Maternal Outcomes Among Pregnant Women With Congenital Heart Disease–Associated Pulmonary Hypertension
Understanding Pulmonary Hypertension: Symptoms & Treatments
When most people hear the word hypertension, they think of high blood pressure. While not as common as high blood pressure, pulmonary hypertension, which affects the lungs, can be harder to diagnose, more challenging to treat, and, tragically, often comes with fatal consequences.
Dr. Talal Dahhan, Division Chief for Pulmonary & Critical Care at Baystate Pulmonary explains, "Nearly 3 to 8% of the world's population is affected by pulmonary hypertension (PH). A serious condition brought on by abnormally high pressure in the blood vessels between the lungs and the heart, most cases of PH cannot be cured. But with early detection and proper treatment, it is possible to improve symptoms and slow the disease's progression."
What is Pulmonary Hypertension?While the signs and symptoms of pulmonary hypertension are felt in the lungs, the cause starts in the heart. Dr. Dahhan explains, "In a healthy body, the heart does its job pumping blood around the body and delivering oxygen to organs and tissue. The oxygen gets taken up by the body and the blood cycles back to the heart. When all things are working well, the blood flows back into the heart and travels to the lungs via the pulmonary artery, picks up fresh oxygen, and the whole cycle begins again. However, in cases of PH, the walls of the pulmonary artery become stiff, damaged and narrow and the amount of oxygen going out to the rest of the body drops to dangerously low levels. Sensing the low levels of oxygen, the heart begins to pump harder to push oxygen-low blood to the lungs. Over time, the low level of oxygen in the blood and the added pressure on the heart can lead to serious complications, including heart failure."
What Causes Pulmonary Hypertension?There are a number of conditions and issues that can lead to PH. Once determined, the cause is used to classify a patient's condition by a Group number (Group 1 PH, Group 2 PH, etc.). This grouping information is later used to help identify appropriate treatment options.
Here's a look at the Groups and causes for PH:
Group 1 PH is due to pulmonary arterial hypertension (PAH), a condition in which the tiny arteries in your lung become thickened and narrowed. While PAH can occur due to unknow reasons (what physicians call idiopathic), some common causes include:
Group 2 PH is due to left-sided heart disease, the most common cause of PH in the United States, left-sided heart disease causes blood to back up in the heart, raising the pressure in the pulmonary arteries.
Group 3 PH is due to lung disease, including interstitial lung disease, chronic obstructive pulmonary disease (COPD), certain sleep apneas, pulmonary fibrosis, and emphysema, all of which reduce the flow of blood through the lungs and oxygen uptake.
Group 4 PH is due to blockages in the lungs and arteries, including clots and scars from chronic thromboembolic pulmonary hypertension (CTEPH).
Group 5 PH is due to other diseases and conditions, including blood disorders, kidney disease, inflammatory disorders, and metabolic disorders.
Dr. Dahhan notes that "PH can also be caused by a specific congenital heart called Eisenmenger syndrome. This occurs when there's a hole, or more than one, between the heart chambers, which causes blood to flow incorrectly in the heart, often increasing the blood flow and pressure in the pulmonary arteries."
No matter the cause, Dr. Dahhan notes that PH in all forms is a very serious condition and left untreated can be life threatening.
What Are the Symptoms of Pulmonary Hypertension?According to Dr. Dahhan, "PH symptoms aren't 'all of the sudden' type symptoms. They develop slowly over the years and are often like symptoms of common heart and lung conditions making them easy to miss."
Pulmonary hypertension symptoms include:
Dr. Dahhan adds, "Most people first recognize a problem when they become short of breath when walking. They may be fine on a flat surface but if there's an incline or they're going up stairs, they may find themselves suddenly out of breath. As the disease progresses, they may even feel out of breath when seated. Typically, that's alarming enough to drive someone to seek medical help."
How is Pulmonary Hypertension Diagnosed?As noted, diagnosing PH can be challenging as its symptoms often resemble those of other lung and heart conditions. In addition to performing a physical exam and reviewing your medical history, your doctor may perform the following:
Diagnostic Tests for raising index of suspicion if we have a possibility of Pulmonary HypertensionThe most definite test for diagnosing PH, right heart catheterization measures the blood pressure in the pulmonary arteries. This information identifies where the high pressure exists in your heart and arteries and the specific type (group) of PH the patient has.
