11: PULMONARY HYPERTENSION FINAL ACC

Definition

Pulmonary Hypertension Definition Pulmonary Hypertension (PH) is a type of high blood pressure that affects the arteries in the lungs and right side of the heart. Pulmonary Hypertension is a silent but serious disease that often goes unnoticed until it becomes life-threatening. It causes you to have high blood pressure in your pulmonary arteries, which carry blood from your heart to your lungs. This disease usually progresses over time, as the pressure damages your arteries, causing them to narrow and restrict blood flow. Once this happens, your lower right heart chamber must work harder to pump blood through the arteries to reach your lungs. The extra work causes your right ventricle to get bigger from the overwork it's doing, which can lead to right-sided heart failure. If you don't treat Pulmonary Hypertension, it can be fatal.

Pulmonary Hypertension is categorized into five different groups based on its cause. Group 1 is the tissue damage in the pulmonary arteries. It is commonly called Pulmonary Arterial Hypertension (PAH). Group 2 occurs when the left side of the heart is not functioning properly. Group 3 is when you start to get problems with your lung functioning. Group 4 is caused by blockages in the pulmonary arteries, often from blood clots, which is known as Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Lastly, Group 5 covers health problems that are connected to PH in ways experts still do not completely understand. Groups 2 and 3 are the most common types. Group 1 (PAH) is rare, but many people mix it up with PH in general. This is why some think Pulmonary Hypertension is rare, but it actually is not. Experts say PH affects about 1 in 100 people worldwide. It is most often seen in adults over 65, but it can happen at any age, even in newborns and young adults (Cleveland Clinic, 2025) .

Discovery

The discovery of Pulmonary Hypertension is often overlooked, as many of the early signs and symptoms are similar to those caused by other circulatory or respiratory diseases, such as congenital heart disease, asthma, COPD, and sleep apnea. Vague symptoms are often associated with early Pulmonary Hypertension. The initial symptoms of many patients are shortness of breath, exertion, lack of exercise tolerance, fatigue, or chest pain (Ley et al., 2023, pp. 823-824). Pulmonary Hypertension is difficult to diagnose with a routine physical checkup and often goes unnoticed until the underlying symptoms worsen. If a person suspects that they may have a form of Pulmonary Hypertension, the best way to assess the suspicion is via an echocardiogram, which is an ultrasound exam of the heart that provides images to assess any possible abnormalities of the heart and also estimate the pulmonary artery pressure and resistance (Cordina, 2019). There are other tests that can be conducted, such as blood tests, chest x-rays, and electrocardiograms, to check for complications and other lung conditions that are known to cause this disease. Despite the wide array of tests available to check for disorders that may cause Pulmonary Hypertension, there is only one test that can allow for the diagnosis. The gold standard test to accurately diagnose it is with a right heart catheterization. RHC allows for the proper categorization and diagnosis of Pulmonary Hypertension based on the 5 main groups.

Symptoms

PH symptoms usually start mild, making them easy to overlook, but they tend to get worse as the condition progresses. No matter which type of PH someone has, many of the early warning signs are similar. People may notice chest pain or discomfort, dizziness or even fainting, and a constant feeling of fatigue that makes daily tasks harder. Loss of appetite is also common, along with shortness of breath that may first appear during activity and later even at rest. As PH continues to develop, swelling in the feet, ankles, legs, or belly can occur due to the strain placed on the heart and lungs. These symptoms together can greatly affect a person’s quality of life and signal the need for medical care.

Pulmonary Hypertension (PH) is categorized into four main stages, called “functional classes,” which describe the severity of symptoms and how they affect daily life. In Class 1, people have no noticeable symptoms and can do all normal activities without difficulty. Class 2 means that symptoms, such as shortness of breath or fatigue, appear during normal everyday activities like cleaning, shopping, or going up the stairs, but the person feels fine while resting. In Class 3, even simple daily tasks become very challenging, causing fatigue or shortness of breath to occur more easily, although rest still provides relief. Class 4 is the most severe stage, where symptoms are present even at rest and worsen with any physical activity, making it extremely difficult to perform normal everyday tasks. As PH progresses through these classes, symptoms become more obvious and disruptive, highlighting the importance of early diagnosis and careful management.

Genetic Passing

Pulmonary Hypertension can be passed down through family genetics, depending on the type of hypertension a person may have. One example of this includes Familial Pulmonary Arterial Hypertension (FPAH). FPAH is harder to diagnose and find due to the disease often skipping generations. FPAH is often caused due to a mutation in the bone protein called bone morphogenetic protein receptor 2 or BMPR2, which affects the artery walls in the lungs (Pha, 2023).

