organs. Heart failure itself is a related factor, but complications such as excess fluid can further impair gas exchange.

Nursing Diagnosis: Impaired Gas Exchange

• Ventilation perfusion imbalance related to altered blood flow 
• Changes to the alveolar-capillary membrane 
• Pulmonary congestion due to fluid retention 
• Changes in mental status 
• Restlessness 
• Anxiety 
• Abnormal ABGs 
• Changes in respiratory rate, depth, or rhythm 
• Patient will maintain ventilation and perfusion as evidenced by ABGs within normal limits.
• Patient will display improvement in ventilation by oxygen saturation above 95%.
• Patient will participate in ambulation and ADLs as allowed by respiratory ability.

1. Auscultate breath sounds. The patient may experience crackles, wheezes, or diminished breath sounds related to excess fluid in the lungs. Monitor closely for acute respiratory changes.

2. Monitor pulse oximetry. Abnormal oxygen saturation levels are a sign of hypoxemia, a lack of oxygen in the blood. This requires oxygen therapy and the underlying cause should be investigated and treated.

3. Monitor arterial blood gases (ABGs). ABGs measure the amount of oxygen and carbon dioxide in the blood. Abnormal or worsening ABGs indicate that the lungs are not ventilating or removing CO2 adequately.

1. Educate on coughing and deep breathing exercises. Clearing the airway and expanding the lungs will assist in promoting oxygenation.

2. Change positions frequently. Movement also assists with the drainage of secretions which can decrease the risk of complications such as atelectasis and/or pneumonia. If the patient is able to ambulate, this should be encouraged multiple times per day.

3. Maintain semi-Fowler’s position. Keeping the head of the bed elevated maintains an open airway. This can also be based on the patient’s comfort as some cannot tolerate high-Fowler’s positioning. If the patient is able to sit in a chair this is recommended.

4. Administer supplemental oxygen as needed. Apply oxygen per provider orders and to maintain the oxygenation of the patient. Patients may need oxygen titrated up or down or may require more significant interventions such as BiPap or mechanical ventilation.

5. Administer medications as ordered. If the impaired gas exchange is in relation to excess fluid volume, medications such as diuretics may be required to treat the underlying cause.

Poor patient understanding or management of their condition can result in worsening symptoms and outcomes.

Nursing Diagnosis: Ineffective Health Maintenance

• Lack of understanding of heart failure and prognosis 
• Difficulty in following recommended treatment plan 
• Poor motivation to make lifestyle changes 
• Insufficient resources (access to cardiologist, finances) 
• Lack of support from family to encourage or monitor condition 
• Demonstrates a lack of knowledge of heart failure 
• Continues with inappropriate diet or behaviors despite education 
• Inconsistent with keeping appointments, taking medications, etc. 
• Patient will seek out information to prevent worsening heart failure.
• Patient will identify (3) lifestyle modifications to improve heart failure.
• Patient will take responsibility for their health outcomes by identifying areas for improvement.

1. Assess the level of understanding of the disease process. Determine the patient’s present knowledge of risk factors, symptoms, treatments, and goals in order to tailor teaching to meet their needs.

2. Assess support system. Management of chronic conditions can be very challenging for patients and having a strong support system can assist in better adherence to the treatment plan.

1. Educate on normal heart function compared to the patient’s current heart function. Understanding the disease process can help the patient understand the goals of treatment and improve adherence. Explaining results of testing, such as the EF, or reviewing the HF classification system helps them feel more involved in their care.

2. Reinforce the rationale of treatments. Furthermore, patients may not grasp the reasoning for certain treatments such as fluid restrictions, weighing themselves daily, or the importance of medications. Explain in simple terms and provide written education if appropriate.

3. Educate on the importance and benefits of regular exercise. This will assist with maintaining muscle strength and organ function to strengthen the heart. Ensure exercise programs are safe for the patient and cleared by their provider.

4. Review medications. Thorough medication reconciliation and review is required before discharge or after each provider visit. The nurse should review changes and instruct on frequencies, side effects, and any considerations with each medication.

Risk for unstable blood pressure (BP) associated with heart failure can be caused by impaired structure and function of the heart muscle to pump blood effectively throughout the body.

Nursing Diagnosis: Risk for Unstable Blood Pressure

• Conditions that compromise the blood supply

A risk diagnosis is not evidenced by signs and symptoms as the problem has not yet occurred and the goal of nursing interventions is aimed at prevention.

• Patient will maintain blood pressure within normal limits.
• Patient will not experience hypotension with activity.
• Patient will maintain strict adherence to antihypertensive medications as ordered.

1. Closely assess the patient’s blood pressure. Heart attack and stroke can result from high systolic and diastolic blood pressure. Advise treating hypertension in heart failure with decreased ejection fraction. The target blood pressure is 130/80 mmHg.

2. Obtain blood samples for lab tests. The following blood tests determine the risk for unstable blood pressure in patients with heart failure:

• Blood urea nitrogen and serum creatinine
• Electrolyte levels
• Thyroid function
• Cholesterol (lipid) levels
• Blood glucose levels
• Liver function

3. Review the patient’s current treatment. Medications and herbal remedies aggravate or induce heart failure because they affect the blood pressure and heart muscles’ ability to pump blood and interact with other treatments and medications for heart failure. Examples of medications include:

• Spironolactone, angiotensin-converting enzyme (ACE) inhibitor, and furosemide can lead to electrolyte imbalances and renal failure
• Opioids and stimulants disturb the natural balance of certain neurotransmitters in the body and brain (catecholamines)
• Ashwagandha, blue cohosh, and Yohimbe are herbs sold in the United States that can cause cardiac toxicity

4. Identify underlying conditions. Systemic diseases, cardiac disorders, and some genetic defects can result in heart failure. The most prevalent underlying causes of heart failure are coronary artery disease, hypertension, and a previous heart attack.

1. Treat the underlying condition. Treatment of heart failure starts with prevention by reducing the risk factors. Patients should work to manage their blood pressure through exercise, weight loss, diet, medications, and smoking cessation.

2. Alert the patient when to seek emergency care. Symptoms of hypertension or hypotension include:

• A rapid heartbeat 
• Dizziness or fainting
• Profuse sweating
• Blurred vision

3. Instruct on how to take an accurate blood pressure reading. If the patient is monitoring their blood pressure at home, ensure they adhere to the following:

• Try to take the blood pressure at the same times each day
• Rest for 5-10 minutes to allow the blood pressure to return to baseline
• Do not cross your legs or ankles while taking a blood pressure
• Do not talk while taking a blood pressure

Ensure the patient and/or family member are using the correct size cuff and placing it correctly on the arm.

4. Advise the patient to keep BP logs. Heart failure (HF) patients’ usual clinical practice includes checking their blood pressure regularly. It is generally recognized that increased BP predicts cardiovascular risk. Advise the patient to keep accurate records to allow the healthcare team to monitor the effectiveness of treatment.

• Ackley, B.J., Ladwig, G.B., Flynn Makic M.B., Martinez-Kratz, M., & Zanotti, M. (2019). Nursing diagnosis handbook: An evidence-based guide to planning care (12th edition). Mosby.
• American Heart Association. (2018, January 11). What is heart failure? www.heart.org. Retrieved February 2023, from https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure
• Blumenthal, R. & Jones, S. (2021). Congestive heart failure: Prevention, treatment, and research. https://www.hopkinsmedicine.org/health/conditions-and-diseases/congestive-heart-failure-prevention-treatment-and-research
• Brown AC. Heart Toxicity Related to Herbs and Dietary Supplements: Online Table of Case Reports. Part 4 of 5. J Diet Suppl. 2018 Jul 4;15(4):516-555. doi: 10.1080/19390211.2017.1356418. Epub 2017 Oct 5. PMID: 28981338.
• Cardiac Rehab for Heart Failure. (2017, May 31). American Heart Association. Retrieved January 26, 2022, from https://www.heart.org/en/health-topics/heart-failure/treatment-options-for-heart-failure/cardiac-rehab-for-heart-failure
• Centers for Disease Control and Prevention. (2022, October 14). Heart failure. Retrieved February 2023, from https://www.cdc.gov/heartdisease/heart_failure.htm
• Cleveland Clinic. (2022, January 21). Heart failure: Common symptoms, causes and treatment. Retrieved March 2023, from https://my.clevelandclinic.org/health/diseases/17069-heart-failure-understanding-heart-failure
• Doenges, M. E., Moorhouse, M. F., & Murr, A. C. (2008). Nurse’s Pocket Guide Diagnoses, Prioritized Interventions, and Rationales (11th ed.). F. A. Davis Company.
• Doenges, M.E., Moorhouse, M.F., & Murr, A.C. (2019). Nursing care plans: Guidelines for individualizing client care across the life span (10th edition). F.A. Davis Company.
• Dumitru, I., & Sharma, G. K. (2021, October 27). Heart Failure Treatment & Management: Approach Considerations, Nonpharmacologic Therapy, Pharmacologic Therapy. Medscape Reference. Retrieved January 26, 2022, from https://emedicine.medscape.com/article/163062-treatment
• Heart failure – Symptoms and causes. (2021, December 10). Mayo Clinic. Retrieved January 26, 2022, from https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142
• Heart Failure: Types, Symptoms, Causes & Treatments. (n.d.). Cleveland Clinic. Retrieved January 26, 2022, from https://my.clevelandclinic.org/health/diseases/17069-heart-failure-understanding-heart-failure
• Heckman, G. A., Patterson, C. J., Demers, C., St Onge, J., Turpie, I. D., & McKelvie, R. S. (2007). Heart failure and cognitive impairment: challenges and opportunities. Clinical interventions in aging, 2(2), 209–218.
• Mayo Clinic. (2021, December 10). Heart failure – Diagnosis and treatment – Mayo Clinic. Retrieved March 2023, from https://www.mayoclinic.org/diseases-conditions/heart-failure/diagnosis-treatment/drc-20373148
• Micaela, I. (2020, June 25). Heart failure – fluids and diuretics. MedlinePlus. Retrieved January 26, 2022, from https://medlineplus.gov/ency/patientinstructions/000112.htm
• National Center for Biotechnology Information. (2022, April 30). Heart failure and ejection fraction – StatPearls – NCBI bookshelf. Retrieved March 2023, from https://www.ncbi.nlm.nih.gov/books/NBK553115/
• Pellicori, P., Kaur, K., & Clark, A. L. (2015). Fluid Management in Patients with Chronic Heart Failure. Cardiac failure review, 1(2), 90–95. https://doi.org/10.15420/cfr.2015.1.2.90
• The Trustees of the University of Pennsylvania. (2020, August 27). Avoid these foods if you have heart failure – Penn medicine. Penn Medicine. Retrieved March 2023, from https://www.pennmedicine.org/updates/blogs/heart-and-vascular-blog/2020/august/avoid-these-foods-if-you-have-heart-failure
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Advances in management of heart failure

• Related content
• Peer review
• Paul Heidenreich , professor of medicine 1 2 ,
• Alexander Sandhu , assistant professor of medicine 1 2
• 1 Department of Medicine, Stanford University School of Medicine, Palo Alto, CA 94306, USA
• 2 VA Palo Alto Health Care System, Palo Alto, CA, USA
• Correspondence to: P Heidenreich heiden{at}stanford.edu

Heart failure is increasing in prevalence in many countries with aging populations. Fortunately, remarkable scientific advances have been made in the past few years that have led to new treatments and improved prognosis for patients with heart failure. This review examines these changes with a focus on the diagnosis and medical management of heart failure. The changes include the increase to four foundational drug classes (pillars of therapy) now recommended for patients with heart failure and reduced left ventricular ejection fraction, use of sodium-glucose cotransporter-2 inhibitors for those with a higher ejection fraction, and the importance of rapid initiation of life prolonging therapies once a diagnosis of heart failure has been made. Device management and other non-drug management have also evolved with the publication of new clinical trials. The review emphasizes evidence published since the recent heart failure guidelines of the European Society of Cardiology and American College of Cardiology/American Heart Association/Heart Failure Society of America in 2021 and 2022. Additional studies are needed to determine how best to implement these new interventions in clinical practice.

Introduction

Heart failure is a common and growing health and economic burden for many of the world’s communities. This growth is pronounced in societies with aging populations. Advances in heart failure care have been dramatic over recent years, including new drugs, devices, and diagnostic care strategies. Clinical guidelines published within the past few years have included many of these changes, but even these recent guidelines are already out of date in their recommendations for treatment and diagnosis. In light of this rapidly changing scientific evidence base, we provide an up-to-date review of the most important aspects of heart failure care.

Sources and selection criteria

We searched PubMed and the Cochrane Database of Systematic reviews for articles published between January 2015 and 7 July 2023 to identify new randomized controlled trials (RCTs) and large cohort studies of treatments and diagnostic strategies for heart failure. We also identified epidemiologic studies published from 2020 to 2023. We included older studies to provide context. We focused on studies not included in the recent European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA) guidelines from 2021 and 2022. 1 2 We prioritized RCTs over observational data when reviewing interventions. We did not consider case reports or case series in our review.

Epidemiology

The Global Burden of Disease Study estimated that 57 million people were living with heart failure in 2019. 3 4 Although this number has been increasing in countries with aging populations, the age standardized rate has fallen from 7.7 per 1000 in 2010 to 7.1 per 1000 in 2019. 3 4 The change over time in the age adjusted prevalence from 2009 to 2019 (an average 0.3% decline per year during this period) has not been linear, with rates initially falling but then increasing by 0.6% per year between 2016 and 2019. 3 4 The reason for this change in prevalence is unclear and requires further investigation. An increase in hospital admissions for heart failure has been noted for young adults (age 18-45) in the US, with rates increasing from 1.8 per 10 000 in 2013 to 2.5 per 10 000 in 2018. 5

Large differences in prevalence are noted across global regions for both men and women ( fig 1 ). 3 4 The region with the highest prevalence of heart failure includes the high income countries of North America, and the lowest prevalence was in central Asia. An estimated 3% of the US population will have heart failure by 2030. 6 The largest declines in age adjusted rates were noted in high income countries of North America and Australasia regions.

Country specific, age adjusted prevalence of heart failure from 1990 to 2019 in men (top) and women (bottom). Estimates are from the Global Burden of Disease Study 3 4

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Survival following a diagnosis of heart failure is poor and is highly influenced by age. In the UK, survival approaches 80% at five years for people aged 45-64 but is closer to 20% at five years for those aged ≥85. 7 Fortunately, survival rates have improved since 2000, particularly among younger patients. 7

Although overall survival is an important outcome, it reflects the combined effects of all the patient’s conditions. The incremental impact of heart failure on survival is difficult to discern, as most patients with heart failure have multiple comorbidities. Years of life lost due to heart failure can be estimated by examining survival relative to actuarial estimates of life expectancy. Data from the UK have shown that heart failure is associated with a 2.4-fold greater loss of time alive than observed in the age and sex matched general population over 10 years. 8 Length of life lost with heart failure varies from five months (women) to one year (men) for people with no comorbidities and from three years (women) to 4.5 years (men) for those with three or more comorbidities. 8

The impact of covid-19 on the incidence of heart failure is uncertain but may be substantial. Studies from the US Veterans Affairs healthcare system have suggested that covid-19 is associated with an increased risk of cardiovascular events including death, myocardial infarction, and stroke. 9 10

Prevention, screening, and identification of heart failure

Heart failure can be largely prevented or delayed with optimal control of risk factors. 11 12 Uncontrolled hypertension remains the most common risk factor for incident heart failure. 13 14 Optimal blood pressure control is associated with a 40% reduction in heart failure events, 15 and multiple therapies for comorbid conditions reduce the risk of progression to heart failure including sodium-glucose cotransporter-2 (SGLT2) inhibitors, which reduce the risk of incident heart failure in patients with diabetes mellitus. 16 17 18 Among patients with chronic kidney disease, both SGLT2 inhibitors and finerenone (in those with diabetes) reduce the risk of incident heart failure. 19 20

Several clinical risk models can identify patients at high risk for progression to heart failure. 21 22 23 24 Concentrations of natriuretic peptide (B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP)) are also elevated among patients at high risk of incident heart failure or asymptomatic systolic dysfunction. 25 26 27 In the STOP-HF (St Vincent’s Screening to Prevent Heart Failure) study, patients with a cardiovascular risk factor were screened using BNP. Patients with elevated concentrations had echocardiography and collaborative cardiology and primary care management. This led to a reduction in subsequent left ventricular systolic dysfunction and emergency hospital admissions for cardiovascular reasons. 28 Similar results were confirmed in a trial among patients with diabetes mellitus. 29 Since these trials, additional treatment options are now available to prevent incident heart failure among people at high risk. 1 2 Expanding natriuretic peptide screening could lead to earlier diagnosis and treatment, substantially reducing the morbidity of heart failure.

Given that heart failure is a progressive condition with high early morbidity, prompt recognition is critical. In the UK, more than 80% of first diagnoses of heart failure are made in the hospital, and more than 40% of these patients have symptoms that should promote earlier assessment. 30 Women were noted to take six times longer to receive a diagnosis of heart failure and were twice as likely to be misdiagnosed. 31 Similar patterns of delayed diagnosis of heart failure have been noted in the US and Canada. 32 33 34 Minimizing the morbidity of heart failure requires increased awareness among patients and primary care clinicians, as well as additional strategies to facilitate disease recognition.