What is the Treatment for Pulmonary Hypertension?While there's no cure for most forms of pulmonary hypertension, various treatments are determined by the type of PH. Treatment can help manage symptoms and improve quality of life.
Among the earliest treatments recommended to consider:The next course of treatment options are medications. "There are a number of medication therapies available to help with different types of PH," says Dr. Dahhan, "Depending upon the type of PH a patient has, we may recommend medications to relax or widen blood vessels and arteries, relax muscles in blood vessels, or to increase blood flow. These don't treat PH, but they can treat and help with complications from PH."
A last resort option, surgery may be recommended for patients with CTEPH, however, as Dr. Dahhan notes, not all PH patients are candidates for thromboendarterectomy. But there are procedures to consider in absence of CTEPH. Options include:
Living with pulmonary hypertension can be challenging, but with proper management and care, it is possible to maintain a good quality of life. "Early diagnosis and treatment are crucial," says Dr. Dahhan. "If you are experiencing persistent shortness of breath or other symptoms, reach out to your doctor to schedule an appointment as soon as possible. The more information you can bring to the appointment—how long have you had symptoms, what makes them worse or better, etc.—the easier it will be to identify if PH is behind your issue and the faster you can begin treatment."
Bosentan For SSc: Long-term Outcomes In PAH And Efficacy For Raynaud Phenomenon
As an orally available inhibitor of endothelin-1, which has been implicated in the pathogenesis of vascular disease in systemic sclerosis (SSc), bosentan is widely used as first-line therapy for SSc patients with vascular complications. Bosentan is known to be effective for SSc-associated pulmonary arterial hypertension (PAH), but data regarding long-term outcomes are scarce. In addition, although it has been shown to prevent the development of new digital ulcers, whether bosentan is also effective in those with SSc-related Raynaud phenomenon (RP) without pre-existing ulcers has not been assessed in a placebo-controlled trial. Two studies recently published in Rheumatology provide new insights into the clinical and functional effects of bosentan for these indications.
In the first study, David Launay, Olivier Sitbon and colleagues aimed to describe the long-term effects of first-line monotherapy with bosentan—followed by the addition of prostanoids or sildenafil, if needed—on PAH, one of the leading causes of death in SSc. Their study prospectively analyzed 49 consecutive patients with SSc-associated PAH at a single pulmonary vascular center who received initial therapy with bosentan. At baseline, 4 months and 12 months, evaluations included physical examination, assessment of New York Heart Association (NYHA) functional class, and measurement of total distance walked during 6 minutes (6MWD). Right-heart catheterization was performed at baseline and after 4 months of therapy, and again at 1 year. Over the follow-up period (mean 23 months) bosentan was discontinued in five patients owing to elevated levels of liver transaminases; three were started on prostanoids, the other two received sildenafil.
NYHA functional class and hemodynamics were substantially improved at 4 months, with stabilization of these effects at 1 year, possibly as a result of continued disease progression. 6MWD did not improve, although the relevance of this outcome measure in SSc-associated PAH is a matter of debate. A total of 23 patients (47%) died during follow-up, including 14 who were treated with bosentan alone and 9 who also received prostanoid therapy. Overall survival estimates were 80%, 56% and 51% at 1, 2 and 3 years, respectively. Although the 1-year survival rate for patients with SSc-associated PAH was better than reported in historical studies, the longer-term outcomes remain poor. These outcomes were substantially worse than those observed in a comparison cohort of 103 consecutive bosentan-treated patients with idiopathic PAH (92%, 89% and 79% at 1, 2 and 3 years, respectively).
"As the long-term prognosis is still poor in SSc-associated PAH, this suggests that we need to further improve patient management and better anticipate the outcome in a single patient," say Launay and Sitbon. The results of this study suggest that evaluating NYHA functional class and cardiac index after 4 months of bosentan therapy could help predict long-term outcomes, as these factors were independently associated with overall survival.
