Heart Failure with Preserved Ejection Fraction (HFpEF)

Definition and Background of HFpEF

Heart Failure with Preserved Ejection Fraction (HFpEF) is a condition characterized by heart failure symptoms, such as shortness of breath and fatigue, with a preserved ejection fraction. The ejection fraction refers to the amount of blood pumped out of the heart’s left ventricle during each heartbeat. In HFpEF, the heart muscle becomes stiff and less compliant, leading to impaired filling of the ventricles and reduced cardiac output.

Understanding the etiology and background of HFpEF is crucial for proper management and treatment. HFpEF is different from heart failure with reduced ejection fraction (HFrEF), where the heart’s muscle is weak and fails to contract effectively.

HFpEF primarily affects the elderly population and is commonly associated with several comorbidities such as hypertension, obesity, diabetes mellitus, coronary artery disease, valvular heart disease, atrial fibrillation, chronic kidney disease, and obstructive sleep apnea. These risk factors contribute to the development and progression of HFpEF.

The prevalence of HFpEF is significant and accounts for almost half of all cases of heart failure. As the population ages and the prevalence of risk factors increases, the incidence of HFpEF is expected to rise further. Therefore, it is vital to accurately diagnose and effectively manage HFpEF to improve patient outcomes and reduce the burden of heart failure.

Risk Factors and Prevalence of HFpEF

Risk Factors

Several risk factors contribute to the development of HFpEF. These include:

  • Hypertension: High blood pressure can lead to the thickening and stiffening of the heart muscle.
  • Obesity: Excess body weight can increase the workload on the heart and contribute to the development of HFpEF.
  • Diabetes Mellitus: Individuals with diabetes have an increased risk of developing heart failure, including HFpEF.
  • Coronary Artery Disease: The narrowing of the blood vessels that supply the heart can impair its function and lead to HFpEF.
  • Valvular Heart Disease: Conditions such as aortic stenosis or mitral valve regurgitation can contribute to HFpEF.
  • Atrial Fibrillation: This irregular heart rhythm can lead to abnormal blood flow and contribute to the development of HFpEF.
  • Advanced Age: Older individuals are more likely to develop HFpEF due to the natural aging process and underlying health conditions.
  • Female Sex: Women have a higher prevalence of HFpEF compared to men.
  • Comorbidities: Chronic kidney disease and obstructive sleep apnea can further increase the risk of HFpEF.


HFpEF is a prevalent condition, accounting for almost half of all cases of heart failure. Its prevalence is expected to rise further due to the aging population and the increasing prevalence of risk factors. It is estimated that around 50% of heart failure cases are attributed to HFpEF. The condition is more common in the elderly, with a higher prevalence in individuals over the age of 65. Additionally, women are more likely to develop HFpEF compared to men. The increasing prevalence of risk factors like hypertension, obesity, and diabetes also contributes to the rising incidence of HFpEF.

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Clinical Presentation and Diagnosis of HFpEF

HFpEF can present with a variety of clinical symptoms, which may vary from person to person. It is essential to consider these symptoms carefully and conduct a thorough diagnostic evaluation to accurately diagnose HFpEF. The following are the key aspects of clinical presentation and diagnosis:


Symptoms commonly associated with HFpEF include:

  • Exertional dyspnea (shortness of breath with physical activity)
  • Fatigue
  • Orthopnea (difficulty breathing while lying flat)
  • Paroxysmal nocturnal dyspnea (sudden shortness of breath during sleep)
  • Fluid retention leading to peripheral edema (swelling in the legs and ankles)

Physical Examination Findings

During a physical examination, certain findings may suggest the presence of HFpEF. These include:

  • Pulmonary crackles (abnormal lung sounds indicating fluid buildup in the lungs)
  • Elevated jugular venous pressure (indicative of increased pressure in the heart)
  • Peripheral edema (swelling in the legs and ankles)

Challenges in Diagnosis

Diagnosing HFpEF can be challenging due to its non-specific symptoms, which can overlap with those of other conditions. It is crucial to differentiate HFpEF from conditions such as chronic obstructive pulmonary disease, obesity, and deconditioning, as they may manifest with similar symptoms.

Diagnostic Tests

To confirm the diagnosis of HFpEF and exclude other potential causes, various diagnostic tests are commonly employed:

  • Echocardiography: This imaging technique evaluates the structure and function of the heart, including the measurement of ejection fraction, left ventricular thickness, and diastolic function.
  • Cardiac magnetic resonance imaging (MRI): MRI provides detailed images of the heart, allowing assessment of cardiac structure and function.
  • Exercise stress testing: This test evaluates the heart’s response to physical activity, helping assess exercise capacity and identifying any abnormalities.
  • Cardiac catheterization with measurement of pulmonary capillary wedge pressure: This invasive procedure measures pressures within the heart chambers, aiding in the diagnosis and assessment of HFpEF.