The diagnosis of heart failure requires the presence of symptoms consistent with cardiac dysfunction along with evidence of either significantly reduced left ventricular systolic function (≤40%) or increased filling pressures. This is now incorporated into the recently published universal definition of heart failure. 35 Heart failure is categorized into three groups based on the left ventricular ejection fraction (LVEF): heart failure with reduced ejection fraction (HFrEF) if the LVEF is ≤40%; heart failure with mildly reduced ejection fraction (HFmrEF) if the LVEF is 41-49%, and heart failure with preserved ejection fraction (HFpEF) if the LVEF is ≥50%. Patients with LVEF >40% require additional evidence of increased filling pressures (at rest or with exercise) to establish a diagnosis of heart failure.

Diagnosis of HFpEF

The diagnosis of HFpEF is particularly challenging, as determining increased filling pressure can be difficult. Most definitions of HFpEF exclude patients with heart failure symptoms due to valve disease, arrhythmia, pericardial constraint, or high cardiac output. Although invasive testing with cardiac catheterization is the gold standard for determining elevated left ventricular filling pressures, the diagnosis can be made non-invasively. Unfortunately, no single non-invasive test result has both a high sensitivity and a high specificity ( fig 2 ).

Test characteristics for common non-invasive tests of increased left ventricular filling pressure. No single test threshold has both sensitivity and specificity above 70%. 10 E/e’=early diastolic mitral inflow velocity to early diastolic mitral annulus velocity; GLS=global longitudinal strain; LA=left atrium; NT-proBNP=N-terminal pro B-type natriuretic peptide

Accordingly, clinical scores have been created using the results from multiple tests to diagnose HFpEF. These include H2FPEF (Heavy, 2 or more Hypertensive drugs, atrial Fibrillation, Pulmonary hypertension (pulmonary artery systolic pressure >35 mm Hg), Elder age >60, elevated Filling pressures, E/e’ >9) 36 and HFA-PEFF (Heart Failure Association—Pre-test assessment; Echocardiography and natriuretic peptide score; Functional testing; Final etiology). 37 A recent evaluation found that these two scores have similar prognostic value, although 28% of patients had discordant findings (HFpEF diagnosed by only one of the algorithms). 38

Perhaps as important as making the diagnosis of heart failure is determining whether the patient will benefit from therapy for HFpEF. Thus, clinicians can use the enrollment criteria from clinical trials showing benefit to make a diagnosis of HFpEF. The two clinical trials of SGLT2 inhibitors that showed benefit for patients with HFpEF used the following enrollment criteria: New York Heart Association (NYHA) II-IV symptoms, treatment with a diuretic, an NT-BNP >300 pg/mL if sinus rhythm (>600 or >900 pg/mL if atrial fibrillation), and evidence of structural heart disease (left atrial enlargement, left ventricular hypertrophy), in the Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial, or a recent hospital admission for heart failure. 39 40

Determining the cause of heart failure

Determining the underlying cause of heart failure symptoms is an important second step after making a diagnosis, as some conditions have specific treatments. 1 2 Additional testing beyond echocardiography is often needed, and although routine screening with cardiac magnetic resonance (CMR) imaging is not clearly beneficial, 41 selected use of CMR often provides useful information. The patterns of late gadolinium enhancement and certain T1 and T2 techniques may suggest a diagnosis of non-compaction, myocarditis, or Chagas disease, as well as infiltrative cardiomyopathies including amyloidosis, iron overload, sarcoidosis, and Fabry disease. 1 2 Patients with dilated cardiomyopathy and those with significant hypertrophy on echocardiography may be most likely to benefit from CMR.

Four medication pillars of HFrEF therapy

For patients with heart failure and a reduced left ventricular ejection fraction to ≤40% (HFrEF), four classes of drugs are now known to improve survival. 1 2 These are renin-angiotensin system inhibitors including angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) or angiotensin receptor/neprilysin inhibitors (ARNI); β blockers; mineralocorticoid receptor antagonists (MRAs); and SGLT2 inhibitors ( table 1 ; fig 3 ). Using the relative risk reduction from the clinical trials, it has been estimated that the combination of the four pillars of HFrEF therapy will lead to a 73% relative risk reduction in mortality and a number needed to treat of four to prevent a death compared with no treatment. 42

Life prolonging medications for heart failure with reduced left ventricular ejection fraction 42

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Schematic of treatment for heart failure with reduced ejection fraction. ARNI=angiotensin receptor/neprilysin inhibitor therapy; BP=blood pressure; CRT=cardiac resynchronization therapy; EF=ejection fraction; HF=heart failure; ICD=implantable cardiac defibrillator; LBBB=left bundle branch block; MRA=mineralocorticoid receptor antagonist; NYHA=New York Heart Association; PA=pulmonary artery; SGLT2i=sodium glucose linked cotransporter 2 inhibitor; TEER=transcatheter edge-to-edge repair

The combination of an ARB and a neprilysin inhibitor is now recommended as one of the pillars of HFrEF therapy. The PARADIGM-HF (Prospective Comparison of ARN Inhibitors with ACE Inhibitors to Determine Impact on Global Mortality and Morbidity in HF) trial randomized 8442 patients with HFrEF. It found a 20% reduction in cardiovascular death or admission to hospital for heart failure with sacubitril and valsartan compared with enalapril (hazard ratio 0.80, 95% confidence interval 0.73 to 0.87). 43 Sacubitril/valsartan was also associated with a significant reduction in symptoms, as measured by the Kansas City Cardiomyopathy Clinical Summary Score (hazard ratio 1.64, 0.63 to 2.65). 43 A second RCT was conducted in patients admitted to hospital with heart failure (PIONEER-HF58: Comparison of Sacubitril-Valsartan vs Enalapril on Effect of N-Terminal Pro–Brain Natriuretic Peptide [NT-proBNP] in Patients Stabilized From an Acute HF Episode). 44 This trial in 881 patients showed a reduction in NT-proBNP concentrations (ratio of change 0.71, 95% confidence interval 0.63 to 0.81) for patients starting sacubitril/valsartan during hospital admission compared with those treated with enalapril. Safety was also demonstrated, with no significant differences in worsening renal function, hyperkalemia, and symptomatic hypotension. The 2022 US Heart Failure Guideline now recommends ARNI as the first line agent with ACE inhibitor or ARB alone for patients unable to take ARNI. 2 Use of ARNI along with an ACE inhibitor is contraindicated.

No benefit with ARNI was observed for patients with advanced heart failure defined as NYHA class IV symptoms or patients taking chronic inotropic therapy. 45 The LIFE (LCZ696 in Advanced HF) study randomized 335 patients with advanced heart failure and found that after 24 weeks of treatment, changes in NT-proBNP were not clearly different between patients treated with sacubitril/valsartan and those treated with valsartan alone (ratio of change 0.95, 0.84 to 1.08).

SGLT2 inhibitors

This new class of drugs (sodium-glucose cotransporter-2 inhibitors) was originally designed to improve glycemic regulation in diabetes but was found to also improve cardiac outcomes, including the prevention of heart failure. Subsequent trials in patients with reduced LVEF have consistently shown a significant reduction in hospital admissions due to heart failure, with several also showing a reduction in cardiovascular mortality. 46 Accordingly, this class (for example, dapagliflozin and empagliflozin) is now one of the four pillars of HFrEF therapy.

Sotagliflozin is a combined SGLT1 and SGLT2 inhibitor, and whether it should be placed in the same class as purer SGLT2 inhibitors is unclear. In a study in 1222 patients with diabetes and recent hospital admission for heart failure, initiation of sotagliflozin before or shortly after discharge reduced death from cardiovascular causes and hospital admissions and urgent visits for heart failure compared with placebo (hazard ratio 0.67, 0.52 to 0.84). 47 A second study randomized 10 584 patients with diabetes and renal dysfunction, 20% of whom had heart failure, to sotagliflozin or placebo. The combined endpoint of cardiovascular death, hospital admission for heart failure, and urgent visits for heart failure was reduced by sotagliflozin, with similar effects for patients with and without heart failure (hazard ratio 0.74, 0.63 to 0.88). 48 The 2021 ESC guideline has grouped sotagliflozin with the SGLT2 inhibitors in its recommendations for patients with heart failure and diabetes. 1 The drug was only recently approved in the US and thus was not eligible for inclusion in the ACC/AHA/HFSA 2022 guideline. 2

Importance of rapid initiation of therapy

The importance of rapid initiation of life prolonging heart failure medication is now recognized owing to results from the Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies (STRONG-HF) trial. 49 This multicenter study with 1078 patients from 87 hospitals in 14 countries examined rapid up-titration of guideline directed medication after an admission for acute heart failure. The intervention group had their medications up-titrated to 100% of recommended doses within two weeks of discharge. The primary endpoint of 180 day readmission to hospital due to heart failure or all cause death was reduced by an absolute percentage of 8.1% (95% confidence interval 2.9% to 13.2%) with rapid titration. We note that the STRONG-HF trial was conducted before SGLT2 inhibitors became standard of care for HFrEF therapy.

Further evidence of the benefit of rapid initiation comes from the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. 50 Among 4744 patients in this trial, the time to clinical benefit was surprisingly fast with a significant reduction in cardiovascular death or worsening heart failure observed by 28 days after randomization to dapagliflozin compared with placebo (hazard ratio 0.51, 95% confidence interval 0.28 to 0.94). 50 Similarly, in 1222 patients treated with sotagliflozin compared with placebo, 47 the time to a sustained and significant reduction in the primary endpoint was 27 days (hazard ratio 9.62, 0.39 to 0.99). However, the time to benefit was twice as long for patients with heart failure and preserved ejection fraction. 51

Although the goal is to initiate all four drug classes in a timely manner, the optimal order and timing of initiation remains controversial. Investigators have modeled the potential benefit of different strategies based on how quickly benefits were observed in clinical trials. 52 They found that a strategy of starting with SGLT2 inhibitors and MRAs should lead to the greatest improvement in outcome. Other authors advocate for a more rapid approach, starting all four drugs at low doses together. 53 Starting drugs rapidly in combination may be the quickest way to reach recommended doses, although it also may increase the risk of temporary side effects (for example, hypotension or elevated creatinine). Side effects may lead clinicians and patients to assume a permanent drug intolerance and reduce the chances that the patient is ultimately treated with all four recommended classes. The patient’s condition may indicate the appropriate drug to use first. For example, an SGLT2 inhibitor or MRA may be the appropriate first drug in those with borderline low blood pressure. Additional studies are needed to determine which initiation strategy leads to the optimal sustained use of recommended treatments. Strategies for implementation of guideline directed medical therapy have been recently reviewed. 54

Although diuretics are a mainstay of treatment for patients with signs or symptoms of congestion, they have not been shown to improve mortality. 2 55 The efficacies of two loop diuretics were compared in the TRANSFORM-HF trial of 2859 patients who were randomized to furosemide or torsemide. 56 The primary outcome of all cause death was similar for the two loop diuretics (hazard ratio with torsemide treatment 1.02, 0.89 to 1.18).

Recently, the efficacy of intravenous acetazolamide in addition to intravenous loop diuretics was examined in the Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) trial. 57 Among 519 patients with heart failure, greater decongestion was seen in the group randomized to acetazolamide (successful decongestion within three days: 42.2% v 30.5%; P<0.001). In the Safety and Efficacy of the Combination of Loop with Thiazide-type Diuretics in Patients with Decompensated Heart Failure (CLOROTIC) trial, 239 patients were randomized to a thiazide diuretic or placebo in addition to a loop diuretic. 58 The addition of the thiazide significantly increased decongestion but with an increase in serum creatinine. Together, the ADVOR and CLOROTIC trials suggest that add-on diuretic therapy can improve decongestion compared with loop diuretics alone, although long term safety is uncertain. 57 58

Treatment of patients with improved ejection fraction

LVEF will improve from below 40% to above 40% during follow-up in about 15% of patients. 59 Some will even have a normalization of their LVEF (>50%). Although this improvement may imply recovery, a randomized trial of 51 patients with predominantly familial/idiopathic dilated cardiomyopathy found that discontinuing medication in those with apparent recovery of left ventricular function (LVEF >50%, NT-proBNP <250 ng/L, normalized left ventricular volume) led to relapses of heart failure in 46% (95% confidence interval 29% to 67%) at six months compared with 0% in those continuing medication (P=0.0001). 60 Accordingly, the ACC/AHA/HFSA guideline was revised in 2022 to use the term “improved” instead of “recovered” when the LVEF increases from ≤40% to >40%. 2

Continued HFrEF treatments are recommended for patients whose LVEF improves, although whether dose escalation or additional medications are beneficial once symptoms have resolved and LVEF has improved remains uncertain. In rare cases, withdrawal of therapy will succeed without relapse of heart failure. These patients with truly recovered LVEF include those whose cardiomyopathy is the result of a toxin, tachycardia, or other insult that has been eliminated. Unfortunately, being certain of the cause of cardiomyopathy is often difficult, and any attempt at withdrawal should be gradual with close follow-up and should be done only in selected cases in which heart failure has a specific and reversible cause.

Treatment of HFmrEF and HFpEF

As noted above, an LVEF of 41-49% is mildly reduced (HFmrEF) whereas patients with an LVEF ≥50% are considered to have preserved ejection fraction (HFpEF). These labels apply only to patients who have not previously had an LVEF ≤40% (these are referred to as heart failure with improved ejection fraction). SGLT2 inhibitors are recommended as the first line medication for patients with mildly reduced or preserved LVEF on the basis of the two trials that enrolled many patients with an LVEF >40%. 39 40

Of the other treatments for HFrEF, ARNI, ACE inhibitors, ARBs, and MRAs are second line therapies as the evidence for benefit is much weaker than for patients with HFrEF. Accordingly, MRAs and ACE inhibitors/ARBs/ARNI have a class 2B recommendation for HFmrEF and HFpEF in guidelines for patients with mildly reduced or preserved LVEF. 2

Of note, β blockers are not recommended for patients with HFpEF (2B recommendation for HFmrEF). 2 Lack of benefit for HFpEF was noted in a meta-analysis of randomized trials of β blockers, which reported a non-significant trend toward increased cardiovascular and all cause mortality in patients with preserved LVEF and sinus rhythm (hazard ratio 1.70, 0.78 to 4.10). 61

LVEF and benefit of medical therapy

LVEF can be difficult to quantify with echocardiography, but it has been routinely used to determine eligibility for clinical trials in heart failure. Given the growing evidence for treatment benefit in patients with higher LVEF levels, some authors have questioned the continued use of the LVEF to classify patients with heart failure. Multiple drug therapies have been tested across the ejection fraction spectrum: β blockers, ACE inhibitors/ARBs, ARNI, MRAs, and SGLT2 inhibitors. Traditionally, trials have stratified patients on the basis of LVEF ≤40% or >40%. However, most therapies have shown a benefit at higher thresholds than the traditional cutoff of reduced LVEF at 40%. For β blockers, a reduction in cardiovascular mortality was observed with LVEF <50%. 61 For MRA therapy, a larger treatment benefit is more likely for patients with LVEF 41-49% than with LVEF ≥50%. 62 The treatment benefit of sacubitril/valsartan was observed with LVEF <60%. 63 For SGLT2 inhibitor therapy, the relative treatment effect was similar across the LVEF spectrum. 64 Overall, these results suggest that the LVEF thresholds for systolic dysfunction used in treatment trials may benefit from reclassification but that LVEF will remain important for determining optimal management.

The association of LVEF with the benefit of early initiation and titration was evaluated in a sub-study of the STRONG-HF trial. 65 This study showed the consistency of the rapid implementation of guideline based medical therapy across the entire spectrum of LVEF after an admission for heart failure.

Other drug treatments

Several additional medications can be used to improve outcomes among patients with HFrEF. This section discusses several of these therapies: hydralazine/isosorbide dinitrate therapy, ivabradine, vericiguat, intravenous iron, and glucagon-like peptide-1 receptor agonists. We discuss their evidence and contemporary role.

Hydralazine/isosorbide dinitrate therapy

The combination of hydralazine and isosorbide dinitrate is a guideline recommended therapy for self-identified Black patients with HFrEF with NYHA class III or IV heart failure despite treatment with optimal medical therapy as described above. 1 2 The combination therapy causes both arterial and venous vasodilation in addition to nitrous oxide augmentation that may have remodeling benefits. 66 A-HeFT (African-American Heart Failure Trial) randomized 1050 self-identified Black patients to hydralazine/isosorbide dinitrate therapy versus placebo. Patients receiving hydralazine/isosorbide dinitrate therapy had a 43% relative reduction in death over a mean follow-up of 10 months (10.2% v 6.2%; P=0.02). 67 However, rates of treatment and adherence to hydralazine/isosorbide dinitrate therapy are low. 68 69 This may be due to multiple factors, including the difficulty of adhering to a three times daily medication and concerns about a race based indication. Additionally, the effectiveness of combined hydralazine and isosorbide nitrate therapy among non-Black patients remains unclear. 65 Although hydralazine/isosorbide dinitrate therapy remains an important tool for reducing morbidity among Black patients with HFrEF, we believe that it should remain a second line therapy for patients with persistent HFrEF after optimization of the four pillars described above ( fig 4 ).

