Overview
Definition:
Pulmonary hypertension (PH) is a complex hemodynamic and pathophysiological condition characterized by elevated mean pulmonary arterial pressure (mPAP) > 20 mmHg at rest
In pediatrics, PH is often secondary to congenital heart disease, lung disease, or genetic conditions
The WHO classification groups PH into five categories, with Group 1 (PAH) being of primary interest for targeted therapies like sildenafil and ERAs.
Epidemiology:
The incidence and prevalence of PH vary significantly by age group and underlying etiology
Idiopathic PAH is rare in children
Congenital heart disease-associated PH and PH due to left heart disease are more common
Neonatal PH is a distinct entity with high morbidity and mortality
Specific data on sildenafil and ERA use in pediatric PH populations are still evolving.
Clinical Significance:
Pediatric PH, regardless of etiology, significantly impacts growth, development, and long-term health
It leads to right ventricular hypertrophy and failure, exercise intolerance, and can be life-limiting
Accurate diagnosis and timely, evidence-based management are crucial for improving outcomes, survival, and quality of life in affected children
Understanding the roles of different pharmacological agents like sildenafil and ERAs is vital for pediatric residents preparing for DNB and NEET SS exams.
Clinical Presentation
Symptoms:
Dyspnea on exertion
Fatigue
Chest pain
Syncope
Cyanosis
Poor feeding and failure to thrive in infants
Tachypnea
Wheezing in neonates with persistent PH.
Signs:
Right ventricular heave
Loud P2 heart sound
Tricuspid regurgitation murmur
Jugular venous distension
Hepatomegaly
Peripheral edema
Clubbing (in older children)
Hypoxemia.
Diagnostic Criteria:
Pulmonary hypertension is defined by mPAP > 20 mmHg at rest
Echocardiography is used for screening and estimating pulmonary pressures
Right heart catheterization (RHC) is the gold standard for confirming diagnosis, assessing severity, and guiding therapy
The 6th World Symposium on Pulmonary Hypertension (WSPH) guidelines provide updated definitions and classifications.
Diagnostic Approach
History Taking:
Detailed birth history (hypoxia, prematurity, meconium aspiration)
Family history of PH or sudden death
History of congenital heart disease, lung disease, or connective tissue disorders
Exercise tolerance and developmental milestones
Presence of cyanosis or syncope episodes.
Physical Examination:
Assess for signs of right heart strain: jugular venous distension, hepatomegaly, peripheral edema
Auscultate for loud P2 and murmurs of tricuspid regurgitation
Evaluate for cyanosis and clubbing
Assess respiratory effort and lung auscultation
Monitor vital signs, including oxygen saturation.
Investigations:
Echocardiography: assesses RV size and function, pulmonary artery pressures, and tricuspid regurgitation
RHC: measures invasively PAP, PCWP, cardiac output, and assesses response to vasoreactivity testing
ECG: may show right axis deviation and RV hypertrophy
Chest X-ray: may show cardiomegaly and prominent pulmonary arteries
Pulmonary function tests: assess for underlying lung disease
Blood tests: CBC, liver function tests, renal function tests, BNP, autoantibodies, genetic testing for PAH syndromes
Ventilation-perfusion scan: to rule out pulmonary embolism (less common in pediatric primary PAH).
Differential Diagnosis:
Congenital heart disease with shunt, left-to-right or bidirectional
Persistent pulmonary hypertension of the newborn (PPHN)
Bronchopulmonary dysplasia
Interstitial lung disease
Sepsis
Anemia
Congenital diaphragmatic hernia
Pulmonary venous obstruction.
Management
Initial Management:
Supportive care including oxygen therapy to maintain saturation >90%
Mechanical ventilation if respiratory failure
Treatment of underlying conditions (e.g., surgical correction of congenital heart disease if appropriate)
Fluid management and diuresis for RV failure
Nutritional support
Sedation and pain control to reduce metabolic demand.
