Heart Failure with Preserved Ejection Fraction

HFpEF, diastolic heart failure

Heart failure with preserved ejection fraction is a complex condition affecting millions of people worldwide, where the heart’s pumping ability appears normal but the muscle becomes stiff and cannot relax properly to fill with blood, leading to symptoms that significantly impact daily life.

Table of contents

• What is Heart Failure with Preserved Ejection Fraction?
• How Common is This Condition?
• Causes and Risk Factors
• How the Condition Affects the Heart
• Signs and Symptoms
• Diagnosis
• Treatment and Management
• Prognosis

What is Heart Failure with Preserved Ejection Fraction?

Heart failure with preserved ejection fraction, also called HFpEF or diastolic heart failure, is a type of heart failure where the heart’s pumping ability appears normal but the heart cannot function properly to meet the body’s needs^[1][2]. In this condition, the left ventricle (the heart’s main pumping chamber) can squeeze and pump blood out normally, but it becomes stiff and cannot relax properly to fill with blood during the resting phase of the heartbeat^[3][5].

The condition is defined by having a left ventricular ejection fraction of 50% or greater^[2][7]. Ejection fraction is a measurement that shows how much blood inside the left ventricle is pumped out with each heartbeat. A normal ejection fraction is more than 55%, meaning that more than 55% of the total blood in the left ventricle is pumped out with each heartbeat^[5]. Although the ejection fraction may be normal in HFpEF, the heart has less blood inside it to pump out because the stiff muscle cannot fill properly^[5].

HFpEF is characterized by the presence of diastolic dysfunction, which refers to problems during the filling phase of the heartbeat, and elevated pressures in the left ventricle^[11]. The hallmark of this condition is a pulmonary capillary wedge pressure (the pressure in blood vessels of the lungs) of 15 mmHg or higher at rest or 25 mmHg or higher after exercise^[1].

How Common is This Condition?

Heart failure with preserved ejection fraction is a significant public health problem. Nearly half of all patients with heart failure have this type, with a normal ejection fraction^[1][2]. In the United States, HFpEF causes almost one-half of the 5 million cases of heart failure^[3]. The condition affects approximately 3 million people in the United States and up to 32 million people worldwide^[11].

The prevalence of this syndrome continues to increase in the developed world, likely because of the increasing prevalence of common risk factors^[1]. Heart failure is estimated to affect 1% to 3% of the global population, and HFpEF comprises at least 50% of all heart failure diagnoses^[2].

Causes and Risk Factors

There are many factors that can lead to heart failure with preserved ejection fraction. These factors can impair the left ventricle’s ability to fill properly with blood during the resting phase of the heartbeat^[5].

Important risk factors and common conditions associated with HFpEF include^[1][7]:

• Older age
• Female sex
• Hypertension (high blood pressure)
• Metabolic syndrome
• Renal dysfunction (kidney problems)
• Obesity
• Diabetes mellitus
• Coronary artery disease
• Chronic kidney disease

Hypertension is a particularly strong risk factor, with 80 to 90 percent of patients with HFpEF having high blood pressure^[1]. HFpEF is more common among older patients and women compared to other types of heart failure^[3][12].

Specific causes that can lead to HFpEF include^[5]:

• Natural effect of aging, as the heart muscle tends to stiffen with age
• Coronary artery disease, which can narrow the arteries that supply blood to the heart
• High blood pressure, which can cause the heart muscle to thicken in an effort to pump against the elevated pressure

The thickened heart muscle that results from these conditions limits the heart’s ability to relax and fill with blood^[5].

How the Condition Affects the Heart

Heart failure with preserved ejection fraction involves complex changes to the heart and blood vessels. Recent investigations suggest a more complex and varied disease process than previously understood^[1].

The disease involves abnormalities of both active ventricular relaxation (how the heart muscle relaxes) and passive ventricular compliance (how easily the heart muscle stretches)^[3][9]. These abnormalities lead to ventricular stiffness and higher pressures inside the heart during the filling phase^[9].

Multiple problems contribute to the condition, including^[1]:

• Problems with how the ventricle functions during both relaxation and contraction phases
• Inability of the heart rate to increase appropriately during activity (chronotropic incompetence)
• Stiffening of ventricular tissue
• Problems with the atrium (upper chamber of the heart)
• Pulmonary hypertension (high blood pressure in the lungs)
• Impaired ability of blood vessels to widen (vasodilation)
• Dysfunction of the endothelium (inner lining of blood vessels)

These abnormalities are often noted only when the circulatory system is stressed, such as during exercise^[1].