In the second study, Van Anh Nguyen and colleagues investigated the effectiveness of bosentan in patients with SSc-related RP without pre-existing digital ulcers. The double-blind, single-center pilot study randomized 17 patients to receive either bosentan (n = 9) or placebo (n = 8) for 16 weeks. At visits every 4 weeks patients were assessed for the presence of digital ulcers and data collected from patients regarding their RP attacks. After 16 weeks, bosentan therapy did not improve overall discomfort, frequency, or duration of RP attacks compared with placebo. In addition, the groups did not differ with respect to vascular markers or the development of digital ulcers. Notably, bosentan-treated patients reported an increase from baseline in severity of pain that persisted until the primary endpoint; no such increase was seen in the placebo group.
In contrast to these results, functional ability status was improved in the bosentan group as compared with the placebo group, as measured by use of the scleroderma Health Assessment Questionnaire disability index (HAQ-DI) and United Kingdom Functional Score.
The authors conclude that bosentan is not effective in patients with SSc-associated RP without pre-existing ulcers, but larger studies are needed to more clearly show any beneficial effects on function in this group.
"Moreover," says Klaus Eisendle, one of the study's investigators, "our results highlight once more that the pathophysiological mechanisms of the vascular dysfunction underlying SSc-associated RP are still unclear." Endothelin-1 has been shown to play an important role in the etiopathogenesis of vascular disease in SSc, but these data support the hypothesis that, in addition to endothelin-1, other factors may contribute to the manifestation of SSc-associated RP.
Lung Association, Merck Partner To Raise Awareness Of PAH
Patients with pulmonary arterial hypertension often experienced delays in obtaining a correct diagnosis.
The American Lung Association (ALA) is hoping to lower rates of undiagnosed pulmonary arterial hypertension (PAH) through a new educational campaign.
The new campaign is a response to the persistent problem of delayed diagnosis among people with PAH, but it also reflects growing attention to the disease by drug developers and scientific investigators.
Left untreated, PAH can be deadly. However, therapy can significantly improve symptoms and extend patient survival. The most recent therapeutic advancement was the FDA's approval of Winrevair (sotatercept) earlier this year. Merck & Co.'s drug is an activin signaling inhibitor therapy, the first of its kind.
The development of Winrevair was part of a wave of new research clarifying the pathogenesis of the disease and identifying potential new drug targets. Yet, that wave of scientific interest in the disease has not necessarily translated into greater public awareness of the disease.
Harold Wimmer, M.S., the ALA's president and CEO, said the goal of the campaign is to improve the lives of people with the disease by helping them get earlier access to therapy.
"Through this campaign, we hope to improve awareness and understanding of PAH, promote early diagnosis, and provide valuable resources for patients and caregivers," he said, in a press release.
The campaign is being supported by Merck, which reported sales of $149 million for Winrevair as of the third quarter of 2024. The company noted that Winrevair was also recently approved in Europe, and has already launched in Germany. Merck said it expects to obtain reimbursement for the drug in most of the other major European markets in the second half of next year.
The ALA estimates that between 500 and 1,000 people are diagnosed with PAH each year in the United States, though it is unknown how many people have undiagnosed cases. Historically, late diagnosis of PAH has been a significant challenge.
An Australian study from 2013 found that the mean time from symptom onset to diagnosis was 47 months among patients with idiopathic PAH. On average, patients reported seeing their primary care doctor 5.3 times and a specialist 3 times before being seen at a PAH center.
A U.S.-based study published in 2011 found that 1 in 5 adult patients in a PAH registry had reported symptoms for more than 2 years before their disease was correctly diagnosed as PAH. The authors of that study found that younger age and a history of common respiratory disorders were associated with delays in PAH diagnosis.
In the early stages of the disease, symptoms may be fewer or non-apparent to patients. When the disease progresses, symptoms of the disease can include shortness of breath, fatigue, swelling of the feet and legs, dizziness, chest pain, and heart palpitations. The ALA noted that asthma and congestive heart failure both have similar symptoms to PAH, which can lead to misdiagnosis in some patients.
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