Medical Management:
Sildenafil: a phosphodiesterase-5 inhibitor, is widely used off-label and now has some approved indications in pediatrics
Typical starting dose is 1-3 mg/kg/day divided TID, titrating to a maximum of 10-20 mg/kg/day
It primarily acts by increasing cGMP, leading to pulmonary vasodilation
Endothelin Receptor Antagonists (ERAs): Bosentan (approved for pediatric PAH >3 years) and Ambrisentan (off-label) block the action of endothelin-1, a potent vasoconstrictor
Bosentan dose: typically 2 mg/kg/dose BID for children weighing 10-20 kg, 62.5 mg BID for 20-40 kg, and 125 mg BID for >40 kg
ERAs require regular liver function monitoring
Other classes: Prostanoids (e.g., epoprostenol, treprostinil) and inhaled nitric oxide are also used but not directly compared here.
Surgical Management:
Surgical correction of congenital heart disease is a cornerstone of management for many pediatric PH cases
Lung transplantation is an option for refractory cases of PAH but is associated with significant morbidity and mortality and is rarely performed in children due to donor limitations
Balloon atrial septostomy may be considered in select cases of severe RV failure to decompress the right ventricle.
Supportive Care:
Regular monitoring of growth and development
Nutritional counseling and support to maintain adequate caloric intake
Immunizations to prevent respiratory infections
Psychological support for the child and family
Rehabilitation programs to improve exercise capacity.
Complications
Early Complications:
Right ventricular failure
Arrhythmias
Syncope
Hypoxemia
Respiratory distress
Fluid overload.
Late Complications:
Progressive RV dysfunction and failure
Pulmonary vascular remodeling
Growth and developmental delay
Pulmonary infections
Thromboembolic events (though less common in pediatric PAH).
Prevention Strategies:
Early diagnosis and initiation of appropriate therapy
Optimizing oxygenation and ventilation
Aggressive management of infections
Careful monitoring for signs of RV failure
Adherence to medication regimens
Regular follow-up with a multidisciplinary team.
Prognosis
Factors Affecting Prognosis:
Age at diagnosis
Underlying etiology
Severity of PH
RV function
Response to therapy
Presence of genetic mutations
Comorbidities.
Outcomes:
Prognosis varies widely
With appropriate management, some children can achieve improved exercise tolerance and quality of life
However, PH remains a progressive disease, and survival is often limited, especially in severe cases
Sildenafil and ERAs have shown to improve exercise capacity, functional class, and hemodynamics in pediatric PAH populations, but long-term survival data are still being gathered.
Follow Up:
Lifelong follow-up is typically required
This includes regular clinical assessments, echocardiography, and potentially RHC to monitor disease progression and treatment response
Close collaboration between pediatric cardiologists, pulmonologists, and other subspecialists is essential for optimal long-term care.
Key Points
Exam Focus:
Understand the WHO classification of PH, with emphasis on Group 1 (PAH)
Differentiate between sildenafil (PDE5i) and ERAs (bosentan, ambrisentan) in terms of mechanism of action, indications, and monitoring requirements
Recall typical pediatric dosing ranges for sildenafil and bosentan
Recognize that RHC is the gold standard for diagnosis and vasoreactivity testing
Congenital heart disease is a major cause of PH in children.
Clinical Pearls:
Always consider PH in a child with unexplained dyspnea, syncope, or failure to thrive
Echocardiography is your initial screening tool, but RHC is definitive
Sildenafil is often a first-line therapy due to its safety profile and availability, especially for milder forms or as add-on
ERAs, particularly bosentan, are reserved for more severe PAH and require careful liver function monitoring
Remember to assess vasoreactivity during RHC to guide therapy selection.
Common Mistakes:
Failing to consider PH in the differential diagnosis of respiratory or cardiac symptoms in children
Relying solely on echocardiography without considering RHC for definitive diagnosis and management guidance
Inappropriate dosing of sildenafil or ERAs
Underestimating the importance of treating the underlying cause of PH, especially congenital heart disease
Neglecting to monitor for side effects, particularly liver enzyme elevation with ERAs.