Pulmonary Hypertension

What is Pulmonary Hypertension?

Pulmonary hypertension is a complex condition involving high blood pressures in the lungs. It is classified by the World Health Organization into five clinical groups based on multiple factors such as how it originates, its characteristics, symptoms, and treatment procedures.

The five groups include:

1. Pulmonary Arterial Hypertension (PAH)
2. Pulmonary Hypertension due to left heart disease (PH-LHD)
3. Pulmonary Hypertension due to Lung Diseases, Hypoxia, or Both
4. Pulmonary Hypertension Due to Pulmonary Artery Obstructions
5. Pulmonary Hypertension with Unclear or Multifactorial Mechanisms

Each group is further subdivided to cover a range of specific conditions. For example, PAH can be caused by drug use, inheritable factors, diseases such as HIV or due to heart or lung issues. Pulmonary hypertension can also be classified based on certain measurements of blood pressure and flow in the lungs, called a hemodynamic classification.

One such measurement is the mean pulmonary artery pressure (mPAP), which if above 20 mm Hg, indicates high pressure. However, high mPAP alone does not confirm pulmonary hypertension, as this could be due to an increase in cardiac output or increased pressure in the pulmonary arteries (PAWP). Therefore, pulmonary hypertension is also classified based on resistance in the pulmonary blood vessels (PVR) and the pressure in the pulmonary artery.

The classification helps to understand whether the high pressure in the lungs is due to issues before (precapillary) or after (postcapillary) the blood passes through the heart chambers. All types of pulmonary hypertension can have precapillary and postcapillary components. Therefore, the diagnosis is usually based on the primary cause of the increased pressure in the pulmonary arteries.

Understanding the structure and function of the pulmonary circulatory system is key to understanding this condition. Here, blood travels from the right part of the heart to the lungs through a network of blood vessels. Within the lungs, harmful carbon dioxide is removed from the blood, and oxygen is added. This oxygenated blood then travels back to the heart, where it gets pumped to the rest of the body.

The blood vessels in the lungs are quite flexible and can expand or contract to adjust to changes in blood flow and pressure. The smooth muscle cells within these blood vessels help regulate blood flow and the pressure inside the pulmonary arteries, which maintain effective blood oxygenation in the lungs – a vital process for our overall health and function.

What Causes Pulmonary Hypertension?

Certain genetic changes are linked to different kinds of high blood pressure in the lungs, including IPAH, HPAH, and hereditary hemorrhagic telangiectasia (HHT) linked with PAH. Those with HPAH inherit these genetic changes, while those with IPAH are genetically prone but the changes are random. Curiously, these groups show the same symptoms. The most common mutations include BMPR2, SMAD1, SMAD9, KCNK3, CAV1, and SOX17 in IPAH/HPAH, and ALK1, ENG, and SMAD4 in HHT.

Some drugs and toxins, such as aminorex, fenfluramine, dexfenfluramine, benfluorex, methamphetamines, dasatinib, and toxic rapeseed oil, have been found to cause PAH. Other substances like cocaine, phenylpropanolamine, L-tryptophan, St. John’s wort, amphetamines, interferon -α and -β, alkylating agents, bosutinib, direct-acting hepatitis C antivirals, leflunomide, and indirubin could also lead to PAH. Certain types of connective tissue diseases have been known to cause PAH, including systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, Raynaud disease, and mixed connective tissue disease (MCTD). Among these, systemic sclerosis is most frequently linked to PAH.

High blood pressure in the lungs linked with congenital heart disease (PH-CHD) can be categorized into CHD that results in Eisenmenger syndrome, PAH linked with prevalent systemic-to-pulmonary leaks, PAH with small or incidental defects, and PAH after defect correction. While PH-CHD is typically classified as group 1 pulmonary hypertension, certain defects fit better in group 2. These may include conditions like mitral valve disease, left ventricular inflow or outflow obstruction, and left ventricular systolic or diastolic dysfunction, which can also cause postcapillary pulmonary hypertension.

Sleep-disordered breathing conditions comprise Group 3 conditions causing low oxygen levels without under-breathing, especially at high altitudes. Factors including chronic disease related to blood clot in the lung, sarcoma, other harmful tumors like renal carcinoma, uterine carcinoma, testicular germ cell tumors, and nonmalignant tumors like leiomyoma, or inflammatory diseases without connective tissue disease, congenital pulmonary artery narrowings, and hydatidosis can block the lung artery and cause high blood pressure in lungs.