In most cases of FPAH, the patient may have one single wrong copy from a parent’s gene, otherwise known as autosomal dominant inheritance. This one faulty gene can increase one’s risk of the disease, but is not an automatic indicator or diagnosis that someone may have Familial Pulmonary Arterial Hypertension. When no harm is done, this is known as incomplete penetrance, where the mutation never develops into a symptomatic issue. In very rare cases, a child may inherit two faulty genes from their parents, known as autosomal recessive inheritance, causing the chances of developing the disease to skyrocket.

BMPR2, or the bone morphogenetic protein type 2 receptor, plays a crucial role in the cell walls and how they work to repair themselves. According to the Pulmonary Hypertension Association (n.d.) (PHA), changes in BMPR2 are the cause of nearly 70% of Familial Pulmonary Arterial Hypertension cases. Gender plays a small role in development as well. While around 40% of women with a BMPR2 mutation are diagnosed with PAH, only 10-20% of men are diagnosed (Pha, 2023). While BMPR2 is the most common gene associated with the disease, there are many other genes, such as KCNK3, SMAD9, ALK1, CAV1, and ENG, that can all cause different types of pulmonary hypertension in a person (Pha, 2023). The Pulmonary Hypertension Association (n.d) mentions that there are around 14 known gene mutations that are connected to pulmonary hypertension.

Due to the risk of passing this trait onto your offspring, many doctors advise genetic testing to be done on those who have been diagnosed with some of the gene mutations related to the disease. Genetic tests may include a medical professional receiving a sample of saliva, blood, or even a cheek swab. Furthermore, getting genetic testing done can show a patient important information, including things such as identifying any disease-causing variants present, explaining how a person may have developed PH, and assess if other family members may be at risk for developing the disease.

The Silent Killer

Pulmonary Hypertension is often referred to as “The Silent Killer” due to its slow and subtle developing nature, as well as its non-specific symptoms that can often be mistaken for other issues. Most patients often report experiencing symptoms including asthma, tiredness, and even mild chest discomfort. Due to the vagueness of these symptoms, in most cases it takes physicians months to accurately diagnose the patient’s disease. This delay in diagnosis further puts back the patient’s care, resulting in worsening symptoms. According to a REVEAL Registry published by the National Library of Medicine, more than 20% of pulmonary arterial hypertension patients go over two years of symptomatic problems before they are accurately diagnosed and treated (Brown, 2011).

Another common reason the disease is nicknamed that way has to do with its difficulty in accurately confirming the disease is found, even when clear symptoms are shown. Pulmonary Hypertension is best diagnosed by performing a right-heart catheterization, an extremely invasive procedure that many patients do not wish to undergo. Although there are non-invasive procedures to go through, including echocardiography, they are less effective at properly diagnosing PH and often miss early cases of the disease. Because of this, patients are not properly treated until the disease is far more advanced. If left untreated for too long, PH can cause irreversible damage to a patient and could ultimately lead to death (Pulmonary Arterial Hypertension).

Non-invasive Procedures

Non-invasive procedures to help deal with Pulmonary Hypertension are often highly favored over surgical procedures. Some typical treatments often include treatments that are meant to be inhaled by the patient, otherwise known as oxygen treatments. This treatment significantly helps to open the patients' airways. Patients living with Pulmonary Hypertension are put on a regular flow of oxygen to help support the lungs with breathing. The oxygen is used all hours of the day and night. The use of blood thinners can also help with the blood flow, including ones such as Warfarin, Jantoven. In addition, Vasodilators, Water pills, and High-dose Calcium blockers are all other common treatments medical physicians may put their patients on. Fortunately, non-invasive treatments are there to help, along with other treatments and surgeries. All the treatments and medications work hand in hand to improve the quality of life for those who suffer from this disease. Another thing to remember is that some medications and treatments are not yet approved, and those left with Pulmonary Hypertension are left with the “what ifs” that have no answers. Let’s take a look at all the different treatments and medications that will improve the lives of those living with Pulmonary Hypertension.

Surgical Procedures

The most important invasive test is the right heart catheterization, which is used to confirm Pulmonary Hypertension and distinguish the WHO categories. In this process, a catheter is inserted into a central vein through the pulmonary artery and the right heart. It is applied to measure pressures and cardiac output (Mandras et al., 2020, pp. 1982-1983). The results of hemodynamics in this study contribute to the choice of a patient to administer vasodilator medications, surgery, or other invasive treatments (Ryan et al., 2012, pp. 112-114).

