Unveiling the Enigma: Heart Failure with Preserved Ejection Fraction (HFpEF) in Children

Abstract

Diastolic dysfunction with impaired left ventricular filling leads to heart failure even when the systolic function is normal. Heart failure with preserved ejection fraction (HFpEF) is a well-recognized entity in adults but remains a more challenging condition to understand and diagnose in children. This review describes the unique landscape of HFpEF in children, emphasizing etiologies and prognostic factors that differ from those seen in adults. We explore the various underlying etiologies, from congenital heart defects to systemic diseases, and discuss their associated pulmonary hypertension profiles. Additionally, we cover the diagnostic challenges in pediatric practice and outline a simplified diagnostic algorithm to help clinicians identify and treat this often-overlooked disease. This work will enhance the awareness and knowledge of HFpEF in children, thus bringing about earlier diagnosis and better prognosis.

Introduction

Heart failure is an important threat to children's health, affecting both their quality of life and their long-term prognosis. Although impaired ventricular contraction or systolic dysfunction is an established cause of heart failure in children, it is increasingly evident that diastolic dysfunction or impaired ventricular relaxation and filling is also an important contributor even in the setting of normal systolic function. This form of HF, known as heart failure with preserved ejection fraction (HFpEF), is a common clinical entity in adults, representing nearly half of all HF hospitalizations. In the pediatric population, however, HFpEF remains underrecognized and poorly understood, despite its potential to have a significant impact on a child's health and well-being. This review will attempt to shed light on the unique challenges and opportunities presented by HFpEF in children, exploring its distinct etiologies, diagnostic complexities, and potential management strategies.

The Distinct Landscape of HFpEF in Children

It differs from adult HFpEF in several respects. Hypertension and coronary artery disease account for the largest proportion of adults with HFpEF, while the etiology in children is much more heterogeneous, encompassing the more diverse spectrum of cardiac and systemic diseases that prevail in this population. The diagnostic criteria and management strategy for HFpEF, for the most part, were adapted from adult information and thus should not be uniformly applied to the pediatric population; instead, strategies may need more personalized application. The developing child's heart would react differently in response to such stressors, which are indeed different from responses seen in adults.

Etiologies of HFpEF in Children: A Tapestry of Causes

The causes of HFpEF in children can be broadly categorized into several groups, each presenting its unique challenges:

• Congenital Heart Defects: Certain congenital heart defects, particularly those causing volume overload or pressure overload on the left ventricle, can predispose to diastolic dysfunction and HFpEF. Examples include ventricular septal defects (VSDs), atrial septal defects (ASDs), and coarctation of the aorta. These defects can alter the hemodynamics of the heart, leading to remodeling and impaired relaxation.

• Cardiomyopathies: Various cardiomyopathies, including hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), and left ventricular non-compaction (LVNC), can impair ventricular relaxation and filling, leading to HFpEF. HCM, characterized by thickening of the left ventricular walls, can stiffen the ventricle and impair relaxation. RCM, on the other hand, is marked by abnormal stiffness of the ventricular walls, restricting filling. LVNC, a condition where the left ventricular muscle doesn't develop properly, can also lead to diastolic dysfunction.

• Systemic Diseases: A range of systemic diseases can also contribute to HFpEF in children. These include chronic kidney disease, which can lead to fluid overload and cardiac remodeling; connective tissue disorders (e.g., systemic lupus erythematosus, scleroderma), which can affect the heart muscle and vasculature; and metabolic disorders (e.g., glycogen storage diseases), which can lead to abnormal accumulation of substances in the heart, impairing its function.

• Pulmonary Hypertension: Elevated pulmonary artery pressure can lead to right ventricular dysfunction, which can secondarily impair left ventricular filling and contribute to HFpEF. The specific pulmonary hypertension profiles associated with HFpEF in children warrant further investigation. The interplay between the right and left ventricles is crucial, and dysfunction in one can often affect the other.

• Other Causes: Other potential causes of HFpEF in children include Kawasaki disease, which can cause inflammation of the heart vessels; neuromuscular disorders (e.g., muscular dystrophies), which can affect the heart muscle; and certain cancer therapies (e.g., anthracyclines), which can have cardiotoxic effects.