It is crucial to perform a comprehensive evaluation, considering both the patient’s symptoms and the results of diagnostic tests, to arrive at an accurate diagnosis of HFpEF. Early and accurate diagnosis allows for timely management and implementation of appropriate treatment strategies.

Pathophysiology and Mechanisms of HFpEF

Heart Failure with Preserved Ejection Fraction (HFpEF) is characterized by impaired diastolic filling and increased ventricular stiffness. Several complex mechanisms contribute to the pathophysiology of HFpEF:

  1. Left Ventricular Hypertrophy: In HFpEF, the heart muscle undergoes structural changes, leading to increased thickness and stiffness of the left ventricle.
  2. Abnormal Relaxation and Compliance: The myocardium loses its ability to relax and become compliant during diastole, resulting in impaired filling of the ventricles.
  3. Increased Extracellular Matrix Deposition: Excessive deposition of collagen and other proteins in the heart tissue further contributes to ventricular stiffness.
  4. Impaired Microvascular Function: Dysfunction of the small blood vessels within the heart can impair blood flow and nutrient delivery to the myocardium.
  5. Systemic Inflammation: Chronic inflammation throughout the body can affect the heart, leading to fibrosis and remodeling of the cardiac tissue.

These underlying mechanisms interact and contribute to the development and progression of HFpEF. The stiff ventricles result in impaired filling during diastole, reducing the amount of blood pumped out of the heart with each heartbeat. This decreased cardiac output leads to the characteristic symptoms of heart failure, such as shortness of breath and fatigue.

Understanding the specific pathophysiological processes involved in HFpEF is crucial for developing targeted therapeutic interventions. By targeting these mechanisms, it may be possible to improve diastolic function, reduce ventricular stiffness, and ultimately improve outcomes for patients with HFpEF.

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Management and Treatment Options for HFpEF

Lifestyle Modifications

  • Implement sodium and fluid restriction to manage fluid retention.
  • Encourage weight management to alleviate strain on the heart.
  • Promote regular exercise within individual capacity to improve overall cardiovascular health.

Pharmacological Therapy

  • Diuretics: Help in reducing fluid retention and relieving symptoms of congestion.
  • Beta-blockers: Control heart rate, improve ventricular function, and manage symptoms.
  • Angiotensin-converting enzyme inhibitors/Angiotensin receptor blockers: Promote vasodilation, reduce afterload, and improve cardiac function.
  • Mineralocorticoid receptor antagonists: Aid in reducing fluid retention and decreasing ventricular stiffness.
  • Sacubitril/Valsartan: A specific drug combination that may be considered in certain cases to improve outcomes.

Addressing Comorbidities

  • Manage and treat hypertension, obesity, diabetes mellitus, coronary artery disease, valvular heart disease, and other underlying conditions contributing to HFpEF.
  • Address chronic kidney disease and obstructive sleep apnea, which can further increase the risk of HFpEF.

Fluid Status Management

  • Monitor and maintain optimal fluid status to prevent congestion and exacerbation of symptoms.
  • Adjust diuretic therapy as needed to achieve an appropriate balance.

Atrial Fibrillation Control

  • Implement strategies to control heart rate in case of atrial fibrillation, as it can worsen symptoms and contribute to HFpEF progression.

Overall, HFpEF management requires a comprehensive approach targeting different aspects of the disease. It involves a combination of lifestyle modifications, pharmacological therapy, addressing comorbidities, monitoring fluid status, and controlling heart rate in atrial fibrillation cases. With proper management, individuals with HFpEF can experience symptom improvement, enhanced quality of life, and reduced risk of complications. Continued research and clinical trials are essential to develop more effective treatments for HFpEF.

Monitoring and Prognosis of HFpEF

Regular monitoring and follow-up are crucial for patients with HFpEF to assess their symptoms, optimize medication regimens, and detect any disease progression or complications. Here are important aspects of monitoring and understanding the prognosis of HFpEF:

Clinical Assessment

Clinical assessment plays a significant role in monitoring HFpEF patients. It involves evaluating their symptoms, such as shortness of breath, fatigue, fluid retention, and exercise tolerance. Assessing vital signs, including heart rate and blood pressure, can provide valuable information about the patient’s condition. Regular physical examinations can help identify any changes in lung sounds, jugular venous pressure, and peripheral edema.