Updates in heart failure since the 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America and 2021 European Society of Cardiology heart failure guidelines. 1 2 Of note, angiotensin receptor/neprilysin inhibitor (ARNI) may not be beneficial in patients with a left ventricular ejection fraction >60%. 63 CV=cardiovascular; HF=heart failure; HFmrEF=heart failure with mildly reduced ejection fraction; HFpEF=heart failure with preserved ejection fraction; HFrEF=heart failure with reduced ejection fraction; HRQOL=health related quality of life; PA=pulmonary artery; SGLT2=sodium-glucose cotransporter-2

Ivabradine inhibits the channel responsible for the cardiac pacemaker current, I(f ), in the sinus node. 70 In SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial), among 6558 patients with HFrEF with sinus rhythm and a heart rate ≥70 bpm, ivabradine led to an 18% relative reduction (hazard ratio 0.82, 0.75 to 0.90) compared with placebo in the composite outcome of cardiovascular death and hospital admission for heart failure. 71 However, only 26% of patients were taking a target dose of β blocker therapy. Given the substantial benefit of β blocker therapy, patients with HFrEF should first have their β blocker dose optimized before initiation of ivabradine therapy.

Vericiguat is a novel heart failure medication that stimulates soluble guanylate cyclase and up-titrates the nitric oxide signaling pathway promoting vasodilation and reduced cardiac remodeling. In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, 5050 patients with HFrEF with recent hospital admission or intravenous diuretic treated with vericiguat versus placebo had a 10% relative reduction (hazard ratio, 0.83 to 0.98) in the risk of cardiovascular death or hospital admission for heart failure. 72 However, patients in the highest quarter of natriuretic peptide concentrations were less likely to benefit from vericiguat compared with placebo. 73 Although vericiguat was effective among a high risk HFrEF cohort, the smaller magnitude of benefit has rendered it a second line therapy for patients at high risk following optimization of the four pillars described above.

Intravenous iron infusion

Multiple studies have shown that iron deficiency and anemia are associated with increased mortality and decreased exertional capacity. 74 75 Several trials have shown that intravenous iron reduces the risk of hospital admission for heart failure and improves patient reported health status among patients with HFrEF. 76 77 78 79 80 Unfortunately, these effects have not been reproduced with oral iron administration. 81 These findings emphasize the importance of screening for iron deficiency and intravenous repletion; hospital admissions for heart failure are an ideal opportunity for screening and intervention.

Glucagon-like peptide-1 receptor agonists

Similarly to SGLT2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP1RA) were initially developed to improve glycemic control among patients with diabetes mellitus. In a meta-analysis of eight trials with cardiovascular outcomes evaluating GLP1RA among patients with type 2 diabetes mellitus, GLP1RA reduced the risk of cardiovascular death (hazard ratio 0.87, 0.80 to 0.94) and hospital admission for heart failure (0.89, 0.82 to 0.98). 82 However, the prevalence of heart failure at baseline was between only 9% and 24% across these trials. 83

GLP1RA were subsequently shown to be potent therapies for weight loss among obese patients without diabetes mellitus. 84 85 In the Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) trial, semaglutide versus placebo was found to significantly reduce the composite outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke among patients with existing atherosclerotic cardiovascular disease who were overweight or obese but without diabetes mellitus. Among enrolled patients, 24% had chronic heart failure at baseline.

Given the high prevalence of both diabetes mellitus and obesity among patients with heart failure, the potential benefits of GLP1RA warrant optimism. The Effect of Semaglutide 2.4 mg Once Weekly on Function and Symptoms in Subjects with Obesity-related Heart Failure with Preserved Ejection Fraction (STEP-HFpEF) trial evaluated the effect of semaglutide versus placebo on patient reported health status among 529 non-diabetic patients with ejection fraction ≥45%, obesity, and evidence of impaired health status (Kansas City Cardiomyopathy Questionnaire (KCCQ) score of <90) at baseline. Participants treated with semaglutide had on average a 7.8 (95% confidence interval 4.8 to 10.9) greater increase in their KCCQ score than patients treated with placebo, in addition to a significant 20.3 m larger improvement in their six minute walk distance.

Concern persists regarding the use of GLP1RA among patients with HFrEF. In a pooled analysis of two GLP1RA trials including patients with HFrEF, treatment with GLP1RA increased hospital admissions for heart failure. 86 Existing data support the use of GLP1RA among patients with obesity and HFpEF, but additional data on the safety and efficacy among patients with HFrEF is needed.

Devices and invasive therapies

Pulmonary artery pressure monitoring.

The CardioMEMS device is an ambulatory pulmonary artery pressure monitor. Ambulatory pulmonary artery pressure monitoring can be used to guide adjustment of medication (for example, loop diuretics) and monitor for signs of decompensation. In the initial CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association (NYHA) Class III Heart Failure Patients) trial, the CardioMEMS device reduced hospital admissions for heart failure and improved patient reported health status among 550 patients with heart failure irrespective of LVEF and a previous admission for heart failure (hazard ratio 0.72, 0.60 to 0.85). 87 Although the GUIDE-HF (hemodynamic-GUIDEed management of Heart Failure) trial failed to show a reduction in hospital admissions for heart failure (1022 patients; hazard ratio 0.88, 0.74 to 1.05), the subsequent MONITOR-HH (remote hemodynamic monitoring of pulmonary artery pressures in patients with chronic heart failure) trial found an improvement in patient reported health status and a reduction in admissions for heart failure with pulmonary artery pressure monitoring (348 patients; improvement in KCCQ overall summary score of 7.1 (95% confidence interval 1.5 to 12.8). 88 89 A meta-analysis of the three trials estimated a 30% reduction in hospital admissions for heart failure with pulmonary artery pressure monitoring (hazard ratio 0.70, 0.58 to 0.86). 90 When considering implementation of pulmonary artery pressure monitoring, it is critical to remember that the effectiveness of any remote monitoring interventions is dependent on the downstream responses to abnormal readings. Maximizing the effectiveness of hemodynamic monitoring requires establishment of workflows to promote active monitoring and appropriate interventions for abnormal hemodynamics.

Implantable cardiac defibrillators and cardiac resynchronization therapy

Implantable cardiac defibrillators (ICDs) and cardiac resynchronization therapy (CRT) remain mainstays of HFrEF therapy. 1 2 Although multiple trials have illustrated the survival benefit with ICD therapy for patients with HFrEF, the more recent DANISH (Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure) trial did not find a significant reduction in all cause mortality among 556 patients with non-ischemic cardiomyopathy (hazard ratio 0.87, 0.68 to 1.12). 91 However, patients under the age of 70 did have a survival benefit with ICD therapy. This likely reflects the fact that ICD therapy prevents only sudden cardiac death; as the competing risk of non-cardiovascular death increases (for example, increasing age) or the risk of sudden cardiac death decreases (for example, non-ischemic cardiomyopathy or effective medical therapy), the absolute benefit of ICD therapy decreases. 92 However, despite improvements in medical therapy, sudden cardiac death remains frequent among patients with HFrEF. 93 The shared decision making around ICD implantation should incorporate not only the patient’s preference but also estimates of an individual patient’s expected benefit. 92 94 95

CRT has shown the greatest benefit in patients with a wide QRS (≥150 ms, typically in a left bundle branch block pattern). CRT has traditionally relied on biventricular pacing. Conduction system pacing is a novel approach of pacing the His bundle or left bundle branch. 96 Small studies have suggested that conduction system pacing may be a potential alternative to promoting ventricular synchrony. 97 98 99 100 Ongoing trials are testing whether this strategy leads to similar clinical outcomes to traditional CRT via coronary sinus pacing.

Mitral transcatheter edge-to-edge repair

HFrEF is often accompanied by severe secondary mitral regurgitation (often described as posterior leaflet restriction on the echocardiography report), which is associated with increased risk of mortality and hospital admission. 101 102 Mitral regurgitation often improves with optimal medical therapy and positive ventricular remodeling. 103 For patients with persistent severe mitral regurgitation, repair of the mitral valve via transcatheter edge-to-edge repair (TEER) is a potential therapy. Two trials of mitral valve TEER had discordant results. In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial in 614 patients, mitral TEER led to a 47% reduction in hospital admission for heart failure (hazard ratio 0.53, 0.40 to 0.70) and reduced all cause mortality by 38% (0.62, 0.46 to 0.82). 104 However, the MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial showed no reduction in mortality or hospital admission for heart failure with mitral valve TEER (304 patients; odds ratio 1.16, 0.73 to 1.84). 105 The discordant results may be due to the degree of mitral regurgitation in relation to the severity of cardiomyopathy. Greater mitral regurgitation in relation to the degree of left ventricular dilation (disproportionate mitral regurgitation) may be more likely to benefit from mitral valve repair. 106 In addition, MITRA-FR did not require optimization of guideline based medical therapy before the procedure.

Revascularization

Coronary artery bypass grafting (CABG) for patients with severe coronary artery disease has been shown to improve outcomes compared with medical therapy, 107 but the early studies showing benefit typically did not include patients with significantly reduced ejection fraction. In addition, medical therapy has advanced substantially since these trials were conducted. In response to these concerns, the Surgical Treatment for Ischemic Heart Failure (STICH) trial randomized 1212 patients with an ejection fraction ≤35% and coronary artery disease amenable to CABG or medical therapy. 108 The primary outcome of all cause mortality was not significantly lower with CABG (hazard ratio 0.86, 0.72 to 1.04). However, the secondary outcome of death from any cardiovascular cause or hospital admission with heart failure showed a benefit with CABG (hazard ratio 0.74, 0.64 to 0.85), and current guidelines recommend bypass grafting if severe disease suitable for bypass is present and the LVEF is <35% 2

The potential benefit of revascularization with percutaneous coronary intervention was recently evaluated in the Revascularization for Ischemic Ventricular Dysfunction (REVIVED) trial. 109 This study found that among 700 patients with extensive coronary artery disease amenable to percutaneous coronary intervention and viable myocardium, the intervention did not improve mortality or hospital admission compared with usual care (hazard ratio 0.99, 0.78 to 1.27). This study is consistent with previous randomized evaluations suggesting that using viability to target revascularization does not improve outcome. 110

Treatment of advanced heart failure

Heart failure can be a progressive condition despite optimal therapy, and appropriate timing of referral to heart failure specialists is important. 111 The I-NEED-HELP acronym provides potential triggers for that referral. 112

Clinical outcomes with left ventricular assist device (LVAD) therapy have continued to improve over time. An improvement in post-implantation survival to more than 50% at five years has been seen, in addition to a reduction in rates of stroke and gastrointestinal bleeding. 113 After recall of the Heartware LVAD, the HeartMate 3 centrifugal flow left ventricular assist device is the only available durable LVAD. In the MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial, the HeartMate 3 had lower rates of reoperation, pump thrombosis, stroke, and gastrointestinal bleeding than the HeartMate 2 axial flow pump. 114

Heart transplant remains the cornerstone of therapy for patients with stage D heart failure. The median survival after heart transplant now exceeds 12 years. 115 The ability to effectively transplant hearts from hepatitis C positive donors and following circulatory arrest has increased the potential donor pool. 116 117 Improvements in donor preservation have also allowed sharing of potential donors across greater distances. 118

Non-drug, non-device therapies

Sodium and fluid restriction.

Restricting dietary sodium intake is commonly recommended to reduce symptoms of heart failure. However, limited data are available to support such restriction. The SODIUM-HF (Study of Dietary Intervention under 100 mmol in Heart Failure) trial randomized 806 patients to a low sodium diet of less than 1500 mg/day or usual care. It found similar rates of cardiovascular hospital admission, cardiovascular emergency department visit, or all cause death (hazard ratio 0.89, 0.63 to 1.26). 119 Of note, patients with a low sodium diet had higher patient reported health status. The US cardiovascular disease guidelines continue to recommend dietary sodium restriction among patients with and without heart failure. 2 120 However, potential concerns include that excessive sodium restriction may contribute to poor nutrition or may exacerbate deleterious neurohormonal activation. 121 Although moderating sodium intake may be reasonable, focusing on optimization of therapies shown to improve outcomes should be prioritized.

Fluid restriction in heart failure has also been tested in several randomized trials. A meta-analysis of six trials found that liberal fluid consumption did not increase readmssions due to heart failure or all cause mortality. 122 Accordingly, heart failure guidelines now state that the benefit of fluid restriction is uncertain or note the gap in evidence for its effectiveness. 1 2

Cardiac rehabilitation

Cardiac rehabilitation has generally been reserved for patients with heart failure with reduced LVEF or those who undergo cardiovascular surgery (for example, CABG). The REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) trial found that dedicated rehabilitation improved physical functioning for older patients admitted to hospital with heart failure regardless of LVEF. 123 A participant level meta-analysis of 13 randomized trials in 3990 participants found (at 12 months of follow-up; most patients had HFrEF) an improvement in six minute walk distance (mean 21.0 (95% confidence interval 1.57 to 40.4) m) and Minnesota Living With Heart Failure score (mean improvement 5.9, 1.0 to 10.9). 124 Additional trials are under way to evaluate the benefit of rehabilitation strategies for patients with HFpEF.

Measuring patient reported outcomes in heart failure

Without treatment, heart failure not only substantially increases the risk of mortality but also impairs quality of life. 125 Improving health related quality of life is an important goal of heart failure treatment. Multiple therapies have been shown to significantly improve quality of life on the basis of patient reported health status ( table 2 ). 87 134 140 141 142 143 144 145 The two most commonly used measures of patient reported health status in treatment trials have been the KCCQ and the Minnesota Living with Heart Failure Questionnaire. 146 147

Heart failure therapies with evidence of improvement in patient reported heart failure health status

Although patient reported health status has been commonly measured in clinical trials, it is rarely used in clinical practice. However, multiple studies have shown that not only is patient reported health status often discordant with the clinician’s assessment but it also has a higher concordance with objective functional testing than does the NYHA classification. 148 149 Patient reported health status is also a strong predictor of hospital admission and death. 150 151 152 153 154 155 Therefore, the call to incorporate routine measurement of patient reported health status into clinical care is increasing. 2 156 157 Theoretically, this could improve clinicians’ understanding of patients’ health status and guide improved shared decision making. Limited data support the potential utility and acceptability of routine assessment of patient reported health status in clinical care, 158 159 160 but no data are available on the clinical impact of such a strategy. Additionally, the challenges of effectively implementing data collection within the electronic health record remain. 161

Inequitable outcomes for health conditions among different groups often exist within societies, and heart failure is no exception. Data from the US suggest race/ethnicity differences in the incidence of and survival with heart failure. 162 163 The cause of disparities in outcome is multifactorial, and these are often driven as much or more by social determinants of health than by differences in patient management. 163 164 A recent analysis from the US found similar use of drug treatments known to prolong survival for patients with heart failure across race and ethnicity groups. 165 Inequitable treatment rates have been observed for device therapies, such as CRT, and therapies for advanced heart failure; these may reflect not only bias but also the critical role of access to care in promoting improved equity. 166 167 168 A focus beyond treatment differences is needed if overall health is to be improved. Improving representation in clinical trials is important to improve our ability to provide appropriate customized care to all patients with heart failure. 169

Several clinical guidelines have been published recently including the ESC (2021) and ACC/AHA/HFSA (2022) guidelines. 1 2 Important differences in guideline recommendations are rare and largely due to differences in the published evidence that occurred between publication. For example, the 2022 ACC/AHA/HFSA guideline includes a 2A recommendation for SGLT2 inhibitors for patients with HFmrEF and HFpEF following the publication of a large clinical trial showing outcome benefit. 2 40 Important studies that were published after these guidelines include a second randomized trial showing benefit of SGLT2 inhibitors in patients with an LVEF >40%, 39 the STRONG-HF trial showing benefit of rapid initiation and titration of medications for those with HFrEF, 49 and a trial showing that pulmonary pressure monitoring using the CardioMEMS device improved outcome. 89 Future guidelines will likely incorporate the trial results into revised recommendations. Figure 4 shows a summary of new evidence published since the 2022 ACC/AHA/HFSA and 2021 ESC heart failure guidelines. 1 2 An update to the 2021 ESC guideline was recently published, 170 and this incorporates new clinical trials of SGLT2 inhibitors, finerenone, and intravenous iron therapy.

Emerging treatments

Continued progress in treatment remains critical given the residual morbidity for patients with heart failure. Omecamtiv mecarbil is a cardiac myosin activator that improves cardiac contractility. In the GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes through Improving Contractility in Heart Failure) trial, 8258 patients with HFrEF who received omecamtiv mecarbil showed an 8% relative reduction (0.92, 0.86 to 0.99) in the risk of cardiovascular death or heart failure event (hospital admission or urgent visit). 171 The benefit was driven by the difference in heart failure events. Multiple secondary analyses have illustrated larger therapeutic benefit among patients with more severe heart failure based on LVEF, systolic blood pressure, NYHA class, or natriuretic peptides. 172 173 174 175 Omecamtiv mecarbil is not available as it was denied approval by the US Food and Drug Administration and is still pursuing approval in Europe.

Several trials will help to clarify the role of existing heart failure therapies. The VICTOR trial is evaluating the efficacy of vericiguat among patients with heart failure who have not had a recent worsening heart failure event (clinicaltrials.gov: NCT05093933 ). The DECISION trial is testing the efficacy and safety of digoxin at low serum concentrations ( NCT03783429 ). Given the controversy of the TOPCAT trial findings, two ongoing trials are evaluating the efficacy of spironolactone among patients with heart failure with LVEF ≥40% ( NCT04727073 ; NCT02901184 ).

Many novel therapies for heart failure are under evaluation in clinical trials. These include multiple trials of finerenone among patients with heart failure across the ejection fraction spectrum ( NCT04435626 ; NCT06033950 ; NCT06024746 ). The SUMMIT trial will evaluate the effect of tirzepatide, another GLP1RA, among patients with HFpEF and obesity ( NCT04847557 ). Other ongoing studies are testing anti-inflammatory therapies among patients with HFmrEF/HFpEF ( NCT05636176 ; NCT04986202 ).