Chronic hemolytic anemia and myeloproliferative disorders are blood disorders that can cause group 5 pulmonary hypertension. Systemic diseases such as pulmonary Langerhans cell histiocytosis, neurofibromatosis type 1, and sarcoidosis or metabolic disorders like glycogen storage diseases and Gaucher disease can also lead to high blood pressure in the lungs.

Risk Factors and Frequency for Pulmonary Hypertension

Pulmonary hypertension is a health condition that can affect anyone, regardless of their age and it’s found in approximately 1% of the world’s population. Different causes can lead to this condition, with the most common being heart disease, especially left heart disease, or lung diseases like chronic obstructive pulmonary disease (COPD). In developing countries, some other common causes are congenital heart disease, infections like schistosomiasis and HIV, and living in high altitudes.

The condition called PAH seems to affect about 6 out of every million adults, with an estimated 49 to 55 people out of a million having the disease. Although it was once thought that this disease mainly affected young women, recent studies show that it’s also common in patients over 65, especially those having other heart-related problems, which evens out the distribution between men and women.

• About half the patients suffering from heart failure with preserved ejection fraction have Pulmonary Hypertension.
• As heart disease gets worse, the chances of having pulmonary hypertension also increase.
• 60 to 70% of people with severe, symptomatic mitral valve disease also have pulmonary hypertension.
• About 50% of people with symptomatic aortic stenosis also suffer from this disease.
• Pulmonary hypertension is a common condition among people having advanced COPD and interstitial lung disease (ILD).
• Only a small percent (1% to 5%) of advanced COPD patients have severe pulmonary hypertension. However, patients with idiopathic pulmonary fibrosis (a type of interstitial lung disease) have a higher percentage (up to 60%) of pulmonary hypertension, particularly those at the end-stage of the disease.

Registry information shows another type of this disease, CTEPH, affects approximately 2 to 6 out of every million adults, with around 26 to 39 out of a million adults living with the disease. Pulmonary hypertension is a frequent condition observed among individuals with sarcoidosis and often results in an increase in death and severe illness rates in these patients.

Signs and Symptoms of Pulmonary Hypertension

Pulmonary hypertension is a medical condition where blood pressure is unusually high in the vessels leading from the heart to the lungs. The main symptom is difficulty breathing, especially during physical activity. Other potential symptoms can include fatigue, chest pain, feeling faint, and palpitations. As the disease becomes more severe, signs of right-sided heart failure can appear, which include weight gain, swelling, bloating and fluid build-up in the stomach. In some cases, a patient’s symptoms can directly link to their underlying diseases, like joint pain, skin rashes or a history of blood clots. If the disease worsens and the patient hasn’t been treated, they could lose consciousness, stop breathing, or their heart could stop, requiring immediate medical attention.

• Difficulty breathing during physical activity
• Fatigue
• Chest pain
• Feeling faint
• Palpitations
• Weight gain
• Swelling
• Bloating and fluid build-up in the stomach
• Symptoms related to underlying diseases
• Lose consciousness, stop breathing or heart stopped in severe cases

During a physical examination, a doctor may notice certain signs of pulmonary hypertension. The sound of the blood flow through the heart can be strange, and there may be a noticeably large vein in the neck. The doctor might also notice a heart murmur, which is an extra or unusual sound heard during the heartbeat. Being pale, breathing difficulties, and cyanosis (blue or purple coloration of the skin) can also be noted as the condition progresses. Of course, a patient with chronic lung diseases may have other distinctive physical traits, such as fingertip enlargement (digital clubbing), small, widened blood vessels on the skin’s surface (telangiectasias), and painful, inflamed joints.

Testing for Pulmonary Hypertension

Despite advances in technology, it still takes more than two years to detect pulmonary hypertension from when symptoms first appear. This condition calls for doctors to be very cautious. If you have unexplained shortness of breath or other signs pointing to pulmonary hypertension, your doctor needs to conduct a thorough check. This check includes looking at your medical and family history, as well as carrying out a physical examination. The doctor also needs to monitor your blood pressure, heart rate, oxygen level, and blood tests. Additionally, a heart tracing known as an electrocardiogram (ECG) may be done.

Once these steps have been taken, the next move is to evaluate your heart using an ultrasound scan called an echocardiogram. If this scan shows signs of lung problems, you may also require lung function tests, a chest x-ray and CT scan or even a cardiopulmonary exercise test.

