Complexity of the Evaluation and Diagnosis of Pulmonary Hypertension

Pulmonary hypertension is a rare condition, and even rarer is pulmonary arterial hypertension.

Pulmonary hypertension is a rare condition, and even rarer is pulmonary arterial hypertension. Pulmonary hypertension is a complex and under-recognized disease present with there is an elevation in mean pulmonary artery pressure > 25 mmHg at rest. PH is caused by something other than the blood vessels. Pulmonary arterial hypertension (PAH) specifically has an elevated mean pulmonary artery pressure > 25 mmHg and an elevation in pulmonary vascular resistance > 3 Woods Units. PAH is a disorder of the pulmonary vasculature caused by endothelial dysfunction, vasoconstriction and vascular remodeling. There are 5 clinical classifications of pulmonary hypertension as defined by the World Heath Organization (WHO). It is imperative to understand and evaluate each patient for the possible conditions that are included within each WHO group to make an accurate diagnosis.

WHO Group Clinical Classification of Pulmonary Hypertension

Pulmonary Arterial Hypertension

1. 1. Idiopathic
   2. Heritable
   3. Congenital
   4. Connective tissue disease/Systemic Sclerosis
   5. Portal hypertension
   6. HIV infection
   7. Drug use/toxins (diet pills, methamphetamines)

Pulmonary Hypertension associated with Left Heart Disease

1. 1. Systolic and diastolic heart dysfunction
   2. Left sided valvular heart disease

Pulmonary Hypertension associated with Lung Disease and/or Hypoxia

1. 1. Chronic obstructive lung disease
   2. Interstitial lung disease
   3. Sleep disordered breathing/obstructive sleep apnea

Pulmonary Hypertension due to Chronic Thrombotic and/or Embolic Disease

1. 1. Obstruction of proximal or distal pulmonary arteries

Multifactorial Pulmonary Hypertension

1. 1. Sarcoidosis
   2. Histiocytosis
   3. Sickle cell anemia
   4. Chronic kidney disease
   5. Thyroid disorders

Symptoms of pulmonary hypertension can be insidious and nonspecific, and often lead to delayed diagnosis. In some cases, diagnosis may be delayed by more than 3 years from symptom onset. Early diagnosis and rapid referral to an expert center are imperative to ensure patients have the best possible outcomes.

So, what can you do to help identify and start the evaluation process in these patients?

It is typical that patients initially present to their primary care providers for evaluation of persistent symptoms of dyspnea on exertion, fatigue, angina or lower extremity edema, to name a few. Often after prolonged, unexplained symptoms or test results are patients referred to a specialist. The initial evaluation should include obtaining a thorough history and physical, taking care to ask the questions that help direct one’s thinking towards the different WHO groups of pulmonary hypertension.

The gold standard for diagnosis of pulmonary hypertension is right heart catheterization.

However, this is not generally, and should not be, the first diagnostic test ordered during initial evaluations. Among the different diagnostic testing available, the most specific and sensitive secondary to right heart catheterization is echocardiography supporting the utility of obtaining it early in the work-up. Echocardiography is a readily available noninvasive imaging of cardiac anatomy, shunts, valvular abnormalities and observation of wall motion contractility and synchrony.

Echocardiography has good accuracy and is a good noninvasive means for evaluating for possible disease, and for monitoring disease progression.

It is also appropriate to evaluate WHO functional class during the initial evaluation to help monitor for symptom changes.

Routine clinic-based screening can include chest x-ray, electrocardiogram monitoring and lab work. Chest x-ray might reveal enlarged right ventricle and/or pulmonary arteries.

Electrocardiogram monitoring can screen for right bundle branch block or right ventricular strain or enlargement. Recommended lab work to evaluate for anemia, kidney and liver function, basic connective tissue disease, arterial blood gas, and brain natriuretic peptide that can evaluate for right ventricular heart failure/myocardial stretch. Based on the patient’s past medical history and risk factors, additional targeted evaluations may be warranted including polysomnography to evaluate for sleep apnea and/or nocturnal hypoxia and pulmonary function testing to monitor for presence or severity of chronic obstructive or restrictive lung disease, and abnormalities in diffusion capacity. A ventilation perfusion scan may be ordered to rule-out pulmonary hypertension related to chronic pulmonary thromboembolism in patients with and without a history of pulmonary embolism. Even with all the information gathered, some patients may require further imaging studies to include magnetic resonance imaging, computerized tomography or ventilation/perfusion scan.

There is not currently a recommendation to screen asymptomatic patients, except in a select patient population, those with systemic sclerosis or sickle cell anemia.

Right heart catheterization, though more invasive, is gold standard for conclusive diagnosis of pulmonary hypertension. Right heart catheterization provides information relevant to the function of the right ventricle, including cardiac output as well as response to vasoreactivity testing. It will differentiate pulmonary arterial hypertension from pulmonary hypertension.

Pulmonary hypertension is a complex disorder that requires a great deal of investigation, interpretation and follow-up for accurate diagnosis and management.

It is important to remain the patients advocate when there is a high level of suspicion for pulmonary hypertension and making an early referral to a pulmonary vascular specialty center is recommended.