Non-drug care of patients with heart failure also continues to evolve. The CABA-HFPEF trial is testing catheter ablation among patients with heart failure with LVEF ≥40% and atrial fibrillation ( NCT05508256 ). Multiple ongoing trials are evaluating tricuspid valve interventions among patients with severe tricuspid regurgitation.

The management of patients with heart failure has changed markedly in the past several years, with evidence for four life prolonging classes of drugs for patients with reduced LVEF and the benefit of SGLT2 inhibitors for those with mildly reduced and preserved LVEF. Device management and other non-drug management have evolved as results from new clinical trials are published. Identification of appropriate candidates for treatment requires accurate diagnosis, which can be challenging for patients with heart failure and preserved ejection fraction. Additional questions remain—in particular, how best to implement these new treatment recommendations into clinical practice.

Glossary of abbreviations

ACC—American College of Cardiology

ACE—angiotensin converting enzyme

AHA—American Heart Association

ARB—angiotensin receptor blocker

ARNI—angiotensin receptor/neprilysin inhibitor

BNP—B-type natriuretic peptide

CABG—coronary artery bypass grafting

CMR—cardiac magnetic resonance

CRT—cardiac resynchronization therapy

ESC—European Society of Cardiology

GLP1RA—glucagon-like peptide-1 receptor agonists

HFmrEF—heart failure with mildly reduced left ventricular ejection fraction

HFpEF—heart failure with preserved left ventricular ejection fraction

HFrEF—heart failure with reduced left ventricular ejection fraction

HFSA—Heart Failure Society of America

HRQOL—health related quality of life

ICD—implantable cardioverter defibrillator

KCCQ—Kansas City Cardiomyopathy Questionnaire

LVAD—left ventricular assist device

LVEF—left ventricular ejection fraction

MRA—mineralocorticoid receptor antagonists

NYHA—New York Heart Association

RCT—randomized controlled trial

SGLT2—sodium-glucose cotransporter-2

TEER—transcatheter edge-to-edge repair

Questions for future research

Does the order of initiation of medications for heart failure with reduced left ventricular ejection fraction affect the ability to achieve sustained treatment with all four pillars of therapy?

Does the simultaneous initiation of medications increase or decrease the probability of sustained drug treatment?

What are the benefits of medications in addition to sodium-glucose cotransporter-2 inhibitors for patients with heart failure with preserved left ventricular ejection fraction?

Which patients should receive a trial of medication withdrawal if their symptoms resolve and their left ventricular function becomes normal?

How patients were involved in the creation of this manuscript

We obtained input from patient representatives/advocates as this manuscript was prepared. The feedback was helpful in defining the specific topics covered. In particular, the patient representatives/advocates highlighted the importance of including a discussion relating to equity.

Series explanation: State of the Art Reviews are commissioned on the basis of their relevance to academics and specialists in the US and internationally. For this reason they are written predominantly by US authors

Contributors: PH and AS have joint authorship on this paper. PH and AS conceived the paper, did the research, and wrote all drafts including the final version of the paper.

Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: PH has received research funding from the VA Health Care System and the American Heart Association and is chair of the 2022 ACC/AHA/HFSA Heart Failure Guideline Writing Committee; AS is a consultant for Lexicon Pharmaceuticals and has received research funding from the American Heart Association, the Gordon and Betty Moore Foundation, Novartis, the National Heart Lung Blood Institute, and Reprieve Cardiovascular.

Provenance and peer review: Commissioned; externally peer reviewed.

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• Research article
• Open access
• Published: 07 October 2024

Safety and efficacy of oxycodone for refractory dyspnea in end-stage heart failure patients with chronic kidney disease: a case series of eight patients

• Masayuki Tanaka 1 , 2 ,
• Hirofumi Maeba 3 , 4 ,
• Takeshi Senoo 3 , 5 ,
• Nana Yoshimiya 6 ,
• Haruna Ozaki 2 ,
• Kazuki Uchitani 2 ,
• Noboru Tanigawa 2 &
• Kazuichi Okazaki 2 , 7  

Journal of Pharmaceutical Health Care and Sciences volume  10 , Article number:  63 ( 2024 ) Cite this article

34 Accesses

Metrics details

Morphine is effective in palliative care for patients with end-stage heart failure; however, its use is avoided in patients with impaired renal function because it tends to induce adverse effects. Although oxycodone has been reported to be a useful alternative, the evidence is insufficient. Therefore, we investigated the safety and efficacy of oxycodone in eight patients with end-stage heart failure complicated by chronic kidney disease. 

This single-center retrospective study reviewed patients with end-stage heart failure who were referred to the heart failure multidisciplinary team at our institution and administered oxycodone for refractory dyspnea during hospitalization between January 2011 and December 2018. We examined the details of oxycodone usage, vital signs, and the Modified Borg Scale (MBS), which quantifies the symptoms of dyspnea and adverse events.

Oxycodone was administered for refractory dyspnea in eight patients with end-stage heart failure [mean age: 81 years, men: 4, New York Heart Association functional class IV: 8, median left ventricular ejection fraction: < 40% ( n  = 6) and ≥ 50% ( n  = 2)]. Renal function was reduced in all patients; the estimated glomerular filtration rate (eGFR) in seven patients was < 30 mL/min/1.73 m 2 . The median initial intravenous dose of oxycodone was 7.05 mg/day (range: 5–10 mg/day), and the average duration of administration was 15.8 days. Significant decreases in MBS (before: median 9, range 7–10 vs. after: median 2.5, range 1–8; p  < 0.01) were observed at a median of 2.0 days (range: 2 h to 7 days) after beginning oxycodone administration. Systolic blood pressure, heart rate, and respiratory rate were not significantly altered after treatment. Adverse events, including constipation, nausea, and tremors, were observed in three patients. However, no lethal adverse events related to oxycodone treatment occurred during treatment.

Conclusions

This study revealed the clinical practice of oxycodone treatment and suggested that it is an alternative therapy as a viable palliative for refractory dyspnea in patients with end-stage heart failure who should avoid the use of morphine.

The major symptoms of end-stage heart failure are dyspnea, general fatigue, pain, anorexia, and depression. Some studies on end-stage heart failure have reported frequent occurrences of dyspnea, general fatigue, and pain (60–88%, 69–82%, and 35–78%, respectively) [ 1 , 2 , 3 ]. These symptoms may stem from physiological dysfunction associated with low cardiac output, including pulmonary congestion, fluid retention, and cardiac insufficiency, as well as from anxiety, anger, pain, and depression related to the intensity of dyspnea [ 4 , 5 , 6 , 7 ]. If a patient continues to experience unbearable distress following conventional therapy for dyspnea, treatment with opioids should be considered palliative care. The European and Japanese heart failure guidelines suggest morphine treatment for refractory dyspnea as palliative care in patients with end-stage heart failure [ 8 ], based on previous studies that reported the effectiveness of morphine administration for dyspnea in patients with chronic heart failure [ 9 , 10 , 11 ]. However, morphine treatment may be avoided in cases of renal failure due to serious adverse effects, such as respiratory depression caused by the accumulation of active metabolites of morphine. In these cases, oxycodone, which is less likely to accumulate during renal failure, may be an alternative to morphine. We previously reported a case where oxycodone improved dyspnea without adverse effects in a patient with end-stage heart failure and renal dysfunction [ 12 ]. However, the safety and efficacy of oxycodone have not been fully established. Accordingly, we aimed to investigate the safety and efficacy of oxycodone in eight patients with end-stage heart failure and renal dysfunction at our institution.

Study design and population

This single-center retrospective study was conducted by members of the heart failure multidisciplinary team at Kansai Medical University Hospital. This study was approved by the ethics review board of our institution (approval number 2018168). We retrospectively reviewed patients who were hospitalized at our institution and referred to the heart failure multidisciplinary team between January 2011 and December 2018. Patients with end-stage heart failure who were hospitalized for heart failure and received oxycodone as palliative care for refractory dyspnea were included in this analysis. The attending doctors finally decided to administer oxycodone to patients with end-stage heart failure who were experiencing intractable severe symptoms unresponsive to ordinary palliative care approaches, considering the preferences of the patients and their families. A multidisciplinary team and the attending doctors determined the administration route based on the patient’s condition and preferences. The oxycodone dose was determined on a case-by-case basis, considering patients’ age, physical constitution, renal function, and symptom severity. Patients with comorbid cancers were excluded.

Definition and measurements

This retrospective study was based on a review of the medical charts. We investigated the detailed data on oxycodone usage, including administration route, dose, and duration. Temporal changes in vital signs, including respiratory rate, blood pressure, and heart rate, were obtained. We evaluated the efficacy of oxycodone treatment using the Modified Borg Scale (MBS), which quantifies dyspnea symptoms on a scale of 0 (no symptoms) to 10 (worst possible symptoms). The MBS enables the assessment of the respiratory discomfort perceived by the patient [ 12 , 13 ] (Table  1 ). MBS scores were collected once every 30 min to 2 h following the initiation of oxycodone treatment and subsequently 1 to 2 times per day based on meal times and nurse shift changes. The data were obtained directly from patients.

Vital signs and symptom scale data were collected both before initiating treatment and when the MBS showed the most improvement following the administration of oxycodone. If oxycodone was discontinued, the reasons for discontinuation were further investigated. Common adverse events of oxycodone, such as nausea, vomiting, constipation, delirium, and tremors, were evaluated from medical chart descriptions.

The Wilcoxon signed-rank test was used to test for differences in MBS, systolic blood pressure, heart rate, and respiratory rate before and after oxycodone treatment. All tests were two-tailed, and statistical significance was set at p  < 0.05. All analyses were performed using JMP Pro version 17.2.0 (SAS Institute, Cary, NC, USA).

Baseline characteristics of patients with heart failure who received oxycodone treatment

During the study period, oxycodone was administered to eight patients with end-stage heart failure for refractory dyspnea at our institution. The baseline patient characteristics and medications administered before oxycodone treatment are presented in Table  2 .

The mean age was 81 years, and four patients were male (50%). All patients were classified as New York Heart Association functional class IV, corresponding to ACCF/AHA stage D, and the left ventricular ejection fractions were < 40% ( n  = 6) and ≥ 50% ( n  = 2). The etiology of heart failure was dilated cardiomyopathy in five cases, ischemia in two cases, and valvular disease in two cases; four of these cases had chronic atrial fibrillation and were on concomitant anticoagulants. Renal function was reduced in all patients; the estimated glomerular filtration rate (eGFR) in seven patients was < 30 mL/min/1.73 m 2 . In all eight cases, loop diuretics were administered, and beta-blockers were also administered in seven cases. An angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) was administered in two cases. In Cases 1–4 and 8, ACE inhibitors or ARBs were discontinued before oxycodone injection, given the decline in renal function and difficulty in maintaining blood pressure. During oxycodone administration, no adjustments were made to the oral medications for Cases 1–3 and 7, and these medications were continued as prescribed. In contrast, in Cases 4, 6, and 8, all oral medications were discontinued after 2, 29, and 2 days of oxycodone initiation, respectively, to prevent aspiration due to the addition of sedatives. In Case 5, warfarin was reduced on the 4th day of oxycodone administration due to a significant increase in PT-INR, but no changes were made to the other medications. Additionally, for Cases 1, 2, and 4–7, in which cardiotonic drugs were administered, no dose increases were made during oxycodone treatment. Specifically, in Case 1, due to an improvement in dyspnea on the 11th day of oxycodone administration, the dose of the cardiotonic drug (dobutamine) was reduced from 7.5γ to 6.5γ, with no recurrence of dyspnea. Oxycodone treatment was discontinued the following day.

Feasibility of oxycodone treatment for refractory dyspnea in patients with end-stage heart failure

The vital signs at baseline and after treatment for each patient are presented in Table  3 .

The median starting dose of oxycodone was 7.05 mg (range: 5–10 mg), and the median maintenance dose was 10 mg (range: 5–10 mg), with increases in Cases 3 and 4. The median elapsed time until MBS improvement was 2.0 days (range: 2 h to 7 days), and seven of the eight cases showed MBS improvement within 2 days. A significant reduction was observed in MBS (before: median 9, range 7–10 vs. after: median 2.5, range 1–8; p  < 0.01) after starting oxycodone administration, as shown in Fig.  1 .

MBS scores before and after oxycodone administration

Other vital signs, including systolic blood pressure, heart rate, and respiratory rate, were not significantly altered before and after starting oxycodone treatment (Fig.  2 ).

Vital signs before and after oxycodone administration. A Systolic blood pressure, B heart rate (bpm), C respiratory rate (breaths per minute)

Adverse events of oxycodone treatment in patients with end-stage heart failure

Oxycodone-induced adverse effects, including constipation, nausea, tremor, and prolonged international normalized ratio of prothrombin time (PT-INR) (in one patient using warfarin), were observed in three patients but were adequately managed with dose adjustment and symptomatic treatment. Constipation was treated with sennoside or lubiprostone, and alternatively, sorbitol solution and lactulose syrup were also effective. The nausea was treated with metoclopramide. The tremors observed in three patients (Cases 1, 5, and 7) were managed by decreasing the oxycodone dosage without precipitating dyspnea. In Case 5, the PT-INR increased from 2.0 to 2.6 after oxycodone treatment, requiring a reduction in the warfarin dose without bleeding.

Outcome of patients with oxycodone administration

Dyspnea in four patients was completely relieved, and oxycodone was eventually discontinued. However, Case 4 experienced fatigue even after a stepwise increase in oxycodone, and midazolam was added on day 4. Similarly, Case 8 reported fatigue despite improvement in dyspnea, and midazolam was administered on day 3. In both cases, fatigue was alleviated after midazolam administration. Finally, four patients (Cases 3, 4, 6, and 8) died from a lack of response to treatment with inotropic agents and diuretics, resulting in an exacerbation of heart failure itself, regardless of the adverse effects of oxycodone. However, dyspnea in these four patients improved at the beginning of their treatment with oxycodone. The mean duration of oxycodone in the symptom improvement and death groups was 14.8 [8, 29] and 17 [4, 35] days, respectively, with no significant differences (Table  3 ).

In this retrospective survey of oxycodone treatment for refractory dyspnea as palliative care in real-world heart failure practice, we found the following results. First, oxycodone treatment significantly decreased MBS without affecting respiratory rate, heart rate, or blood pressure. Second, adverse effects due to oxycodone were effectively managed with dosage adjustment and symptomatic treatment without inducing serious adverse effects, such as respiratory depression. This study’s findings indicate that oxycodone may be a new treatment option for patients with end-stage heart failure in real-world practice.

Dose and timing of oxycodone treatment in end-stage heart failure practice

The efficacy of morphine for dyspnea in patients with end-stage heart failure has been reported, with its effect at smaller doses than those for pain control [ 9 , 10 , 14 ]. Although no consensus on the dosage exists for heart failure, symptomatic relief has been reported with morphine tablets 5 mg four times a day (morphine injection equivalent 10 mg/day) [ 10 ]. In the field of heart failure, there are numerous reports on the introduction of morphine at 5–10 mg/day or smaller doses by continuous intravenous or subcutaneous infusion, similar to that in the field of oncology. However, caution should be exercised in patients with impaired renal function (creatinine clearance should be less than 30 mL/min), as the accumulation of morphine-3-glucuronide and 6-glucuronide, the active metabolites of morphine, may cause hypersedation, delirium, and respiratory depression [ 15 , 16 ]. However, oxycodone, similar to morphine, has been reported to be useful for dyspnea in oncology [ 16 , 17 ]. It can be used relatively safely even in cases of impaired renal function (as a rule of thumb, creatinine clearance of 10 mL/min or more) and can be administered to patients who have difficulty receiving morphine [ 18 ]. In heart failure, continuous intravenous or subcutaneous administration of oxycodone 4.8–10 mg/day has been reported to improve dyspnea, and it can be safely administered to patients with severe renal dysfunction [ 12 , 19 ]. In this study, induction was conducted at 5–10 mg/day, and its efficacy was confirmed. Oxycodone should be carefully considered as an alternative drug in cases where morphine is difficult to use, such as in patients with impaired renal function who develop delirium. The method for initiating opioids for dyspnea is detailed in the “Approaches to Managing Pharmacotherapy in Palliative Care for Heart Failure,” published by the Japan Society of Hospital Pharmacists in April 2021. However, it should be noted that, in Japan, oxycodone is indicated only for cancer pain and is not applicable to patients with heart failure. Introducing opioids in patients with end-stage heart failure experiencing dyspnea even after adequate heart failure treatment should be considered. As demonstrated in this study, there were cases where dyspnea significantly improved and oxycodone was withdrawn; therefore, it is necessary to consider its introduction at an earlier stage in the future. Because of the retrospective study design, we could not determine the optimal dose and timing of oxycodone administration in our survey, and these issues should be further investigated in future studies.