Echocardiography is a non-invasive diagnostic test that uses ultrasound waves to create images of the heart. It is instrumental in monitoring HFpEF patients by assessing various parameters of cardiac structure and function. Echocardiographic measurements, such as left ventricular diastolic function, left atrial size, and estimated pulmonary artery pressures, can provide valuable insights into the progression of HFpEF and guide treatment decisions.

Laboratory Investigations

Laboratory investigations play a crucial role in monitoring HFpEF patients. Natriuretic peptides, such as B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), are biomarkers that can indicate the severity of heart failure and help in risk stratification. Serial measurements of natriuretic peptides can provide insights into disease progression and response to treatment. Additionally, renal function tests, including serum creatinine and estimated glomerular filtration rate (eGFR), are essential for monitoring kidney function, as impaired renal function is associated with worse outcomes in HFpEF.

Prognostic Markers and Risk Stratification

Recognizing prognostic markers and employing risk stratification tools are crucial for identifying HFpEF patients who may require more aggressive management and closer monitoring. Prognostic markers include natriuretic peptides, renal function, age, comorbidities (such as diabetes mellitus and chronic kidney disease), and exercise capacity. Risk stratification tools, such as the Seattle Heart Failure Model (SHFM) and the MAGGIC (Meta-analysis Global Group in Chronic Heart Failure) risk score, integrate various patient characteristics to estimate their prognosis and guide treatment decisions.

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It is essential to remember that HFpEF generally has a worse prognosis compared to heart failure with reduced ejection fraction. HFpEF patients have a higher risk of hospitalization and mortality. Therefore, regular monitoring and timely intervention are crucial in managing these patients effectively.

Emerging Therapies and Future Directions in HFpEF

  • Novel pharmacological agents: Researchers are investigating several promising treatments, including medications that target specific pathways involved in HFpEF. These drugs aim to improve diastolic filling, reduce ventricular stiffness, and enhance overall cardiac function. Examples of these novel pharmacological agents include selective heart rate-lowering agents, phosphodiesterase-5 inhibitors, and soluble guanylate cyclase stimulators.
  • Device-based therapies: Device-based interventions, such as cardiac resynchronization therapy (CRT) and implantable hemodynamic monitors, are being explored as potential treatment options for HFpEF. CRT involves the implantation of a device that coordinates the contractions of the heart’s chambers, which can help improve cardiac output and overall heart function. Implantable hemodynamic monitors provide real-time data on pulmonary artery pressures, allowing for early detection of fluid retention and optimization of medical therapy.
  • Modulating pathophysiological mechanisms: Future treatments for HFpEF may involve targeting specific pathophysiological mechanisms. Researchers are studying interventions aimed at reducing left ventricular hypertrophy, enhancing myocardial relaxation and compliance, and improving microvascular function. These approaches may include the use of peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, myosin activators, and anti-inflammatory agents.
  • Personalized medicine: The concept of personalized medicine is gaining attention in HFpEF research. By identifying specific biomarkers, genetic factors, and patient characteristics, clinicians can tailor treatment strategies to individual patients. This approach may help optimize therapeutic interventions and improve outcomes for patients with HFpEF.
  • Early diagnosis and prognosis: Efforts are underway to identify biomarkers that can aid in the early diagnosis and prognosis of HFpEF. Natriuretic peptides, such as B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), have shown promise in this regard. These biomarkers can help identify patients at higher risk of HFpEF and guide treatment decisions.
  • Multidisciplinary approaches: Recognizing the complex nature of HFpEF, multidisciplinary approaches are being explored to improve outcomes. Collaboration between cardiologists, nephrologists, endocrinologists, and other specialists can ensure comprehensive management of comorbidities and optimize overall care for HFpEF patients.
  • Research and clinical trials: Continued research and clinical trials are crucial for advancing our understanding of HFpEF and developing effective treatments. Ongoing studies are investigating the efficacy and safety of various therapies, and their results will contribute to the future management of HFpEF.

For more information on emerging therapies and future directions in HFpEF, please refer to the following sources:

  1. Circulation: Heart Failure – Emerging Therapies for Heart Failure With Preserved Ejection Fraction
  2. Journal of the American College of Cardiology – Treatment of Heart Failure With Preserved Ejection Fraction: Current Status and Future Directions
  3. European Society of Cardiology – Heart Failure With Preserved Ejection Fraction: Challenges and Future Directions

Stay informed about the latest research and developments in HFpEF by following reputable medical journals and cardiovascular societies.

Category: Cardiac Health