Pulmonary Hypertension (PH)

• Pulmonale hypertensie (PH) is a general term for conditions with increased blood pressure in the pulmonary arteries.

• There are five main groups of causes for high pressure in the pulmonary arteries

Classification of Underlying Causes of Pulmonary Hypertension

• Group 1: Pulmonary arterial hypertension (PAH):

  • Idiopathic (IPAH, unknown cause)
  • Heritable/familial (identified genes)
  • Associated with medical conditions (connective tissue diseases, HIV, portal hypertension, sickle cell disease, congenital heart defects).
  • Exposure to drugs and toxins and pulmonary veno-occlusive disease
  • Persistent PH in newborns.

• Group 2: Pulmonary hypertension due to left heart disease.

• Group 3: Pulmonary hypertension due to lung diseases and/or hypoxia.

• Group 4: Chronic thromboembolic pulmonary hypertension (CTEPH).

• Group 5: Pulmonary hypertension with unclear multifactorial mechanisms (e.g., sarcoidosis).

• In PAH, a disorder of the inner lining of blood vessels (endothelial dysfunction) occurs initially

• It increases contractility of smooth muscle cells, leading to vasoconstriction

• It causes proliferation of endothelial and smooth muscle cells, and increased collagen and fibrosis, resulting in stiffening and thickening of the vessel walls

• In some cases, blood clots (thrombosis) can form, further narrowing the vessels

Cellular Changes in Pulmonary Arterial Hypertension

• Healthy endothelium regulates the balance between vasodilation and vasoconstriction, and inhibits smooth muscle cell proliferation

• Endothelial dysfunction disrupts this balance, leading to increased contractility

• Abnormal smooth muscle cell proliferation leads to muscle formation in peripheral lung vessels (media hypertrophy) and intima fibrosis

• Late-stage disease: plexiform lesions and in situ thrombus lead to vessel occlusion

• These events progressively reduce blood flow, causing PAH

Pulmonary Arterial Hypertension Mechanisms

• ET-1(endothelin-1) stimulates vasoconstriction, while NO (nitric oxide), PGI2(prostacyclin), and TXA2(thromboxane A2) are all for vasodilation

• This process is progressive; early changes are reversible, but later changes become irreversible, affecting treatment options

• Decreased vessel diameter increases vascular resistance(PVR-Pulmonary Vascular Resistance), raising the pressure the right ventricle must pump against

• The right ventricle compensates initially but eventually fails, reducing cardiac output and causing oxygen deficiency in tissues

• Manifestations include shortness of breath, fatigue, chest pain, fluid retention, dizziness/fainting, arrhythmias, sudden death, and cyanosis

Pulmonary Arterial Hypertension in Congenital Heart Defects

• PH development in patients with congenital heart defects (CHD) is multifactorial

• Structural abnormality causes blood shunting from the left to right heart, increasing pulmonary blood flow

• Increased blood flow leads to endothelial damage and negative remodeling of lung vessels, increasing PVR

• Shunt size and location determine the extent of vascular damage and PVR increase

• Shunt duration also dictates remodeling

• Reversible pressure allows for shunt resolution; irreversible, elevated pressure is managed with medication

Eisenmenger Syndrome

• Most severe form
• Uncorrected shunt leads to high pulmonary vascular pressure and bidirectional blood flow
• Right ventricle pressure exceeds left, causing deoxygenated blood to enter the left heart, resulting in chronically low blood oxygen levels
• This leads to multi-organ damage and decreased life expectancy.

Pulmonary Artery Damage

• Uncorrected left-to-right shunt increases pulmonary blood flow and damages the endothelium of pulmonary vessels and leads to severe pressure increase, resulting in a progressive right-to-left shunt and systemic low blood oxygen (systemic hypoxemia).
• PVR is pulmonary vascular resistance. SVR is systemic vascular resistance.

Definition and Classification of Pulmonary Hypertension

• Invasive pressure measurement (direct pressure reading) through cardiac catheterization is the gold standard for diagnosing pulmonary hypertension.
• The process involves guiding a thin tube called a catheter into the heart and pulmonary vessels to measure pressures and diagnose pulmonary hypertension

Cardiac Catheterization

• Pulmonary hypertension is defined by an invasively measured mean pulmonary arterial pressure (MPAP) > 20 mmHg at rest- European Society of Cardiology (ESC)

• Using catheter, pressure is measured in the superior vena cava SVC or vena jugularis or vena subclavia

• Pressure is also measured in the inferior vena cava IVC or vena lienali, the right atrium RA, right central RV, and the pulmonary artery PA

• The following calculations can be performed -*Gemiddelde druk in de arteria pulmonalis (MPAP)= SPAP + (2x DPAP) / 3, SPAP/ DPAP is systolic/diastolic PAP -*Transpulmonale gradiënt = MPAP – PAWP -PAWP is Pulmonale arteriële wiggedruk: represents the pressure in the lung vessel -*Pulmonale Vaatweerstand (PVR) = Transpulmonale gradiënt/ cardiac output

• PVR = Pulmonary Vascular Resistance represents the resistance that blood encounters as it flows through vessels, PVR levels of > 2WU is hightened

• mPAP, PAWP, Cardiac output are measured during right heart catheterization, with them PVR may be measured

• If the calculated PVR value is under 3WU, its normally safe to close the portion that conducts the shunt, otherwise the right ventricle wont be effective against low pulmonary vascular tension

• If PVR is above 5 WU closing the heart portion is risky due to the work against low pulmonale vaatweerland in pump

• If pressure continues to increase the right chamber will continue to push blood right to the left, therefore avoiding strain

• For values between 3 and 5 the closing will be considered per individual

• For the closing a additional vasoreactivity will be perofmred to test vasoconstriction is reversible under reactive stffs or in the event the vaatwand is damaged

• The PVR needs to drop 25% due to the vasoactieve stoffen, if the person may be predisposed or vorgeehnadel by the medidcated shut

• People without the portion closing keep CHDN with vascoreactiv medication, lowering tension in the longer makes the chamber much more loose

• Any heart problems should be dealt with specialized physician