Efficacy of oxycodone for refractory dyspnea in patients with end-stage heart failure

Opioid treatment has been reported to be effective in the treatment of dyspnea due to cancer and/or non-cancer diseases such as chronic obstructive pulmonary disease [ 20 , 21 ]. Oxycodone has also been reported to be as effective as morphine in the treatment of dyspnea in patients with terminal cancer [ 16 , 17 ]. Although the mechanism of action of morphine and other opioids in improving dyspnea has not been fully elucidated, decreased perception of the central nervous system and sensitivity of the medullary respiratory center to carbon dioxide have been reported [ 22 ]. However, in heart failure, the opioid group showed significantly improved symptoms compared with the placebo group, although symptoms did not disappear. Although the goal of opioid treatment for dyspnea is to alleviate symptoms, the symptoms of dyspnea in patients with heart failure are highly severe, and opioids may be useful in improving their quality of life. MBS, a measure of dyspnea, in hospitalized patients with end-stage heart failure is shown in Fig.  1 . The MBS score significantly decreased, suggesting the efficacy of oxycodone in treating refractory dyspnea in patients with end-stage heart failure. However, the study’s sample size was small, and thus it did not adequately demonstrate the efficacy of dyspnea. Further studies, including high-quality, large-scale prospective cohort studies and possibly randomized controlled trials, are required to determine the efficacy of oxycodone treatment compared with morphine for refractory dyspnea in patients with end-stage heart failure.

Safety of oxycodone in patients with end-stage heart failure

Adverse events, including respiratory depression, nausea, vomiting, constipation, and delirium, are often experienced by cancer patients receiving morphine treatment [ 23 ]. Although there are concerns that oxycodone may cause adverse effects similar to those of morphine, in this study, the adverse effects caused by oxycodone were adequately managed with dose adjustments and symptomatic treatments. In two patients in this study, midazolam was concomitantly administered after oxycodone initiation; however, no serious adverse effects, such as respiratory depression, were observed. Morphine undergoes glucuronidation in the liver, whereas oxycodone is primarily metabolized by the CYP enzymes 2D6 and 3A4. Because the beta-blockers bisoprolol and carvedilol are metabolized by CYP2D6 and CYP3A4, it was hypothesized that their concomitant use with oxycodone could potentiate the effects of beta-blockers and decrease blood pressure and heart rate. However, in this study, no effects on these parameters were observed because the doses were small. Oxycodone does not inhibit CYP2C9, the major metabolizing enzyme of warfarin; therefore, its effect on warfarin pharmacokinetics and action is expected to be minimal. However, in this study, a prolonged PT-INR was observed in patients treated with the combination of oxycodone and warfarin. In particular, Case 5, involving a patient who was started on oxycodone while receiving warfarin showed a prolonged PT-INR. Although serum albumin level fluctuations are considered to be a potential contributing factor, the serum albumin level in this case remained stable between 2.7 and 3.0 g/dL during the entire treatment period, suggesting that there were no significant fluctuations. Therefore, it was hypothesized that oxycodone may have enhanced the anticoagulant effects of warfarin. This observation aligns with the findings of Hosokawa et al., who reported that the anticoagulant effects of warfarin were significantly enhanced when co-administered with oxycodone in patients with cancer. Specifically, the PT-INR increased significantly, and the Warfarin Sensitivity Index also increased, indicating an enhanced anticoagulant effect despite a reduction in the warfarin dose [ 24 ]. Therefore, it is recommended that PT-INR be closely monitored when initiating oxycodone therapy in patients receiving warfarin to prevent potential complications from enhanced anticoagulant effects [ 25 ].

Study limitations

This study has several limitations. First, this was a single-center retrospective study with a small sample size; therefore, it was subject to various biases inherent to the data. Second, this study was conducted at a single institution, which limits its generalizability. Third, we could not ascertain whether dyspnea was relieved by treatment with oxycodone alone because of the various simultaneous treatments for heart failure. Fourth, we retrospectively evaluated adverse events based on descriptions in medical records. The frequency of adverse events may have been falsely decreased owing to the failure to record all events in the medical records, even though there were unacceptable symptoms. Fifth, clear inclusion/exclusion criteria and protocols for oxycodone administration were not established in this study. Moreover, the frequency of symptom evaluation and titration of oxycodone administration generally depended on the attending medical staff and varied among patients during the study period.

This case series suggests that oxycodone may be a feasible treatment for refractory dyspnea in patients with heart failure. Side effects were also sufficiently eliminated by symptomatic treatments or adjustments to the oxycodone dosage without any serious adverse effects, such as respiratory depression. Oxycodone may be an alternative treatment option for dyspnea due to end-stage heart failure, in which morphine must be avoided because of renal dysfunction. Nevertheless, further studies are warranted to evaluate the safety and efficacy of oxycodone treatment, and oxycodone administration should be discussed by a multidisciplinary team.

Availability of data and materials

Data used in this report will not be shared owing to the risk of identifying the individuals.

Abbreviations

Modified Borg Scale

Estimated glomerular filtration rate

Angiotensin receptor blocker

Angiotensin-converting enzyme

International normalized ratio of prothrombin time

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MS conceptualized and designed the study. MS drafted the manuscript. HM, TS, KU, NT, and KO advised on the interpretation of the therapeutic course in this case and revised the manuscript. MS, NK, and HO monitored the patients and acquired their data. All authors contributed to the preparation of the final manuscript.

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Tanaka, M., Maeba, H., Senoo, T. et al. Safety and efficacy of oxycodone for refractory dyspnea in end-stage heart failure patients with chronic kidney disease: a case series of eight patients. J Pharm Health Care Sci 10 , 63 (2024). https://doi.org/10.1186/s40780-024-00384-4

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Heart Failure Case Studies

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Heart failure patients presenting to primary care clinics often have multiple, complex comorbidities. Several different disease processes and treatment options may need to be considered simultaneously in the setting of acute on chronic exacerbation of symptoms. This chapter will exemplify complex heart failure patient vignettes and provide practical guidance for the primary care provider, highlighting HF guideline-directed medical therapy.

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Dellise, N.R., Hayes, K.M.S. (2023). Heart Failure Case Studies. In: Hayes, K.M.S., Dellise, N.R. (eds) Managing Heart Failure in Primary Care: A Case Study Approach. Springer, Cham. https://doi.org/10.1007/978-3-031-20193-6_19

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Introduction

Mechanism of action, evidence of inotropic therapy in different hf settings, conclusion and future perspectives, conflict of interest statement, funding sources, author contributions, use of inotropic agents in advanced heart failure: pros and cons.

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Benjamin Lautrup Hansen , Søren Lund Kristensen , Finn Gustafsson; Use of Inotropic Agents in Advanced Heart Failure: Pros and Cons. Cardiology 2 October 2024; 149 (5): 423–437. https://doi.org/10.1159/000536373

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Background: Use of inotropic agents in advanced heart failure (HF) has over time been evaluated in several randomized, controlled clinical trials (RCTs). However, the evidence for both efficacy and safety is conflicting. Summary: In this narrative review, the evidence for and role of inotropes in advanced HF are outlined. Readers are provided with a comprehensive overview of key-findings from 23 important RCTs comparing orally or intravenously administered inotropes. Clinically relevant pros and cons of inotropic regimens are summarized to guide the clinician in the management of advanced HF patients in different settings (e.g., out-patient, in-patient, and intensive care unit). Finally, future perspectives and potential new agents are discussed. Key Messages: Long-term use of inotropes in advanced HF is controversial and should only be considered in selected patients (e.g., as palliative or bridging strategy). However, short-term use continues to play a large role in hospitalized patients with cardiogenic shock or severe decompensated acute HF.

Advanced heart failure (HF) is defined by persisting severe signs and symptoms of HF despite implementation of optimal tolerable guideline-directed medical therapy (GDMT) [ 1‒3 ]. Signs and symptoms of advanced HF can be related to either congestion or organ hypoperfusion. As improvements in GDMT and device therapy over the last decades have increased survival in non-advanced HF, the prevalence of advanced HF continues to increase [ 4‒8 ]. This entails HF patients to reach advanced stages later in life consequently presenting with more co-morbidity before being evaluated for advanced HF therapy – namely heart transplant and left ventricular assist device (LVAD). As a result, many patients are medically ineligible for these definitive treatments due to contraindications. Consequently, and because of donor organ shortage, heart transplant and LVAD will remain a treatment for a limited proportion of the advanced HF population. This leaves an enormous potential for a long-lasting oral or intravenous positive inotropic agent to alleviate symptoms and improve outcomes in this group of patients. Since the 1980s several large randomized, controlled trials (RCTs) have evaluated different inotropes in varying populations and settings of both acute and chronic HF. With this narrative review, we aim to provide the clinician with pros and cons related to commonly used inotropes in the management of patients with advanced HF, as illustrated in Figure 1 . In doing so we revisit relevant RCTs reporting patient-relevant outcomes and summarize and discuss current evidence in this complex field. Focus of this review is on inotropic agents in patients with advanced HF with reduced left ventricular ejection fraction (LVEF).

Pros and cons of inotropes in advanced HF. Oral or intravenous inotropic support may be considered in selected patients with advanced HF. Understanding pros and cons is essential to utilize potential benefits of inotropes and to obtain appropriate informed consent from the patient.

The overall classification system of inotropes consists of three categories (i) calcitropes, (ii) myotropes, and (iii) mitotropes. Calcitropes cover catecholamines, phosphodiesterase (PDE) inhibitors, and calcium sensitizers. Myotropes covers so far only one novel drug, omecamtiv mecarbil. Finally, mitotropes include several heterogenous agents such as perhexiline, sodium–glucose co-transporter 2 inhibitors, and others and their effect in advanced HF is not fully clarified. Thus, mitotropes will not further be described. Mechanism of action, dosing, and hemodynamic effects are summarized and pictured in Table 1 and Figure 2 , respectively.

Classification, dosing, and hemodynamic effects of commonly used inotropes and vasopressors in advanced HF

cAMP, cyclic adenosine monophosphate; CO, cardiac output; HR, heart rate; IV, Intravenous; MAP, mean arterial pressure; PCWP, pulmonary capillary wedge pressure; PDE-3, phosphodiesterase-3; PO, per oral; SVR, systemic vascular resistance.

Pharmacological inotropic targets. Different pharmacological inotropic targets are pictured. There are two target domains: the cardiac myocyte (left side) and the vascular system (right side). SR, sarcoplasmic reticulum.

Catecholamines

Dobutamine, adrenaline (or epinephrine), noradrenaline (or norepinephrine), and dopamine represent the most frequently used catecholamines or sympathomimetic agents. With varying affinity, they all stimulate α and β-receptors. Depending on the receptor-affinity, these drugs cause either vasoconstriction (α1-receptor), increased inotropy and chronotropy (β1-receptor), or vasodilation (β2-receptor). However, sympathomimetic drugs may induce reflex counterreactions through the autonomic nervous system (e.g., vasodilation after β1-receptor stimulation). Stimulation of the β-receptor causes activation of adenylate cyclase and thereby increases cyclic adenosine monophosphate production which results in increased cardiac contractility [ 9 ]. Noradrenaline is an endogenous catecholamine and acts on α1 and β1-receptors causing vasoconstriction and to some extent increased cardiac contractility but does not increase heart rate significantly. Dobutamine is a synthetic catecholamine which primarily acts as a β1-receptor agonist and thus increases inotropy and chronotropy. In addition, dobutamine exerts moderate vasodilating effect via the peripheral β2-receptor. Adrenaline stimulates all adrenoreceptors. At low doses, adrenaline predominantly increases inotropy and chronotropy, whereas at high doses it increases systemic vasoconstriction. Dopamine is the endogenous precursor of noradrenaline and at low doses stimulates selectively dopamine receptors causing renal vasodilation, whereas at high doses dopamine exerts inotropy and vasoconstriction. Catecholamines share several side effects including tachyarrhythmia and myocardial ischemia (increased oxygen consumption).

PDE Inhibitors and Calcium Sensitizers

Cyclic nucleotide phosphodiesterase subtype 3 enzyme (PDE-3) catalyzes the degradation of cyclic adenosine monophosphate and are important targets in the vascular and cardiac myocyte, implying that several PDE-3-inhibiting agents such as amrinone, milrinone, and enoximone have been designed to inhibit this enzyme. Milrinone and enoximone are the most frequently used PDE-3-inhibitors and both exert positive inotropic and lusitropic hemodynamic effects [ 10‒13 ]. Pharmacokinetically, milrinone is primarily eliminated through the kidneys and enoximone by hepatic metabolism. The chronotropic effect of PDE-3-inhibiting agents is modest at low dose and importantly causes less tachyarrhythmias compared with catecholamines, and milrinone and enoximone in particular have more distinct vasodilating effect compared with dobutamine, especially in β-blocker treated patients [ 14, 15 ].

Levosimendan exerts its inotropic effects through calcium-sensitizing properties. Depending on inherent cytosolic calcium levels in the cardiomyocyte, levosimendan binds and stabilizes troponin C and prolongs the duration of actin-myosin cross-bridges without impairing diastolic relaxation [ 16, 17 ]. Levosimendan has an active metabolite (OR-1896) with a long half-life (70–80 h) responsible for the prolonged effect of the drug [ 18 ]. PDE-3-inhibiting agents and levosimendan both act downstream of the β-receptor, and so their effect is not attenuated by concomitant use of β-blockers. Thus, these drugs are often preferred over β-adrenergic agents in patients treated with high-dose β-blockers [ 15, 19 ]. Because of their potent vasodilating effect, PDE-3-inhibitors and levosimendan are referred to as inodilators. The vasodilating mechanism is caused by opening of adenosine triphosphate-sensitive potassium channels in the smooth muscle cells of the vasculature, which may result in clinically significant hypotension requiring concomitant administration of vasopressors (namely noradrenaline). Serious adverse effects of PDE-3-inhibitors and levosimendan include hypotension and ventricular arrhythmias. The choice between different inotropes based on a hemodynamic profile including cardiac index and systemic vascular resistance is presented in Figure 3 .

Choice of inotrope based on hemodynamic profile in advanced HF and CS. The figure assumes that preload has been optimized. IV, intravenous; GDMT, guideline-directed medical therapy. *Addition of an inodilator may be required. **Addition of a vasoconstrictor may be required.

Myosin Activators

Omecamtiv mecarbil, a first-in-class selective myosin activator which binds to the motor domain of myosin and increases the transition rate of myosin into the strongly actin-bound, force-generating state, which ultimately leads to improved myocardial systolic function. Compared with catecholamines and PDE-3-inhibitors, omecamtiv mecarbil has no effect on calcium transients [ 20 ]. Favorable hemodynamic effects include improved left ventricular systolic function and reduction in left ventricular volumes, N-terminal pro-brain natriuretic peptide (NT-proBNP) or BNP, and heart rate without clinically significant changes in blood pressure. Although omecamtiv mecarbil may cause a small increase in plasma troponin, chronic administration is generally well-tolerated and no excess myocardial ischemia or ventricular arrhythmias were reported in phase 2 and 3 clinical studies [ 21‒23 ].

Patients with advanced HF often do not tolerate recommended doses of GDMT, or they suffer from severe symptoms and recurrent hospitalizations despite optimal doses of GDMT. Patients with advanced HF typically require large doses of diuretics and experience worsening of kidney and/or liver function. Clearly, some patients may require inotropic therapy as part of a palliative strategy or as bridge to heart transplant or LVAD. The identification of patients with advanced HF can be challenging and even the definition of advanced HF has changed over time, which must be taken into consideration when assessing the available data. In the following, we will review the evidence for the use of inotropic therapy in the settings of out-patient advanced HF, acute decompensated HF (ADHF), and cardiogenic shock (CS). A comprehensive and chronological overview of important RCTs of inotropes across these settings is displayed in Table 2 , and clinically relevant pros and cons of frequently used inotropes are shown in Table 3 .

Chronological overview of important RCTs on inotropes stratified by setting

ACEi, angiotensin-converting enzyme inhibitors; BID, twice daily; CHF, chronic heart failure; CO, cardiac output; CS, cardiogenic shock; CV, cardiovascular; IHD, ischemic heart disease; IQR, interquartile range; IV, intravenous; LVEF, left ventricular ejection fraction; NP, natriuretic peptides; NYHA, New York Heart Association functional class; PCWP, pulmonary capillary wedge pressure; PO, per oral; QID, four times daily; QoL, quality of life; RCT, randomized controlled trial; SCAI, Society for Cardiovascular Angiography and Interventions; TID, three times daily; 6MWD, 6-min walking distance.

Clinically relevant pros and cons of frequently used inotropes

CS, cardiogenic shock; HF, heart failure; IHD, ischemic heart disease; PVR, pulmonary vascular resistance; QoL, quality of life.

*Inodilator.

