Pulmonary Hypertension and Thromboembolic disease

Steps in diagnosing Pulmonary Hypertension

1. Evaluate imaging studies for signs suggestive of pulmonary hypertension (PH).
   Do not disregard incidental imaging findings that may indicate the presence of PH.
2. Subsequently, assess for imaging features that may help determine the underlying etiology of PH. These may include cardiovascular abnormalities, pulmonary parenchymal disease, or evidence of chronic thromboembolic pulmonary hypertension (CTEPH), and can guide the selection of further diagnostic imaging modalities.

Imaging features of PH

The following imaging findings on CT indicate a high resistance and high pressure in the pulmonary vascular bed, suggestive of PH:

1. Main pulmonary artery (PA) enlargement
   PA diameter >30 mm
   PA/Ao ratio >1.
   Segmental artery-to-bronchus ratio >1 suggests PH, especially in upper lobes.
2. Right ventricular dilatation
   RV/LV ratio >1 on axial images.
3. Flattened or bowed interventricular septum
   Abnormal projection (ie. flattening) of the interventricular septum with an angle ≥140° on a short axis view is a sign of RV pressure overload.
4. Hypertrophy of RV wall
   Right ventricle outflow tract wall thickness ≥ 6 mm.
   
   

Additional findings include:

• Right atrial dilation, commonly observed in the setting of chronically elevated right atrial pressure.
• Contrast reflux into the inferior vena cava or hepatic veins, indicative of elevated right-sided cardiac pressures.

Possible causes of PH

When there is a  suspicion of PH, the next step is to look for features that help identify the cause and guide further imaging.

Radiologic approach to PH etiology:

1. Cardiac causes?
   Check for congenital defects (e.g., ASD, partial anomalous pulmonary venous return (PAPVR), valvular disease, or pericardial thickening or calcification).
   
2. Severe lung disease?
   Look for fibrosis or emphysema.
3. Chronic thromboembolic disease?
   Look for filling defects, vessel caliber changes, or mosaic attenuation.
   PH results from unresolved blood clots that scar and block pulmonary arteries. Identification is important, because chronic emboli can be treated surgically (PEA) or with balloon angioplasty (BPA), making it potentially curable.
4. Subtle signs of pulmonary arterial hypertension (PAH) or pulmonary venoocclusive disease (PVOD)?
   Look for centrilobular ground-glass opacities, smooth septal thickening, or a dilated main pulmonary artery.

Cardiac remodelling in PH

1. Initial Compensation – Right Ventricular (RV) Adaptation

• Increased pressure in the pulmonary arteries will raise the RV afterload.
• RV hypertrophy: The right ventricle adapts by increasing muscle mass (concentric hypertrophy) to generate higher pressure.
• Preserved function: Initially, this adaptation helps maintain cardiac output.

2. Progressive Strain – Maladaptation

• RV dilation: Over time, the RV begins to dilate as it struggles to overcome resistance.
• Decreased contractility: The hypertrophied RV eventually weakens, leading to reduced stroke volume.
• Tricuspid regurgitation: RV dilation can cause valve annulus enlargement, worsening volume overload.

3. Right Heart Failure

• RV failure: The ventricle can no longer pump effectively.
• Systemic congestion: Leads to liver congestion, ascites, peripheral edema.
• Decreased left heart preload: As RV fails, less blood reaches the left heart, reducing systemic output.

Dilatation of RV

The images show a normal right and left ventricle compared to a dilated right ventricle.

Proposed cut-off values for right heart dilation on axial CT:

• Right atrium: ≥ 65mm (women) and   ≥ 70mm (men)
• Right ventricle: ≥ 55mm (women) and   ≥ 60mm (men)

In the short-axis view, a normal left ventricle demonstrates a circular to elliptical configuration.
The interventricular septum contributes to the circular contour of the ventricular wall.

Evidence of interventricular septal flattening or leftward bowing is suggestive of right ventricular dilation and possible pressure overload.