Medications

Pulmonary Hypertension is misdiagnosed more than you could imagine. On average, it takes a patient three different doctors before getting a proper diagnosis. Medications to relax blood vessels are called Vasodilators. These medications help open blood vessels and improve blood flow. It is given continuously through a small pump attached to the body. Some of these medications consist of: Epoprostenol (Flolan, Veletri), Treprostinil (Remodulin, Tyvaso), Iloprost, and Selexipay (Uptravi). To go a little more in depth, there is the Remodulin pump- this device delivers the medication (Treprostinil) via continuous subcutaneous or intravenous infusion. This is one of the treatments my niece was on in May of 2016, the procedure was performed by Surgeon Dr Nathan Taggart,MD, at St Mary’s Mayo Clinic Rochester MN. Soluble guanylate cyclase stimulators are for relaxing the pulmonary arteries, which helps lower the pressure in the lungs. Riociguat (Adempas) is not to be taken while pregnant. Medications such as Bosentan (Tracleer, Macitentan (Opsumit) and Ambrisentan (Letairis) are all used to widen blood vessels. They are Endothelin receptor antagonists. To increase the blood flow, you are going to take some Sildenafil (Revatio, Viagra) and Tadalafil (Adcirca, Alyq, Cialis)- these medications are also used to treat erectile dysfunction. Let’s move on to Calcium blockers like Amlodipine (Norvasc), Diltiazem (Cardizem, Tiazac). Although effective, a small number of patients with pulmonary hypertension improved while taking them. Nitric oxide dilates blood vessels in the lungs, reducing pulmonary arterial pressure and improving oxygenation. In 2019, my niece was in this study. Inhaled treatments consist of Treprostinil dry inhalation powder (Tyvaso DPI), Inhaled Treprostinil (Tyvaso), and Yutrepia (Treprostinil) inhalation powder (Garaygordobil, 2025).

Treatments

Getting down to the root cause of Pulmonary Hypertension instead of just treating the symptoms is what researchers at the Mayo Clinic and other facilities are working on. Patients who are living with PH are more than likely taking medications that are just managing their symptoms, but soon they may have other options at their fingertips, as researchers are working on developing medications that will target the actual root cause. According to Kelsey Stalvey, Pharm. D., and Zoe Owrutsky, Ph.D, this paradigm shift will offer hope in better outcomes and a longer survival rate, also medically reviewed by Diego Araiza Garaygordobil, M.D. One point in the study is for the use of Sotatercept (FDA approved in 2024), which is a game-changer for those who suffer from PH. The more others are aware of this disease, the more information can be collected, and the more treatments can be available, which in turn can save more lives. Of course, while we sometimes take for granted the simple breaths of air we take, some people living with Pulmonary Hypertension use pure oxygen therapy to be able to breathe. Also, think about when you have a cold or the flu, if you have Pulmonary Hypertension and you are on certain medications, you can’t just grab any off the shelf, otherwise known as OTC (over the counter) medicines, many may have negative side effects to the medications you are already on. Did you know that the FDA has only approved two medications- Bosentan, a receptor, and Sildenafil, an inhibitor, for kids living with Pulmonary Hypertension? Let’s talk about Subcutaneous and Intravenous treatments- for the delivery of medications like Treprostinil, which is just under the skin using a tiny tube and portable pump with 24/7 delivery than that is Subcutaneous. Now, delivering medication directly to a large vein in the chest via a catheter that was surgically placed would be Intravenous treatment. This example is another treatment my niece had endured, called the Hickman line. This is an intravenous treatment surgically inserted into the neck or chest. It is also used for giving and taking blood-infused medications and other treatments such as Chemotherapy or Stem Cell Transplant. Surgical procedures that are possible if medications do not help, to name a few: Atrial Septostomy, Lung or Heart Transplant, Potts Shunt, and the Reversed Potts Shunt. The Reversed Potts Shunt is a procedure my niece had in 2017, performed by Surgeon Dr Sameh Mahmoud Mo Said, M.D. Potts shunt creates a connection between the pulmonary artery to the descending aorta (pop-off valve)- the tissue is taken from another part of the body and used to gap the connection between the pulmonary artery to the lower aorta, allowing the oxygen-poor blood to bypass the lungs and directly into the systemic circulation. What about during the procedure: - First, the patient is given a sedative to help relax them; It is common for patients to be awake during a Right Heart Catheterization. Catheter- thin, flexible tubes that are placed by a doctor in the neck or groin area, which are then inserted into a blood vessel. The doctor then guides the catheters to the heart. Recovery times vary. Stem cells are not approved yet and are still being researched. While still unproven and experimental, it has been showing potential in animal models; there has been a reduction in inflammation, which promotes vascular repair, and it inhibits the disease's progression (Huang et al., 2016). Therapeutic benefits of induced pluripotent stem cells in Monocrotaline-induced Pulmonary Arterial Hypertension. While Pulmonary Hypertension only affects 1 in 100 people globally, it is crucial to remember the countless numbers of doctors, therapies, and money that goes into living with the disease. Although there is not a lot of awareness about this disease, clinical studies are on the rise to give a better understanding to readers. Dr Zannos Grekos, an assistant clinical professor of Cardiology at Nova Southeastern University and a member of the international team that developed the stem cell treatment protocol. “It goes against traditional theory that we should try to fix the existing pulmonary vasculature, but we are generating new blood vessels with impressive results!” Despite all the available treatments out there today, Pulmonary Hypertension remains incurable, with the main focus being on managing symptoms and improving quality of life. Pediatric Pulmonary Hypertension has been understudied, and little is known, which creates a limited understanding of the disease.