Inotropes in Out-Patient Advanced HF

DiBianco et al. [ 24 ] and the Prospective Randomized Milrinone Survival Evaluation (PROMISE) trial [ 26 ] studied oral milrinone and included stable patients with a prior diagnosis of HF. The studies were conducted in an era before widespread implantation of angiotensin converting enzyme inhibitors (ACE-inhibitors), β-blockers, and implantable cardiac defibrillators as background therapy. DiBianco et al. randomized 230 patients in NYHA class II-IV and sinus rhythm to receive either milrinone, digoxin, milrinone, and digoxin in combination, or placebo. After 12 weeks of follow-up, milrinone improved treadmill exercise time and reduced worsening HF events. However, milrinone alone or in combination with digoxin was not significantly better than digoxin alone. PROMISE enrolled 1,088 patients in NYHA III-IV with LVEF ≤0.35 to receive either milrinone or placebo. Over a 6-month period, long-term therapy with milrinone did not lead to symptomatic improvement and even had a detrimental effect on hospitalizations and mortality, and consequently the study was terminated early. Additionally, no subgroup showed signs of benefit of milrinone. Following the disappointing yet definite results, no later phase III clinical trial has investigated oral milrinone in its conventional form. However, Uretsky [ 25 ] and Cowley et al. [ 27 ] hypothesized that the harmful effect of milrinone was not a PDE-3-inhibitor class effect and investigated oral enoximone. In 102 patients with chronic HF but no ACE-inhibitors, Uretsky et al. found a worse survival rate and no improvement of symptoms or exercise capacity after 16 weeks of enoximone therapy. Cowley et al. [ 27 ] randomized 151 advanced HF patients who remained severely incapacitated despite optimal treatment including ACE-inhibitors and followed them for more than 1 year. However, the study was early terminated due to excess mortality in the enoximone group. Especially, patients with baselineheart rate above 85 beats per minute and HF disease-duration less than 2 years had increased mortality. However, enoximone was associated with a short-term (within 2 weeks) improved quality of life, and so the dilemma about the balance between quantity or quality of life emerges ( Fig. 1 ). The Studies of Oral Enoximone Therapy in Advanced HF program (ESSENTIAL) explored if the widespread implantation of β-blockers could counteract the harmful effects of enoximone and thereby maintain (or even enhance) the favorable effects [ 13, 29 ]. Based on 17 months of follow-up of 1,854 contemporary advanced HF patients on optimal GDMT, low-dose enoximone proved to be safe but no improvement in mortality, cardiovascular hospitalizations, and 6-min walking distance was observed.

Effects of Peroral Levosimendan in the prevention of further hospitalizations in patients with chronic HF trial (PERSIST) was a moderate-size (307 patients), placebo-controlled pilot-study on 1–2 mg daily dose of oral levosimendan exploring a new type of primary outcome designed to describe the HF patient’s journey and comprised three endpoint components: repeated subjective symptom assessments, worsening HF events and all-cause mortality [ 28, 48 ]. The study showed no difference in endpoints at 60 days or 6 months. Nonetheless, levosimendan significantly improved quality of life questionnaire scores and decreased natriuretic peptides.

Oral omecamtiv mecarbil was recently evaluated in a phase III, global, double-blind, placebo-controlled RCT which enrolled 8,232 patients (27% with severe HF) [ 23 ]. The primary composite outcome of first HF event or death from cardiovascular causes was very modestly reduced with omecamtiv mecarbil (8% relative risk reduction [95% CI: 0.86–0.99]). However, the benefit appeared to be larger in subgroup analyses of patients with low systolic blood pressure and more advanced symptoms of HF (NYHA III-IV). In 276 less advanced HF patients, another study of oral omecamtiv mecarbil assessed the effects on exercise capacity (peak VO 2 ) and found no benefit with omecamtiv mecarbil [ 32 ].

Efficacy and safety of the pulsed infusions of levosimendan in outpatients with advanced HF (LevoRep) study evaluated the efficacy and safety of pulsed ambulatory infusion of levosimendan in 120 advanced HF patients in NYHA class III-IV with a 6-min walking distance under 300 meters [ 30, 31 ]. Recent hospitalization (≤1 month) for ADHF and de novo HF were excluded in the study. The primary outcome was a composite of changes in functional capacity and quality of life measured by 6-min walking distance and Kansas City Cardiomyopathy Questionnaire (KCCQ) after 24 weeks. No statistically significant difference between the levosimendan and placebo group was found. Two other studies examined the effect of pulsed levosimendan versus placebo. In the Levosimendan ® Intermittent administration in Outpatients: effects on Natriuretic peptides in advanced chronic HEART failure (LION-HEART), investigators observed significant reduction in NT-proBNP and combined incidence of all-cause mortality and hospitalization in levosimendan-treated patients [ 49 ]. In the Long-Term Intermittent Administration of Levosimendan in Patients with Advanced Heart Failure (LAICA) study, levosimendan lead to a statistically nonsignificant reduction in the incidence of hospital readmission for ADHF and a significant improvement in 1-year survival [ 50, 51 ]. However, both trials were too small to assess hard clinical outcomes. The recently published Repetitive Levosimendan infusions in advanced heart failure (LeoDOR) trial specifically included recently hospitalized patients with ADHF in the so-called vulnerable phase [ 33 ]. Patients had LVEF ≤0.30 and markedly elevated NT-proBNP or BNP (≥2,500 ng/L or ≥900 ng/L, respectively). Patients were randomized to two different out-patient intermittent levosimendan regimens (i) 6-h infusion (rate 0.2 μg/kg/min) every other week or (ii) 24-h infusion (rate 0.1 μg/kg/min) every 3 weeks for 12 weeks, or placebo. The primary endpoint was an assessment of post-discharge clinical stability consisting of a 3-tier global rank endpoint including time to death or urgent heart transplant or LVAD implantation, time to non-fatal urgent HF event requiring intravenous vasoactive therapy, and time-averaged proportional change in NP from baseline to week 14. The trial demonstrated no improvement in clinical stability with levosimendan, but due to COVID-19 only 145 participants were included, causing a substantial loss of power. Therefore, no definitive assumptions should be made about the efficacy or safety of levosimendan upon this trial.

Regarding treatment of advanced HF patients as a palliative strategy, several of the above-mentioned trials included stable advanced HF patients, but information on palliative status or candidacy for advanced therapies was not provided. Thus, evidence on the efficacy of or inotropic support as a palliative strategy is of low quality and mainly extrapolated from RCTs not exclusively including palliative patients [ 52 ]. Since the study populations in LevoRep and LeoDOR on average were 5 years older (mean age 70 years) and more comorbid compared with other trials, LevoRep and LeoDOR most likely included a greater proportion of patients where a palliative strategy was intended. As mentioned, both trials failed to demonstrate a benefit with chronic levosimendan. A meta-regression analysis concluded that adrenergic inotropic agents in general were associated with excess mortality but also with improved symptoms [ 53 ]. In addition, most studies examining adrenergic agents or PDE-3-inhibitors were conducted before widespread use of ICDs and primarily focus on hemodynamics or hard clinical endpoints rather than quality of life or functional status. However in 1999, an Italian trial randomized 38 advanced end-stage HF palliative out-patients with documented cardiac index ≤2.2 L/min/m 2 and previously requiring inotropes to once weekly 48-h low-dose dobutamine infusions through a central line or optimized standard of care [ 54 ]. Results showed no significant improvement on functional status over 6 months of follow-up. Thus, with the available evidence, guidelines acknowledge that long-term inotropes may be attempted for selected palliative patients with refractory advanced end-stage HF ineligible or opting not to undergo heart transplant or LVAD to improve functional status and quality of life [ 1 ]. Due to the potential harmful side effects, every non-pharmacological intervention should be considered (e.g., refer for hospice, cardiac nurse home visits, or switching off ICD therapy) before start of therapy and a clear goal of the strategy should be formulated for each patient. Since no oral preparation is currently available, inotropes (e.g., dobutamine, milrinone, or levosimendan) must be given parenterally via a peripheral or central venous line or a permanent, indwelling catheter with a portable pump, and the risk of infection is not negligible with the use of central lines [ 52 ]. Thus, depending on local preferences, intravenous inotropes may also be administered intermittently at the hospital or in the patient’s own home to improve quality of life [ 55 ]. While some observational data suggest that continuous home-inotropic infusion may be feasible and cost-effective as bridge to heart transplant, little evidence to inform about cost-effectiveness of these regimens exists in patients selected for a palliative strategy [ 34, 56, 57 ].

Inotropes in ADHF

Early experience with the safety and efficacy of dobutamine for hospitalized ADHF patients with preexisting advanced HF originates from a post hoc analysis from the Flolan International Randomized Survival Trial (FIRST) where 471 patients were randomized in an unblinded fashion to continuous home-epoprostenol (prostacyclin) infusions through a permanent indwelling catheter versus standard care [ 35, 36 ]. Eighty patients receiving dobutamine at randomization were compared with 391 patients not receiving dobutamine. Although used in a sicker population, dobutamine was associated with increased mortality at 6 months. Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) was the first prospective large-scale phase 3 trial ( n = 951) investigating intravenous infusion of an inotrope (in this case milrinone) as an adjunct to standard care in patients with decompensated HF without CS [ 40, 58 ]. Milrinone did not reduce the primary endpoint of length of hospitalization, nor did it improve survival or the ability to institute GDMT at discharge. A post hoc analysis showed that milrinone might be specifically harmful in patients with ischemic HF [ 41 ].

Two major RCTs investigated the role of low-dose dopamine as a renal adjuvant therapy in hospitalized ADHF patients (regardless of LVEF) not requiring vasoactive support. Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE-AHF) trial randomized 360 patients (26% of which had preserved LVEF) to 72-h intravenous infusions of either dopamine or nesiritide versus placebo but found no effect of either drug on 72-h urine output and change in cystatin C [ 37, 43 ]. Efficacy and safety of high dose versus low dose furosemide with or without dopamine infusion: the Dopamine in Acute Decompensated Heart Failure II (DAD-HF II) was a single-blind study of 161 ADHF patients which revealed no clinical benefit of adding low-dose dopamine to low-dose furosemide [ 38 ]. Likely due to the evidence from these two trials, low-dose dopamine for optimizing end-organ function is not mentioned in current guidelines.

Phase II clinical trials of levosimendan in ADHF (vs. dobutamine) and ADHF after acute myocardial infarction (vs. placebo) found evidence for symptomatic and hemodynamic improvement, and reduced risk of worsening HF and mortality, although the studies were not powered for assessing hard outcomes [ 39, 42 ]. Therefore, The Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) study hypothesized that a short-term intervention with levosimendan (bolus followed by 24-h infusion) could improve long-term hard clinical outcomes when compared with dobutamine in ADHF patients requiring inotropic support [ 59 ]. Levosimendan failed to prove beneficial effect on all-cause mortality but did markedly reduce natriuretic peptide concentrations. The Randomized EValuation of Intravenous LeVosimendan Efficacy (REVIVE I and II) trials re-evaluated levosimendan in 700 less sick ADHF patients (only 11% requiring inotropic support) compared to placebo in a US population [ 44 ]. Investigators found that levosimendan had a favorable short-term symptomatic effect, albeit caused more atrial and ventricular arrhythmias with no difference in long-term survival. Presumably the conflicting evidence between levosimendan trials relates partly to the fact that phase III trials (e.g., SURVIVE and REVIVE) involved less congested patients, not all monitored with pulmonary artery catheters or even, in the end, requiring inotropic support. Furthermore, the finding that levosimendan appears to outperform dobutamine in chronic HF patients tolerating high-dose β-blockers may have diluted the overall effect in trials involving both de novo ADHF (β-blocker naïve patients) and ADHF with preexisting HF. Accordingly, a subgroup analysis of data from SURVIVE demonstrated that levosimendan-treated patients with preexisting HF and/or previous β-blocker treatment may have improved 5-day and 14-day survival [ 60 ].

A phase II clinical trial tested 48-h infusion of omecamtiv mecarbil in ADHF patients [ 46 ]. Although no improvement in symptoms was seen in the overall population of 606 patients, greater relief of dyspnea was seen in patients receiving the highest dose and unlike other agents such as levosimendan and milrinone, no difference in hypotension, ischemic events, or ventricular or atrial arrhythmias was reported. In conclusion, there is no clear evidence of benefit from routine administration of inotropes in ADHF patients without CS.

Inotropes in CS and Post-CS Management

CS is a life-threatening phenotype of pump failure characterized by hypotension (systolic blood pressure below 90 mm Hg) and clinical and biochemical signs or symptoms of severe end-organ hypoperfusion (e.g., mentally confusion or oliguria), despite adequate filling pressures [ 61 ]. Guidelines recommend intravenous inotropic support to immediately stabilize blood pressure and restore end-organ perfusion [ 1, 2 ]. Because of ethical concerns, no trial has compared noradrenaline, dobutamine, or milrinone with placebo. However, several studies have demonstrated a significant increase in mortality or other adverse events with dopamine and adrenaline compared with noradrenaline [ 47 , 62‒66 ]. Thus, noradrenaline is now the preferred first-line vasopressor for hypotension in CS, including CS complicating myocardial infarction.

The recently published Dobutamine Compared with Milrinone (DOREMI) trial prospectively enrolled 192 CS patients and compared milrinone with dobutamine [ 67 ]. Results suggested no significant difference between milrinone and dobutamine on the primary composite endpoint of in-hospital death or several cardiovascular events (risk ratio 0.90 [95% CI: 0.69–1.19]). A propensity score analysis based on 1,772 patients with CS concluded that use of a vasopressor alone (e.g., adrenaline, noradrenaline, or dopamine) was associated with a higher 30-day mortality as compared with the use of a vasopressor plus an inodilator (e.g., dobutamine, levosimendan, or a PDE-3-inhibitor) [ 45 ]. An updated Cochrane meta-analysis from 2018 identified six RCTs comparing levosimendan and dobutamine in patients with low cardiac output syndrome or CS caused by cardiac surgery, myocardial infarction, or worsening chronic HF. Although the authors report a lower short-term all-cause mortality with levosimendan, the beneficial effect decreased over time [ 68 ]. Thus, dobutamine and levosimendan are considered equal options in current guidelines. However, due to the long half-life, levosimendan may not be the preferred choice in the initial treatment of CS patients in the intensive care unit, and so in clinical practice levosimendan is primarily reserved for stabilized patients, still dependent on other inotropes. If stabilization is achieved with inotropes and subsequent repeated weaning-attempts fail, patients may be deemed inotrope-dependent. The Oral Enoximone in Intravenous Inotrope-Dependent Subjects (EMOTE) trial evaluated low-dose oral enoximone as a wean off strategy in 201 intravenous (intermittently or continuously) inotrope-dependent ultra-advanced HF patients [ 13, 69 ]. Patients were randomized 1:1 to receive either low-dose oral enoximone (25–75 mg three times daily) or placebo. Enoximone failed to meet the primary endpoint of a weaning benefit over placebo in the first 30 days.

In conclusion, guideline suggest noradrenaline as the first-line agent to treat hypotension in CS. Additional adjunctive inotropic agents such as dobutamine, milrinone, or levosimendan can be added to reverse ongoing end-organ hypoperfusion, but the evidence to do so is limited. Because of robust evidence of deleterious effects, major guidelines only recommend intravenous inotropic support as a bridge strategy in CS (a class IIb recommendation) [ 1, 2 ]. However, extensive gaps in the management of CS remain [ 61 ], and a recent expert consensus statement from the Heart Failure Association of the European Society of Cardiology advocates for a role of intravenous inotropic support in selected scenarios outside CS, including short-term assessment of reversibility end-organ dysfunction, hemodynamic optimization prior to LVAD, or in patients awaiting heart transplant [ 70 ].

Over time, several RCTs have assessed the efficacy and safety of inotropes in advanced HF patients. Disappointingly, most studies have shown neutral or even worse outcomes with the active agent. Thus, inotropes in advanced HF remain controversial and long-term use should be considered as bridging to definite therapy or in select cases as a palliative strategy and not routinely used. However, short-term inotropic support continues to play a large role in hospitalized patients with CS or in severe decompensated acute HF. There are few ongoing trials in the space of inotropic support in advanced HF, although there is a definite unmet need [ 71 ]. Especially in palliative care, the selection of subgroups who potentially benefit from inotropic support represent a major gap in evidence. Thus, further research in this growing population is warranted. In conclusion, the potential for an ideal inotrope in acute and advanced HF remains unredeemed.

B.L.H.: none to declare. S.L.K.: my institution has received speaker fees/advisory board fee from Bayer and Astra Zeneca outside the submitted work. F.G.: Advisor Abbott, Bayer, Pfizer, Astra-Zeneca, Ionis, Alnylam, Pharmacosmos. Speaker: Orion Pharma, Novartis.

This study was funded by Novo Nordisk Foundation (NNF20OC0060561).

B.L.H. drafted the initial manuscript. S.L.K. and F.G. critically reviewed and revised the content before final submission.

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3 Sample Nursing Care Plan for CHF [Congestive Heart Failure] (with rationales and case scenario)

Last updated on December 28th, 2023

Sample Nursing Care Plan for CHF [Congestive Heart Failure]

What is congestive heart failure.

Heart failure is a chronic, progressive condition. It occurs when the heart is unable to pump effectively and produce enough cardiac output to successfully perfuse the rest of the body’s tissues and organs. An individual can have right-sided or left-sided heart failure as well as systolic or diastolic heart failure.

Left-sided heart failure is also known as Congestive Heart Failure (CHF) . In CHF, the heart is either unable to contract completely or fill completely during relaxation. It can lead to an inadequate amount of blood pumping out of the heart. Thereby, backing up into the right side and then ultimately to the lungs and throughout the body causing congestion.

Systolic heart failure means the heart is not able to contract completely and affects its ability to pump blood out of the heart.

Diastolic heart failure means the heart is unable to relax fully between heartbeats and allows the appropriate amount of blood into the ventricle.

In this post, we’ll formulate a sample nursing care plan for a patient with Congestive Heart Failure (CHF) based on a hypothetical case scenario .

CHF Case Scenario

A 74-year old Hispanic male presents to the Emergency Department with complaints of increased dyspnea, reduced activity tolerance, ankle swelling, and weight gain in recent days. He has a known history of hypertension and heart failure. He reports over the past 3 days his shortness of breath, particularly with activity, has increased significantly.

He is also now using 3 pillows to sleep at night instead of his usual 1 pillow, and he has experienced a 10-pound weight gain in 3 days. He states he is now only able to ambulate 1 block before needing to stop and rest whereas in the past he could walk half a mile. 