The gold standard for diagnosing PH is right heart catheterization, which directly measures the mean pulmonary artery pressure (mPAP).
PH is diagnosed when mPAP is  ≥ 20 mmHg at rest.
Under normal conditions, the pulmonary vascular bed is characterized by low resistance and low pressure, accompanied by a high blood flow.

Elevated pulmonary arterial pressure can result from:

• Precapillary PH
  Increased pulmonary vascular resistance due to small vessel obstruction or loss of pulmonary vasculature as a result of chronic emboli.
• Postcapillary PH
  Elevated left heart pressures as a result of left-sided heart disease leading to increased pulmonary venous and capillary pressure.
  
  

Pulmonary Capillary Wedge Pressure (PCWP)
Also known as wedge pressure—is a key hemodynamic measurement used to estimate left atrial pressure and assess left heart function and helps distinguish between pre-capillary and post-capillary PH.
The wedge pressure is measured as follows:

• During right heart catheterization, a catheter (Swan-Ganz) is inserted into a pulmonary artery branch.
• The balloon at the tip is inflated to temporarily occlude the vessel.
• This isolates the pressure distal to the occlusion, which reflects left atrial pressure because there are no valves between the pulmonary capillaries and the left atrium. The wedge pressure will be high in left heart disease and low in other causes of PH.

Intravascular pressure measurements through right-sided catherization, as well as clinical and imaging findings, help to subdivide PH into five different groups, as defined by the World Health Organization (WHO).   

WHO groups

The WHO classifies pulmonary hypertension (PH) into five groups based on their underlying causes and mechanisms. 

Group 1 – Pulmonary Arterial Hypertension (PAH)
PH caused by disease of the pulmonary arteries, which become narrowed or stiff. This increases resistance for the right ventricle, eventually leading to failure. PAH can be idiopathic, inherited, or related to conditions like HIV or systemic sclerosis.

Group 2 – PH due to Left Heart Disease
PH resulting from left heart dysfunction, leading to blood backup and elevated lung pressures. It can be caused by systolic or diastolic heart failure, or valve disease. This is the most common form of PH.

Group 3 – PH due to Lung Disease or Hypoxia
PH caused by chronic lung conditions (e.g., COPD, pulmonary fibrosis) or low oxygen levels (sleep apnea and prolonged high-altitude exposure). These conditions reduce the pulmonary vascular bed and raise pressure.

Group 4 – PH due to pulmonary arterial obstruction
The most common cause of arterial obstruction is chronic thromboemboli. PH results from unresolved blood clots that scar and block pulmonary arteries. Although rare, this form is important, because it can be treated surgically (PEA) or with balloon angioplasty (BPA), making it potentially curable.

Group 5 – PH with Unclear or Multifactorial Causes
PH linked to conditions with complex or unknown mechanisms, such as sarcoidosis, blood disorders, splenectomy, metabolic disease, or congenital heart defects.

Pressure measuraments

In all five WHO groups the mean pulmonary arterial pressure (mPAP) is above 20 mmHg.
In all groups except for PH resulting from left heart disease (group 2) the wedge pressure (PAWP) will be low and the pulmonary vascular resistance (PVR) will be high.
In isolated post-capillary PH resulting from left heart disease or unclear causes (group 2 and 5) the wedge pressure is high and the pulmonary vascular resistance is low.
Sometimes there is a combined pre- and post-capillary PH with a high wedge pressure and a high vascular resistance.

PAH

Pulmonary arterial hypertension (PAH) is classified under WHO group 1.
PAH, also known as primary pulmonary hypertension, is a form of pulmonary hypertension caused by pathological changes in the pulmonary arteries, which become thickened, stiffened, or narrowed.

As a result of this arteriopathy, the right side of the heart must work against increased pulmonary vascular resistance. Over time, this leads to right ventricular dysfunction and an inability to maintain adequate pulmonary blood flow.
PAH may be idiopathic (IPAH), heritable (HPAH), or associated with other conditions such as HIV infection, systemic sclerosis, congenital heart disease or PAH with features of venous involvement (PVOD).