At the cellular level, cardiac muscle cells in patients with HFpEF are thicker and shorter than normal muscle cells, and the amount of collagen (a type of structural protein) is increased^[1]. The increased pressures inside the heart are transmitted through the atrium and into the blood vessels of the lungs, reducing lung flexibility^[9]. A combination of decreased lung flexibility and reduced cardiac output leads to the symptoms experienced by patients^[9].

As the heart muscle stiffens, it develops myocardial stiffening, reduced left ventricular flexibility, and impaired relaxation during the filling phase^[12]. Problems with left atrial myopathy (disease of the left atrium) are associated with worse blood flow characteristics, likely due to greater transmission of pressure^[12].

Signs and Symptoms

Heart failure with preserved ejection fraction should be suspected in patients with typical symptoms and signs of chronic heart failure^[3]. The most common symptom is difficulty breathing, particularly with exertion, but the condition can also affect exercise ability and cause fluid buildup in various parts of the body^[7].

Common symptoms include^[3][9]:

• Fatigue and weakness
• Dyspnea (shortness of breath), especially during activity
• Orthopnea (difficulty breathing when lying flat)
• Paroxysmal nocturnal dyspnea (sudden shortness of breath at night)
• Edema (swelling), particularly in the legs, ankles, and abdomen

Physical examination findings that suggest heart failure include^[3]:

• S3 heart sound (an extra heart sound heard with a stethoscope)
• Displaced apical pulse (the place where the heartbeat can be felt on the chest is shifted)
• Jugular venous distension (visible swelling of neck veins)

Patients with HFpEF demonstrate symptoms including dyspnea (shortness of breath), fatigue, and congestion, which are demonstrative of the heart’s inability to pump blood to the body commensurate with its needs, or to do so only at the cost of increased filling pressures^[2].

Diagnosis

The diagnosis of HFpEF is clinically challenging due to clinical variability and the fact that symptoms and abnormalities often appear primarily with exertion^[12]. The condition is defined by a left ventricular ejection fraction of at least 50%, in combination with elevated biomarkers and imaging findings showing structural or functional problems^[12].

Diagnosis is based on several factors^[7]:

• Symptoms (commonly shortness of breath)
• Clinical evidence of fluid buildup
• Measurement of natriuretic peptides (substances in the blood that indicate heart stress)
• Comprehensive echocardiography (ultrasound of the heart)

Findings on echocardiography showing normal ejection fraction with impaired diastolic function confirm the diagnosis^[3]. Up to 15% of patients can have normal levels of natriuretic peptides at rest, and the sensitivity of resting echocardiography is limited^[12]. The presence of an enlarged left atrium, with a preserved ejection fraction and normal mitral valve function, should prompt consideration of HFpEF^[12].

Measurement of natriuretic peptides, specifically brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP), is useful in evaluating patients with suspected heart failure with preserved ejection fraction in the outpatient setting^[3].

Scoring systems have been created to better recognize this syndrome. Two important diagnostic tools include^[11]:

• The 2018 H2FPEF score
• The 2020 HFA-PEFF algorithm

The H2FPEF score combines clinical and imaging characteristics and is a useful and clinically validated screening tool for patients presenting with shortness of breath^[12]. It can help guide clinicians to refer patients for exercise-based evaluation, either with invasive pressure measurements or stress testing with echocardiography^[12].

Right heart catheterization at rest and during exercise is the diagnostic gold standard for an accurate HFpEF diagnosis^[1]. However, direct measurement of pressures inside the heart during exercise is not widely available, is an invasive procedure, and should be kept for very selected cases^[1].

When considering HFpEF, it is important to exclude infiltrative cardiomyopathies (diseases where abnormal substances build up in the heart muscle). Approximately 13% of patients with HFpEF have cardiac amyloidosis^[12]. Patients with significantly increased wall thickness, low blood flow velocities measured by ultrasound, early-onset bilateral carpal tunnel syndrome, and other signs of amyloidosis should undergo more detailed evaluation^[12].