Prognostic Factors in Pediatric HFpEF: Charting the Course

Understanding the prognostic factors associated with HFpEF in children is crucial for risk stratification and guiding management strategies. While data are limited, several factors are thought to influence the prognosis of HFpEF in children, including:

• Underlying Etiology: The specific underlying cause of HFpEF can significantly impact the prognosis. For example, children with certain congenital heart defects or cardiomyopathies may have a different clinical course compared to those with systemic diseases.

• Severity of Diastolic Dysfunction: The degree of diastolic dysfunction, as assessed by echocardiographic parameters, can provide insights into the severity of HFpEF and its potential impact on long-term outcomes.

• Pulmonary Hypertension: The presence and severity of pulmonary hypertension can significantly influence the prognosis of HFpEF in children, as it can contribute to both right and left ventricular dysfunction.

• Comorbidities: The presence of other medical conditions, such as chronic kidney disease or other systemic illnesses, can also affect the prognosis of HFpEF.

Pulmonary Hypertension and HFpEF: A Complex Interplay

The relationship between pulmonary hypertension and HFpEF in children is complex and bidirectional. Pulmonary hypertension can lead to right ventricular dysfunction, which can subsequently impair left ventricular filling and contribute to HFpEF. Conversely, chronic left ventricular diastolic dysfunction can also lead to elevated pulmonary venous pressure and secondary pulmonary hypertension. Further research is needed to fully characterize the different pulmonary hypertension profiles associated with HFpEF in children and to determine their impact on prognosis and treatment strategies.

Diagnostic Challenges: Recognizing the Hidden Threat

Diagnosing HFpEF in children can be challenging due to several factors:

• Non-Specific Symptoms: The symptoms of HFpEF, such as dyspnea, fatigue, and exercise intolerance, can be non-specific and may overlap with other common childhood illnesses. This can lead to delays in diagnosis.

• Lack of Awareness: HFpEF is often under-recognized in children, leading to delays in diagnosis and appropriate management. Many clinicians are more focused on systolic dysfunction.

• Diagnostic Tools: While echocardiography is the primary tool for assessing diastolic function, its interpretation in children can be challenging due to age-related variations in cardiac structure and function. Standardized pediatric-specific criteria are needed.

A Simplified Diagnostic Algorithm for Pediatric HFpEF

To improve the recognition and diagnosis of HFpEF in children, we propose a simplified diagnostic algorithm:

1. Clinical Suspicion: Maintain a high index of suspicion for HFpEF in children presenting with suggestive symptoms, particularly in the presence of known risk factors (e.g., congenital heart defects, cardiomyopathies, systemic diseases).

2. Echocardiography: Perform a comprehensive echocardiographic evaluation to assess left ventricular systolic and diastolic function. Pay close attention to parameters of diastolic function, such as mitral inflow patterns, tissue Doppler imaging, and left atrial size.

3. Exclusion of Other Causes: Exclude other potential causes of the child's symptoms, such as other forms of heart failure, respiratory diseases, or other systemic illnesses.

4. Consider Pulmonary Hypertension: Assess for the presence of pulmonary hypertension, as it can be a significant contributor to HFpEF in children.

5. Multidisciplinary Evaluation: In complex cases, a multidisciplinary evaluation involving cardiologists, pulmonologists, and other specialists may be necessary to establish the diagnosis and develop an appropriate management plan.

Management of Pediatric HFpEF: A Multifaceted Approach

The management of HFpEF in children should be tailored to the individual patient and should address the underlying cause of the diastolic dysfunction. Treatment strategies may include:

• Management of Underlying Disease: Treating the underlying condition contributing to HFpEF is crucial. This may involve surgical correction of congenital heart defects, medical management of cardiomyopathies, or treatment of systemic diseases.

• Symptom Management: Medications such as diuretics may be used to manage symptoms of congestion, such as dyspnea and edema.

• Lifestyle Modifications: Encouraging healthy lifestyle habits, such as regular exercise and a balanced diet, can be beneficial.

Conclusion

HFpEF in children, though not as common as in adults, is a clinical challenge of a different character. Increasing sensitivity to this diagnosis will make the diagnosis at an earlier stage of the disease and its appropriate management crucial. In this regard, further studies may be needed to develop diagnostic criteria to better identify the prognostic factors for HFpEF and the proper therapy for this population of children for improved outcomes. Improved collaboration between pediatric cardiologists and other specialists will be crucial in improving the care of these children with HFpEF.