These images are of a young female with idiopathic PAH.

Imaging findings 

1. Mild dilation of the main pulmonary artery
2. Mild dilation of the right ventricle.
3. Mild wall thickening of the right ventricle outflow tract (arrow).
   The left atrium has a normal size.
4. Normal lung parenchyma.

PVOD

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension and is also classified under WHO group 1.
It is caused by obstruction of the small pulmonary veins, leading to post-capillary pulmonary hypertension, but it can mimic pre-capillary pulmonary arterial hypertension in clinical and hemodynamic presentation.

The classic CT triad in PVOD includes:

1. Smooth interlobular septal thickening
   
2. Centrilobular ground-glass opacities
   
3. Enlarged mediastinal and hilar lymph nodes resulting from chronic lymphatic congestion and inflammation.

Partial anomalous pulmonary venous return

Partial anomalous pulmonary venous return (PAPVR) is also asseigned to WHO group 1.
In PAPVR, one or more pulmonary veins abnormally drain into the right atrium or systemic venous circulation (e.g., the superior vena cava) instead of the left atrium.

Illustration
In this case, the pulmonary veins from the left lung drain normally into the left atrium (green arrows).
However, the right upper lobe pulmonary vein is anomalous and drains into the right atrium rather than the left atrium (red arrow).
This anomalous venous return creates a left-to-right shunt, leading to volume overload of the right atrium and right ventricle.

Chronic pulmonary overcirculation from this shunt results in endothelial injury, smooth muscle hypertrophy, and vascular fibrosis, ultimately leading to elevated pulmonary vascular resistance (PVR) and the development of pulmonary hypertension (PH).

These images are of a patient with pulmonary hypertension secondary to partial anomalous pulmonary venous return (PAPVR).

Imaging Findings
The right lower lobe pulmonary veins are not connected to the left atrium (LA) but instead drain into the superior vena cava (arrows).
Note the bilateral dilation of the pulmonary arteries, consistent with elevated pulmonary arterial pressure.

Pulmonary hypertension due to left heart disease  is asseigned to WHO group 2.
It occurs when the left heart is unable to effectively accommodate or eject the blood returning from the lungs.
This results in a backward transmission of pressure into the pulmonary circulation, leading to elevated pulmonary venous and arterial pressures.

It may result from:

• Systolic dysfunction (i.e., impaired left ventricular contraction)
• Diastolic dysfunction (i.e., reduced ventricular compliance due to myocardial or pericardial stiffness)
• Severe valvular disease, particularly mitral or aortic valve pathology.

Given the high prevalence of cardiac disease, this is the most common form of pulmonary hypertension.

Partial anomalous pulmonary venous return (PAPVR)

In partial anomalous pulmonary venous return (PAPVR), one or more pulmonary veins abnormally drain into the right atrium or systemic venous circulation (e.g., the superior vena cava) instead of the left atrium.

Illustration
In this case, the pulmonary veins from the left lung drain normally into the left atrium (green arrows).
However, the right upper lobe pulmonary vein is anomalous and drains into the right atrium rather than the left atrium (red arrow).
This anomalous venous return creates a left-to-right shunt, leading to volume overload of the right atrium and right ventricle.

Chronic pulmonary overcirculation from this shunt results in endothelial injury, smooth muscle hypertrophy, and vascular fibrosis, ultimately leading to elevated pulmonary vascular resistance (PVR) and the development of pulmonary hypertension (PH).

These images are of a patient with pulmonary hypertension secondary to partial anomalous pulmonary venous return (PAPVR).

Imaging Findings
The right lower lobe pulmonary veins are not connected to the left atrium (LA) but instead drain into the superior vena cava (arrows).
Note the bilateral dilation of the pulmonary arteries, consistent with elevated pulmonary arterial pressure.

