Pulmonary Hypertension

Defining Pulmonary Hypertension:

Pulmonary hypertension is the term used to describe increased pressure in the arteries of the lungs. Its manifestation is usually mild and found in association with many forms of lung and heart disease. The more severe forms of pulmonary hypertension are usually very rare. Primary care physicians may likely never see a case, and most cardiologists and pulmonologists may see a handful in their careers. A considerable amount of experience and technology is required to establish the correct diagnosis and treat the various causes and stages of pulmonary hypertension. Pulmonary hypertension is classified in four stages by the World Health Organization (WHO) and range in severity from Class I to Class IV functional status.

UCSD Medical Center developed a world renown Pulmonary Vascular Center which is a multi-disciplinary program. Since its inception in 1988 (?) physicians, surgeons and researchers have developed techniques to facilitate the diagnosis and management of patients with primary and secondary forms of pulmonary hypertension. The Pulmonary Vascular Center serves as an international referral center for hospitals and physicians throughout the world.

Multi-Disciplinary Team:

Faculty include experts from each of the following areas:

• Cardiology
• Pulmonary and Critical Care Specialists
• Thoracic and Cardiovascular Surgeons
• Interventional Radiology
• Lung Transplant Team
• Pathology
• Hematology
• Molecular Biology
• Research

The faculty at the Center have been specializing in the care of patients with pulmonary hypertension for over twenty years. The multi-disciplinary approach was designed to maximize patient care and foster research that would result in better treatment options and facilitate a cure. Ongoing studies and trials allow the staff to follow the progress, evaluate outcome of treatment strategies, and notify patients of the opportunity of new options. One new option that was made available to patients was the use of Tracleer (bosentan), a controlled study which was undertaken at the Center in 2001 through 2003 with the release of this new medication for the treatment of pulmonary hypertension.

The most common diagnosis in patients who are referred to the Pulmonary Vascular Center are primary pulmonary hypertension (PPH), chronic thromboembolic pulmonary hypertension (CTEPH) which is due to blood clots in the lungs known as pulmonary embolus, collagen disease such as lupus and scleroderma, portal-pulmonary hypertension, and congenital heart disease.

Patients with known or suspected pulmonary hypertension are evaluated as an outpatient upon referral by a pulmonologist or cardiologist. Those patients who are deemed unstable are transferred to UCSD Medical Center for emergent evaluation and treatment. The diversity of our patient population includes those with mild to severe (WHO Class I to Class IV) symptoms.

Referrals to our Center are made for one or more of the following:

• Assistance in diagnosis and selection of management strategy
• Complex treatment including Flolan or epoprostenol
• Special testing: magnetic resonance angiography and high resolution chest CT
• Evaluation for thromboendarterectomy in chronic thromboembolic pulmonary hypertension
• Evaluation for lung and or lung/heart transplant
• Genetic counseling and family screening in familial disorders
• Treatment with new study and trial medications

Criteria for Pulmonary Hypertension Diagnosis

Patients who are referred to the Center are requested to have their medical records forwarded to one of our pulmonary specialists to assess the urgency. Patients are encouraged to have not only their medical records forwarded but any diagnostic studies (including films or CD). Patients are encouraged to bring a family member with them to the initial visit.

The initial clinic visit includes an extended evaluation of medical history, physical exam and review of previous studies (CXR, CT scans, nuclear, cardiac catheterization and laboratory). A considerable amount of time will be spent on patient and family education regarding the diagnosis, testing required, treatment options, and the disease process.

• Ventilation and perfusion scan (V/Q scan): an isotope study to diagnose pulmonary embolus
• Ultrasound or Doppler of the legs: detects clots in the veins
• Non-invasive magnetic resonance pulmonary angiography or an invasive contrast pulmonary angiogram used to diagnose thromboembolic pulmonary hypertension and determine the value of clot busting enzymes or thromboendarterectomy
• Surface and/or trans-esophageal echocardiogram which detects congenital heart defects including atrial septal defect and patent foramen ovale
• Rest and recumbent exercise echocardiogram: establish severity of pulmonary hypertension
• Rest and exercise pulmonary function testing (PFT's) and blood gases to help diagnose lung disease
• Sleep study which helps identify patients with sleep apnea
• Six minute walk with measurement of oxygen saturation to help determine functional capacity and need for oxygen
• High resolution computer tomography (CT) which identifies interstitial lung disease
• Lung biopsy used to determine type of pulmonary hypertension and associated lung disease (very seldom required)
• Immunologic studies to check for blood or serum markers for collagen disease studies of blood coagulation which identifies the tendency to form blood clots
• Coronary ateriography is performed to exclude coronary disease
• Right heart catheterization with inhaled nitric oxide helps determine the type of treatment best suited for those who respond to inhaled nitric oxide
• Consultation with specialists in the fields of neurology, rheumatology, or hematology

What is Pulmonary Hypertension?