Types of PH

Pulmonary Hypertension is a persistent increase in blood pressure within the arteries of the lungs. The World Health Organization divides it into five types according to cause and the pattern of hemodynamics (Mandras, 2020). (WHO group 1)(PAH) Pulmonary Arterial Hypertension is a disease characterized by the constrictions and obstructive remodeling of the pulmonary vascular bed. Pulmonary Arterial Hypertension is divided into seven subgroups determined by cause: Idiopathic PAH (group 1.1), Heritable PAH (group 1.2), drug and toxin induced PAH (group 1.3), PAH associated with various conditions including connective tissue diseases, HIV infection, portal hypertension, and congenital heart disease (group 1.4), PAH in long term responders to calcium channel blockers (group 1.5), PAH with venous/ capillary involvement (group 1.6), and persistent PH of the newborn (group 1.7) (Mandras, 2020). (WHO group 2)(PH-LHD) Pulmonary Hypertension due to left-sided heart disease occurs in response to an increase in left atrial pressure and is usually a consequence of an underlying cardiac disorder. (WHO group 3)(PH-CLD) Pulmonary Hypertension due to chronic lung disease can occur in many lung diseases, including COPD, interstitial lung disease, and sleep disordered breathing. (WHO group 4)(CTEPH) Chronic Thromboembolic Pulmonary Hypertension is characterized by obstruction of the pulmonary vasculature by organized thromboembolic material and vascular remodeling, resulting from prior pulmonary embolism. CTEPH is likely undiagnosed, and its incidence and prevalence have not recently been established. (WHO group 5) Group 5 is for patients with unclear and or multifactorial causes. The group is composed of four subgroups based on primary cause. (group 5.1) consists of chronic hemolytic anemia or myeloproliferative disorders. (group 5.2) is primarily caused by systemic and metabolic disorders such as glycogen storage disease, sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, and neurofibromatosis. (group 5.3) Pulmonary Hypertension associated with fibrosing mediastinitis or chronic renal failure forms. (group 5.4) is associated with a complex congenital heart disease (Mandras, 2020).

Aftermath

Although there are no currently known cures for Pulmonary Hypertension, it is common for patients to be able to live a somewhat comfortable life with the disease. Aspects of life such as physical mobility, energy, sleep, and emotional well-being are all affected significantly due to PH. Because PH affects the ability to exert oneself, even routine tasks can become difficult: walking, climbing stairs, household chores, or shopping may take much more effort or become impractical. A European-wide survey of patients and caregivers found that over half described “very significant” impacts on daily life — including limitations in physical activity, self-care, and domestic responsibilities.

Although it is possible to live with the harsh disease of Pulmonary Hypertension, it is not easy. Many patients have to live with lifelong problems due to their own bodies failing them. The loneliness and discomfort the disease brings to people create many mental problems for patients as well. Patients with PH often feel symptoms of guilt, depression, and fear of the future. With the funding for more research and time spent on finding a cure for Pulmonary Hypertension, there is a chance to help save up to 70 million people from having to deal with this life-threatening disease.

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