Atrial Septal Defect

In an Atrial Septal Defect (ASD), there's a communication between the left and right atria.
Since left atrial pressure is higher, blood flows from the left atrium to the right atrium.
This increases blood volume in the right heart and pulmonary circulation.
The chronically elevated flow and pressure in the lung circulation causes endothelial damage and an increased pulmonary vascular resistance.

Illustration
Example of a sinus venosus superior defect.
This is a subtype of ASD, in which there is an abnormal interatrial communication between the left atrium and the superior cavo-atrial junction (arrow).

Example of a sinus venosus superior defect.

Images

1. There is an abnormal communication between the left atrium and the superior cavo-atrial junction (arrow). 
2.  Dilation of the pulmonary artery.
3. Coronal reconstruction demonstrating the abnormal communication between the left atrium and the superior cavo-atrial junction (arrowheads).
4. Severe dilation of the right atrium and ventricle due to the left-to-right shunt.    

Pulmonary hypertension due to chronic lung disease and/or hypoxia (WHO group 3) arises from structural and functional changes in the pulmonary vasculature secondary to underlying pulmonary pathology.
In this setting, peripheral pulmonary arteries may undergo vasoconstriction and remodeling, leading to a reduction in the vascular bed and subsequent elevation of pulmonary arterial pressure.
Common causes include chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis.
Obstructive sleep apnea and chronic exposure to high altitude may also contribute to this disorder.
Pulmonary hypertension (PH) may also occur in rare diseases such as pulmonary veno-occlusive disease (PVOD). PVOD is characterized by a typical radiologic triad of interlobular septal thickening, centrilobular ground-glass nodules, and mediastinal lymphadenopathy.

Images
This patient has a combination of emphysema and pulmonary fibrosis, as well as PH.
Note the dilated and hypertrophic right ventricle, and flattening of the intraventricular septum.

The most important cause of pulmonary arterial obstruction (WHO group 4) is chronic thromboembolic pulmonary hypertension (CTEPH).
CTEPH occurs when thrombi fail to fully resolve following an acute pulmonary embolism.
This results in persistent thrombotic obstruction, vascular scarring, and arterial remodeling, which impair pulmonary blood flow and elevate pulmonary artery pressure.

Because these obstructions can potentially be treated with pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA), CTEPH is the only potentially curable form of pulmonary hypertension.

Imaging findings
These images are of a patient with severe CTEPH.

1. Dilation of RA and RV with muscular hypertrophy of RV (white arrow).
2. Tapering of pulmonary artery consistent with chronic thromboembolic disease (grey arrow)
3. Tapering of pulmonary artery and filling defects on angiography.
4. Perfusion defects on ventilation perfusion scan.

Differentiation Acute vs Chronic Emboli

When pulmonary emboli are present, how do we differentiate acute from chronic disease?

1. The diameter of occluded vessels in acute PE is normal or slightly increased, while in chronic PE the occluded vessels are tapered.
   
2. Partial filling defects in acute PE typically show acute angles to the vessel lumen, while obtuse angles are seen in chronic disease due to the wall adhering morphology.
3. Intraluminal webs and bands may be seen in chronic disease due to partial recanalization of the prior occlusive thrombus.
4. Bronchial artery dilation further points towards longstanding abnormalities in the pulmonary arterial flow, with recruitment of the systemic arterial blood flow as alternate source.

Please note that a combination of cloth morphology may be present, which should point you towards the diagnosis of acute PE on top of pre-existing chronic thromboembolic disease.

Computed tomography pulmonary angiography (CTPA) is the imaging modality of choice for the diagnosis of pulmonary embolism (PE).

When interpreting a CTPA, several diagnostic considerations should be evaluated:

• Normal findings
• No evidence of PE, but presence of alternative (cardiac or non-cardiac) pathology potentially explaining pulmonary hypertension
• Acute pulmonary embolism, with or without hemodynamic compromise due to flow obstruction
• Acute-on-chronic thromboembolic disease
• Chronic thromboembolic disease (CTED) without radiologic or clinical signs of pulmonary hypertension
• CTED with features of established pulmonary hypertension

Accurate diagnosis requires familiarity with the distinguishing imaging features of each condition.

