Influence of the Modern Era on Pulmonary Hypertension

Introduction

Pulmonary hypertension is the increased blood pressure of the pulmonary vasculature (pulmonary arteries) and is estimated to affect more than 100 million people worldwide. Untreated pulmonary hypertension (PH), a condition that causes unusually high pulmonary pressures and right heart failure, can result in early mortality. Pulmonary hypertension is divided into five types based on the etiology, pathological characteristics, and hemodynamic results. Given it has a poor short-term prognosis and severe effects on quality of life, pulmonary arterial hypertension (PAH) has drawn the most attention in recent years. The hemodynamic definition of pulmonary hypertension was updated in 2018 to identify people with pulmonary hypertension at an earlier stage. Although there are 14 approved medications available, pulmonary hypertension is still a difficult condition with a high morbidity and mortality rate. The core of this problem is the disease's progressive nature, which finally eludes medical treatment and gives the patient limited options for life-saving procedures.

Despite these encouraging advancements, researchers and clinical practitioners still encounter difficulties treating pulmonary hypertension. For instance, the poor animal models available to investigate pulmonary hypertension and the challenge of converting benchwork discoveries into clinically effective interventions constrain basic and medical scientists. It is still difficult for clinicians to recognize patients at high risk of disease progression and death regardless of their hemodynamics or the available treatments. The timing is now perfect for the scientific and medical communities to unite and plan how to address these issues to increase our chances of discovering a treatment for this severe illness.

What Is the Pathophysiology of Pulmonary Hypertension?

A thorough understanding of the physiology and pathophysiology of pulmonary vasculature is mandatory for the proper diagnosis and effective treatment planning and implementation. Deoxygenated blood is carried from the heart to the lungs by pulmonary circulation, which transports oxygenated blood back to the heart for systemic circulation. Although the entire cardiac output is directed towards the pulmonary circulation, the low pressure is maintained by many small pulmonary arteries and capillaries with a large cross-sectional area.

Activities like exercise increase the number of capillaries contributing to the maintenance of low pulmonary pressure. When the radius of the blood vessel decreases, it contributes to an increase in pulmonary pressure leading to pulmonary hypertension. Thus, the pulmonary pressure can increase dramatically with only a minor change in the radius. The trunk structurally divides into two pulmonary arteries and roughly 15 higher-order branches before reaching the pre-capillary level. They comprise three layers:

• Inner intima (pulmonary artery endothelial cells).

• Middle medial layer (pulmonary artery smooth muscle cells).

• Outer adventitial layer (fibroblasts).

The abnormal functioning and structural changes in these cell layers have been associated with the narrowing of the vessels leading to pulmonary arterial hypertension. Pulmonary hypertension can be classified based on the pathological features, etiology, and hemodynamic findings:

1. Group 1: Pulmonary Arterial Hypertension (PAH). It is the high blood pressure of the lungs' arteries and the heart's the right side.

2. Group 2: Due to Left Heart Disease. It occurs due to a passive increase in left atrial pressure.

3. Group 3: Due to Lung Diseases. Chronic lung disease causes a thickening of the pulmonary artery lumen resulting in pulmonary hypertension.

4. Group 4: Pulmonary Hypertension Due to Chronic Blood Clots in the Lungs.

5. Group 5: Pulmonary Hypertension Due to Unknown Causes.

What Is the Conventional Treatment Modality for Pulmonary Hypertension?

There are several treatment modalities for pulmonary hypertension, and they are implemented depending on the causative factors and symptoms. The treatments include

• Anticoagulants: To prevent blood clot formation. For example, Warfarin.

• Diuretics: Removes excess fluid from the body.

• Oxygen Treatment: Supplying oxygen that contains a higher concentration of oxygen.

• Digoxin: Strengthens the heart muscle contractions and slows down the heart rate.

Additionally, several specialized pulmonary arterial hypertension treatments aid in lowering pulmonary blood pressure and relaxing the arteries in the lungs. These medications may even and partially restore some heart and lung damage while slowing the progress of pulmonary arterial hypertension.

What Is the Influence of the Modern Era on Pulmonary Hypertension?

In the last 20 years, considerable improvements have been made in diagnosing and medical interventions for pulmonary hypertension. The sixth world symposium on pulmonary hypertension was conducted in 2018 to develop an action plan to improve patient outcomes and identify future research areas to help develop an action plan to convert current knowledge into practical recommendations. That will improve the patient's prognosis.

Updated Treatment Algorithm on Different Groups of Hypertension.

1. Update for Group 1 Pulmonary Hypertension: Calcium channel blockers monotherapy is recommended for vasoreactive patients (positive response to vasodilators). The preferred treatment for low and intermediate-risk non-vasoreactive patients is initial oral combination therapy with an endothelin receptor antagonist and a phosphodiesterase-5 inhibitor. The combination therapy with ambrisentan and tadalafil has shown a marked decrease in morbidity and mortality.

2. Update for Group 2 Pulmonary Hypertension: Clinical trials and studies suggest that pulmonary hypertension-specific treatment modalities have no benefit on left-sided heart failure pulmonary hypertension. Based on several trials, the sixth world symposium of pulmonary hypertension's task force put forward a strong recommendation against pulmonary hypertension-specific therapies for left-sided heart failure.

3. Update for Group 3 Pulmonary Hypertension: In patients with chronic lung diseases, oxygen should be given when indicated. Pulmonary hypertension-specific therapy will improve the symptoms and hemodynamics in pulmonary hypertensive patients with chronic obstructive pulmonary disease (COPD). Pulmonary hypertensive therapy is not recommended for patients with severe lung disease or mild pulmonary hypertension.

4. Update for Group 4 Pulmonary Hypertension: The recommended first-line treatment is pulmonary endarterectomy for patients with chronic thromboembolic pulmonary hypertension. About 40 percent of the patients are non-operable, and for them, Riociguat (soluble guanylate cyclase stimulators) is the drug of choice. Other medications include Bosentan and Macitentan. However, they are not recommended for routine use.

5. Update for Group 5 Pulmonary Hypertension: This group needs further studies because the cause of pulmonary hypertension is unclear and multifactorial in this group.

Conclusion

In conclusion, further research on genetics and genomics, molecular processes in pulmonary hypertension, and the development of innovative imaging techniques and clinical studies indicate ongoing interest in pulmonary hypertension research. The combined efforts of numerous researchers continue to advance our knowledge of disease pathobiology and available treatments for people with pulmonary hypertension.