Based on the results of the echocardiogram, your doctor can classify the likelihood of you having pulmonary hypertension as either low, intermediate, or high. If the echocardiogram suggests a moderate to high probability, or a low probability but with other risk factors for either PAH (Pulmonary Arterial Hypertension) or CTEPH (Chronic Thromboembolic Pulmonary Hypertension) present, you will be referred to a specialist for further testing.

There are specific risk factors that your doctor would consider for PAH and CTEPH. For PAH, these include HIV, family history of PAH, systemic lupus erythematosus and portal hypertension. For CTEPH, these include a history of blood clots in the lung, having a permanent implantable device, cancer, inflammatory bowel diseases and having taken high-dose thyroid replacement.

When it comes to testing, your doctor will want to run a variety of blood tests such as full blood count, kidney and liver function tests, iron profiles, and thyroid tests. In some cases, additional tests for specific conditions such as HIV, hepatitis, and connective tissue diseases, may also be necessary.

An ECG, while not always revealing problems related to pulmonary hypertension, if abnormal, can suggest severe disease. Your doctor will also want to evaluate your chest x-ray for any signs of disease. Lung function tests and arterial blood gases can also offer useful information about the state of your lung and heart function.

More advanced diagnostic tools like CT scans, echocardiography, cardiopulmonary exercise testing, and even genetic testing may also be employed to help confirm a diagnosis and guide treatment. In cases where the screening tests suggest a high likelihood of pulmonary hypertension, a procedure known as a right heart catheterization may be necessary to confirm the diagnosis.

In the end, the key to dealing with pulmonary hypertension is suspicion, prompt testing, and specialist referral if needed. With this approach, it is possible to identify and manage the condition effectively.

Treatment Options for Pulmonary Hypertension

The treatment process for pulmonary arterial hypertension (PAH) is guided by systematic risk assessment. This takes into account several factors including clinical symptoms, exercise capacity, and heart function. The central goal of treatment is to reduce the patient’s risk in terms of anticipated one-year mortality to a low level.

In every appointment, doctors use multiple risk assessment tools like the REVEAL risk score and the ESC/ERS guidelines risk table among others. These risk tools classify patients into different categories based on their one-year mortality risk. Nevertheless, these systems have their limitations, and so, a treatment strategy combining these assessments with professional clinical judgment is essential for each patient’s care.

Individuals with PAH are advised to participate in supervised exercise programs and access psychosocial support. Overexertion and stress should however be avoided. Vaccinations against influenza, SARS-CoV-2, and Streptococcus pneumonia are also recommended. Women of childbearing age are advised against pregnancy due to PAH-related risks and should use contraception. In cases of fluid retention and heart failure, diuretics are usually prescribed.

Pulmonary arterial hypertension can be quite challenging to manage, especially when it happens without any identifiable cause. The primary aim of medication use in these cases is to alleviate symptoms and slow disease progression. Calcium channel blockers, endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclin receptor agonists are usually prescribed.

In some severe cases of PAH, procedures such as balloon atrial septostomy and Potts shunt, which help decompress the heart, might be considered. Also, in such cases, lung transplantation is often recommended for patients who fail to respond to combination therapies or if the disease progresses despite therapy.

Treatment for PAH linked to factors like drug use, immune disorders, viral infections, and heart defects usually starts with addressing the underlying conditions. The effectiveness of drug therapies in these instances has been proven, but continuation or stopping depends on factors like risk level and improvement of the underlying condition.

For pulmonary hypertension resulting from heart disease, the primary approach involves managing the underlying cardiac condition effectively. This helps to improve the patients’ symptoms, their quality of life, and prevents the worsening of pulmonary hypertension.

Treatment decision for those with lung disease-associated pulmonary hypertension should be individualized, preferably in expert centers. This similarly applies to those with chronic thromboembolic pulmonary hypertension (CTEPH), where lifelong anticoagulation is needed after diagnosis.

For those whose pulmonary hypertension falls under group 5, the focus of treatment is on managing the underlying condition. Symptomatic treatment, assessing therapeutic response, and vigilance for disease progression is crucial.

What else can Pulmonary Hypertension be?

