An overview of heart failure with preserved ejection fraction HFpEF

What is heart failure?
Heart failure is a condition that impairs the heart’s ability to pump blood effectively, resulting in symptoms such as breathlessness, fatigue, and fluid retention. While it is usually linked to lower ejection fraction, a significant proportion of individuals suffers from heart failure despite their ejection fraction falling within the normal or borderline range. This type is referred to as heart failure with preserved ejection fraction (HFpEF).

Defining HFpEF
Persons with HFpEF are characterized by the presence of heart failure symptoms yet have left ventricular ejection fraction (LVEF) that is normal or near-normal, typically defined as LVEF ≥50 percent. Despite the heart’s preserved pumping ability, patients still present with clinical manifestations of heart failure, thus necessitating additional diagnostic parameters. These additional parameters include elevated natriuretic peptide levels e.g., NT-Pro BNP, and advanced imaging techniques like tissue Doppler imaging via echocardiography to assess diastolic function and cardiac pressures.

Pathophysiology
Diastolic dysfunction is the defining feature of HFpEF, which includes impaired relaxation and increased stiffness of the left ventricle. This causes elevated filling pressures which lead to fluid accumulation in the lungs and systemic tissues, resulting in pulmonary and systemic congestion. Left unchecked, these pressures can result over time in structural changes to the heart such as left ventricular hypertrophy and atrial enlargement.

Obesity, along with diabetes, chronic kidney disease, hypertension, and HFpEF, form a complex web of conditions where one affects the other in one way or another. Obesity is often recognized as a major associated risk factor for HFpEF, but its prevalence goes unnoticed and this often results in these symptoms being attributed to being overweight alone. Other factors such as aortic stenosis and infiltrative diseases, for example, amyloidosis, also serve to further confuse the clinical picture of HFpEF.

Is it HFpEF or HFrEF?
HFpEF is very different from heart failure with reduced ejection fraction (HFrEF). Both conditions share symptoms but differ in pathophysiology and treatment strategies. The main problem in HFrEF is loss of systolic function, which is defined by loss of pumping activity of the heart characterized by low ejection fraction. Whereas in HFpEF there is preserved systolic function but impaired diastolic function.

HFpEF remains underdiagnosed and underappreciated despite having an approximate 50 percent representation of heart failure cases. The lack of appreciation is misunderstanding that a normal ejection fraction excludes heart failure. This misconception leaves many patients to wait unnecessarily for long periods of time without appropriate diagnosis or treatment. Evidence based practice  therapies in HFrEF have significantly improved outcomes. However, unlike HFrEF, HFpEF has no real proven treatment options, which is the main problem with clinical management.

Clinical presentation of HFpEF
The major presenting symptoms of a patient with HFpEF are exertional dyspnea, orthopnea and swelling of the peripheral body parts. These symptoms stem from congestion and elevated cardiac filling pressure. Physical examination may note the presence of pulmonary rales, jugular venous distension, and lower extremity edema. Importantly, those suffering from HFpEF are at risk of frequent hospital readmissions due to exacerbation of symptoms and often have medical care seeking behavior visiting multiple hospitals prior to being diagnosed.

At-risk populations
Older patients suffer more from HFpEF, and its prevalence is greater among females, to some extent due to their longer longevity. The disease is closely linked with comorbidities, either alone or in cluster. Among the afflicted, there is a notable presence of hypertension, diabetes, chronic kidney disease, and obesity. There is emerging evidence that some degree of systemic inflammation, characteristic of some rheumatologic disorders, may predispose someone to develop HFpEF, highlighting the need for careful screening in these populations.

Treatment strategies
The treatment for HFpEF focuses on symptom management, dealing with any associated comorbidities, and addressing the pathophysiological factors of the condition. Diuretics like furosemide or bumetanide’s are commonly prescribed in treating fluid overload and congestion. However, excessive volume depletion and hypotension should be monitored to avoid risks.

Recent HFpEF specific treatments promise to improve outcomes for patients. These include sodium-glucose cotransporter-2 (SGLT2) inhibitors for symptom relief. It has also led to a reduction in hospitalizations. Additionally, the use of mineralocorticoid receptor antagonists (MRAs) has also increased, and particularly finerenone has shown to be efficient in mitigating fibrosis and reducing cardiac remodeling, thus managing HFpEF.

One of the main strategies of HFpEF management is addressing comorbidities. On top of weight management via lifestyle changes, optimal blood pressure and blood sugar control is imperative. Additionally, supervised exercise programs and cardiac rehabilitation have proved to be effective in improving functional capacity and quality of life. Emerging therapies, such as glucagon-like peptide-1 (GLP-1) receptor agonists, offer potential in simultaneously addressing HFpEF and the associated obesity, making it a promising option for future treatment.

The important role of SGLT2 inhibitors in heart failure treatment
SGLT2 inhibitors were developed for the management of diabetes but recently, they have become an important treatment option for HF, especially HFpEF. Their exact mechanism in HF is still being studied, but it seems that attenuating inflammation and fibrosis; and improving energy utilization at the cellular level have positive effects on the stiffening of the heart and blood vessels.

There is solid evidence from clinical trials regarding the use of empagliflozin and dapagliflozin (both SGLT2 inhibitors) in HFpEF, showing reduction in hospitalizations and improved functional outcomes with few side effects. While they are mostly safe, the main concern is for genitourinary infections and, in rare cases, ketoacidosis. Infection risk can be minimized through adequate hygiene. There is also a small, albeit important, risk of developing ketoacidosis—a condition where the body produces a lot of acid following a stressful period such as fasting, bouts of illness or undergoing major surgical procedures and patients should be warned to withhold their SGLT2 inhibitors if anticipating any of the above. SGLT2 inhibitors are well tolerated and effective medications in the management of HFpEF, which has changed the treatment paradigm of HFpEF.

Significance of comorbidities
Management of comorbidities is important in the treatment of HFpEF. For example, obesity is associated with increased visceral adipose tissue and inflammation, which contributes to myocardial stiffness and vascular dysfunction. The integration of advanced imaging techniques such as cardiac computed tomography (CT) and magnetic resonance imaging (MRI) have greatly improved the understanding of these processes and has enabled the early identification and treatment of the affected areas.

Poorly controlled hypertension and diabetes add to the burden [of obesity] by causing additional cardiac and peripheral vascular injury via endothelial dysfunction and other forms of oxidative stress. These pathologies require strict control to avoid worsening HFpEF. While it is critical to understand that inflammation is a major driving component, it must also be appreciated that HFpEF is a complex disease dominated by other irreversible factors such as aging.

Conclusion
HFpEF is a complicated and often overlooked type of heart failure distinguished by diastolic dysfunction alongside several other comorbidities. Despite the commonness of HFpEF, it remains a significant diagnostic and therapeutic challenge. Efforts to understand and improve the clinical management of this condition continues with the hope of better patients outcomes.

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