Positive winds of change for pulmonary hypertension

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Positive winds of change for pulmonary hypertension

Treatments that offer help and hope for people with high blood pressure in the lungs.

High blood pressure is never a good sign. It’s especially dangerous when it appears in the blood vessels in the lungs.

This condition, called pulmonary hypertension, can arise when the lungs don’t get enough oxygen, as happens with emphysema or severe sleep apnea. Heart failure or heart-valve problems can also boost blood pressure in the lungs. The kind we’ll focus on here, technically called pulmonary arterial hypertension, is a different beast altogether, with a variety of causes and its own specific treatments.

Pulmonary hypertension was once a relatively quick killer. Experimental approaches that include the impotence drug Viagra are breathing new life into treating this as-yet-incurable disease.

What is it?

Normally, the heart needs relatively little pressure to pump oxygen-poor blood to the lungs. The arteries and veins that run in and over the lungs (see figure below) are generally open and relaxed. They offer little resistance to the two ounces or so of blood the right ventricle delivers with each beat. But if they narrow, tighten up, or become blocked, the right side of the heart must contract more forcefully to push blood through the lungs. That can make it harder for the heart to supply the body with the oxygen it so insistently needs. Over time, the extra stress and strain can cause the right side of the heart to fail.

Sometimes there’s no apparent reason for the problem. This is called primary pulmonary hypertension. The problem can also stem from diseases such as scleroderma, rheumatoid arthritis, lupus, or HIV infection; from blood clots that form or get trapped in the lung’s blood vessels; from congenital heart disorders; or from the use of diet drugs (such as the infamous fen-phen combination) or cocaine. About 100,000 Americans have pulmonary hypertension, with 2,000–3,000 new cases a year.

Pulmonary hypertension is a sneaky disease. At first, there’s no hint of trouble because the heart and circulatory system compensate for the increased resistance to blood flow through the lungs. Eventually, the heart and lungs can’t keep up with the body’s demand for oxygen during activity or exercise. This leads to shortness of breath, fatigue, or chest pain. As the disease gets worse, symptoms appear with slight activity, like walking across a room, or even at rest.

Pulmonary hypertension often goes undiagnosed because its early symptoms resemble those of coronary artery disease, heart failure, or lung disease. They include

• shortness of breath

• unusual fatigue

• dizziness when standing or with activity

• fainting

• chest pain

• swelling in the legs and ankles.

It usually takes a battery of tests to diagnose pulmonary hypertension and to try to pinpoint its cause.

What goes wrong in pulmonary hypertension The right ventricle pumps oxygen-poor blood through the lungs; it returns to the left atrium. Inflammation and subsequent cell growth can narrow the space available for blood flow inside lung arteries, and small blood clots can block pulmonary veins. Over time, the right ventricle can enlarge and weaken.

Standard treatments

At one time, doctors could do little beyond relieving some of the symptoms of pulmonary hypertension. Standard treatments included inhaled oxygen to improve blood flow and ease symptoms such as breathlessness, the blood-thinner warfarin to prevent the formation of tiny blood clots that might block lung blood vessels, and diuretics to reduce swelling and keep excess fluid out of the bloodstream.

Approved and experimental treatments are changing the outlook for people with pulmonary hypertension. “Although we can’t yet cure the disease, we can help many patients live longer and better,” says Dr. David H. Roberts, a pulmonary hypertension expert at Harvard-affiliated Beth Israel Deaconess Medical Center.

These treatments, along with guidelines for diagnosing and managing pulmonary hypertension, are described in detail in a special July 2004 issue of the medical journal Chest.

Calcium-channel blockers open the lung’s arteries in about 1 in 10 people with pulmonary hypertension. For people who respond to a vasodilator (a drug that relaxes the smooth muscle lining blood vessels), calcium-channel blockers improve symptoms and extend life. For people who don’t, calcium-channel blockers can cause problems. That’s why the latest guidelines mandate testing before someone starts taking a calcium-channel blocker.

Treprostinil (Remodulin) and epoprostenol (Flolan) boost the body’s production of prostacyclin, which signals blood vessels to relax and open. Unfortunately, using these drugs isn’t easy. Both must be pumped continuously into the body, which means constantly being tethered to a portable pump. An inhaled version (iloprost) and an oral version (beraprost) are in the works.

Bosentan (Tracleer) blocks the action of endothelin, a substance made by the body that sends powerful “contract now” signals to blood vessels. Other possibly more potent endothelin blockers, such as sitaxsentan and ambrisentan, are being tested in clinical trials.

A heart-lung transplant is sometimes the only option for people with severe pulmonary hypertension. The first successful heart-lung transplant, in 1981, was done for a woman with pulmonary hypertension. Because the wait for a transplant can take a year or more, an operation known as atrial septostomy, which creates a channel between the right and left sides of the heart, can offer temporary relief.

On the horizon

The three drugs approved for treating pulmonary hypertension — Remodulin, Flolan, and Tracleer — do more than just ease symptoms. They may slow or even reverse the cycle of inflammation and cell growth that causes pulmonary arteries to narrow and stiffen. But these drugs are expensive, costing as much as $100,000 a year. And Remodulin and Flolan require complicated pumps and permanent connections to the body that can be sources of infection.

Research on nitric oxide, a small molecule that relaxes and opens blood vessels, is generating plenty of buzz among experts. One drug that boosts nitric oxide levels is sildenafil (Viagra), the little blue pill that made it okay to talk about erectile dysfunction. A few small studies have shown that Viagra eases blood flow through lung blood vessels without elevating blood pressure elsewhere in the body. It also improves breathing and the ability to exercise and decreases fatigue.

Viagra can be taken by mouth, a big advantage over some of the usual drugs. And a year’s worth would cost “only” $10,000 or so. The results of larger, longer-term studies should be available soon. Another nitric oxide booster is L-arginine, a dietary supplement touted by bodybuilders. Breathing a mixture of oxygen and nitric oxide from a tank, although cumbersome, could also prove helpful.

Other possible approaches to treating pulmonary hypertension include blocking serotonin and thromboxane. Serotonin is a hormone with many functions in the body. Thromboxane signals blood vessels to constrict and makes platelets in the bloodstream stick together, which can lead to a heart attack.

Last updated:	August 21, 2006