Treatment and Management

Despite the marked burden of HFpEF, treatment options have historically been limited. Multiple trials have not found medications to be effective treatments, except for diuretics^[3][9]. However, this paradigm has recently changed, and the unmet clinical need for HFpEF treatment has found a proper response with new classes of drugs^[11].

The goals of treatment are to reduce symptoms, reduce hospitalizations, and improve patients’ functional status^[7].

Management includes several key components^[7]:

• Identification and treatment of underlying causes and other health conditions
• Implementing lifestyle measures where appropriate (exercise, diet, weight control)
• Pharmacotherapy (medication treatment)

Medication Treatment:

Patients with congestive symptoms should be treated with a diuretic (medication that helps remove excess fluid)^[3][9]. Patients with HFpEF who have signs and symptoms of fluid overload should be treated with diuretics^[3].

A new class of drugs called sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) has shown beneficial effects across the whole spectrum of ejection fraction^[11]. These medications are now included in pharmacotherapy recommendations along with diuretics as needed^[7].

Other medications that may be considered include^[7]:

• Aldosterone antagonists (such as spironolactone)
• Angiotensin receptor-neprilysin inhibitors
• Angiotensin-II receptor antagonists

However, the use of nitrates, spironolactone, and angiotensin receptor blockers should be avoided in patients with HFpEF, and digoxin should also be avoided in patients 65 years and older who have HFpEF^[3][9].

Blood Pressure Management:

If hypertension is present, it should be treated according to evidence-based guidelines^[3][9]. Hypertension in patients with HFpEF should be treated according to evidence-based hypertension treatment guidelines^[3].

Exercise and Cardiac Rehabilitation:

Patients with HFpEF should be referred for endurance and resistance training^[3][9]. Exercise and treatment by multidisciplinary teams may be helpful^[3]. If you have heart failure, you should be offered an exercise-based cardiac rehabilitation programme^[15].

Treatment of Related Conditions:

Atrial fibrillation (an irregular heart rhythm) should be treated using a rate-control strategy and appropriate anticoagulation (blood thinning medication)^[3][9]. Revascularization (procedures to restore blood flow) should be considered for patients with heart failure with preserved ejection fraction and coronary artery disease^[3][9].

Common health conditions that occur with HFpEF include coronary artery disease, atrial fibrillation, obesity, diabetes, kidney problems, and pulmonary hypertension. These conditions should be considered in all patients and treatment optimized^[12].

Self-Care and Lifestyle:

Looking after yourself is very important if you have heart failure^[15]. Key self-care measures include:

• Having a healthy, balanced diet that includes plenty of fruits and vegetables, meals based on starchy foods, some protein sources, and low levels of saturated fat, salt, and sugar^[15]
• You may be given advice about dietary changes that can specifically help with heart failure, such as limiting the amount of fluid you drink^[15]
• If you smoke, stopping smoking can improve your overall health^[15]
• You can usually continue to drink alcohol if you have heart failure, but it’s advisable not to exceed the recommended limits of more than 14 alcohol units a week^[15]
• Everyone with heart failure should be offered the annual flu vaccine and the one-off pneumococcal vaccination^[15]

Most patients with HFpEF can be managed by general cardiologists. However, patients who are poorly responsive to diuretic therapy, have frequent hospitalizations for heart failure, worsening organ dysfunction, low blood pressure, and other conditions with heart failure should be cared for at a heart failure center by a heart failure specialist^[7].

Prognosis

Patients with HFpEF demonstrate increased all-cause mortality, reduced quality of life, and a significant economic healthcare burden^[2]. Patients are hospitalized approximately 1.4 times per year and have a mortality rate of approximately 15% per year^[11].

The prognosis is comparable to that of heart failure with reduced ejection fraction^[3][9]. Several factors worsen the prognosis, including^[3][9]:

• Higher levels of brain natriuretic peptide
• Older age
• A history of myocardial infarction (heart attack)
• Reduced diastolic function

Heart failure is frequently a progressive disease process, and progression is associated with decreased survival, regardless of underlying cause^[2].

You’ll have regular contact with your care team to monitor your condition at least every 6 months. These appointments may involve talking about your symptoms, discussing your medications and any side effects, and tests to monitor your health^[15]. It’s also a good opportunity to ask any questions you have or raise any other issues you’d like to discuss with your care team^[15].