Diagnosis of CTEPH

For the definitive diagnosis of Chronic Thromboembolic Pulmonary Hypertension (CTEPH), the following criteria are required:

• CT findings consistent with chronic thromboembolic disease.
• Intravascular measurements confirming the presence of pre-capillary pulmonary hypertension.
• Mismatched perfusion defects on ventilation/perfusion (V/Q) scan or SPECT/CT perfusion imaging.
• A history of continuous anticoagulation therapy for at least 3 months.

Cardiac remodeling in pulmonary emboli

Looking at remodelling of the right ventricle can help to differentiate between acute and chronic emboli.

 Here we have two examples of patients with pulmonary emboli and cardiac remodelling.

Images

1. There is right ventricular dilation with septal flattening, but no evidence of RV wall hypertrophy (black arrow), consistent with an acute increase in RV afterload.
   This can be seen in patients with acute pulmonary embolism.
2. In contrast, in this patient there is dilatation of the right ventricle and atrium with interventricular septal flattening, accompanied by RV wall thickening (white arrow).
   This suggests chronic pressure overload and is indicative of longstanding pulmonary hypertension.
   This can be seen in patients with chronic thromboembolic pulmonary hypertension.

Bronchial artery hypertrophy in CTEPH

Bronchial artery dilation further suggests longstanding abnormalities in pulmonary arterial flow, with recruitment of systemic arterial circulation as an alternative source of pulmonary perfusion.

Image
Dilation of bronchial arteries (arrows) in a patient with PH.
Notice the widened pulmonary arteries.  

Surgical endarterectomy in CTEPH

Surgical endarterectomy for CTEPH is a complex procedure performed under cardiopulmonary bypass with deep hypothermic circulatory arrest.
The goal is to excise organized thromboembolic material from the pulmonary arteries.

Imaging:

• Pre-endarterectomy (Images 1-2): Thrombotic material is seen in both the right and left pulmonary arteries (indicated by white arrows). Notable dilation of the main pulmonary artery (asterix) and hypertrophy of the wall of the right ventricular outflow tract (green arrowhead) is also present.
• Post-endarterectomy (Images 3-4): The pulmonary arteries on both sides are cleared of thrombotic material.

This is the organized clot material that was removed from both right and left pulmonary artery, including segmental branches.

Balloon Pulmonary Angioplasty in CTEPH

Balloon Pulmonary Angioplasty (BPA)  is a catheter-based interventional procedure used to treat  CTEPH. 

BPA is a minimally invasive alternative to surgery for patients with:

• Inoperable CTEPH (e.g., distal disease not accessible by surgery),
• High surgical risk, or
• Residual pulmonary hypertension after pulmonary endarterectomy (PEA).

Images
Before BPA there is acute tapering of the pulmonary artery of the right lower lobe.
After BPA the artery is patent.

Pulmonary artery sarcoma

The most important mimicker of chronic thromboembolic disease is pulmonary artery sarcoma (PAS), a rare primary malignant tumor arising from the vessel wall.

It typically presents as a central filling defect within the pulmonary artery and may initially be mistaken for thrombus.
Although signs of flow obstruction and right heart strain may be present, right ventricular hypertrophy is often absent due to the rapid progression of the tumor.

Imaging features suggestive of PAS include:

• An expansile intraluminal mass, often with an extravascular infiltrative component
• Involvement of the pulmonary valve and/or right ventricular outflow tract
• Absence of ancillary signs of chronic thromboembolic disease (e.g., webs, bands, or calcified thrombi)

Images
There is a large filling defect within the central pulmonary arteries.
Notably, there is no evidence of right ventricular hypertrophy.
Progressive growth despite anticoagulation therapy, along with increased metabolic activity on PET-CT, supports a malignant etiology.

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