Address for Correspondence :Bibhuti B. Das, Division of Pediatric Cardiology, Kochair Children's Hospital, University of Louisville, Louisville, KY-40202, USA. E-mail: bdas99@hotmail.com

Abstract
This is a brief review article and provides an overview of diagnostic and treatment strategies of pulmonary hypertension. This will provide the reader an understanding of how to approach a child with pulmonary hypertension.

Pulmonary hypertension (PH) is an angioproliferative pulmonary vasculopathy, characterized by loss of normal endothelial function, abnormal response of vascular smooth muscle cell to stimuli, and from the activation of multiple molecular pathways. Normal pulmonary artery (PA) pressure in children is 20/12 mmHg with a mean of 15 mmHg at sea level. PH is defined as a mean PA pressure of 25 mmHg at rest measured by right-heart catheterization with a normal pulmonary capillary wedge pressure (PWCP) of =15 mmHg and pulmonary vascular resistance (PVR) index of >3 Woods units x sq.m.(1) The pediatric cardiologist plays a critical role in the diagnosis and management of the child with PH.

In normal PA vasculature smooth muscle tone is balanced by natural homeostatic mechanisms governed by genes, vasodilators (prostacyclin and nitric oxide (NO) and vasoconstrictors (thromboxane A2 and endothelin-1) which balance each other. (2) Transforming growth factor gene is one such gene that has long been implicated in tissue repair, connective tissue growth, control and production of cytokines, synthesis of endothelin, ion channel regulation and angiogenesis. In genetically susceptible individuals, when there is insult to pulmonary vasculature in the form of shear stress or stretch, all the components of the PA (endothelium, smooth muscle cells and fibroblasts) react excessively resulting in an imbalance between vasodilator and vasoconstrictor mediators, defect in potassium ion channel, and increased synthesis of inflammatory mediators, which result in vasoconstriction, thrombosis, and remodeling (distal extension of smooth muscle into small peripheral, normally non muscular pulmonary arteries).(3) Thus, PH is associated with conditions causing chronic vasoconstriction, thrombosis, or abnormalities of vessel function.

PH is classified according to the World Health Organization (WHO) revised criteria (2003) which reflects the underlying etiology to be the primary contributor to disease.(4) The major causes of PH in children are (1) persistent pulmonary hypertension of the newborn (PPHN); (2) pulmonary arterial hypertension secondary to congenital systemic-to-pulmonary vascular shunts; (3) pulmonary venous hypertension arising from left sided heart disease; (4) PH with major venous or capillary involvement; (4) PH arising from chronic lung disease associated with hypoxia; (6) PH associated with chronic thrombotic-embolic disease; and (7) miscellaneous disorders that are associated with extrinsic compression of the vasculature.

Children with PH may present with shortness of breath, exercise intolerance, and failure to thrive. They may experience chest pain, chronic cough, hemoptysis and recurrent syncope. Those with right-to-left shunting in the setting of elevated right-sided pressures may present with worsening cyanosis. Infants may present with irritability, poor feeding, or tachypnea. These findings are nonspecific and require careful evaluation before a diagnosis of PH can be established. The most important aspect of the clinical presentation is to assign the patient to a functional class (I to IV) according to the WHO Guidelines, which are a modification of the New York Heart Association (NYHA) heart failure classification.(5) This classification scale allows prognosis of long-term outcomes and provides treatment recommendations.

First step- History and physical examination: including onset and duration of symptoms, heart defect(s) and previous surgery, birth history including prematurity and chronic lung disease, sleep disorder, medications and toxins such as cocaine, methamphetamine, anorexigens, and a thorough family history to explore whether hereditary factors may contribute to their risk for the disease. Cardiac examination may reveal a right ventricular heave, palpable second heart sound, systolic murmur due to tricuspid regurgitation and a diastolic murmur of pulmonary insufficiency. The child with right heart failure may have increased jugular venous pressure, hepatomegaly, ascites, or pedal edema.

Second step- Cardiac non-invasive tests: Chest X-ray, ECG and echocardiography. Echocardiogram is the most commonly used modality to diagnose PH and right ventricular systemic pressure (RVSP) which is equivalent to PA pressure in the absence of significant pulmonary valve stenosis, is calculated by using Bernouli's equation (RVSP= 4 x tricuspid regurgitation jet velocity2).

Third test - Additional laboratory tests are performed to rule out secondary forms of PH. A diagnostic workup algorithm for children with PH is shown in figure-1.

Figure-1: Pulmonary hypertension workup

Fourth step- Most important is cardiac catheterization and testing for pulmonary vasoreactivity. Although non-invasive tests are useful in the evaluation of suspected PH, cardiac catheterization remains the "gold standard" for the diagnosis and severity of PH. Cardiac catheterization helps in the assessment and the selection of appropriate treatment.