Pulmonary hypertension in the family - Wicked Local Watertown

Posted: 19 Apr 2020 12:00 AM PDT

Question: My sister died of pulmonary hypertension. Does this run in families?

Answer: Pulmonary hypertension (PH) is a serious disease, affecting up to 100 or more per 100,000 people, and is more common in women than men. There are many causes, and only a small percentage of cases are familial.

PH is when the blood pressure in the arteries of the lungs is elevated to over 25 mmHg at rest; normal is 8 to 20 mmHg. It is thought that this may be caused when something happens to the layer of cells that line the blood vessels in the lungs. These vessels then scar and so blood does not flow easily through them. It is vital that blood get to the lungs to be recharged with oxygen, and so the body reacts to this inhibited flow by increasing the blood pressure to push the blood through these compromised vessels. The need for this high blood pressure also puts a severe strain on the right side of the heart, since the right side of the heart is responsible for pumping the blood to the lungs (the left side of the heart pumps the blood around the body), causing right-sided heart failure to develop.

PH is classified by the cause, being primary PH (PPH) or being due to one or more contributing conditions (data from the PH Association):

Group 1, primary pulmonary hypertension (PPH), is diagnosed in about 5% of all PH cases and is when the primary cause seems to be some mechanism in the arteries themselves, whether from an inherited condition (10% of Group 1 cases), from toxicity to a drug or toxin, due to a systemic connective tissue disease such as scleroderma, lupus or other, due to an infection such as HIV or others, due to a liver disease causing portal hypertension such an infection or other causes, or due to some other condition.
Group 2, contributing to around two thirds of cases, is when PH occurs secondary to a condition in the left side of the heart.
Group 3, contributing to about 10% of cases, is when PH is due to some chronic lung disease that causes chronic low oxygenation.
Group 4, identified in less than 5% of cases, is when PH is due to repeated blood clots blocking some of the arteries in the lungs.
Group 5 is when PH is due to unclear causes, and is diagnosed in about 15% of cases.

Most patients with PH present with increasing shortness of breath on exertion, chest pain, fainting, or fatigue, and in more advanced cases symptoms from the right side of the heart being compromised such as leg swelling or other symptoms. These symptoms are not specific to PH and may occur from many other diseases, making the diagnosis of PH challenging. On a physical exam your doctor may appreciate signs of right-sided heart failure, which include changes in your heart sounds (an increased P2) as well as certain heart murmurs (pulmonic regurgitation or the Graham Steell murmur).

The evaluation for PH will include checking for other conditions that may be associated with it (see above), including blood tests, lung function tests, a chest CT and/or other tests. An echocardiogram will help verify the diagnosis, and a right sided heart catheterization may be indicated to check the actual pressures involved. Occasionally a lung biopsy may be needed as well.

About half of PH patients die within three years if left untreated. Treatment is aimed at addressing the underlying condition, and the prognosis for these patients is determined by the prognosis for the underlying condition and how severe the PH is at diagnosis. Advanced treatments that directly address the increased pulmonary high blood pressure, such as with certain medications that dilate these vessels or with other treatments, may be indicated for Group 1 patients and sometimes for patients in other Groups when other treatments are not helping.

Unfortunately, even with aggressive treatment, about one-third of PH patients die within 5 years. Risk factors for a poor prognosis include age over 50, failure to respond to initial treatments, as well as other factors. Lung transplantation may improve survival for some patients.

There is research being done to better understand this devastating disease, and new treatment options are being sought. For now the best thing is to seek care from a doctor who specializes in this disease to improve the patient's quality of life as well as improve their overall survival.

Jeff Hersh, Ph.D., M.D., can be reached at DrHersh@juno.com.

Ambrisentan and Tadalafil Combination Therapy Appropriate for CTD-PAH - Pulmonology Advisor

Posted: 06 Apr 2020 12:00 AM PDT

Combination therapy is appropriate for patients with typical pulmonary arterial hypertension (PAH) categorized as low and intermediate risk at baseline, while high-risk patients could possibly be considered for more advanced therapy, according to study results published in the Annals of the Rheumatic Diseases.¹

Connective tissue disease-associated PAH (CTD-PAH) is the second most common etiology of PAH and has the most severe disease characteristics and the highest mortality of all PAH subgroups.¹ The Ambrisentan and Tadalafil in Patients with PAH study (AMBITION; ClinicalTrials.gov Identifier: NCT01178073) demonstrated that patients with CTD-PAH benefited from initial combination therapy with ambrisentan plus tadalafil compared with either agent alone when patients with risk factors for left heart disease were excluded.²

Researchers conducted a post hoc subgroup analysis of the AMBITION modified intention-to-treat CTD-PAH population to assess the relationship between baseline characteristics and outcome and evaluated the utility of an abbreviated, 3-parameter noninvasive risk stratification score in predicting outcomes in patients with CTD-PAH.¹

This analysis included 216 patients (combination therapy, n=117; monotherapy, n=99), and they found that the risk for clinical failure was lower with combination therapy vs monotherapy, specifically 51.7% lower in the CTD-PAH population (hazard ratio [HR], 0.48; 95% CI, 0.28%-0.81%) and 53.7% in the systemic sclerosis-PAH population (HR, 0.46; 95% CI, 0.24%-0.89%). The risk for clinical failure was lower with combination therapy vs monotherapy in the baseline low-risk group, baseline intermediate-risk group, and in the week 16 low-risk group.

"In patients with CTD-PAH, the risk of clinical failure was lower with combination therapy versus monotherapy, particularly in those with baseline hemodynamic parameters characteristic of typical PAH, without features of left heart disease and/or restrictive lung disease,"¹ the investigators wrote. "A simplified risk stratification score at baseline may help inform disease management in patients with CTD-PAH, but further studies with larger patient populations are required."

Disclosure: This clinical trial was supported by GlaxoSmithKline and Gilead Sciences, Inc. Please see the original reference for a full list of authors' disclosures.

References

1. Kuwana M, Blair C, Takahashi T, Langley J, Coghlan JG. Initial combination therapy of ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) in the modified intention-to-treat population of the AMBITION study: post hoc analysis [published online March 11, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-216274

2. Galiè N, Barberà JA, Frost AE, et al; for the AMBITION Investigators. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015;373:834-844.

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