Diagnosing pulmonary hypertension (high blood pressure in the lungs) can often take time because the initial symptoms can look a lot like those of other illnesses. Doctors have to check to make sure that these symptoms aren’t actually a sign of other conditions, such as:

• Congestive heart failure (a condition where the heart isn’t pumping blood as well as it should)
• Coronary artery disease (plaque buildup in the walls of the arteries that supply blood to your heart)
• Pulmonary fibrosis (a lung disease that occurs when lung tissue becomes damaged and scarred)
• COPD (chronic obstructive pulmonary disease, a type of obstructive lung disease characterized by long-term breathing problems)
• Valvular heart disease (any disease process involving one or more of the valves of the heart)
• CHD (congenital heart disease, a defect in the heart’s structure that you’re born with)
• Pulmonary embolism (a blood clot in one of the pulmonary arteries in your lungs)

It’s crucial for doctors to carefully rule out these possible conditions and perform necessary tests to confirm the diagnosis.

What to expect with Pulmonary Hypertension

If left untreated, PAH (or Pulmonary Arterial Hypertension) can lead to progressive heart failure on the right side of the heart, and even death. According to recent data from the United States, there is a possibility of 8% mortality within a year for patients at a moderate risk, and 19% mortality for those at high risk. For these same groups, the mortality rates rise to 20% and 55% respectively within three years.

This information underlines the importance of early diagnosis and aggressive treatment strategies. However, it’s worth mentioning that the prognosis can vary significantly among different PAH patient groups depending on the root cause of the condition.

For instance, patients with lung heart disease (LHD) with pulmonary hypertension and dysfunction in their right ventricular often have high mortality rates. Also, even non-severe pulmonary hypertension can be harmful for patients with lung disease, often leading to reduced survival rates and frequent hospitalizations.

The situation becomes even more complicated for people with severe pulmonary hypertension as they tend to experience worse outcomes compared to those with non-severe pulmonary hypertension. However, for those with operable CTEPH (Chronic thromboembolic pulmonary hypertension), the long-term prognosis can be quite encouraging.

Possible Complications When Diagnosed with Pulmonary Hypertension

Pulmonary hypertension can lead to several complications. These can include:

• Right ventricular dysfunction, which can cause heart failure on the right side
• Rapid heart rhythms like atrial fibrillation and atrial flutter, with less common ventricular arrhythmias
• Coughing up blood
• Mechanical issues like enlargement, tearing, or rupture of the pulmonary artery, or compression of the left main heart artery, pulmonary veins, main windpipe branches, and repeated laryngeal nerves
• Diseases like congestive liver disease and cirrhosis

These complications can cause a variety of heart-related and systemic symptoms that can significantly affect a patient’s health outcomes and quality of life. It’s important to identify and address these complications early on in the disease to ensure the best patient care and long-term results for individuals with pulmonary hypertension.

Preventing Pulmonary Hypertension

Preventing pulmonary hypertension largely involves managing risk factors and maintaining a healthy heart. This includes making lifestyle changes like exercising regularly, maintaining a healthy weight, eating a balanced diet, and quitting smoking. Smoking is a major risk factor not only for pulmonary hypertension but also for other heart diseases. Managing related conditions such as obstructive sleep apnea, COPD, and CTDs can also prevent pulmonary hypertension. For people with a genetic risk, genetic testing and counseling can be useful in assessing risk and planning preventive actions.

Usually, pulmonary hypertension is detected after more than 2 years of symptoms appearing. Doctors need to be vigilant about these signs to ensure early diagnosis. They should have a systematic approach for evaluation and should refer patients to specialized centers for accurate diagnosis and early treatment. Because pulmonary hypertension is a serious disease, such measures are critical for the best possible patient outcomes.

For those who have been diagnosed with pulmonary hypertension, the goal should be to prevent the disease from getting worse and to minimize complications. Regular check-ups are important to monitor the disease and treatment results, and to detect complications early. Medication plays a key role in managing the disease and slowing it down. The treatment may include oxygen therapy and drugs to reduce fluid and prevent blood clots. Patients who need to take medications through a shot or an IV line need to be taught how to manage those medications.

Lifestyle changes like regular exercise and a low-salt diet can also improve heart health and overall well-being in people with pulmonary hypertension. Avoiding triggers like high elevations and certain medications can prevent symptoms from getting worse.

Patients should be aware of common symptoms, like being short of breath during exercise, gaining weight, and feeling fatigued. They should be especially careful if they have a family history of pulmonary hypertension. Patients should understand that it often takes a long time to get a diagnosis for pulmonary hypertension, and they might need to see several doctors before getting a clear answer. This process can be stressful and frustrating. Patients can expect to have a number of tests like blood tests, lung function tests, sleep studies, heart ultrasounds, and heart catheterization in order to get a diagnosis. Healthcare providers, patients, and caregivers need to work together to prevent pulmonary hypertension and achieve the best outcomes for those living with this condition.