The nurse notes dyspnea upon minimal excretion with position changes.  Upon physical assessment his breathing is shallow and labored, respiratory rate is 30 breaths per minute, heart rate 115 beats per minute, oxygen saturation 83% on room air, blood pressure 179/98 mm Hg, he has +4 pitting edema in bilateral lower extremities, and crackles are heard in his lung fields throughout.

The patient’s lab work reveals an elevated BNP level of 954pg/mL and a chest x-ray shows pulmonary congestion. The last echocardiogram in the patient’s chart (completed 3 months prior) showed an Ejection Fraction (EF) of 40%.

The patient is to be admitted to the hospital for Acute Exacerbation of Congestive Heart Failure (CHF) . 

Case Discussion

The main assessment findings the nurse should be aware of for this patient begin with his vital signs, all of which are listed are abnormal.

The patient has labored, tachypneic, breathing. He is also tachycardic and has a decreased oxygen saturation. This demonstrates to the nurse that the patient is not hemodynamically stable and the main goal is stabilizing the patient’s respiratory status. 

In addition, the nurse should also note the reported weight gain and visibly apparent edema. These assessment findings are able to help the nurse critically think and identify a potential list of differential diagnoses prior to lab and imaging results becoming available.

When assessing this patient, the nurse will want to remember ABCs (airway, breathing, circulation) of care.  The patient’s airway is protected and he is able to breathe on his own.

However, his breathing is compromised due to excessive fluid. Therefore, that becomes the priority for the patient and the nurse should begin by improving his oxygen saturation and breathing status.  

Once the patient’s breathing status is stabilized the next likely task will be to diuresis the patient.  In doing this, it will help to remove additional fluid thereby improving his oxygen and breathing capability further.

#1 Sample nursing care plan for CHF – Impaired gas exchange

Nursing assessment.

Subjective Data:

• Reported increased shortness of breath
• Using 3 pillows to sleep at night (increase from usual 1 pillow)
• Decreased activity level due to shortness of breath

Objective Data:

• Tachypneic, respiratory rate of 30 breaths/minute
• Crackles in lung fields
• Oxygen saturation 83% on room air
• Congestion on chest x-ray
• +4 pitting edema

Nursing Diagnosis [ Impaired gas exchange ]

Impaired gas exchange related to fluid overload as evidenced by labored, tachypneic breathing, decreased oxygen saturation, crackles in lung fields, pitting edema, congestion on chest x-ray.

Short-term goal

To increase oxygen saturation ≥92% prior to transfer from ED and admission to hospital floor unit

Nursing Interventions with Rationales

Long-term goal

To decrease excess fluid by 10 pounds by discharge to return patient to baseline dry weight

Expected Outcome

• This will reduce hypoxemia resulting in improved oxygen saturation and reduce dyspnea.
• Excess fluid will be removed and the patient’s weight will return to baseline.
• Reduced congestion will improve gas exchange.

#2 Sample nursing care plan for CHF – Decreased cardiac output

• Needs 3 pillows at night to sleep
• 10-pound weight gain
• Ankle swelling
• Tachycardia
• Hypertension
• Crackles in lung fields throughout
• Ejection fraction (EF) 40%
• Elevated BNP 954pg/mL
• Congestion seen on chest x-ray

Nursing Diagnosis [ Decreased cardiac output ]

Decreased cardiac output related to altered contractility as evidenced by tachycardia, hypertension, orthopnea, edema, abnormal lab work, and reduced EF.

To stabilize vital signs and maintain adequate oxygen saturation prior to transfer from ED to the hospital unit.

To improve cardiac contractility by discharge

• Maintain oxygen saturation above 92%
• Decrease in blood pressure to patient’s baseline (ideally <120/80)
• Improved contractility by decreasing excess fluid, improvement in breathing status, and stabilization of vital signs

#3 Sample nursing care plan for CHF – Decreased activity tolerance

• Only able to ambulate 1 block
• Reduced activity level
• Dyspnea on minimal exertion
• Tacypnea (RR 30 bpm)
• Tachycardia (PR 115 bpm)
• Decreased oxygen saturation (83% at room air)

Nursing Diagnosis [ Decreased activity tolerance ]

Decreased activity tolerance related to imbalance between oxygen supply and demand as evidenced by dyspnea, tachypnea, tachycardia, decreased oxygen saturation, and fatigue.

To limit activity to decrease oxygen demand while also increasing oxygen supply

To increase activity level to patient’s baseline prior to discharge.

• Improved oxygenation status (≥92%)
• Patient’s activity level will return to baseline

It is vital to monitor patients admitted with congestive heart failure closely.  In particular, detailed and accurate intake and output records should be kept to show the progress and success of treatments being administered.

This will also help to determine if additional medications are warranted or dosage adjustments need to be made.

Close monitoring of types of food and drinks is also important. Because some food may cause patient to retain more fluid than others. Providing proper patient education is key for these patients to support them in understanding their condition and diagnosis.  

Likewise, education will help the patient to be aware of specific things to avoid at home in terms of food or drink and why these should be avoided.

Click here to see a full list of Nursing Diagnoses related to Congestive Heart Failure (CHF).

Congestive heart failure is a chronic condition that can progress over time. Acute exacerbations of this chronic condition can also be very common especially if an individual is not following or is unaware of the appropriate guidelines and recommendations.

It is important for nurses to understand the various symptoms a patient may present with when experiencing an acute exacerbation. It is also imperative that the nurse assesses the individual’s airway and breathing status immediately and prioritizes this above any other nursing intervention. 

Lastly, providing thorough patient education both verbally and in writing is essential for these individuals to help them understand their diagnosis and what measures they can take at home to prevent additional exacerbations.

Ackley, B.J., Ladwig, G.B., Flynn-Makic, M.B., Martinez-Kratz, M.R., & Zanotti, M. (2020). Nursing Diagnosis Handbook: An Evidence-based Guide to Planning Care [eBook edition]. Elsevier.

Comer, S. and Sagel, B. (1998). CRITICAL CARE NURSING CARE PLANS . Skidmore-Roth Publications.

Doenges, M.E., Moorhouse, M.F., & Murr, A.C. (2019). Nursing Care Plan: Guidelines for Individualizing Client Care Across the Lifespan [eBook edition]. F.A. Davis Company.

Herdman, T., Kamitsuru, S. & Lopes, C. (2021). NURSING DIAGNOSES: Definitions and Classifications 2021-2023 (12th ed.). Thieme.

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Different ecls pump configurations for temporary right ventricular assist device in lvad patients: a retrospective case–control study.

1. Introduction

2. materials and methods, 2.1. ethical statement, 2.2. study design and data collection, 2.3. rvad implantation and weaning protocol, 2.4. endpoints, 2.5. statistical analysis, 3.1. the patient characteristics, 3.2. the study endpoints, 4. discussion, 5. conclusions, author contributions, institutional review board statement, informed consent statement, data availability statement, conflicts of interest.

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Opacic, D.; Klüß, C.; Radakovic, D.; El-Hachem, G.; Becker, T.; Rudloff, M.; Lauenroth, V.; Deutsch, M.-A.; Velasquez-Silva, C.; Fox, H.; et al. Different ECLS Pump Configurations for Temporary Right Ventricular Assist Device in LVAD Patients: A Retrospective Case–Control Study. Life 2024 , 14 , 1274. https://doi.org/10.3390/life14101274

Opacic D, Klüß C, Radakovic D, El-Hachem G, Becker T, Rudloff M, Lauenroth V, Deutsch M-A, Velasquez-Silva C, Fox H, et al. Different ECLS Pump Configurations for Temporary Right Ventricular Assist Device in LVAD Patients: A Retrospective Case–Control Study. Life . 2024; 14(10):1274. https://doi.org/10.3390/life14101274

Opacic, Dragan, Christian Klüß, Darko Radakovic, Georges El-Hachem, Tobias Becker, Markus Rudloff, Volker Lauenroth, Marcus-André Deutsch, Claudio Velasquez-Silva, Henrik Fox, and et al. 2024. "Different ECLS Pump Configurations for Temporary Right Ventricular Assist Device in LVAD Patients: A Retrospective Case–Control Study" Life 14, no. 10: 1274. https://doi.org/10.3390/life14101274

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Beyond Human Babesiosis: Prevalence and Association of Babesia Coinfection with Mortality in the United States, 2015–2022: A Retrospective Cohort Study

Paddy Ssentongo and Natasha Venugopal co-first authors.

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Paddy Ssentongo, Natasha Venugopal, Yue Zhang, Vernon M Chinchilli, Djibril M Ba, Beyond Human Babesiosis: Prevalence and Association of Babesia Coinfection with Mortality in the United States, 2015–2022: A Retrospective Cohort Study, Open Forum Infectious Diseases , Volume 11, Issue 10, October 2024, ofae504, https://doi.org/10.1093/ofid/ofae504

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The prevalence of Babesia coinfecting tick-borne zoonoses and mortality outcomes are not fully elucidated. The objective of the present study was to determine babesiosis coinfection prevalence rates and estimate the association with severe disease and mortality.

We queried the TriNetX database between 2015 and 2022 for patients with babesiosis. The prevalence of Babesia coinfecting tick-borne zoonoses was estimated. The analysis focused on babesiosis coinfection with Borrelia burgdorferi , ehrlichiosis, and anaplasmosis. The exposure was coinfection, and the control group was the Babesia -only group. The primary outcome was 90-day mortality from the diagnosis of Babesia . Secondary outcomes were prevalence of coinfection, association of coinfection with acute respiratory distress syndrome, multiorgan failure, and disseminated intravascular coagulation. A multivariable logistic regression model was employed to estimate the disease severity and mortality risk associated with coinfections.

Of the 3521 patients infected with Babesia , the mean age (SD) was 56 (18) years, 51% were male, and 78% were White. The frequency of overall malignancies, lymphomas, and asplenia was 19%, 2%, and 2%, respectively. Temporal distribution of coinfections followed the overall babesiosis pattern, peaking in the summer months. The prevalence of 1 or more coinfections was 42% (95% CI, 40%–43%). The rate of coinfection with Borrelia burgdorferi was the highest at 41% (95% CI, 39%–42%), followed by ehrlichiosis at 3.7% (95% CI, 3.1%–4.4%) and anaplasmosis at only 0.3% (95% CI, 0.2%–0.6%). Doxycycline was more likely to be prescribed in the coinfection group than the Babesia -only group (25% vs 18%; P < .0001). Overall, 90-day mortality was 1.4% (95% CI, 1.0%–1.8%). After adjusting for potential confounding factors, compared with the babesiosis-only group, the likelihood of 90-day mortality was lower in the coinfection group (adjusted odds ratio, 0.43; 95% CI, 0.20–0.91). Severe disease did not differ significantly between the 2 groups.

In this extensive study of >3000 patients with babesiosis in the United States, 4 in 10 patients had coinfecting tick-borne zoonoses. The prevalence rates of coinfection were highest with Borrelia burgdorferi, followed by ehrlichiosis, and lowest with anaplasmosis. Coinfection with other tick-borne infections was not associated with severe disease. It is plausible that this finding is due to the likelihood of treatment of coinfections with doxycycline. Future studies are needed to investigate the possible therapeutic benefits of doxycycline in babesiosis patients as, to date, no trials with doxycycline have been conducted in human patients with Babesia infections.

Human babesiosis is a tick-borne illness caused by the Apicomplexan intraerythrocytic parasites known as Babesia spp. [ 1 ]. Six different Babesia species, 3 in the United States alone, have been confirmed as human pathogens. These include Babesia crassa –like agent, Babesia divergens, Babesia duncani, Babesia microti, Babesia motasi, and Babesia venatorum [ 1 ]. Human babesiosis prevalence in the United States is on the rise, partly due to climate change influencing the distribution and population of vectors, and the predominant species is Babesia microti, which is endemic in the northeastern and northern Midwestern region [ 1–3 ]. Babesia microti is transmitted by the blacklegged tick vector Ixodes scapularis, although other tick species are vectors for other Babesia spp. [ 4 , 5 ]. Individuals with cellular immunodeficiency such as functional or anatomic asplenia and the elderly tend to have more severe disease and mortality, and among survivors, babesiosis complications are associated with a higher health burden including chronic fatigue, renal failure, and congestive heart disease, among others [ 3 , 6 , 7 ]. Clinical presentation can vary significantly, ranging from asymptomatic, mild disease to death via multiorgan dysfunction and depending on the degree of immunocompromise in the affected individual [ 4 ].

In the case of confirmed diagnosis of babesiosis, testing for other tick-borne illnesses such as Borrelia burgdorferi (the bacterium that causes Lyme disease), anaplasmosis, ehrlichiosis, hard-tick relapsing fever (caused by Borrelia miyamotoi ), and sometimes Powassan virus disease is often a common practice as the Ixodes scapularis tick vector can carry and transmit multiple organisms [ 5 , 8 ]. In >16 000 ticks collected from the entire United States that underwent molecular testing for pathogens, Borrelia burgdorferi was detected in 20% of Ixodes scapularis adult ticks, 11% of nymphs, and 5.1% of larvae [ 9 ]. The presence of Anaplasma phagocytophilum and Babesia microti was detected in 4% and 2% of Ixodes scapularis ticks, respectively. Nearly 1% of tested ticks were coinfected with Anaplasma phagocytophilum and Borrelia burgdorferi ; these accounted for the most coinfection. The prevalence of triple infections of Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia microti was only 0.1%. However, in the northeastern United States, the coinfection rate in tick vectors reached 28% of ticks tested [ 10 ], with a median range of 2%–16% and 0%–19% for adult and nymphal Ixodes ticks, respectively [ 11–13 ]. The most commonly reported coinfection was Borrelia burgdorferi with either Anaplasma phagocytophilum or Babesia microti.

Globally, studies have reported varying rates of tick-borne disease co-exposure in the human population [ 14 ]. In the United States, serological evidence has shown that 54% of patients with babesiosis test positive for immunoglobulin (Ig) G and IgM antibodies to spirochetes causing Lyme disease [ 15 ]. Furthermore, 24% of babesiosis-associated hospitalizations list Lyme disease as a codiagnosis [ 16 ]. Despite the reported high prevalence of coinfecting tick-borne zoonoses, disease severity and the mortality risk of babesiosis coinfection need further characterization [ 11 ]. Various studies have explored the prevalence and impact of babesiosis-associated coinfection [ 17–20 ]. Previous reports of concurrent human Lyme disease and babesiosis suggest that coinfection may exacerbate illness [ 20–22 ]. For example, 50% of patients with concurrent Lyme disease and babesiosis were symptomatic for 3 months or longer compared with 4% of patients with Lyme disease alone [ 20 ]. These patients experienced more symptoms and a more persistent episode of illness than did those experiencing Babesia infection alone. In contrast, there is no evidence that Babesia infection or anaplasmosis enhances the dissemination of B. burgdorferi into the joint, nerve, or heart tissue [ 17 ]. Likewise, animal studies have provided mixed findings with respect to the association of coinfection with disease dissemination.

Some of the coinfection studies have been limited by small sample sizes. The hypothesis of the present study is that individuals with Babesia who are coinfected with other tick-borne infections have severe disease and higher mortality risk. The objective of this study was to characterize babesiosis coinfection prevalence rates and estimate severe disease and mortality outcomes using a large diverse representative sample size of the US population.

Data Source

We obtained all cases of babesiosis using the International Classification of Diseases, 10th Revision (ICD-10), code B60.0 from the TriNetX database between 1980 and 2023. The data used in this study were collected on August 25, 2023, from the TriNetX Research Network. TriNetX operates as a federated, multi-institutional health research network, aggregating de-identified data from Electronic Health Records across a diverse range of health care organizations [ 23 ]. This network includes academic medical centers, specialized physician practices, and community hospitals, representing >250 million patients from >120 health care organizations [ 23 ]. As a federated network, TriNetX received a waiver from the Western Institutional Review Board (IRB) as only aggregated counts and statistical summaries of de-identified information were used; no protected health information was received, and no study-specific activities were performed in this retrospective analysis. This report follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines for reporting observational studies in epidemiology [ 24 ].

To reduce the risk of misclassification due to the differences between ICD-9 and ICD-10 codes in identifying Babesia cases, we excluded all ICD-9 cases, which is equivalent to data before October 1, 2015, as the ICD-10 came into effect in October of 2015 [ 25 ]. The remaining sample size consisted of 3521 individuals ( Figure 1 ). We extracted demographics directly from the database including age in years, sex, race/ethnicity, and obesity (body mass index in kg/m 2 of 30 and above). Next, we extracted antimicrobial treatment types including azithromycin and atovaquone, clindamycin, quinine, and doxycycline using RxNorm codes. As presented in Supplementary Table 1 , we extracted potential confounding comorbidities (congestive heart failure, chronic obstructive pulmonary disease, diabetes, hypertension, chronic kidney disease, all malignancies, lymphoma, rheumatoid arthritis, obesity, HIV, depression) and surrogate markers of babesiosis severity (anemia and blood transfusion), as well as additional factors known to influence severe babesiosis (asplenia). Of note, we also extracted parasitemia density, which we could not use for analysis as few records were available. Coinfections were defined as babesiosis infection (ICD-10: B60.0) with 1 or more additional tick-borne infections: Borrelia burgdorferi , ehrlichiosis, and anaplasmosis [ 26 ]. The coinfection group was created by the authors using the ICD-10 codes for Lyme disease (A69.20), ehrlichiosis (A77.40), and anaplasmosis (A79.82). A complete list of ICD-10 codes including potential confounding factors and other secondary outcomes can be found in Supplementary Table 1 .