Pulmonary hypertension is an increase in pressure in the arteries of the lungs which often occurs in lung and heart disease and is categorized as secondary pulmonary hypertension. When pulmonary hypertension is due largely to collagen disease such as lupus or scleroderma it is known as secondary. Primary pulmonary hypertension is not associated with lung or heart disease.

Primary Pulmonary Hypertension

As recently as 20 years ago, PPH was considered rare and was estimated to affect about 2-5 in a million adults and children. The usual onset of symptoms is between 30 to 45 years and women are affected two to three times as frequently as men. It can occur in young children and adults into their seventies. Since the use of Echocardiography, the gold standard for the detection of PPH, for evaluating persons with shortness of breath, the number of persons suspected and confirmed to have PPH has increased markedly.

The Pulmonary Vascular Center identifies and treats approximately 200 new patients every year. PPH occurs without any explanation or may be associated with triggering mechanisms. Triggers for those individuals susceptible to PPH include weight reducing drugs (Redux or Fen-phen), tryptophane, cocaine and heroin, AIDS, and cirrhosis of the liver. About one in fifteen cases is familial.

A large number of patients with symptoms have had pulmonary hypertension for several years. The rate of disease progression varies considerably. The best prognosis is usually in persons who have mild symptoms, preserved heart function, and pulmonary arteries that relax in response to various drugs. In the 1980's very few treatment options were available to PPH patients and the overall prognosis was very poor. For those who did not respond to treatment, lung transplantation was the only treatment option.

In the most recent years, the Pulmonary Vascular Center at UCSD has been the focus of much research and medical breakthroughs, we continue our pursuit of a cure. Approximately one in four/five patients respond to high dose channel blocking drugs. Those patients who are identified as responders have less symptoms, an improved outcome, and in a minority, resting pulmonary artery pressures drop to near normal levels. Calcium channel blockers are commonly used for high blood pressure (hypertension) and in most cases well tolerated, however, in PPH can be very dangerous and even fatal. A breakthrough procedure studied and implemented at UCSD Pulmonary Vascular Center was the use of right heart catheterization with inhaled nitric oxide used to identify potential responders. The pulmonary artery pressure response to five minutes of inhaled nitric oxide is safe and a highly accurate method to predict the response to calcium channel blockers

Advances for the treatment of PPH continue at the Pulmonary Vascular Center.

- 1996 Treatment of Flolan (prostacyclin) Intravenous Therapy

- 2002 Treatment of Tracleer (bosentan) Oral Therapy

- 2005/6 UCSD Pulmonary Vascular Center is scheduled to begin a clinical trial for off-label use of sildenafil in the treatment and management of primary pulmonary hypertension.

Predicting outcome in PPH is very difficult, however, the following tests can be of value and may be periodically necessary in monitoring a patient's response to treatment and possible need for lung or heart lung transplant.

• Six minute walk
• Right ventricular function on echocardiography or nuclear studies
• Resting and exercise right ventricular pressure on echocardiography
• Pulmonary artery resistance and right heart function during right heart catheterization
• Response to inhaled nitric oxide

http://content.nejm.org/cgi/content/full/346/12/896

http://www.phassociation.org/Medical/Advances_in_PH/Autumn_2003/recap.asp

To refer a patient or if you are a potential patient and you have questions, please contact

Alecia Vultaggio
Assistant to Director
Division of Pulmonary and Critical Care Medicine
UCSD Medical Center - Thornton Hospital, La Jolla
Pulmonary Vascular Center
9300 Campus Point Drive, M/C 7372
La Jolla, CA 92037-7372
Phone: 858-657-7105
Fax: 858-657-7144

e-mail: Avultaggio@ucsd.edu