Study flowchart. Abbreviation: ICD-9/10, International Classification of Diseases, 9th/10th Edition.

Statistical Analysis

On the basis of previously published mortality data among babesiosis patients [ 27 ] and with a sample size of 3521 patients, we consistently had sufficient power (>0.90) to detect the effect size (odds ratio) for mortality, ranging from 0.30 to 0.60. A power analysis was conducted using PASS, version 12 (NCSS, Kaysville, UT, USA) [ 28 , 29 ]. Details of the power analysis are provided in Supplementary Text 1 . Data were summarized using means and SDs for continuous variables. Categorical variables were summarized using frequency distributions, reporting numbers and percentages for each variable.

The primary outcome was a 90-day mortality rate comparison between coinfecting tick-borne zoonoses and the Babesia -only group. The rationale of 90-day mortality stems from a babesiosis and Lyme disease study that demonstrated that symptoms in coinfected patients lasted >3 months; spirochete-specific DNA was detected at a median of 91 days in coinfected patients [ 20 ]. However, as bloodstream infection–attributable death rates decay significantly over the first 2 weeks following infection, 30- rather than 90-day composite end points have been proposed [ 30 ]. Therefore, 30-day mortality was also estimated in a post hoc analysis.

Secondary outcomes were mortality risk ratio of the coinfected group vs the Babesia -only group in regard to acute respiratory distress syndrome (ARDS), multiorgan failure (MOF), and disseminated intravascular coagulation (DIC). Multivariable logistic regression models were conducted while adjusting for age, sex, asplenia, congestive heart failure, chronic obstructive pulmonary disease, diabetes, hypertension, chronic kidney disease, malignancy, lymphoma, rheumatoid arthritis, obesity, depression, blood loss anemia, and blood transfusion.

Because the association of babesiosis with severe disease has been shown to be modified by asplenia and anemia severity [ 3 ], we tested for potential interactions of babesiosis coinfection with asplenia and anemia severity in the regression analysis. Prevalence and associated 95% CIs were estimated using an exact binomial test.

To determine the temporal association between frequencies of babesiosis cases, we fitted generalized linear mixed-effects models assuming a Poisson distribution with log link function. We fitted time (from 2015 through 2022). A log-linked linear fit with time was estimated as log(μ) = β 0 + β (T), where μ was the expected number of babesiosis cases, T was time, and β 0 and β were model parameters. All statistical analysis and figures were created using R statistical software (R Team, Vienna, Austria). Statistical significance was set at <.05.

A total of 3521 patients were analyzed. Table 1 shows a demographic summary of the study cohort. The mean age of the study participants (SD) was 56 (18) years, 51% were male, and the majority of the patients were White (78%), followed by Blacks and Asians (2% each). Regarding the frequency of coinfection, 41% were coinfected with Borrelia burgdorferi, 4% with ehrlichiosis, and 0.3% with anaplasmosis ( Figure 2 ). In terms of comorbidities, 16% of patients were obese, 2% had asplenia, 11% had rheumatoid arthritis, 18% had chronic obstructive pulmonary disease, 42% had hypertension, 14% had diabetes, and 0.3% had HIV. The overall malignancy rate was 19%, and 2% had lymphoma (0.34% Hodgkin's and 1.6% non-Hodgkin's). Over three-quarters of Babesia patients resided in the Northeastern United States and 9% in the Midwestern region, 8% in the Southern region, and 3% in the Western region. There was a statistically significant upward slope of the generalized linear model with dependency on time of the temporally averaged babesiosis cases over the 8-year interval in the United States (slope of 0.082, corresponding to an exp [0.082 = 9% increase in babesiosis per year between 2015 through 2022]; P < .0001; slope standard error = 0.009) ( Figure 3 ). Seasonality of cases was observed, with higher rates of cases observed between June and September ( Supplementary Figure 1 ).

Prevalence of babesiosis coinfections.

Temporal distribution of babesiosis cases in the United States (2015–2022). Cases peaked in June through September.

Baseline Characteristics of Babesiosis Patients, Overall and According to Coinfection Status

Obesity was extracted from the database. Per the Centers for Disease Control and Prevention, obesity was defined as body mass index in kg/m 2 of 30 and above.

a One hundred two patients had parasitemia data.

Next, we compared the above sociodemographic and comorbidity distribution between the coinfection and Babesia -only groups. The Babesia -only patients were older (58 years vs 54 years), more likely to be male than female (55% vs 46%), more likely to have anatomical asplenia (2.5% vs 1.4%), chronic kidney disease (10% vs 8%), and congestive heart disease (11% vs 8%), and more likely to be treated with atovaquone (44% vs 39%) and azithromycin (52% vs 47%). Conversely, the babesiosis-only group was less likely to be treated with doxycycline (18% vs 25%) and less likely to be diagnosed with rheumatoid arthritis than the coinfection group.

Next, the multivariable logistic regression model was fitted to estimate the risk of mortality between those with coinfection and those without coinfection. In the full adjusted model, the likelihood of mortality was lower in the group of patients with coinfections (adjusted odds ratio [aOR], 0.43; 95% CI, 0.20–0.92) ( Table 2 , Figure 4A ). When we limited coinfection to only Borrelia burgdorferi , the association was similar to the primary analysis of any coinfection ( Figure 4B ). However, due to the small sample size, no association was observed when an analysis was conducted between coinfection with ehrlichiosis (n = 131) and anaplasmosis (n = 11) ( Figure 4C and D ). In sensitivity analysis of 30-day mortality, although in a univariate logistic regression model coinfection was associated with lower mortality (OR, 0.40; 95% CI, 0.17–0.94) ( Supplementary Figure 2 ), in the fully adjusted multivariable logistic model the association did not reach statistical significance (aOR, 0.62; 95% CI, 0.26–1.50).

Cumulative incidence graphs showing the association of coinfection and 90-day mortality for overall coinfection (A), coinfection with Borrelia burgdorferi (B), coinfection with ehrlichiosis (C), and coinfection with anaplasmosis (D).

Multiple Logistic Regression for the Primary Analysis for the Primary Outcome of Association of Coinfection and 90-Day Mortality

Major confounding variables included in the model were demographics (age, sex), comorbidities (congestive heart failure, chronic obstructive pulmonary disease, diabetes, hypertension, chronic kidney disease, lymphoma, rheumatoid arthritis, obesity, depression), surrogate markers of babesiosis severity (anemia, and blood transfusion), and factors known to influence severe babesiosis (asplenia).

a Coinfection was defined as babesiosis with 1 or more additional tick-borne infections: Lyme disease, anaplasmosis, or ehrlichiosis. Effect estimates of the confounding variables are also reported in the table to show other important clinical variables that could be associated with mortality in babesiosis populations.

Next, we estimated the association between coinfection status and secondary outcomes: acute respiratory distress syndrome, multiorgan failure, and disseminated intravascular coagulopathy. These results are summarized in Figure 5A–C . There was no association between coinfection status and acute respiratory distress syndrome (aOR, 1.56; 95% CI, 0.68–3.56), multiorgan failure (aOR, 0.82; 95% CI, 0.65–1.05), or disseminated intravascular coagulopathy (aOR, 0.99; 95% CI, 0.35–2.70).

Association of coinfection with secondary outcomes from multivariable logistic regression models. A, Acute respiratory distress syndrome. B, Disseminated intravascular coagulopathy. C, Multiorgan failure. Covariates adjusted in the model include demographics (age, sex), comorbidities (congestive heart failure, chronic obstructive pulmonary disease, diabetes, hypertension, chronic kidney disease, lymphoma, rheumatoid arthritis, obesity, depression), surrogate markers of babesiosis severity (anemia and blood transfusion), and factors known to influence severe babesiosis (asplenia). Abbreviations: ARDS, acute respiratory distress syndrome; COPD, chronic obstructive pulmonary disease; CHF, congestive heart failure; DIC, disseminated intravascular coagulopathy; MOF, multiorgan failure.

In the present study of >3000 babesiosis patients, nearly 4 in 10 patients with Babesia had coinfecting tick-borne zoonoses, including Borrelia burgdorferi , ehrlichiosis, and anaplasmosis. This study does not support our hypothesis that Babesia patients coinfected with other tick-borne pathogens have a higher mortality risk. Also, this study does not specifically support that coinfected patients have a higher severity of disease. The observed association was not cofounded by major chronic comorbidities.

Studies investigating the effect of babesiosis coinfections have reported conflicting findings [ 18–20 ]. Mareedu and colleagues characterized risk factors for severe infection and hospitalization among babesiosis patients in northern Wisconsin [ 18 ]. They found an overall coinfection rate of 37%, with Borrelia burgdorferi documented as the highest rate of coinfection at 30%, followed by anaplasmosis at 4.5%, and both Borrelia burgdorferi and anaplasmosis at 2.3%. Our findings are in agreement with those of Mareedu et al., showing similar coinfection prevalence and that coinfection did not lead to higher severity of disease. In their study, coinfection with Borrelia burgdorferi or anaplasmosis was associated with a 27% lower risk of hospitalization (risk ratio, 0.73; 95% CI, 0.53–0.99; P = .03) [ 18 ]. The frequency of disease severity and duration of antibiotic treatment were similar between the babesiosis-only and coinfection groups. It was postulated that concurrent use of doxycycline (and other Lyme disease treatment) could have therapeutic benefit in Babesia infection, although such a therapeutic effect has not been elucidated in clinical trials. Additionally, another study found no association between co-exposure to B. burgdorferi and B. microti and increased Lyme disease severity [ 17 ]. Conversely, a study based in Rhode Island and Connecticut found that symptom quantity and duration were increased in patients with coinfection with babesiosis/Lyme disease compared with patients with either babesiosis or Borrelia burgdorferi alone [ 20 ].

The pathophysiological mechanisms for the lack of severe disease in patients with Babesia coinfection are not fully elucidated. Murine models of concurrent Borrelia burgdorferi and Babesia microti have been inconclusive. In a murine model study by Moro et al., the severity of disease from coinfection was strain dependent; no differences in severity of symptoms were found in coinfected C3H/HeJ mouse cohorts, but coinfected BALB/c mice had a significant increase in arthritis severity at day 30 [ 31 ]. In the murine model strain that demonstrated increased disease severity in the coinfected group, it is believed that a significant reduction in expression of the cytokines interleukin (IL)-10, and IL-13 in the spleen resulted in more severe disease and duration of infection in coinfected mice [ 31 ]. These findings suggest that genetic variation may be a determinant in symptom severity among coinfected individuals. Additionally, in a murine study by Bhanot and Parveen, coinfection with B. burgdorferi and B. microti attenuated Babesia spp. parasite growth while exacerbating Lyme disease symptoms [ 32 ]. Another murine model found that the immune activity in response to Borrelia burgdorferi, such as increased activation of Th1 and Th17 cells, decreased the Babesia parasite burden [ 33 ]. A high level of gamma interferon (IFN-γ) produced by CD4 + T cells has been shown to play a key role in the resolution of acute Babesia infection and to be involved in protection against other intracellular parasites [ 34 ].

Babesiosis has a varying, nonspecific presentation, ranging from asymptomatic infection or mild symptoms to death via multiorgan dysfunction. For example, babesiosis can cause anemia, fever, chills, headache, and sweats, but these presentations can be associated with a plethora of other conditions and, thus, are not specific to babesiosis. Conversely, Borrelia burgdorferi has a distinct and well-known temporal symptom profile, including skin, joint, cardiac, and neurological findings. Initial onset of symptoms usually occurs between 1 and 2 weeks after a tick bite in the case of Borrelia burgdorferi , which can be earlier than the onset of babesiosis symptoms, which is typically between 1 and 6 weeks following tick bite. As such, in coinfected patients, concern for Borrelia burgdorferi could lead to evaluation for tick-borne illnesses, resulting in more prompt diagnosis of babesiosis compared with patients with babesiosis alone. This would allow for earlier initiation of treatment in coinfected patients and therefore improve outcomes compared with patients with babesiosis alone, whose diagnosis and treatment might be delayed due to the patients’ initial presentation being unclear.

The mortality rate in our cohort was low at 1.4%. In the literature, the mortality rate of babesia ranges from 1.6% to 13% depending on the severity of the disease. In our cohort, ∼50% of patients received azithromycin and atovaquone, the mainstay antimicrobial treatment for babesiosis patients. Clindamycin was prescribed in ∼15% of the cases, and doxycycline was more likely to be prescribed for the coinfection group than the Babesia- only group. The treatment of Babesia infection depends on disease severity, with a combination of azithromycin and atovaquone as the preferred treatment for symptomatic individuals with mild to moderate disease [ 35 ]. Oral clindamycin and quinine are an alternative option, although they are associated with higher risk of adverse events (including diarrhea, rash, tinnitus, vertigo, and decreased hearing) compared with azithromycin and atovaquone (duration of therapy of 7–10 days) [ 35 ]. Severe babesiosis, defined as parasitemia ≥4% (but can also occur with parasitemia <4%), is associated with severe complications including multiple organ dysfunction. Persistent or relapsing disease is treated with intravenous azithromycin plus oral atovaquone or IV clindamycin plus oral quinine as the alternative. Red cell exchange transfusion is reserved for patients with parasitemia >10% or severe organ impairment (such as pulmonary, renal, or hepatic dysfunction) [ 36 ]. We did not observe a difference in terms of severe disease between the coinfection and Babesia- only patients in our study.

Our findings have potential clinical and public health implications. Health care providers should have a low threshold to examine carefully for an erythema migrans rash or test for other tick-borne confections among hospitalized patients with babesiosis, favoring presumptive treatment for Borrelia burgdorferi in this patient population. Therefore, the addition of doxycycline and other anti– Borrelia burgdorferi therapy to the most common Babesia spp. antimicrobial regimen of atovaquone and azithromycin could facilitate improved outcomes. It is important to note that doxycycline also has both in vitro and in vivo activity against Babesia gibsoni and Babesia canis ; however, activity against human babesiosis has only been described in isolated case reports [ 37–40 ]. To date, no trials with doxycycline have been conducted in human patients with Babesia infections. Conversely, Borrelia burgdorferi laboratory testing usually consists of Lyme disease antibody testing. This test provides limited sensitivity and specificity because the presence of antibodies may be delayed for several weeks after the onset of acute disease, and the presence of antibodies may be due to a previous infection. Thus, testing everyone who has babesiosis for Lyme disease would probably not be cost-effective and would create both false-positive and false-negative results. Lyme disease antibody testing might be more cost-effective for those who do not have erythema migrans rash but have clinical findings suggestive of Lyme disease, such as arthritis, carditis, or meningitis. Selective laboratory testing for other coinfections would also be appropriate in those with persistent symptoms despite anti- Babesia antimicrobial agents. Furthermore, coinfection of babesiosis patients, other than those with Lyme disease, is uncommon. For example, Powassan coinfection of babesiosis patients is very infrequent, and laboratory testing is not generally available. Laboratory testing for Powassan infection in babesiosis patients would be reserved for those with signs and symptoms of encephalitis.

Our study has several strengths, including the large sample size using real-world data and the inclusion of patients from most regions of the United States, particularly regions where Babesia is endemic or an emerging infection. Due to the large sample size, the study had adequate power to adjust for multiple potential confounding factors for the association between coinfecting tick-borne zoonoses and severe disease. However, the findings of the present study should be interpreted in light of some limitations. Although we adjusted for major confounding factors in the multivariable logistic regression models, we did not adjust for parasite burden. We were unable to find adequate parasitemia-level data in the TriNetX data set as just a few patients had these data available; the data were therefore not adequate for subgroup analysis. However, our statistical models included biomarkers of severe Babesia disease, such as anemia and the need for blood transfusion, which were surrogate biomarkers of severe babesiosis in the absence of parasitemia level. Additionally, it is plausible that there was residual confounding induced by comorbidities not included in the models.

In this extensive study of >3000 patients with babesiosis in the United States, the prevalence of coinfection was highest with Borrelia burgdorferi , followed by ehrlichiosis, and lowest with anaplasmosis. This study does not support our hypothesis that Babesia coinfection with other tick-borne pathogens is associated with higher severity of disease and higher mortality risk. Future studies are needed to investigate possible therapeutic benefit of doxycycline in babesiosis as to date no trials with doxycycline have been conducted in human patients with Babesia infections.

Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.

Author contributions . Dr. Ssentongo had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr. Ssentongo and Dr. Venugopal contributed equally as first authors. Concept and study design: Ssentongo. Acquisition of data from database: Ba, Zhang. Statistical analysis: Ssentongo, Chinchilli. Drafting of the manuscript: Ssentongo, Venugopal. Critical revision of the manuscript for important intellectual content: all authors. Obtained funding: Ssentongo.

Role of the funder/sponsor. The funding organization had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

Additional information. To facilitate replication of these findings, R code and data to reproduce the results in this article are archived at GitHub. The link to the GitHub code and data is https://github.com/ssentongojeddy/Babesia_Coinfection/tree/main .

Patient consent. Data are from the TriNetX database, a federated network, and received a waiver from the Western IRB as only aggregated counts and de-identified information were used. Additionally, the protocol of this study was reviewed and received a determination of non–human subjects research by the Penn State Institutional Review Board. The individual informed consent requirement was waived for this secondary analysis of de-identified data.

Financial support . This work was supported by start-up funds from the Department of Public Health Sciences, College of Medicine, Penn State University, which is part of the package for a tenure-track professorship (P.S.).

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